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KE Relationships

ID Upstream Event Downstream Event Creation Date Last Updated AOPs
3326 Reduction, 17beta-estradiol synthesis by ovarian granulosa cells Reduction, Vitellogenin synthesis in liver Jul 26, 2024 Jul 26, 2024
  • Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production
5 Reduction, 17beta-estradiol synthesis by ovarian granulosa cells Reduction, Plasma 17beta-estradiol concentrations Nov 29, 2016 Mar 20, 2017
  • Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female
  • Aromatase inhibition leading to reproductive dysfunction
  • Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
  • Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation
  • Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
  • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
9 Decreased, 3-hydroxyacyl-CoA dehydrogenase type-2 activity Decreased, Mitochondrial fatty acid beta-oxidation Nov 29, 2016 Dec 3, 2016
  • Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis
750 Activation, 5HT2c N/A, Unknown Nov 29, 2016 Dec 3, 2016
  • Kidney toxicity induced by activation of 5HT2C
454 ACh Synaptic Accumulation Increased, Atrioventricular block and bradycardia Nov 29, 2016 Nov 29, 2016
    456 ACh Synaptic Accumulation Increased Cholinergic Signaling Nov 29, 2016 Dec 20, 2019
    • Acetylcholinesterase inhibition leading to acute mortality
    • Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement​
    • Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function
    459 ACh Synaptic Accumulation AchE Inhibition Nov 29, 2016 Dec 3, 2016
    • Various neuronal effects induced by elavl3, sox10, and mbp
    1857 ACh Synaptic Accumulation Activation, Muscarinic Acetylcholine Receptors Feb 13, 2019 Sep 3, 2023
    • Acetylcholinesterase Inhibition Leading to Neurodegeneration
    452 AchE Inhibition Increased Mortality Nov 29, 2016 Dec 20, 2019
    • Acetylcholinesterase inhibition leading to acute mortality
    453 AchE Inhibition Decreased, Population trajectory Nov 29, 2016 Dec 20, 2019
      11 AchE Inhibition ACh Synaptic Accumulation Nov 29, 2016 Sep 10, 2023
      • Acetylcholinesterase inhibition leading to acute mortality
      • Acetylcholinesterase Inhibition Leading to Neurodegeneration
      • Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement​
      • Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function
      449 AchE Inhibition Increased, Atrioventricular block and bradycardia Nov 29, 2016 Dec 3, 2016
        450 AchE Inhibition Respiratory distress/arrest Nov 29, 2016 Dec 20, 2019
        • Acetylcholinesterase inhibition leading to acute mortality
        451 AchE Inhibition Increased Cholinergic Signaling Nov 29, 2016 Dec 20, 2019
        • Acetylcholinesterase inhibition leading to acute mortality
        • Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement​
        2653 AchE Inhibition Activation of Cyp2E1 May 16, 2022 May 16, 2022
        • Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality
        3430 AchE Inhibition Activation, Muscarinic Acetylcholine Receptors Nov 22, 2024 Nov 22, 2024
        • Inhibition of acetylcholinesterase (AChE) leading to arrhythmias
        2014 AchE Inhibition Impaired coordination and movement Dec 20, 2019 Dec 20, 2019
        • Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement​
        2016 AchE Inhibition Decrease, Population growth rate Dec 20, 2019 Dec 20, 2019
        • Acetylcholinesterase inhibition leading to acute mortality
        2007 AchE Inhibition Cardiovascular dysregulation Nov 25, 2019 Dec 20, 2019
        • Acetylcholinesterase inhibition leading to acute mortality
        3063 AchE Inhibition Increase, CNS Neural cell death Oct 17, 2023 Oct 17, 2023
        • Various neuronal effects induced by elavl3, sox10, and mbp
        3064 AchE Inhibition Dysfunctional synapses Oct 17, 2023 Oct 17, 2023
        • Various neuronal effects induced by elavl3, sox10, and mbp
        16 Altered expression of AHR/ARNT pathway-dependent genes Altered, Cardiovascular development/function Nov 29, 2016 Dec 3, 2016
          17 Altered expression of AHR/ARNT pathway-dependent genes Up Regulation, CYP1A1 Nov 29, 2016 Dec 3, 2016
            18 Activation, AhR Altered expression of AHR/ARNT pathway-dependent genes Nov 29, 2016 Dec 3, 2016
              19 Activation, AhR Up Regulation, CYP1A1 Nov 29, 2016 Dec 3, 2016
              • AhR activation leading to hepatic steatosis
              2888 Activation, AhR N/A, Liver Steatosis Apr 13, 2023 Apr 13, 2023
                2883 Activation, AhR Induction, Upregulation of glucuronyltransferase activity Apr 12, 2023 Apr 12, 2023
                • AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                473 Activation, AhR Inhibition, Mitochondrial fatty acid beta-oxidation Nov 29, 2016 Dec 3, 2016
                • AhR activation leading to hepatic steatosis
                495 Activation, AhR Up Regulation, CD36 Nov 29, 2016 Dec 3, 2016
                • AhR activation leading to hepatic steatosis
                496 Activation, AhR Increased, FA Influx Nov 29, 2016 Dec 3, 2016
                  499 Activation, AhR Decreased, PCK1 expression (control point for glycolysis/gluconeogenesis pathway) Nov 29, 2016 Dec 3, 2016
                  • AhR activation leading to hepatic steatosis
                  506 Activation, AhR Up Regulation, LDLR (low density lipoprotein receptor) Nov 29, 2016 Dec 3, 2016
                  • AhR activation leading to hepatic steatosis
                  509 Activation, AhR Suppression, VLDL secretion Nov 29, 2016 Dec 3, 2016
                  • AhR activation leading to hepatic steatosis
                  984 Activation, AhR Increase, Early Life Stage Mortality Nov 29, 2016 Apr 14, 2019
                  • Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF
                  • Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2
                  • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity
                  • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development
                  869 Activation, AhR Induction, CYP1A2/CYP1A5 Nov 29, 2016 May 7, 2018
                  • Aryl hydrocarbon receptor activation leading to uroporphyria
                  • AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                  972 Activation, AhR dimerization, AHR/ARNT Nov 29, 2016 Mar 22, 2018
                  • Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF
                  • Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2
                  • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                  • AhR activation leading to preeclampsia
                  • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development
                  • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity
                  • Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosis
                  1992 Activation, AhR Increase, DNMT expression Oct 30, 2019 Oct 30, 2019
                    3482 Activation, AhR Decreased, ovarian reserve Jan 22, 2025 Jan 22, 2025
                      3219 Activation, AhR Increased, Liver Steatosis May 14, 2024 Jan 30, 2025
                      • AhR activation leading to liver fibrosis
                      2687 Activation, AhR Increase, slincR expression Jun 30, 2022 Jun 30, 2022
                        2688 Activation, AhR Decrease, sox9 expression Jun 30, 2022 Apr 13, 2023
                        • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development
                        • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity
                        2689 Activation, AhR Smaller and morphologically distorted facial cartilage structures Jun 30, 2022 Apr 13, 2023
                        • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development
                        2765 Activation, AhR Altered, Cardiovascular development/function Sep 27, 2022 Oct 21, 2022
                        • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity
                        2572 Activation, AhR Increased, Invasion Feb 15, 2022 Mar 5, 2024
                        • Activation of the AhR leading to metastatic breast cancer
                        2571 Activation, AhR Increased, Migration (Endothelial Cells) Feb 15, 2022 Feb 29, 2024
                        • Activation of the AhR leading to metastatic breast cancer
                        2570 Activation, AhR Increased, Motility Feb 15, 2022 Feb 29, 2024
                        • Activation of the AhR leading to metastatic breast cancer
                        2569 Activation, AhR Apoptosis Feb 15, 2022 Dec 20, 2022
                        • Activation of the AhR leading to metastatic breast cancer
                        2568 Activation, AhR Increase, Inflammation Feb 15, 2022 Mar 5, 2024
                        • Activation of the AhR leading to metastatic breast cancer
                        1656 Activation, AhR Up Regulation, SCD-1 Aug 31, 2017 Aug 31, 2017
                        • AhR activation leading to hepatic steatosis
                        1384 Agonism, Androgen receptor Reduction, 17beta-estradiol synthesis by ovarian granulosa cells Mar 17, 2017 Mar 20, 2017
                        • Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
                        1385 Agonism, Androgen receptor Reduction, Vitellogenin synthesis in liver Mar 17, 2017 Mar 20, 2017
                        • Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
                        3392 Agonism, Androgen receptor Altered, Transcription of genes by the AR Nov 16, 2024 Nov 16, 2024
                        • Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
                        • Androgen receptor activation leading to prostate cancer
                        3450 Agonism, Androgen receptor Increase, cell proliferation (hepatocytes) Dec 23, 2024 Dec 23, 2024
                        • Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                        3463 Agonism, Androgen receptor Decreased, Apoptosis (Epithelial Cells) Dec 31, 2024 Dec 31, 2024
                        • Androgen receptor activation leading to prostate cancer
                        3462 Agonism, Androgen receptor Inflammatory events Dec 31, 2024 Dec 31, 2024
                        • Androgen receptor activation leading to prostate cancer
                        3378 Agonism, Androgen receptor Androgen receptor activation, increased Nov 2, 2024 Nov 24, 2024
                        • Androgen receptor agonism leading to long anogenital distance in female offspring
                        31 Agonism, Androgen receptor Reduction, Gonadotropins, circulating concentrations Nov 29, 2016 Mar 20, 2017
                        • Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
                        32 Agonism, Androgen receptor Reduction, Testosterone synthesis by ovarian theca cells Nov 29, 2016 Mar 20, 2017
                        • Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
                        2926 Agonism, Androgen receptor Reduction, the ratio of E2/11-KT in plasma May 22, 2023 May 22, 2023
                          2349 Agonism, Androgen receptor Increased, Male Biased Sex Ratio Apr 12, 2021 Jan 3, 2023
                          • Androgen receptor agonism leading to male-biased sex ratio
                          2260 Agonism, Androgen receptor Increased, Differentiation to Testis Jan 12, 2021 Jan 3, 2023
                          • Androgen receptor agonism leading to male-biased sex ratio
                          2201 Antagonism, Androgen receptor Altered, Transcription of genes by the AR Nov 2, 2020 Feb 2, 2021
                          • Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)
                          2130 Antagonism, Androgen receptor Decrease, AR activation May 11, 2020 Mar 18, 2025
                          • Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring
                          • Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspring
                          • Androgen receptor (AR) antagonism leading to hypospadias in male (mammalian) offspring
                          • Androgen receptor (AR) antagonism leading to decreased fertility in females
                          2133 Antagonism, Androgen receptor nipple retention, increased May 11, 2020 Jan 11, 2023
                          • Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspring
                          3397 Antagonism, Androgen receptor Alteration, Wnt pathway Nov 18, 2024 Nov 18, 2024
                          • Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)
                          2123 Antagonism, Androgen receptor AGD, decreased May 11, 2020 Aug 7, 2020
                            36 Reduction, Angiogenesis Impairment, Endothelial network Nov 29, 2016 Jan 18, 2022
                            • Disruption of VEGFR Signaling Leading to Developmental Defects
                            43 Decrease, Aromatase (Cyp19a1) Reduction, 17beta-estradiol synthesis by ovarian granulosa cells Nov 29, 2016 Dec 3, 2016
                              45 Inhibition, Aromatase Reduction, 17beta-estradiol synthesis by ovarian granulosa cells Nov 29, 2016 Nov 30, 2016
                              • Aromatase inhibition leading to reproductive dysfunction
                              1767 Inhibition, Aromatase Altered regulation, Alpha hemoglobin Sep 13, 2018 Sep 13, 2018
                                3394 Inhibition, Aromatase Inhibition, plasma aromatase activity Nov 16, 2024 Nov 16, 2024
                                • Aromatase inhibition leads to reproductive toxicity (including growth and developmental toxicity) in adult female zebrafish
                                3523 Inhibition, Aromatase Decreased, E2 Apr 8, 2025 Apr 8, 2025
                                  2144 Inhibition, Aromatase Reduction, E2 Synthesis by the undifferentiated gonad Jun 15, 2020 Jul 11, 2022
                                  • Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation
                                  2167 Inhibition, Aromatase Increased, Differentiation to Testis Jul 28, 2020 Dec 28, 2022
                                  • Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation
                                  2350 Inhibition, Aromatase Increased, Male Biased Sex Ratio Apr 13, 2021 Jan 10, 2023
                                  • Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation
                                  2412 Increased Cholinergic Signaling Cognitive function, decreased Jun 24, 2021 Sep 1, 2021
                                  • Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function
                                  2410 Increased Cholinergic Signaling Neuronal network function, Decreased Jun 24, 2021 Sep 1, 2021
                                  • Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function
                                  2005 Increased Cholinergic Signaling Cardiovascular dysregulation Nov 25, 2019 Dec 20, 2019
                                  • Acetylcholinesterase inhibition leading to acute mortality
                                  2011 Increased Cholinergic Signaling Impaired coordination and movement Dec 20, 2019 Dec 20, 2019
                                  • Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement​
                                  51 Increased Cholinergic Signaling Decrease, Population growth rate Nov 29, 2016 Dec 3, 2016
                                    434 Increased Cholinergic Signaling Increased Mortality Nov 29, 2016 Dec 3, 2016
                                      457 Increased Cholinergic Signaling Respiratory distress/arrest Nov 29, 2016 Dec 20, 2019
                                      • Acetylcholinesterase inhibition leading to acute mortality
                                      3455 Decrease, Mitochondrial ATP production Disruption, Glucolipid metabolism Dec 24, 2024 Dec 24, 2024
                                      • DBDPE-induced inhibition of mitochondrial complex Ⅰ leading to population decline via neurotoxicity and metabotoxicity.
                                      3456 Decrease, Mitochondrial ATP production Disruption, neurotransmitter release Dec 24, 2024 Dec 24, 2024
                                      • DBDPE-induced inhibition of mitochondrial complex Ⅰ leading to population decline via neurotoxicity and metabotoxicity.
                                      1670 Decrease, Mitochondrial ATP production Decrease, Leaf cell mitosis Oct 10, 2017 Oct 10, 2017
                                      • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                      1682 Decrease, Mitochondrial ATP production Increase, Cytotoxicity (renal tubular cell) Oct 25, 2017 Oct 25, 2017
                                      • Renal protein alkylation leading to kidney toxicity
                                      1601 Decrease, Mitochondrial ATP production Decrease, Oogenesis Jun 29, 2017 Jun 29, 2017
                                        1739 Decrease, Mitochondrial ATP production Decrease, Growth May 24, 2018 May 24, 2018
                                          1750 Decrease, Mitochondrial ATP production Increase, Apoptosis Jun 12, 2018 Jun 12, 2018
                                            2823 Decrease, Mitochondrial ATP production Decrease, Cardiac contractility Jan 5, 2023 Jan 5, 2023
                                            • Mitochondrial complexes inhibition leading to heart failure via decreased ATP production
                                            1873 Decrease, Mitochondrial ATP production Increase, Necrosis Mar 19, 2019 Mar 19, 2019
                                              2551 Decrease, Mitochondrial ATP production Decrease, Reproduction Jan 21, 2022 Jan 21, 2022
                                              • Deposition of ionising energy leading to population decline via mitochondrial dysfunction
                                              927 Inhibition, Bile Salt Export Pump (ABCB11) Bile accumulation, Pathological condition Nov 29, 2016 Dec 3, 2016
                                              • Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
                                              59 Reduction, Ca and HCO3 transport to shell gland Reduction, Eggshell thickness Nov 29, 2016 Dec 3, 2016
                                              • Cyclooxygenase inhibition leading reproductive failure
                                              60 Increase, Ca++ (intracellular) Disruption, Mitochondrial electron transport chain Nov 29, 2016 Dec 3, 2016
                                              • Calcium-mediated neuronal ROS production and energy imbalance
                                              61 Inhibition, Ca++ ATPase Increase, Ca++ (intracellular) Nov 29, 2016 Dec 3, 2016
                                              • Calcium-mediated neuronal ROS production and energy imbalance
                                              62 Decreased, Calcium influx Impairment, Learning and memory Nov 29, 2016 Dec 3, 2016
                                                347 Decreased, Calcium influx BDNF, Reduced Nov 29, 2016 Jun 13, 2018
                                                • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging
                                                • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
                                                66 Up Regulation, CD36 Increase, FA Influx Nov 29, 2016 Mar 27, 2024
                                                • LXR activation leading to hepatic steatosis
                                                • Pregnane X Receptor (PXR) activation leads to liver steatosis
                                                501 Up Regulation, CD36 Increased, FA Influx Nov 29, 2016 Dec 3, 2016
                                                • AhR activation leading to hepatic steatosis
                                                • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                2262 Up Regulation, CD36 Increased, Fatty acid uptake Jan 15, 2021 Jan 15, 2021
                                                  924 Cell injury/death Release, Cytokine Nov 29, 2016 Nov 9, 2018
                                                    3198 Cell injury/death Mitochondrial dysfunction Apr 17, 2024 Apr 17, 2024
                                                      3197 Cell injury/death Disruption of the intestinal barrier Apr 17, 2024 Apr 17, 2024
                                                      • Endocytotic lysosomal uptake leads to intestinal barrier disruption
                                                      3244 Cell injury/death Increase, Cardiac remodelling Jun 4, 2024 Jun 4, 2024
                                                      • Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress
                                                      3245 Cell injury/death Decrease, Cardiac contractility Jun 4, 2024 Jun 4, 2024
                                                      • Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress
                                                      67 Cell injury/death Increased, Activation and Recruitment of Hepatic macrophages (Kupffer Cells) Nov 29, 2016 Nov 29, 2016
                                                        68 Cell injury/death Activation, Stellate cells Nov 29, 2016 Nov 29, 2016
                                                        • Protein Alkylation leading to Liver Fibrosis
                                                        • AhR activation leading to liver fibrosis
                                                        355 Cell injury/death Synaptogenesis, Decreased Nov 29, 2016 Nov 29, 2016
                                                        • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
                                                        364 Cell injury/death N/A, Neurodegeneration Nov 29, 2016 Sep 10, 2023
                                                        • Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.
                                                        • Acetylcholinesterase Inhibition Leading to Neurodegeneration
                                                        365 Cell injury/death Neuroinflammation Nov 29, 2016 Jul 15, 2022
                                                        • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging
                                                        • Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory
                                                        • Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.
                                                        1718 Cell injury/death Tissue resident cell activation Feb 1, 2018 Aug 2, 2018
                                                        • Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory
                                                        • Protein Alkylation leading to Liver Fibrosis
                                                        1688 Cell injury/death Neuronal network function, Decreased Nov 9, 2017 Feb 5, 2020
                                                        • Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory
                                                        1830 Cell injury/death Necrotic Tissue Jan 7, 2019 Mar 7, 2019
                                                        • IKK complex inhibition leading to liver injury
                                                        • Mitochondrial complex inhibition leading to liver injury
                                                        1831 Cell injury/death Activation, Tissue resident cells (Kuppfer cells) Jan 7, 2019 Jan 7, 2019
                                                        • IKK complex inhibition leading to liver injury
                                                        1863 Cell injury/death Neurodegeneration Feb 19, 2019 Feb 19, 2019
                                                          1776 Cell injury/death Increased pro-inflammatory mediators Nov 12, 2018 Nov 12, 2018
                                                          • Endocytic lysosomal uptake leading to liver fibrosis
                                                          2890 Cell injury/death Leukocyte recruitment/activation Apr 13, 2023 Apr 13, 2023
                                                            2875 Cell injury/death Hippocampal Physiology, Altered Apr 5, 2023 Apr 5, 2023
                                                            • Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms
                                                            2767 Cell injury/death Decrease, Growth Sep 27, 2022 Sep 27, 2022
                                                            • Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calcium
                                                            • Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell death
                                                            • Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity
                                                            • Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swelling
                                                            • Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell death
                                                            • Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and cell death
                                                            • Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and cell death
                                                            69 Proliferation, Cell proliferation in the absence of cytotoxicity Hyperplasia, Hyperplasia Nov 29, 2016 Dec 3, 2016
                                                            • Uncharacterized liver damage leading to hepatocellular carcinoma
                                                            70 Induction, Chitin degradation and resorption Induction, Pre-mature molting Nov 29, 2016 Dec 3, 2016
                                                              667 Reduction, Ionotropic GABA receptor chloride channel conductance Reduction, Neuronal synaptic inhibition Nov 29, 2016 Apr 29, 2019
                                                              • Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain
                                                              483 Activation, ChREBP Increased, De Novo FA synthesis Nov 29, 2016 Dec 3, 2016
                                                              • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                              77 Activation, ChREBP Synthesis, De Novo Fatty Acid (FA) Nov 29, 2016 Dec 3, 2016
                                                              • LXR activation leading to hepatic steatosis
                                                              82 Accumulation, Collagen N/A, Liver fibrosis Nov 29, 2016 Dec 5, 2018
                                                              • Protein Alkylation leading to Liver Fibrosis
                                                              • Endocytic lysosomal uptake leading to liver fibrosis
                                                              2139 Accumulation, Collagen Lung fibrosis May 15, 2020 May 15, 2020
                                                              • Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis
                                                              • Binding to ACE2 leading to lung fibrosis
                                                              1629 Accumulation, Collagen Pulmonary fibrosis Jul 26, 2017 May 18, 2023
                                                              • Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis
                                                              • Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis
                                                              1700 N/A, Covalent binding to protein, possibly lysine residue Activation, Dendritic Cells Dec 7, 2017 Sep 24, 2020
                                                                88 N/A, Covalent binding to protein, possibly lysine residue Activation, Inflammatory cytokines, chemokines, cytoprotective gene pathways Nov 29, 2016 Sep 24, 2020
                                                                  93 Production, Critical Metabolites (CGA 330050 and CGA 265307) Induction, Liver “Dysfunctional” Changes by CGA 330050 Nov 29, 2016 Dec 3, 2016
                                                                  • Inhibition of iNOS, hepatotoxicity, and regenerative proliferation leading to liver tumors
                                                                  94 Reduction, Cumulative fecundity and spawning Decrease, Population growth rate Nov 29, 2016 Mar 20, 2017
                                                                  • Aromatase inhibition leading to reproductive dysfunction
                                                                  • Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
                                                                  • Estrogen receptor antagonism leading to reproductive dysfunction
                                                                  • Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation
                                                                  • Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
                                                                  • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                                                                  • Inhibition of 5α-reductase leading to impaired fecundity in female fish
                                                                  • Deposition of energy leading to population decline via DNA strand breaks and follicular atresia
                                                                  • Deposition of energy leading to population decline via DNA strand breaks and oocyte apoptosis
                                                                  • Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production
                                                                  • Deposition of energy leading to population decline via DNA oxidation and follicular atresia
                                                                  • Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis
                                                                  2142 Reduction, Cumulative fecundity and spawning Decline, Population May 25, 2020 May 25, 2020
                                                                    2924 Reduction, Cumulative fecundity and spawning Decreased, Population trajectory May 22, 2023 May 22, 2023
                                                                    • Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
                                                                    • Aromatase inhibition leads to reproductive toxicity (including growth and developmental toxicity) in adult female zebrafish
                                                                    670 Inhibition, Cyclooxygenase activity Reduced, Prostaglandin F2alpha synthesis, ovary Nov 29, 2016 Dec 3, 2016
                                                                    • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior
                                                                    681 Inhibition, Cyclooxygenase activity Decreased, Prostaglandin F2alpha synthesis, ovary Nov 29, 2016 Dec 3, 2016
                                                                    • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release
                                                                    686 Inhibition, Cyclooxygenase activity Reduced, Prostaglandins, ovary Nov 29, 2016 Dec 3, 2016
                                                                    • Cyclooxygenase inhibition leading to reproductive dysfunction
                                                                    689 Inhibition, Cyclooxygenase activity Reduced, Prostaglandin E2 concentration, hypothalamus Nov 29, 2016 Dec 3, 2016
                                                                    • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition
                                                                    • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
                                                                    95 Inhibition, Cyclooxygenase activity Reduction, Prostaglandin E2 concentration Nov 29, 2016 Dec 3, 2016
                                                                    • Cyclooxygenase inhibition leading reproductive failure
                                                                    96 Up Regulation, CYP1A1 Peptide Oxidation Nov 29, 2016 Dec 3, 2016
                                                                      104 Up Regulation, CYP1B1 Reduction, 17beta-estradiol synthesis by ovarian granulosa cells Nov 29, 2016 Dec 3, 2016
                                                                        108 Release, Cytokine Increase, Inflammation Nov 29, 2016 Dec 3, 2016
                                                                        • Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
                                                                        2455 Release, Cytokine Neutrophil activation, Increased Aug 4, 2021 Aug 4, 2021
                                                                        • Endothelial cell dysfunction leading to thromboinflammation
                                                                        2454 Release, Cytokine Platelet activation, Increased Aug 4, 2021 Aug 4, 2021
                                                                        • Endothelial cell dysfunction leading to thromboinflammation
                                                                        925 Release, Cytokine Infiltration, Inflammatory cytokines Nov 29, 2016 Dec 3, 2016
                                                                          994 Release, Cytokine Infiltration, Inflammatory cells Nov 29, 2016 Nov 29, 2016
                                                                            1963 Release, Cytokine Recruitment of inflammatory cells Jul 3, 2019 Jul 3, 2019
                                                                            • Frustrated phagocytosis-induced lung cancer
                                                                            • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                            110 Synthesis, De Novo Fatty Acid (FA) Accumulation, Triglyceride Nov 29, 2016 Mar 29, 2024
                                                                            • LXR activation leading to hepatic steatosis
                                                                            • Liver X Receptor (LXR) activation leads to liver steatosis
                                                                            23 Alkylation, DNA Increase, Heritable mutations in offspring Nov 29, 2016 Nov 29, 2016
                                                                            • Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutations
                                                                            24 Alkylation, DNA Inadequate DNA repair Nov 29, 2016 Dec 10, 2019
                                                                            • Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutations
                                                                            • Alkylation of DNA leading to cancer 1
                                                                            • Alkylation of DNA leading to reduced sperm count
                                                                            25 Alkylation, DNA Increase, Mutations Nov 29, 2016 Nov 29, 2016
                                                                            • Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutations
                                                                            • Alkylation of DNA leading to cancer 1
                                                                            901 Alkylation, DNA Increase, Cancer Nov 29, 2016 Dec 3, 2016
                                                                            • Alkylation of DNA leading to cancer 1
                                                                            999 Increase, EcR agonism Decreased, synthesis and secretion of molting fluid proteases Nov 29, 2016 Dec 3, 2016
                                                                              998 Increase, EcR agonism Decrease, Circulating ETH Nov 29, 2016 Dec 3, 2016
                                                                                1007 Increase, EcR agonism Decreased, Synthesis of molting fluid proteases Nov 29, 2016 Dec 3, 2016
                                                                                  1343 Increase, EcR agonism Increase, E75b expression Feb 9, 2017 Feb 9, 2017
                                                                                  • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                  116 Increase, EcR agonism Induction, Chitin degradation and resorption Nov 29, 2016 Dec 3, 2016
                                                                                    2821 Inhibition, ETC complexes of the respiratory chain Mitochondrial dysfunction Jan 5, 2023 Jan 5, 2023
                                                                                    • Mitochondrial complexes inhibition leading to heart failure via decreased ATP production
                                                                                    • Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress
                                                                                    2636 Inhibition, ETC complexes of the respiratory chain Decrease, MMP Apr 8, 2022 Apr 8, 2022
                                                                                    • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                    3241 Inhibition, ETC complexes of the respiratory chain Oxidative Stress May 31, 2024 May 31, 2024
                                                                                    • Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity
                                                                                    123 Reduction, Eggshell thickness N/A, Reproductive failure Nov 29, 2016 Dec 3, 2016
                                                                                    • Cyclooxygenase inhibition leading reproductive failure
                                                                                    125 Impairment, Endothelial network Insufficiency, Vascular Nov 29, 2016 Jan 18, 2022
                                                                                    • Disruption of VEGFR Signaling Leading to Developmental Defects
                                                                                    976 Impairment, Endothelial network Altered, Cardiovascular development/function Nov 29, 2016 Jun 9, 2017
                                                                                    • Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF
                                                                                    126 Agonism, Estrogen receptor Altered, Reproductive behaviour Nov 29, 2016 Dec 3, 2016
                                                                                    • Estrogen receptor agonism leading to reproductive dysfunction
                                                                                    127 Agonism, Estrogen receptor Impaired development of, Reproductive organs Nov 29, 2016 Dec 3, 2016
                                                                                    • Estrogen receptor agonism leading to reproductive dysfunction
                                                                                    128 Agonism, Estrogen receptor Increase, Vitellogenin synthesis in liver Nov 29, 2016 Jun 24, 2024
                                                                                    • Estrogen receptor agonism leading to reproductive dysfunction
                                                                                    • Estrogen receptor agonism leading to reduced survival and population growth due to renal failure
                                                                                    • Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liver
                                                                                    3525 Agonism, Estrogen receptor Decreased, Progesterone from corpus luteum Apr 17, 2025 Apr 17, 2025
                                                                                    • Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)
                                                                                    129 Antagonism, Estrogen receptor Reduction, Vitellogenin synthesis in liver Nov 29, 2016 Nov 30, 2016
                                                                                    • Estrogen receptor antagonism leading to reproductive dysfunction
                                                                                    3120 Antagonism, Estrogen receptor inhibition, EKR1/2 signaling pathway Jan 25, 2024 Jan 25, 2024
                                                                                    • Estrogen antagonism leading to increased risk of autism-like behavior
                                                                                    2613 Antagonism, Estrogen receptor EMT Mar 22, 2022 Aug 27, 2023
                                                                                    • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                    132 Increase, FA Influx Accumulation, Triglyceride Nov 29, 2016 Mar 29, 2024
                                                                                    • LXR activation leading to hepatic steatosis
                                                                                    • Pregnane X Receptor (PXR) activation leads to liver steatosis
                                                                                    133 Activation, FAS Synthesis, De Novo Fatty Acid (FA) Nov 29, 2016 Dec 3, 2016
                                                                                    • LXR activation leading to hepatic steatosis
                                                                                    1422 Activation, FAS Increased, lipogenesis Apr 13, 2017 Apr 13, 2017
                                                                                      136 N/A, Gap Reduction, Ca and HCO3 transport to shell gland Nov 29, 2016 Dec 3, 2016
                                                                                      • Cyclooxygenase inhibition leading reproductive failure
                                                                                      385 Activation, Glucocorticoid Receptor Induction, IKB inhibitory protein Nov 29, 2016 Dec 3, 2016
                                                                                      • Glucocorticoid Receptor Activation Leading to Increased Disease Susceptibility
                                                                                      3526 Activation, Glucocorticoid Receptor Altered cell differentiation signaling Apr 18, 2025 Apr 18, 2025
                                                                                      • Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
                                                                                      2041 Activation, Glucocorticoid Receptor Decreased, PPAR-alpha activation Feb 22, 2020 Feb 22, 2020
                                                                                        2039 Activation, Glucocorticoid Receptor Decreased, Mitochondrial Fatty Acid Beta Oxidation Feb 22, 2020 Feb 22, 2020
                                                                                          1451 Activation, Glucocorticoid Receptor Reduced, BDNF Apr 14, 2017 Apr 14, 2017
                                                                                          • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                          2266 Activation, Glucocorticoid Receptor Decrease, ACAD Jan 15, 2021 Jan 15, 2021
                                                                                          • Glucocorticoid Receptor activation leading to hepatic steatosis
                                                                                          2261 Activation, Glucocorticoid Receptor Up Regulation, CD36 Jan 15, 2021 Jan 15, 2021
                                                                                            143 Reduction, Gonadotropins, circulating concentrations Reduction, Testosterone synthesis by ovarian theca cells Nov 29, 2016 Mar 20, 2017
                                                                                            • Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
                                                                                            2878 Depletion, GSH Increase, ROS Apr 5, 2023 Sep 14, 2023
                                                                                            • Glutathione conjugation leading to reproductive dysfunction via oxidative stress
                                                                                            146 Increased, Activation and Recruitment of Hepatic macrophages (Kupffer Cells) Peptide Oxidation Nov 29, 2016 Dec 3, 2016
                                                                                              147 Increased, Activation and Recruitment of Hepatic macrophages (Kupffer Cells) Up Regulation, TGFbeta1 expression Nov 29, 2016 Nov 29, 2016
                                                                                                996 N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects Alterations, Cellular proliferation / hyperplasia Nov 29, 2016 Dec 2, 2016
                                                                                                • Sustained AhR Activation leading to Rodent Liver Tumours
                                                                                                154 Decreased, HSD17B10 expression Decreased, 3-hydroxyacyl-CoA dehydrogenase type-2 activity Nov 29, 2016 Dec 3, 2016
                                                                                                • Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis
                                                                                                158 Hyperplasia, Hyperplasia Promotion, Hepatocelluar carcinoma Nov 29, 2016 Dec 3, 2016
                                                                                                • Uncharacterized liver damage leading to hepatocellular carcinoma
                                                                                                386 Induction, IKB inhibitory protein Inhibition, Nuclear factor kappa B (NF-kB) Nov 29, 2016 Dec 3, 2016
                                                                                                • Glucocorticoid Receptor Activation Leading to Increased Disease Susceptibility
                                                                                                159 Inhibition, Inducible Nitric Oxide Synthase by Metabolite CGA 265307 Induction, Sustained Hepatotoxicity Nov 29, 2016 Dec 3, 2016
                                                                                                • Inhibition of iNOS, hepatotoxicity, and regenerative proliferation leading to liver tumors
                                                                                                781 Increase, Inflammation Increase, Regenerative cell proliferation (forestomach epithelial cells) Nov 29, 2016 Dec 3, 2016
                                                                                                • Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)
                                                                                                929 Increase, Inflammation Cholestasis, Pathology Nov 29, 2016 Dec 3, 2016
                                                                                                • Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
                                                                                                2976 Increase, Inflammation General Apoptosis Jul 31, 2023 Oct 19, 2023
                                                                                                • Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway
                                                                                                1839 Increase, Inflammation Fibroproliferative airway lesions Jan 30, 2019 Jan 30, 2019
                                                                                                • α-diketone-induced bronchiolitis obliterans
                                                                                                3357 Increase, Inflammation Oligodendrocyte death, increased Oct 1, 2024 Oct 1, 2024
                                                                                                • Inhibition of neuropathy target esterase leading to delayed neuropathy via increased inflammation
                                                                                                3358 Increase, Inflammation Demyelination, increased Oct 1, 2024 Oct 1, 2024
                                                                                                • Inhibition of neuropathy target esterase leading to delayed neuropathy via increased inflammation
                                                                                                1724 Increase, Inflammation EMT Mar 18, 2018 Jan 30, 2019
                                                                                                • Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis
                                                                                                • α-diketone-induced bronchiolitis obliterans
                                                                                                1722 Increase, Inflammation Expression of Collagen Mar 18, 2018 Mar 18, 2018
                                                                                                  2573 Increase, Inflammation Increased, Invasion Feb 15, 2022 Mar 5, 2024
                                                                                                  • Activation of the AhR leading to metastatic breast cancer
                                                                                                  2574 Increase, Inflammation Increase, angiogenesis Feb 15, 2022 Dec 20, 2022
                                                                                                  • Activation of the AhR leading to metastatic breast cancer
                                                                                                  1699 Activation, Inflammatory cytokines, chemokines, cytoprotective gene pathways Activation, Dendritic Cells Dec 7, 2017 Dec 3, 2020
                                                                                                    388 Suppression, Inflammatory cytokines Decreased, Lymphocytes Nov 29, 2016 Dec 3, 2016
                                                                                                    • Glucocorticoid Receptor Activation Leading to Increased Disease Susceptibility
                                                                                                    164 Inadequate DNA repair Increase, Mutations Nov 29, 2016 Mar 8, 2024
                                                                                                    • Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutations
                                                                                                    • Alkylation of DNA leading to cancer 2
                                                                                                    • Alkylation of DNA leading to cancer 1
                                                                                                    • Oxidative DNA damage leading to chromosomal aberrations and mutations
                                                                                                    • Deposition of energy leading to lung cancer
                                                                                                    • Bulky DNA adducts leading to mutations
                                                                                                    • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                                    • Deposition of energy leading to occurrence of cataracts
                                                                                                    1910 Inadequate DNA repair Increase, DNA strand breaks May 19, 2019 Jan 9, 2023
                                                                                                    • Oxidative DNA damage leading to chromosomal aberrations and mutations
                                                                                                    • Alkylation of DNA leading to reduced sperm count
                                                                                                    1912 Inadequate DNA repair Increase, Chromosomal aberrations May 19, 2019 Dec 17, 2024
                                                                                                    • Oxidative DNA damage leading to chromosomal aberrations and mutations
                                                                                                    • Deposition of energy leading to lung cancer
                                                                                                    • Deposition of energy leading to occurrence of cataracts
                                                                                                    2817 Inadequate DNA repair Cataracts Dec 18, 2022 Mar 11, 2024
                                                                                                    • Deposition of energy leading to occurrence of cataracts
                                                                                                    168 N/A, Interferences with SH-/selen-proteins Depletion, GSH Nov 29, 2016 Dec 3, 2016
                                                                                                      169 Increase, Liver and splenic hemosiderosis N/A, Methemoglobinemia, decreased hemoglobin, hematocrit, red blood cell number Nov 29, 2016 Dec 3, 2016
                                                                                                      • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                      170 Induction, Liver “Dysfunctional” Changes by CGA 330050 Inhibition, Inducible Nitric Oxide Synthase by Metabolite CGA 265307 Nov 29, 2016 Dec 3, 2016
                                                                                                      • Inhibition of iNOS, hepatotoxicity, and regenerative proliferation leading to liver tumors
                                                                                                      172 Activation, Long term AHR receptor driven direct and indirect gene expression changes N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects Nov 29, 2016 Nov 29, 2016
                                                                                                      • Sustained AhR Activation leading to Rodent Liver Tumours
                                                                                                      874 Activation, Long term AHR receptor driven direct and indirect gene expression changes Changes/Inhibition, Cellular Homeostasis and Apoptosis Nov 29, 2016 Nov 29, 2016
                                                                                                      • Sustained AhR Activation leading to Rodent Liver Tumours
                                                                                                      875 Activation, Long term AHR receptor driven direct and indirect gene expression changes Alterations, Cellular proliferation / hyperplasia Nov 29, 2016 Nov 29, 2016
                                                                                                      • Sustained AhR Activation leading to Rodent Liver Tumours
                                                                                                      876 Activation, Long term AHR receptor driven direct and indirect gene expression changes Formation, Hepatocellular and Bile duct tumors Nov 29, 2016 Nov 29, 2016
                                                                                                      • Sustained AhR Activation leading to Rodent Liver Tumours
                                                                                                      479 Activation, LXR Activation, SREBF1 Nov 29, 2016 Dec 3, 2016
                                                                                                      • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                      490 Activation, LXR Up Regulation, FAS Nov 29, 2016 Dec 3, 2016
                                                                                                      • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                      491 Activation, LXR Up Regulation, SCD-1 Nov 29, 2016 Dec 3, 2016
                                                                                                      • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                      510 Activation, LXR Inhibition, PPAR alpha Nov 29, 2016 Dec 3, 2016
                                                                                                      • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                      516 Activation, LXR Up Regulation, Acetyl-CoA carboxylase-1 (ACC-1) Nov 29, 2016 Dec 3, 2016
                                                                                                      • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                      176 Activation, LXR Activation, SCD-1 Nov 29, 2016 Dec 3, 2016
                                                                                                      • LXR activation leading to hepatic steatosis
                                                                                                      173 Activation, LXR Up Regulation, CD36 Nov 29, 2016 Dec 3, 2016
                                                                                                      • LXR activation leading to hepatic steatosis
                                                                                                      • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                      177 Activation, LXR Activation, SREBP-1c Nov 29, 2016 Dec 3, 2016
                                                                                                      • LXR activation leading to hepatic steatosis
                                                                                                      174 Activation, LXR Activation, ChREBP Nov 29, 2016 Dec 3, 2016
                                                                                                      • LXR activation leading to hepatic steatosis
                                                                                                      • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                      175 Activation, LXR Activation, FAS Nov 29, 2016 Dec 3, 2016
                                                                                                      • LXR activation leading to hepatic steatosis
                                                                                                      3103 Activation, LXR Increased, Expression of LXR activated genes Dec 7, 2023 Mar 29, 2024
                                                                                                      • Liver X Receptor (LXR) activation leads to liver steatosis
                                                                                                      390 Decreased, Lymphocytes Suppression, Immune system Nov 29, 2016 Dec 3, 2016
                                                                                                      • Glucocorticoid Receptor Activation Leading to Increased Disease Susceptibility
                                                                                                      389 Decreased, Lymphocytes Increased, Disease susceptibility Nov 29, 2016 Dec 3, 2016
                                                                                                        182 N/A, Methemoglobinemia, decreased hemoglobin, hematocrit, red blood cell number N/A, Cyanosis occurs Nov 29, 2016 Dec 3, 2016
                                                                                                        • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                        363 Mitochondrial dysfunction Cell injury/death Nov 29, 2016 Nov 29, 2016
                                                                                                        • Endocytic lysosomal uptake leading to liver fibrosis
                                                                                                        • Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.
                                                                                                        • Endocytotic lysosomal uptake leads to intestinal barrier disruption
                                                                                                        3141 Mitochondrial dysfunction Increase, ROS Mar 6, 2024 Apr 11, 2024
                                                                                                        • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
                                                                                                        • Mitochondrial complex inhibition leading to liver injury
                                                                                                        3132 Mitochondrial dysfunction increased,Vascular endothelial dysfunction Feb 21, 2024 Feb 21, 2024
                                                                                                        • Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction
                                                                                                        • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                        3131 Mitochondrial dysfunction Increase, Apoptosis Feb 21, 2024 Feb 21, 2024
                                                                                                        • Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction
                                                                                                        • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                        3134 Mitochondrial dysfunction Increase, Cytotoxicity (renal tubular cell) Feb 28, 2024 Mar 6, 2024
                                                                                                        • Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity
                                                                                                        • Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity
                                                                                                        3136 Mitochondrial dysfunction Proteasomal dysfunction Feb 29, 2024 Feb 29, 2024
                                                                                                        • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                        2822 Mitochondrial dysfunction Decrease, Mitochondrial ATP production Jan 5, 2023 Jan 5, 2023
                                                                                                        • Mitochondrial complexes inhibition leading to heart failure via decreased ATP production
                                                                                                        • Renal protein alkylation leading to kidney toxicity
                                                                                                        1684 Mitochondrial dysfunction Oxidative Stress Nov 9, 2017 Nov 9, 2017
                                                                                                        • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                        • Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress
                                                                                                        1152 Mitochondrial dysfunction impaired, Hive thermoregulation Nov 29, 2016 Dec 3, 2016
                                                                                                        • Nicotinic acetylcholine receptor activation contributes to impaired hive thermoregulation and leads to colony loss/failure
                                                                                                        1154 Mitochondrial dysfunction Weakened, Colony Nov 29, 2016 Dec 3, 2016
                                                                                                        • Nicotinic acetylcholine receptor activation contributes to mitochondrial dysfunction and leads to colony loss/failure
                                                                                                        1311 Mitochondrial dysfunction Altered, Ca2+-calmodulin activated signal transduction Nov 29, 2016 Dec 3, 2016
                                                                                                        • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1
                                                                                                        • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure
                                                                                                        582 Mitochondrial dysfunction Neuronal network function, Decreased Nov 29, 2016 Dec 3, 2016
                                                                                                        • Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1
                                                                                                        660 Mitochondrial dysfunction Overwhelmed, Mitochondrial DNA repair mechanisms Nov 29, 2016 Dec 3, 2016
                                                                                                        • Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure
                                                                                                        664 Mitochondrial dysfunction impaired, Thoracic shivering Nov 29, 2016 Dec 3, 2016
                                                                                                          904 Mitochondrial dysfunction Impaired, Proteostasis Nov 29, 2016 Aug 25, 2017
                                                                                                          • Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits
                                                                                                          • Mitochondrial complex inhibition leading to liver injury
                                                                                                          908 Mitochondrial dysfunction Degeneration of dopaminergic neurons of the nigrostriatal pathway Nov 29, 2016 Aug 25, 2017
                                                                                                          • Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits
                                                                                                          2228 Mitochondrial dysfunction Decrease, ATP pool Dec 4, 2020 Dec 4, 2020
                                                                                                            3152 Mitochondrial dysfunction Apoptotic cell death Mar 13, 2024 Mar 13, 2024
                                                                                                            • Immune mediated hepatitis
                                                                                                            3161 Mitochondrial dysfunction Impaired insulin signaling Mar 13, 2024 Mar 13, 2024
                                                                                                            • ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
                                                                                                            3158 Mitochondrial dysfunction Occurrence, Cytoplasmic vacuolization (Bile duct cell) Mar 13, 2024 Mar 13, 2024
                                                                                                            • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                            3157 Mitochondrial dysfunction Occurrence, Cytoplasmic vacuolization (kupffer cell) Mar 13, 2024 Mar 13, 2024
                                                                                                            • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                            3156 Mitochondrial dysfunction Occurrence, Ballooning degeneration (hepatocyte) Mar 13, 2024 Mar 13, 2024
                                                                                                            • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                            3155 Mitochondrial dysfunction Occurrence, Cytoplasmic vacuolization (hepatocyte) Mar 13, 2024 Mar 13, 2024
                                                                                                            • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                            3164 Mitochondrial dysfunction Altered expression of NRF2 pathway-dependent genes Mar 14, 2024 Mar 14, 2024
                                                                                                            • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                            3153 Mitochondrial dysfunction ER stress Mar 13, 2024 Mar 13, 2024
                                                                                                            • Immune mediated hepatitis
                                                                                                            3150 Mitochondrial dysfunction cell injury Mar 13, 2024 Mar 13, 2024
                                                                                                            • AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment
                                                                                                            3149 Mitochondrial dysfunction Necrosis Mar 13, 2024 Mar 13, 2024
                                                                                                            • AOP from chemical insult to cell death
                                                                                                            3165 Mitochondrial dysfunction Inhibition, Nuclear factor kappa B (NF-kB) Mar 14, 2024 Mar 14, 2024
                                                                                                            • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                            3146 Mitochondrial dysfunction Apoptosis Mar 13, 2024 Mar 13, 2024
                                                                                                            • AOP from chemical insult to cell death
                                                                                                            • NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
                                                                                                            3493 Disruption, Mitochondrial electron transport chain Increase, ROS Feb 25, 2025 Feb 25, 2025
                                                                                                            • Calcium-mediated neuronal ROS production and energy imbalance
                                                                                                            188 Disruption, Mitochondrial electron transport chain Decrease, Mitochondrial ATP production Nov 29, 2016 Dec 3, 2016
                                                                                                            • Calcium-mediated neuronal ROS production and energy imbalance
                                                                                                            • DBDPE-induced inhibition of mitochondrial complex Ⅰ leading to population decline via neurotoxicity and metabotoxicity.
                                                                                                            190 Decreased, Mitochondrial fatty acid beta-oxidation Accumulation, Fatty acid Nov 29, 2016 Dec 3, 2016
                                                                                                            • Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis
                                                                                                            • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                            3159 Decreased, Mitochondrial fatty acid beta-oxidation Mitochondrial dysfunction Mar 13, 2024 Mar 13, 2024
                                                                                                            • ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
                                                                                                            3209 Decreased, Mitochondrial fatty acid beta-oxidation Disrupted Lipid Storage May 8, 2024 May 28, 2024
                                                                                                            • Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
                                                                                                            617 Decreased, Mitochondrial fatty acid beta-oxidation Increased, Liver Steatosis Nov 29, 2016 Dec 3, 2016
                                                                                                              2931 Decreased, Mitochondrial fatty acid beta-oxidation Mitochondrial dysfunction EMPTY May 25, 2023 May 25, 2023
                                                                                                                1025 Abnormal, Morphogenesis Increased, Developmental Defects Nov 29, 2016 Dec 3, 2016
                                                                                                                  196 Abnormal, Morphogenesis Increased, Lethality Nov 29, 2016 Dec 3, 2016
                                                                                                                    197 Abnormal, Morphogenesis Increased, Structural malformations Nov 29, 2016 Dec 3, 2016
                                                                                                                      202 Increase, Mutations Increase, Heritable mutations in offspring Nov 29, 2016 Nov 29, 2016
                                                                                                                      • Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutations
                                                                                                                      899 Increase, Mutations Increase, Cancer Nov 29, 2016 Dec 3, 2016
                                                                                                                      • Alkylation of DNA leading to cancer 2
                                                                                                                      • Alkylation of DNA leading to cancer 1
                                                                                                                      1978 Increase, Mutations Increase, Cell Proliferation Aug 29, 2019 Mar 8, 2024
                                                                                                                      • Deposition of energy leading to lung cancer
                                                                                                                      • Deposition of energy leading to occurrence of cataracts
                                                                                                                      1896 Increase, Mutations Increase, Cell Proliferation (Epithelial Cells) May 7, 2019 May 8, 2019
                                                                                                                      • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                      • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                      1984 Increase, Mutations Increase, lung cancer Aug 29, 2019 Jan 10, 2023
                                                                                                                      • Deposition of energy leading to lung cancer
                                                                                                                      2609 Increase, Mutations Increase,miRNA levels Mar 22, 2022 Aug 27, 2023
                                                                                                                      • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                                                      203 Altered, Neuroanatomy Altered, Neurophysiology Nov 29, 2016 Nov 29, 2016
                                                                                                                      • XX Inhibition of Sodium Iodide Symporter and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                      208 Neuroinflammation N/A, Neurodegeneration Nov 29, 2016 Feb 23, 2021
                                                                                                                      • Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.
                                                                                                                      • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging
                                                                                                                      • Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on brain cells (neuronal and non-neuronal) leads to neuroinflammation resulting in encephalitis
                                                                                                                      • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                      2500 Neuroinflammation Neuronal network function, Decreased Oct 26, 2021 Oct 26, 2021
                                                                                                                      • A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants
                                                                                                                      3255 Neuroinflammation Impairment, Learning and memory Jun 19, 2024 Jun 19, 2024
                                                                                                                      • Binding and activation of GPER leading to learning and memory impairments
                                                                                                                      2717 Neuroinflammation Increase, Cell death Jul 25, 2022 Jul 25, 2022
                                                                                                                        906 Neuroinflammation Degeneration of dopaminergic neurons of the nigrostriatal pathway Nov 29, 2016 Aug 25, 2017
                                                                                                                        • Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits
                                                                                                                        • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                        759 Neuroinflammation Synaptogenesis, Decreased Nov 29, 2016 Dec 3, 2016
                                                                                                                          1687 Neuroinflammation Cell injury/death Nov 9, 2017 Nov 7, 2019
                                                                                                                          • Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory
                                                                                                                          • Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms
                                                                                                                          2288 Neuroinflammation Encephalitis Feb 23, 2021 Feb 23, 2021
                                                                                                                          • Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on brain cells (neuronal and non-neuronal) leads to neuroinflammation resulting in encephalitis
                                                                                                                          2941 Neuronal dysfunction Neurological disorder Jun 15, 2023 Jun 15, 2023
                                                                                                                          • Increased LCN2/iron complex leading to neurological disorders
                                                                                                                          • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                          210 Neuronal dysfunction Neuroinflammation Nov 29, 2016 Nov 29, 2016
                                                                                                                            384 Altered, Neurophysiology Cognitive function, decreased Nov 29, 2016 Nov 29, 2016
                                                                                                                            • XX Inhibition of Sodium Iodide Symporter and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                            212 Decreased, Nitric Oxide Decreased, Long-term potentiation (LTP) Nov 29, 2016 Dec 3, 2016
                                                                                                                            • Calcium-mediated neuronal ROS production and energy imbalance
                                                                                                                            213 Inhibition, NMDARs Decreased, Calcium influx Nov 29, 2016 Apr 7, 2018
                                                                                                                            • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
                                                                                                                            • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging
                                                                                                                            214 Inhibition, NMDARs Impairment, Learning and memory Nov 29, 2016 Dec 3, 2016
                                                                                                                              215 Inhibition, NMDARs Neuronal dysfunction Nov 29, 2016 Dec 3, 2016
                                                                                                                                3124 Inhibition, NMDARs Aberrant, synaptic formation and plasticity Jan 25, 2024 Jan 25, 2024
                                                                                                                                • Estrogen antagonism leading to increased risk of autism-like behavior
                                                                                                                                228 Binding of antagonist, NMDA receptors Impairment, Learning and memory Nov 29, 2016 Dec 3, 2016
                                                                                                                                  229 Binding of antagonist, NMDA receptors Inhibition, NMDARs Nov 29, 2016 Jun 13, 2018
                                                                                                                                  • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
                                                                                                                                  • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging
                                                                                                                                  387 Inhibition, Nuclear factor kappa B (NF-kB) Suppression, Inflammatory cytokines Nov 29, 2016 Dec 3, 2016
                                                                                                                                  • Glucocorticoid Receptor Activation Leading to Increased Disease Susceptibility
                                                                                                                                  2306 Inhibition, Nuclear factor kappa B (NF-kB) Increased proinflammatory mediators Mar 30, 2021 Mar 30, 2021
                                                                                                                                    2644 Inhibition, Nuclear factor kappa B (NF-kB) Increase in inflammation Apr 8, 2022 Apr 8, 2022
                                                                                                                                    • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                    2003 Inhibition, Nuclear factor kappa B (NF-kB) Suppression of T cell activation Nov 17, 2019 Mar 2, 2023
                                                                                                                                    • Impaired IL-1R1 signaling leading to Impaired T-Cell Dependent Antibody Response
                                                                                                                                    1921 Inhibition, Nuclear factor kappa B (NF-kB) Impaired T cell activation May 23, 2019 Jun 25, 2019
                                                                                                                                      1828 Inhibition, Nuclear factor kappa B (NF-kB) Activation, Caspase 8 pathway Jan 7, 2019 Mar 7, 2019
                                                                                                                                      • IKK complex inhibition leading to liver injury
                                                                                                                                      1871 Inhibition, Nuclear factor kappa B (NF-kB) Impairment of TDAR Mar 12, 2019 Mar 12, 2019
                                                                                                                                        764 Peptide Oxidation Increase, hepatocellular adenomas and carcinomas Nov 29, 2016 Dec 3, 2016
                                                                                                                                          765 Peptide Oxidation Increase, Cytotoxicity Nov 29, 2016 Dec 3, 2016
                                                                                                                                          • Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                                                                                                                                          980 Peptide Oxidation Decrease, GTPCH-1 Nov 29, 2016 Sep 28, 2017
                                                                                                                                          • Peptide Oxidation Leading to Hypertension
                                                                                                                                          992 Peptide Oxidation Decrease, AKT/eNOS activity Nov 29, 2016 Oct 16, 2017
                                                                                                                                          • Peptide Oxidation Leading to Hypertension
                                                                                                                                          922 Peptide Oxidation Mitochondrial dysfunction Nov 29, 2016 Nov 29, 2016
                                                                                                                                            923 Peptide Oxidation Release, Cytokine Nov 29, 2016 Dec 3, 2016
                                                                                                                                              932 Peptide Oxidation Cholestasis, Pathology Nov 29, 2016 Dec 3, 2016
                                                                                                                                              • Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
                                                                                                                                              948 Peptide Oxidation Oxidation, Glutathione Nov 29, 2016 Nov 29, 2016
                                                                                                                                                236 Peptide Oxidation Increased, Activation and Recruitment of Hepatic macrophages (Kupffer Cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                  1698 Peptide Oxidation S-Glutathionylation, eNOS Nov 16, 2017 Nov 20, 2017
                                                                                                                                                  • Peptide Oxidation Leading to Hypertension
                                                                                                                                                  1379 Peptide Oxidation Activation, JNK Feb 15, 2017 Feb 15, 2017
                                                                                                                                                  • Activation of c-Jun N-terminal kinase (JNK) and Forkhead box O (FOXO) and reduction of WNT pathways leading to reproductive failure: Integrated multi-OMICS approach for AOP building
                                                                                                                                                  1467 Peptide Oxidation Increase, DNA Damage Apr 15, 2017 Apr 15, 2017
                                                                                                                                                    1237 Peptide Oxidation Increased activation, Nuclear factor kappa B (NF-kB) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                      3323 N/A, Parent compound is converted to the reactive metabolite and forms free radicals leadin Oxidative Stress Jul 24, 2024 Jul 24, 2024
                                                                                                                                                      • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                      245 N/A, Parent compound is converted to the reactive metabolite and forms free radicals leadin Damaging, Red blood cells; hemolysis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                      • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                      243 N/A, Parent compound is converted to the reactive metabolite and forms free radicals leadin Formation, Formation of hemoglobin adducts Nov 29, 2016 Dec 3, 2016
                                                                                                                                                      • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                      242 N/A, Parent compound is converted to the reactive metabolite and forms free radicals leadin Altered regulation, Alpha hemoglobin Nov 29, 2016 Dec 3, 2016
                                                                                                                                                      • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                      248 Bile accumulation, Pathological condition Activation of specific nuclear receptors, Transcriptional change Nov 29, 2016 Dec 3, 2016
                                                                                                                                                      • Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
                                                                                                                                                      928 Bile accumulation, Pathological condition Release, Cytokine Nov 29, 2016 Dec 3, 2016
                                                                                                                                                      • Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
                                                                                                                                                      3510 Bile accumulation, Pathological condition Increase, ROS Apr 3, 2025 Apr 3, 2025
                                                                                                                                                      • Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
                                                                                                                                                      503 Decreased, PCK1 expression (control point for glycolysis/gluconeogenesis pathway) Accumulation, Fatty acid Nov 29, 2016 Dec 3, 2016
                                                                                                                                                      • AhR activation leading to hepatic steatosis
                                                                                                                                                      392 Reduction, Plasma 17beta-estradiol concentrations disrupted, ovarian cycle Nov 29, 2016 Dec 3, 2016
                                                                                                                                                      • Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female
                                                                                                                                                      253 Reduction, Plasma 17beta-estradiol concentrations Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development Nov 29, 2016 Nov 29, 2016
                                                                                                                                                        252 Reduction, Plasma 17beta-estradiol concentrations Reduction, Vitellogenin synthesis in liver Nov 29, 2016 Mar 20, 2017
                                                                                                                                                        • Aromatase inhibition leading to reproductive dysfunction
                                                                                                                                                        • Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
                                                                                                                                                        • Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation
                                                                                                                                                        • Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
                                                                                                                                                        • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                                                                                                                                                        2922 Reduction, Plasma 17beta-estradiol concentrations Reduction, the ratio of E2/11-KT in plasma May 22, 2023 May 22, 2023
                                                                                                                                                        • Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
                                                                                                                                                        1386 Reduction, Plasma 17beta-estradiol concentrations Reduction, Plasma vitellogenin concentrations Mar 17, 2017 Oct 18, 2018
                                                                                                                                                        • Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
                                                                                                                                                        • Aromatase inhibition leading to reproductive dysfunction
                                                                                                                                                        • Inhibition of thyroid peroxidase leading to impaired fertility in fish
                                                                                                                                                        • Inhibition of 5α-reductase leading to impaired fecundity in female fish
                                                                                                                                                        • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                                                                                                                                                        • Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
                                                                                                                                                        • Aromatase inhibition leads to reproductive toxicity (including growth and developmental toxicity) in adult female zebrafish
                                                                                                                                                        254 Increase, Plasma vitellogenin concentrations Increase, Renal pathology due to VTG deposition Nov 29, 2016 Jun 24, 2024
                                                                                                                                                        • Estrogen receptor agonism leading to reproductive dysfunction
                                                                                                                                                        • Estrogen receptor agonism leading to reduced survival and population growth due to renal failure
                                                                                                                                                        3259 Increase, Plasma vitellogenin concentrations Impaired development of, Reproductive organs Jul 3, 2024 Jul 3, 2024
                                                                                                                                                        • Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liver
                                                                                                                                                        1882 Reduction, Plasma vitellogenin concentrations Reduction, egg production and spawning Apr 18, 2019 Apr 18, 2019
                                                                                                                                                          1769 Reduction, Plasma vitellogenin concentrations Reduction, Cumulative fecundity and spawning Sep 18, 2018 Sep 18, 2018
                                                                                                                                                          • Inhibition of thyroid peroxidase leading to impaired fertility in fish
                                                                                                                                                          • Inhibition of 5α-reductase leading to impaired fecundity in female fish
                                                                                                                                                          255 Reduction, Plasma vitellogenin concentrations Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development Nov 29, 2016 Mar 20, 2017
                                                                                                                                                          • Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
                                                                                                                                                          • Aromatase inhibition leading to reproductive dysfunction
                                                                                                                                                          • Estrogen receptor antagonism leading to reproductive dysfunction
                                                                                                                                                          • Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation
                                                                                                                                                          • Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
                                                                                                                                                          • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                                                                                                                                                          • Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
                                                                                                                                                          • Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production
                                                                                                                                                          • Aromatase inhibition leads to reproductive toxicity (including growth and developmental toxicity) in adult female zebrafish
                                                                                                                                                          369 Activation, PPARα Decrease, Steroidogenic acute regulatory protein (STAR) Nov 29, 2016 Dec 2, 2016
                                                                                                                                                          • PPARα activation in utero leading to impaired fertility in males
                                                                                                                                                          370 Activation, PPARα Decrease, Translocator protein (TSPO) Nov 29, 2016 Dec 2, 2016
                                                                                                                                                          • PPARα activation in utero leading to impaired fertility in males
                                                                                                                                                          535 Activation, PPARα Activation, LXR alpha Nov 29, 2016 Dec 3, 2016
                                                                                                                                                          • NFE2L2/FXR activation leading to hepatic steatosis
                                                                                                                                                          2252 Activation, PPARα Increase, cell proliferation (hepatocytes) Dec 31, 2020 Dec 31, 2020
                                                                                                                                                          • PPARα activation leading to hepatocellular adenomas and carcinomas in rodents
                                                                                                                                                          2253 Activation, PPARα Increase, hepatocellular adenomas and carcinomas Dec 31, 2020 Dec 31, 2020
                                                                                                                                                          • PPARα activation leading to hepatocellular adenomas and carcinomas in rodents
                                                                                                                                                          2134 Activation, PPARα Decreased, 11KT May 11, 2020 May 11, 2020
                                                                                                                                                            1410 Activation, PPARα Activation, HSD17B4 Apr 12, 2017 Apr 12, 2017
                                                                                                                                                              1229 Activation, PPARα Increase, Phenotypic enzyme activity Nov 29, 2016 Dec 31, 2020
                                                                                                                                                              • PPARα activation leading to hepatocellular adenomas and carcinomas in rodents
                                                                                                                                                              1233 Activation, PPARα Increase, Genes involved in fatty acid oxidation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                1236 Activation, PPARα Activation, NADPH Oxidase Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                  2073 Activation, PPARα Decreased, cholesterol Apr 6, 2020 May 1, 2020
                                                                                                                                                                  • PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone
                                                                                                                                                                  395 demethylation, PPARg promoter reduction in ovarian granulosa cells, Aromatase (Cyp19a1) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                    411 demethylation, PPARg promoter Up Regulation, CD36 Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                    • LXR activation leading to hepatic steatosis
                                                                                                                                                                    256 demethylation, PPARg promoter Decrease, Aromatase (Cyp19a1) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                      487 demethylation, PPARg promoter Activation, SREBF1 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                      • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                      2988 demethylation, PPARg promoter Activation of PPAR Aug 20, 2023 Aug 20, 2023
                                                                                                                                                                      • Demethylation of PPAR promotor leading to vascular disrupting effects
                                                                                                                                                                      1659 demethylation, PPARg promoter Increased, FA Influx Aug 31, 2017 Aug 31, 2017
                                                                                                                                                                      • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                      1402 demethylation, PPARg promoter Activation, SREBP-1 Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                        1424 demethylation, PPARg promoter Activation, FAS Apr 13, 2017 Apr 13, 2017
                                                                                                                                                                          1608 demethylation, PPARg promoter Activation of specific nuclear receptors, PPAR-gamma activation Jul 24, 2017 Jul 24, 2017
                                                                                                                                                                          • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                          257 Decreased, PPAR-alpha activation Decreased, HSD17B10 expression Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                          • Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis
                                                                                                                                                                          2042 Decreased, PPAR-alpha activation Increased, Liver Steatosis Feb 22, 2020 Feb 22, 2020
                                                                                                                                                                            259 Decreased, PPAR-beta activation Decreased, HSD17B10 expression Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                            • Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis
                                                                                                                                                                            260 Decreased, PPAR-gamma activation Decreased, HSD17B10 expression Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                            • Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis
                                                                                                                                                                            3093 Decreased, PPAR-gamma activation Alteration, lipid metabolism Oct 18, 2023 Oct 19, 2023
                                                                                                                                                                            • Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway
                                                                                                                                                                            261 Induction, Pre-mature molting Decrease, Fecundity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                              262 Induction, Pre-mature molting Increase, Mortality Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                263 Induction, Pre-mature molting Increased Mortality Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                  2482 Activation, Pregnane-X receptor, NR1l2 Induction, Upregulation of glucuronyltransferase activity Sep 14, 2021 Sep 14, 2021
                                                                                                                                                                                  • Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                  3365 Activation, Pregnane-X receptor, NR1l2 Decreased, INSIG1 protein activity Oct 22, 2024 Feb 10, 2025
                                                                                                                                                                                  • Activation, Pregnane-X receptor, NR1l2 leads to increased plasma low-density lipoprotein (LDL) cholesterol via increased cholesterol synthesis
                                                                                                                                                                                  • Activation, Pregnane-X receptor, NR1l2 leads to increased plasma low-density lipoprotein (LDL) cholesterol via increased PCSK9 protein expression
                                                                                                                                                                                  3100 Activation, Pregnane-X receptor, NR1l2 Up Regulation, CD36 Nov 30, 2023 Mar 27, 2024
                                                                                                                                                                                  • Pregnane X Receptor (PXR) activation leads to liver steatosis
                                                                                                                                                                                  266 Feminisation or incomplete development, Primary and accessory male sex organs N/A, Impairment of reproductive capacity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                  • Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)
                                                                                                                                                                                  268 Reduction, Prostaglandin E2 concentration N/A, Gap Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                  • Cyclooxygenase inhibition leading reproductive failure
                                                                                                                                                                                  269 Alkylation, Protein Cell injury/death Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                  • Protein Alkylation leading to Liver Fibrosis
                                                                                                                                                                                  271 Alkylation, Protein Peptide Oxidation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                    3135 Alkylation, Protein Mitochondrial dysfunction Feb 28, 2024 Feb 28, 2024
                                                                                                                                                                                    • Renal protein alkylation leading to kidney toxicity
                                                                                                                                                                                    518 Activation, PXR/SXR Inhibition, FoxA2 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                    • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                    526 Activation, PXR/SXR Up Regulation, SCD-1 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                    • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                    529 Activation, PXR/SXR Up Regulation, CD36 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                    • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                    272 Increase, RBC congestion in liver N/A, Methemoglobinemia, decreased hemoglobin, hematocrit, red blood cell number Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                    • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                                                    277 Damaging, Red blood cells; hemolysis Increase, Liver and splenic hemosiderosis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                    • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                                                    278 Damaging, Red blood cells; hemolysis N/A, Methemoglobinemia, decreased hemoglobin, hematocrit, red blood cell number Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                    • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                                                    279 Damaging, Red blood cells; hemolysis Increase, RBC congestion in liver Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                    • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                                                    280 Increase, Renal pathology due to VTG deposition Altered, Larval development Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                    • Estrogen receptor agonism leading to reproductive dysfunction
                                                                                                                                                                                    3258 Increase, Renal pathology due to VTG deposition Increased Mortality Jun 24, 2024 Jun 24, 2024
                                                                                                                                                                                    • Estrogen receptor agonism leading to reduced survival and population growth due to renal failure
                                                                                                                                                                                    1404 Activation, SCD-1 Increased, lipogenesis Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                      284 Activation, SCD-1 Synthesis, De Novo Fatty Acid (FA) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                      • LXR activation leading to hepatic steatosis
                                                                                                                                                                                      287 Binding, SH-/selen-proteins N/A, Interferences with SH-/selen-proteins Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                        294 Activation, SREBP-1c Synthesis, De Novo Fatty Acid (FA) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                        • LXR activation leading to hepatic steatosis
                                                                                                                                                                                        295 Activation, Stellate cells Accumulation, Collagen Nov 29, 2016 Dec 5, 2018
                                                                                                                                                                                        • Protein Alkylation leading to Liver Fibrosis
                                                                                                                                                                                        • Endocytic lysosomal uptake leading to liver fibrosis
                                                                                                                                                                                        3217 Activation, Stellate cells Increased, Liver Steatosis May 14, 2024 May 14, 2024
                                                                                                                                                                                          2892 Activation, Stellate cells Increased extracellular matrix deposition Apr 13, 2023 Jan 30, 2025
                                                                                                                                                                                          • AhR activation leading to liver fibrosis
                                                                                                                                                                                          436 Decrease, Steroidogenic acute regulatory protein (STAR) Reduction, Cholesterol transport in mitochondria Nov 29, 2016 Apr 8, 2025
                                                                                                                                                                                          • PPARα activation in utero leading to impaired fertility in males
                                                                                                                                                                                          298 Induction, Sustained Cell Proliferation Formation, Liver tumor Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                          • Inhibition of iNOS, hepatotoxicity, and regenerative proliferation leading to liver tumors
                                                                                                                                                                                          299 Induction, Sustained Hepatotoxicity Induction, Sustained Cell Proliferation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                          • Inhibition of iNOS, hepatotoxicity, and regenerative proliferation leading to liver tumors
                                                                                                                                                                                          301 Activation/Proliferation, T-cells N/A, Allergic contact dermatitis on challenge Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                            3332 Activation/Proliferation, T-cells Activation of gluten- and TG2-reactive B cells Aug 13, 2024 Aug 13, 2024
                                                                                                                                                                                              3334 Activation/Proliferation, T-cells Disruption of the intestinal barrier Aug 13, 2024 Aug 13, 2024
                                                                                                                                                                                                3337 Activation/Proliferation, T-cells Formation of HLA-DQ2/8-gluten complexes Aug 13, 2024 Aug 13, 2024
                                                                                                                                                                                                  835 Activation/Proliferation, T-cells sensitisation, skin Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                  • Covalent Protein binding leading to Skin Sensitisation
                                                                                                                                                                                                  1701 Activation/Proliferation, T-cells Increase, Allergic Respiratory Hypersensitivity Response Dec 7, 2017 Aug 1, 2022
                                                                                                                                                                                                  • Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response
                                                                                                                                                                                                  302 Reduction, Testosterone synthesis by ovarian theca cells Reduction, 17beta-estradiol synthesis by ovarian granulosa cells Nov 29, 2016 Mar 20, 2017
                                                                                                                                                                                                  • Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
                                                                                                                                                                                                  303 Up Regulation, TGFbeta1 expression Accumulation, Collagen Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                    304 Up Regulation, TGFbeta1 expression Activation, Stellate cells Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                      305 TH synthesis, Decreased T4 in serum, Decreased Nov 29, 2016 Oct 10, 2022
                                                                                                                                                                                                      • Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                      • XX Inhibition of Sodium Iodide Symporter and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                      • Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                      • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                      • Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure
                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to altered visual function via decreased eye size
                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning
                                                                                                                                                                                                      • Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)
                                                                                                                                                                                                      • Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse)
                                                                                                                                                                                                      • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                      • Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                      • Pendrin inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                      • Dual oxidase (DUOX) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                      • Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine
                                                                                                                                                                                                      • AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                      1504 TH synthesis, Decreased BDNF, Reduced May 10, 2017 Apr 4, 2019
                                                                                                                                                                                                      • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                                                                                                      1505 TH synthesis, Decreased GABAergic interneurons, Decreased May 10, 2017 May 29, 2018
                                                                                                                                                                                                      • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                                                                                                      1506 TH synthesis, Decreased Impairment, Learning and memory May 10, 2017 May 29, 2018
                                                                                                                                                                                                      • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                                                                                                      810 TH synthesis, Decreased Increased, Serum creatinine Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                      • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                      1768 TH synthesis, Decreased Reduction, Plasma 17beta-estradiol concentrations Sep 18, 2018 Sep 18, 2018
                                                                                                                                                                                                      • Inhibition of thyroid peroxidase leading to impaired fertility in fish
                                                                                                                                                                                                      309 Thyroperoxidase, Inhibition TH synthesis, Decreased Nov 29, 2016 Nov 4, 2022
                                                                                                                                                                                                      • Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                      • Inhibition of thyroid peroxidase leading to impaired fertility in fish
                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure
                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to altered visual function via decreased eye size
                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning
                                                                                                                                                                                                      • Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)
                                                                                                                                                                                                      383 Thyroperoxidase, Inhibition Cognitive function, decreased Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                        366 Thyroperoxidase, Inhibition T4 in serum, Decreased Nov 29, 2016 Jul 8, 2022
                                                                                                                                                                                                        • Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                        • Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                        • Thyroperoxidase inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                        • Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure
                                                                                                                                                                                                        790 Thyroperoxidase, Inhibition Decrease, Incorporation of active iodide into iodotyrosines Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                          1040 Thyroperoxidase, Inhibition Reduced, Anterior swim bladder inflation Nov 29, 2016 Feb 22, 2019
                                                                                                                                                                                                            746 T4 in neuronal tissue, Decreased Hippocampal gene expression, Altered Nov 29, 2016 Aug 11, 2018
                                                                                                                                                                                                            • Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                            • Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                            • Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                            • AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                            • AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                            444 T4 in neuronal tissue, Decreased BDNF, Reduced Nov 29, 2016 Apr 4, 2019
                                                                                                                                                                                                            • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                                                                                                            403 T4 in serum, Decreased Cognitive function, decreased Nov 29, 2016 Aug 11, 2018
                                                                                                                                                                                                            • Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                            • XX Inhibition of Sodium Iodide Symporter and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                            • Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                            • AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                            312 T4 in serum, Decreased T4 in neuronal tissue, Decreased Nov 29, 2016 Apr 4, 2019
                                                                                                                                                                                                            • Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                            • XX Inhibition of Sodium Iodide Symporter and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                            • Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                            • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                                                                                                            • Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                            • AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                            • AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                            2473 T4 in serum, Decreased Occurrence, Cytoplasmic vacuolization (Renal tubule) Sep 9, 2021 Sep 9, 2021
                                                                                                                                                                                                            • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                            2474 T4 in serum, Decreased Occurrence, Cystic dilatation (renal tubule) Sep 9, 2021 Sep 9, 2021
                                                                                                                                                                                                            • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                            2475 T4 in serum, Decreased Occurrence, Cytoplasmic vacuolization (podocyte) Sep 9, 2021 Sep 9, 2021
                                                                                                                                                                                                            • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                            2168 T4 in serum, Decreased Altered, Amphibian metamorphosis Aug 25, 2020 Aug 25, 2020
                                                                                                                                                                                                            • Thyroperoxidase inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                            • Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                            • Hepatic nuclear receptor activation leading to altered amphibian metamorphosis
                                                                                                                                                                                                            • Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis
                                                                                                                                                                                                            • Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis
                                                                                                                                                                                                            • Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                            • Pendrin inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                            • Dual oxidase (DUOX) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                            2420 T4 in serum, Decreased Increase, Thyroid-stimulating hormone (TSH) Jul 7, 2021 Jul 7, 2021
                                                                                                                                                                                                              2422 T4 in serum, Decreased Increased, Thyroid-stimulating hormone (TSH) Jul 7, 2021 Jul 7, 2021
                                                                                                                                                                                                              • Enhanced hepatic clearance of thyroid hormones leading to thyroid follicular cell adenomas and carcinomas in the rat and mouse
                                                                                                                                                                                                              • Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse)
                                                                                                                                                                                                              • Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)
                                                                                                                                                                                                              2038 T4 in serum, Decreased Decreased, Triiodothyronine (T3) Feb 19, 2020 Oct 10, 2022
                                                                                                                                                                                                              • Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                              • Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure
                                                                                                                                                                                                              • Thyroperoxidase inhibition leading to altered visual function via decreased eye size
                                                                                                                                                                                                              • Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning
                                                                                                                                                                                                              2865 T4 in serum, Decreased Insulin resistance, increased Apr 3, 2023 Apr 20, 2023
                                                                                                                                                                                                              • Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine
                                                                                                                                                                                                              1039 T4 in serum, Decreased Reduced, Anterior swim bladder inflation Nov 29, 2016 Oct 10, 2022
                                                                                                                                                                                                              • Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                              1143 T4 in serum, Decreased Decreased, Thyroxine (T4) in tissues Nov 29, 2016 Sep 3, 2020
                                                                                                                                                                                                                1387 T4 in serum, Decreased Hippocampal gene expression, Altered Mar 24, 2017 Aug 11, 2018
                                                                                                                                                                                                                • Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                1388 T4 in serum, Decreased Hippocampal anatomy, Altered Mar 24, 2017 Aug 11, 2018
                                                                                                                                                                                                                • Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                1389 T4 in serum, Decreased Hippocampal Physiology, Altered Mar 24, 2017 Aug 11, 2018
                                                                                                                                                                                                                • Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                315 Reduction, Vitellogenin synthesis in liver Reduction, Plasma vitellogenin concentrations Nov 29, 2016 Mar 20, 2017
                                                                                                                                                                                                                • Aromatase inhibition leading to reproductive dysfunction
                                                                                                                                                                                                                • Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
                                                                                                                                                                                                                • Estrogen receptor antagonism leading to reproductive dysfunction
                                                                                                                                                                                                                • Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation
                                                                                                                                                                                                                • Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
                                                                                                                                                                                                                • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                                                                                                                                                                                                                • Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production
                                                                                                                                                                                                                316 Altered, Transcription of genes by the AR Feminisation or incomplete development, Primary and accessory male sex organs Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                • Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)
                                                                                                                                                                                                                317 Altered, Transcription of genes by the AR Alteration, Wnt pathway Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                • Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)
                                                                                                                                                                                                                2127 Altered, Transcription of genes by the AR AGD, decreased May 11, 2020 May 11, 2020
                                                                                                                                                                                                                • 5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                • Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                • Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                2132 Altered, Transcription of genes by the AR nipple retention, increased May 11, 2020 May 11, 2020
                                                                                                                                                                                                                • Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspring
                                                                                                                                                                                                                2273 Altered, Transcription of genes by the AR Reduced granulosa cell proliferation Jan 28, 2021 Mar 18, 2025
                                                                                                                                                                                                                • Androgen receptor (AR) antagonism leading to decreased fertility in females
                                                                                                                                                                                                                2909 Altered, Transcription of genes by the AR Increase, AR protein expression/abundance May 11, 2023 May 11, 2023
                                                                                                                                                                                                                • Androgen receptor activation leading to prostate cancer
                                                                                                                                                                                                                319 Activation of specific nuclear receptors, Transcriptional change Cholestasis, Pathology Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                • Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
                                                                                                                                                                                                                437 Decrease, Translocator protein (TSPO) Reduction, Cholesterol transport in mitochondria Nov 29, 2016 Dec 2, 2016
                                                                                                                                                                                                                • PPARα activation in utero leading to impaired fertility in males
                                                                                                                                                                                                                399 Decrease, Translocator protein (TSPO) Reduction, Testosterone synthesis in Leydig cells Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                  3162 Accumulation, Triglyceride Mitochondrial dysfunction Mar 13, 2024 Mar 13, 2024
                                                                                                                                                                                                                  • LXR activation leading to hepatic steatosis
                                                                                                                                                                                                                  2265 Accumulation, Triglyceride Increased, Liver Steatosis Jan 15, 2021 Mar 27, 2024
                                                                                                                                                                                                                  • Glucocorticoid Receptor activation leading to hepatic steatosis
                                                                                                                                                                                                                  • Pregnane X Receptor (PXR) activation leads to liver steatosis
                                                                                                                                                                                                                  • Liver X Receptor (LXR) activation leads to liver steatosis
                                                                                                                                                                                                                  • Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
                                                                                                                                                                                                                  • AhR activation leading to hepatic steatosis
                                                                                                                                                                                                                  324 N/A, Unknown Proliferation, Cell proliferation in the absence of cytotoxicity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                  • Uncharacterized liver damage leading to hepatocellular carcinoma
                                                                                                                                                                                                                  751 N/A, Unknown Increased, Kidney Failure Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                  • Kidney toxicity induced by activation of 5HT2C
                                                                                                                                                                                                                  2235 Induction, Upregulation of glucuronyltransferase activity Increase, Biliary excretion TH glucuronide Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                    2428 Induction, Upregulation of glucuronyltransferase activity Increased, T4/T3 catabolism Jul 7, 2021 Jul 7, 2021
                                                                                                                                                                                                                      2483 Induction, Upregulation of glucuronyltransferase activity T4 in serum, Decreased Sep 14, 2021 Sep 14, 2021
                                                                                                                                                                                                                        2478 Induction, Upregulation of glucuronyltransferase activity Increased, Clearance of thyroxine from serum Sep 10, 2021 Sep 10, 2021
                                                                                                                                                                                                                        • Hepatic nuclear receptor activation leading to altered amphibian metamorphosis
                                                                                                                                                                                                                        • Enhanced hepatic clearance of thyroid hormones leading to thyroid follicular cell adenomas and carcinomas in the rat and mouse
                                                                                                                                                                                                                        • Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                        • AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                        2884 Induction, Upregulation of glucuronyltransferase activity Increase, Glucuronidation of T4 Apr 12, 2023 Apr 12, 2023
                                                                                                                                                                                                                          1036 Insufficiency, Vascular Increased, Developmental Defects Nov 29, 2016 Jan 18, 2022
                                                                                                                                                                                                                          • Disruption of VEGFR Signaling Leading to Developmental Defects
                                                                                                                                                                                                                          329 Insufficiency, Vascular Abnormal, Morphogenesis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                            330 Binding, VEGF-A Decreased, VegfR2 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                              331 Binding, VEGF-A Inhibition, VegfR2 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                332 Production, VEGF-A Binding, VEGF-A Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                  333 Production, VEGF-A Decreased, VegfR2 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                    334 Decreased, VegfR2 Inhibition, VegfR2 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                      335 Inhibition, VegfR2 Reduction, Angiogenesis Nov 29, 2016 Jul 20, 2022
                                                                                                                                                                                                                                      • Disruption of VEGFR Signaling Leading to Developmental Defects
                                                                                                                                                                                                                                      336 Increase, Vitellogenin synthesis in liver Increase, Plasma vitellogenin concentrations Nov 29, 2016 Jun 24, 2024
                                                                                                                                                                                                                                      • Estrogen receptor agonism leading to reproductive dysfunction
                                                                                                                                                                                                                                      • Estrogen receptor agonism leading to reduced survival and population growth due to renal failure
                                                                                                                                                                                                                                      • Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liver
                                                                                                                                                                                                                                      337 Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development Reduction, Cumulative fecundity and spawning Nov 29, 2016 Mar 20, 2017
                                                                                                                                                                                                                                      • Aromatase inhibition leading to reproductive dysfunction
                                                                                                                                                                                                                                      • Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
                                                                                                                                                                                                                                      • Estrogen receptor antagonism leading to reproductive dysfunction
                                                                                                                                                                                                                                      • Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation
                                                                                                                                                                                                                                      • Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
                                                                                                                                                                                                                                      • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                                                                                                                                                                                                                                      • Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
                                                                                                                                                                                                                                      • Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production
                                                                                                                                                                                                                                      • Aromatase inhibition leads to reproductive toxicity (including growth and developmental toxicity) in adult female zebrafish
                                                                                                                                                                                                                                      3396 Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development Growth, reduction Nov 16, 2024 Nov 16, 2024
                                                                                                                                                                                                                                      • Aromatase inhibition leads to reproductive toxicity (including growth and developmental toxicity) in adult female zebrafish
                                                                                                                                                                                                                                      338 Alteration, Wnt pathway Feminisation or incomplete development, Primary and accessory male sex organs Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                      • Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)
                                                                                                                                                                                                                                      977 Altered, Cardiovascular development/function Increase, Pericardial edema Nov 29, 2016 Jun 9, 2017
                                                                                                                                                                                                                                        1352 Altered, Cardiovascular development/function Increase, Mortality Feb 9, 2017 Feb 9, 2017
                                                                                                                                                                                                                                          1567 Altered, Cardiovascular development/function Increase, Early Life Stage Mortality Jun 9, 2017 Mar 23, 2018
                                                                                                                                                                                                                                          • Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF
                                                                                                                                                                                                                                          • Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2
                                                                                                                                                                                                                                          • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity
                                                                                                                                                                                                                                          472 Accumulation, Fatty acid Accumulation, Triglyceride Nov 29, 2016 May 28, 2024
                                                                                                                                                                                                                                          • Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
                                                                                                                                                                                                                                          514 Accumulation, Fatty acid Increased, Triglyceride formation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                          • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                          515 Accumulation, Fatty acid Increased, Liver Steatosis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                          • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                          • Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis
                                                                                                                                                                                                                                          • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                                                                          • AhR activation leading to hepatic steatosis
                                                                                                                                                                                                                                          135 Decrease, Fecundity Decline, Population Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                            1886 Decrease, Fecundity Decrease, Population growth rate Apr 22, 2019 Apr 22, 2019
                                                                                                                                                                                                                                            • DNA methyltransferase inhibition leading to population decline (1)
                                                                                                                                                                                                                                            • DNA methyltransferase inhibition leading to population decline (2)
                                                                                                                                                                                                                                            • DNA methyltransferase inhibition leading to population decline (3)
                                                                                                                                                                                                                                            • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                            2621 Decrease, Fecundity Decrease, Reproduction Mar 28, 2022 Mar 28, 2022
                                                                                                                                                                                                                                            • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                            1472 Decrease, Fertility Decrease, Population growth rate Apr 15, 2017 Apr 15, 2017
                                                                                                                                                                                                                                              1644 Impairment, Learning and memory Decreased, locomotion Aug 11, 2017 Aug 11, 2017
                                                                                                                                                                                                                                              • Histamine (H2) receptor antagonism leading to reduced survival
                                                                                                                                                                                                                                              564 Impairment, Learning and memory Abnormal, Roll change within caste Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                              • Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2
                                                                                                                                                                                                                                              • Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1
                                                                                                                                                                                                                                              583 Impairment, Learning and memory Abnormal, Foraging activity and behavior Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                              • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure
                                                                                                                                                                                                                                              • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1
                                                                                                                                                                                                                                              • Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure
                                                                                                                                                                                                                                              • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within caste
                                                                                                                                                                                                                                              2872 Impairment, Learning and memory decreased, IQ Apr 4, 2023 Apr 4, 2023
                                                                                                                                                                                                                                              • Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms
                                                                                                                                                                                                                                              2889 N/A, Liver Steatosis Cell injury/death Apr 13, 2023 Apr 13, 2023
                                                                                                                                                                                                                                                405 Malformation, Male reproductive tract decreased, Fertility Nov 29, 2016 Dec 2, 2016
                                                                                                                                                                                                                                                • PPARα activation in utero leading to impaired fertility in males
                                                                                                                                                                                                                                                199 Increase, Mortality Decline, Population Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                  198 Increase, Mortality Decrease, Fecundity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                    1004 Increase, Mortality Decreased, population 1 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                      1013 Increase, Mortality Decreased, Population size Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                        2463 Increase, Mortality Decrease, Population growth rate Aug 5, 2021 Aug 5, 2021
                                                                                                                                                                                                                                                          2486 Increased Mortality Decline, Population trajectory Oct 8, 2021 Oct 8, 2021
                                                                                                                                                                                                                                                            756 Increased Mortality Decreased, population 1 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                            • Glutamate-gated chloride channel activation leading to acute mortality
                                                                                                                                                                                                                                                            1191 Increased Mortality Decreased, Population size Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                              2013 Increased Mortality Decrease, Population growth rate Dec 20, 2019 Jul 8, 2022
                                                                                                                                                                                                                                                              • Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement​
                                                                                                                                                                                                                                                              • Acetylcholinesterase inhibition leading to acute mortality
                                                                                                                                                                                                                                                              • Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                                                                                                                              • Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                                                                              • Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                                                                                                                              • Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                                                                              • Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                                                                              • Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure
                                                                                                                                                                                                                                                              • Thyroperoxidase inhibition leading to altered visual function via decreased eye size
                                                                                                                                                                                                                                                              • Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning
                                                                                                                                                                                                                                                              • Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)
                                                                                                                                                                                                                                                              • GSK3beta inactivation leading to increased mortality via defects in developing inner ear
                                                                                                                                                                                                                                                              • Estrogen receptor agonism leading to reduced survival and population growth due to renal failure
                                                                                                                                                                                                                                                              • DBDPE-induced inhibition of mitochondrial complex Ⅰ leading to population decline via neurotoxicity and metabotoxicity.
                                                                                                                                                                                                                                                              200 Increased Mortality Decline, Population Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                428 Increased Mortality Decreased, Population trajectory Nov 29, 2016 Dec 20, 2019
                                                                                                                                                                                                                                                                  368 N/A, Neurodegeneration Neuronal network function, Decreased Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                    207 N/A, Neurodegeneration Neuroinflammation Nov 29, 2016 Jun 13, 2018
                                                                                                                                                                                                                                                                    • Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.
                                                                                                                                                                                                                                                                    • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging
                                                                                                                                                                                                                                                                    647 N/A, Neurodegeneration Decreased, Neuronal network function in adult brain Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                    • Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.
                                                                                                                                                                                                                                                                    • Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality
                                                                                                                                                                                                                                                                    3070 N/A, Neurodegeneration Overactivation, NMDARs Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                    • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                    3075 N/A, Neurodegeneration impaired, Learning and memory Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                    • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                    3081 N/A, Neurodegeneration Increase, seizure Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                    • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                    1069 N/A, Neurodegeneration Impairment, Learning and memory Nov 29, 2016 Apr 11, 2024
                                                                                                                                                                                                                                                                    • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging
                                                                                                                                                                                                                                                                    • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
                                                                                                                                                                                                                                                                    2287 N/A, Neurodegeneration Encephalitis Feb 23, 2021 Feb 23, 2021
                                                                                                                                                                                                                                                                    • Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on brain cells (neuronal and non-neuronal) leads to neuroinflammation resulting in encephalitis
                                                                                                                                                                                                                                                                    • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                    1265 Decline, Population Alteration, Food-web structures Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                    • Juvenile hormone receptor agonism leading to male offspring induction associated population decline
                                                                                                                                                                                                                                                                    3260 Impaired development of, Reproductive organs Reduction, Cumulative fecundity and spawning Jul 3, 2024 Jul 3, 2024
                                                                                                                                                                                                                                                                    • Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liver
                                                                                                                                                                                                                                                                    296 Increased, Structural malformations Increased, Lethality Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                      344 Formation, Pro-mutagenic DNA Adducts Increased, Proliferation/Clonal Expansion of Mutant Cells (Pre-Neoplastic Lesions/Altered H Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                        345 Formation, Pro-mutagenic DNA Adducts Tumorigenesis, Hepatocellular carcinoma Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                        • AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
                                                                                                                                                                                                                                                                        352 Formation, Pro-mutagenic DNA Adducts Increased, Clonal Expansion / Cell Proliferatin to form Pre-Neoplastic Altered Hepatic Foci Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                          548 Formation, Pro-mutagenic DNA Adducts Increased, Insufficient repair or mis-repair of pro-mutagenic DNA adducts Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                          • AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
                                                                                                                                                                                                                                                                          551 Formation, Pro-mutagenic DNA Adducts Clonal Expansion/Cell Proliferation, to form Altered Hepatic Foci (AHF) Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                          • AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
                                                                                                                                                                                                                                                                          549 Increased, Induced Mutations in Critical Genes Clonal Expansion/Cell Proliferation, to form Altered Hepatic Foci (AHF) Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                          • AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
                                                                                                                                                                                                                                                                          891 Increased, Induced Mutations in Critical Genes Increase, Site of Contact Nasal Tumors Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                            342 Increased, Induced Mutations in Critical Genes Increased, Proliferation/Clonal Expansion of Mutant Cells (Pre-Neoplastic Lesions/Altered H Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                              346 Increased, Induced Mutations in Critical Genes Tumorigenesis, Hepatocellular carcinoma Nov 29, 2016 Nov 30, 2016
                                                                                                                                                                                                                                                                              • AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
                                                                                                                                                                                                                                                                              351 Increased, Induced Mutations in Critical Genes Increased, Clonal Expansion / Cell Proliferatin to form Pre-Neoplastic Altered Hepatic Foci Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                343 Increased, Proliferation/Clonal Expansion of Mutant Cells (Pre-Neoplastic Lesions/Altered H Tumorigenesis, Hepatocellular carcinoma Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                  340 Activation, Pre-MIE: Metabolism of AFB1 Formation, Pro-mutagenic DNA Adducts Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                    348 BDNF, Reduced Aberrant, Dendritic morphology Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                    • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
                                                                                                                                                                                                                                                                                    354 BDNF, Reduced Reduced, Presynaptic release of glutamate Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                    • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
                                                                                                                                                                                                                                                                                    353 BDNF, Reduced Cell injury/death Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                    • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging
                                                                                                                                                                                                                                                                                    • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
                                                                                                                                                                                                                                                                                    445 BDNF, Reduced Down Regulation, K-Cl co-transporter 2 (KCC2) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                      448 BDNF, Reduced Synaptogenesis, Decreased Nov 29, 2016 Apr 4, 2019
                                                                                                                                                                                                                                                                                      • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                                                                                                                                                                                      870 BDNF, Reduced GABAergic interneurons, Decreased Nov 29, 2016 Jan 19, 2018
                                                                                                                                                                                                                                                                                      • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                                                                                                                                                                                      1507 BDNF, Reduced Impairment, Learning and memory May 10, 2017 May 29, 2018
                                                                                                                                                                                                                                                                                      • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                                                                                                                                                                                      356 Aberrant, Dendritic morphology Synaptogenesis, Decreased Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                      • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
                                                                                                                                                                                                                                                                                      357 Reduced, Presynaptic release of glutamate Synaptogenesis, Decreased Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                      • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
                                                                                                                                                                                                                                                                                      350 Increased, Clonal Expansion / Cell Proliferatin to form Pre-Neoplastic Altered Hepatic Foci Tumorigenesis, Hepatocellular carcinoma Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                        358 Synaptogenesis, Decreased Neuronal network function, Decreased Nov 29, 2016 May 25, 2018
                                                                                                                                                                                                                                                                                        • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
                                                                                                                                                                                                                                                                                        • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                                                                                                                                                                                        656 Synaptogenesis, Decreased Neuroinflammation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                          2411 Neuronal network function, Decreased Cognitive function, decreased Jun 24, 2021 Aug 27, 2021
                                                                                                                                                                                                                                                                                          • Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function
                                                                                                                                                                                                                                                                                          2501 Neuronal network function, Decreased Memory Loss Oct 26, 2021 Oct 26, 2021
                                                                                                                                                                                                                                                                                          • A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants
                                                                                                                                                                                                                                                                                          3123 Neuronal network function, Decreased autism-like behavior Jan 25, 2024 Jan 25, 2024
                                                                                                                                                                                                                                                                                          • Estrogen antagonism leading to increased risk of autism-like behavior
                                                                                                                                                                                                                                                                                          2953 Neuronal network function, Decreased Neurological disorder Jun 21, 2023 Jun 21, 2023
                                                                                                                                                                                                                                                                                          • Excessive iron accumulation leading to neurological disorders
                                                                                                                                                                                                                                                                                          359 Neuronal network function, Decreased Impairment, Learning and memory Nov 29, 2016 Jul 15, 2022
                                                                                                                                                                                                                                                                                          • Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2
                                                                                                                                                                                                                                                                                          • Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1
                                                                                                                                                                                                                                                                                          • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                                                                                                                                                                                          • Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory
                                                                                                                                                                                                                                                                                          • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
                                                                                                                                                                                                                                                                                          • Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons
                                                                                                                                                                                                                                                                                          360 Binding of agonist, NMDARs Overactivation, NMDARs Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                            361 Overactivation, NMDARs Increased, Intracellular Calcium overload Nov 29, 2016 Sep 10, 2023
                                                                                                                                                                                                                                                                                            • Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.
                                                                                                                                                                                                                                                                                            • Acetylcholinesterase Inhibition Leading to Neurodegeneration
                                                                                                                                                                                                                                                                                            • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                            • Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons
                                                                                                                                                                                                                                                                                            3038 Overactivation, NMDARs Increase, Cell membrane depolarization Sep 14, 2023 Sep 14, 2023
                                                                                                                                                                                                                                                                                            • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                            3068 Overactivation, NMDARs AchE Inhibition Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                            • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                            3069 Overactivation, NMDARs Decreased, Neuronal network function in adult brain Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                            • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                            3071 Overactivation, NMDARs Neuroinflammation Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                            • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                            2781 Overactivation, NMDARs Status epilepticus Oct 12, 2022 Sep 3, 2023
                                                                                                                                                                                                                                                                                            • Acetylcholinesterase Inhibition Leading to Neurodegeneration
                                                                                                                                                                                                                                                                                            2806 Overactivation, NMDARs Loss of drebrin Dec 11, 2022 Jul 17, 2024
                                                                                                                                                                                                                                                                                              2710 Increased, Intracellular Calcium overload Endoplasmic reticulum stress Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                              • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                              2709 Increased, Intracellular Calcium overload Decrease, OXPHOS Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                2704 Increased, Intracellular Calcium overload Activation, calpain Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                892 Increased, Intracellular Calcium overload Decreased, Neuronal network function in adult brain Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                  2140 Increased, Intracellular Calcium overload Status epilepticus May 21, 2020 May 21, 2020
                                                                                                                                                                                                                                                                                                    3248 Increased, Intracellular Calcium overload Oxidative Stress Jun 19, 2024 Jun 19, 2024
                                                                                                                                                                                                                                                                                                    • Binding and activation of GPER leading to learning and memory impairments
                                                                                                                                                                                                                                                                                                    3256 Increased, Intracellular Calcium overload Disruption, neurotransmitter release Jun 19, 2024 Jun 19, 2024
                                                                                                                                                                                                                                                                                                    • Binding and activation of GPER leading to learning and memory impairments
                                                                                                                                                                                                                                                                                                    3426 Increased, Intracellular Calcium overload Decrease, Cardiac contractility Nov 21, 2024 Nov 21, 2024
                                                                                                                                                                                                                                                                                                    • Decreased Na/K ATPase activity leading to heart failure
                                                                                                                                                                                                                                                                                                    • Phosphodiesterase inhibition leading to heart failure
                                                                                                                                                                                                                                                                                                    3042 Increased, Intracellular Calcium overload Mitochondrial dysfunction EMPTY Sep 14, 2023 Sep 14, 2023
                                                                                                                                                                                                                                                                                                      3091 Increased, Intracellular Calcium overload Loss of drebrin Oct 18, 2023 Apr 4, 2025
                                                                                                                                                                                                                                                                                                      • Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons
                                                                                                                                                                                                                                                                                                      362 Increased, Intracellular Calcium overload Mitochondrial dysfunction Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                      • Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.
                                                                                                                                                                                                                                                                                                      • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                      1860 Increased, Intracellular Calcium overload Occurrence, Epileptic seizure Feb 13, 2019 Feb 13, 2019
                                                                                                                                                                                                                                                                                                        1862 Increased, Intracellular Calcium overload Cell injury/death Feb 19, 2019 Sep 3, 2023
                                                                                                                                                                                                                                                                                                        • Acetylcholinesterase Inhibition Leading to Neurodegeneration
                                                                                                                                                                                                                                                                                                        2202 Covalent Binding, Protein Activation, Inflammatory cytokines, chemokines, cytoprotective gene pathways Nov 5, 2020 Feb 11, 2021
                                                                                                                                                                                                                                                                                                          833 Covalent Binding, Protein Activation, Keratinocytes Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                          • Covalent Protein binding leading to Skin Sensitisation
                                                                                                                                                                                                                                                                                                          2650 Covalent Binding, Protein Increase, Allergic Respiratory Hypersensitivity Response Apr 28, 2022 Aug 1, 2022
                                                                                                                                                                                                                                                                                                          • Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response
                                                                                                                                                                                                                                                                                                          2649 Covalent Binding, Protein Increased proinflammatory mediators Apr 28, 2022 Sep 8, 2022
                                                                                                                                                                                                                                                                                                          • Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response
                                                                                                                                                                                                                                                                                                          377 Covalent Binding, Protein Activation, Dendritic Cells Nov 29, 2016 Nov 5, 2020
                                                                                                                                                                                                                                                                                                          • Covalent Protein binding leading to Skin Sensitisation
                                                                                                                                                                                                                                                                                                          • Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response
                                                                                                                                                                                                                                                                                                          376 Covalent Binding, Protein Response, Keratinocytes Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                            380 Response, Keratinocytes Activation/Proliferation, T-cells Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                              378 Response, Keratinocytes Activation, Dendritic Cells Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                379 Activation, Dendritic Cells Activation/Proliferation, T-cells Nov 29, 2016 Aug 22, 2022
                                                                                                                                                                                                                                                                                                                • Covalent Protein binding leading to Skin Sensitisation
                                                                                                                                                                                                                                                                                                                • Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response
                                                                                                                                                                                                                                                                                                                2236 Increase, Biliary excretion TH glucuronide T4 in serum, Decreased Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                  570 Suppression, Immune system Increased, Viral susceptibility Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                  • Suppression of immune system contributes to impaired development and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                  • Suppression of immune system contributes to abnormal foraging and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                  394 disrupted, ovarian cycle decreased, Fertility Nov 29, 2016 Mar 18, 2025
                                                                                                                                                                                                                                                                                                                  • Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female
                                                                                                                                                                                                                                                                                                                  • Decreased ALDH1A (RALDH) activity leading to decreased fertility via disrupted meiotic initiation of fetal oogonia
                                                                                                                                                                                                                                                                                                                  • Androgen receptor (AR) antagonism leading to decreased fertility in females
                                                                                                                                                                                                                                                                                                                  393 disrupted, ovarian cycle Decrease, Fertility Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                    2292 decreased, Fertility Decrease, Population growth rate Mar 26, 2021 Mar 26, 2021
                                                                                                                                                                                                                                                                                                                    • Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory
                                                                                                                                                                                                                                                                                                                    • Inhibition of 11β-hydroxylase leading to decresed population trajectory
                                                                                                                                                                                                                                                                                                                    2387 decreased, Fertility Decrease of egg production and cummulative fecundity May 12, 2021 May 12, 2021
                                                                                                                                                                                                                                                                                                                    • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                    396 reduction in ovarian granulosa cells, Aromatase (Cyp19a1) Reduction, 17beta-estradiol synthesis by ovarian granulosa cells Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                    • Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female
                                                                                                                                                                                                                                                                                                                    402 Metabolism of AFB1, Production of Reactive Electrophiles Formation, Pro-mutagenic DNA Adducts Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                    • AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
                                                                                                                                                                                                                                                                                                                    439 Reduction, Testosterone synthesis in Leydig cells Reduction of testosterone Nov 29, 2016 Dec 2, 2016
                                                                                                                                                                                                                                                                                                                      2125 Reduction, Testosterone synthesis in Leydig cells Decrease, circulating testosterone levels May 11, 2020 May 1, 2024
                                                                                                                                                                                                                                                                                                                      • PPARα activation in utero leading to impaired fertility in males
                                                                                                                                                                                                                                                                                                                      • PPARα activation leading to impaired fertility in adult male rodents
                                                                                                                                                                                                                                                                                                                      • Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
                                                                                                                                                                                                                                                                                                                      461 Increase, Luteinizing hormone (LH) Increase proliferation, Leydig cell Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                      • PPARα activation leading to impaired fertility in adult male rodents
                                                                                                                                                                                                                                                                                                                      462 Hyperplasia, Leydig cell decreased, Fertility Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                      • PPARα activation leading to impaired fertility in adult male rodents
                                                                                                                                                                                                                                                                                                                      398 Increase proliferation, Leydig cell Hyperplasia, Leydig cell Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                      • PPARα activation leading to impaired fertility in adult male rodents
                                                                                                                                                                                                                                                                                                                      442 Inhibition, Na+/I- symporter (NIS) Thyroidal Iodide, Decreased Nov 29, 2016 May 29, 2018
                                                                                                                                                                                                                                                                                                                      • Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                      • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                                                                                                                                                                                                                      • Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                      552 Inhibition, Na+/I- symporter (NIS) TH synthesis, Decreased Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                      • XX Inhibition of Sodium Iodide Symporter and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                      • Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse)
                                                                                                                                                                                                                                                                                                                      2232 Inhibition, Na+/I- symporter (NIS) T4 in serum, Decreased Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                      • Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                      1503 Inhibition, Na+/I- symporter (NIS) Impairment, Learning and memory May 10, 2017 Apr 4, 2019
                                                                                                                                                                                                                                                                                                                      • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                                                                                                                                                                                                                      872 Thyroidal Iodide, Decreased TH synthesis, Decreased Nov 29, 2016 Jun 4, 2018
                                                                                                                                                                                                                                                                                                                      • Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                      • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                                                                                                                                                                                                                      • Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                      • Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                      443 Thyroidal Iodide, Decreased T4 in serum, Decreased Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                        446 Down Regulation, K-Cl co-transporter 2 (KCC2) Delay, Developmental GABA shift Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                          447 Delay, Developmental GABA shift Synaptogenesis, Decreased Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                            1491 Decreased, Population trajectory Increased Mortality Apr 18, 2017 Apr 18, 2017
                                                                                                                                                                                                                                                                                                                              432 Increased, Atrioventricular block and bradycardia Increased Mortality Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                591 Increased, Atrioventricular block and bradycardia Respiratory distress/arrest Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                • Sodium channel inhibition leading to congenital malformations
                                                                                                                                                                                                                                                                                                                                592 Respiratory distress/arrest N/A, hypoxia Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                • Sodium channel inhibition leading to congenital malformations
                                                                                                                                                                                                                                                                                                                                433 Respiratory distress/arrest Increased Mortality Nov 29, 2016 Dec 20, 2019
                                                                                                                                                                                                                                                                                                                                • Acetylcholinesterase inhibition leading to acute mortality
                                                                                                                                                                                                                                                                                                                                460 Reduction of testosterone Increase, Luteinizing hormone (LH) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                  608 Reduction of testosterone Malformation, Male reproductive tract Nov 29, 2016 Dec 2, 2016
                                                                                                                                                                                                                                                                                                                                    1649 Reduction of testosterone Decreased sperm quantity or quality in the adult, Decreased fertility Aug 11, 2017 Aug 11, 2017
                                                                                                                                                                                                                                                                                                                                      438 Reduction, Cholesterol transport in mitochondria Reduction, Testosterone synthesis in Leydig cells Nov 29, 2016 Dec 2, 2016
                                                                                                                                                                                                                                                                                                                                      • PPARα activation in utero leading to impaired fertility in males
                                                                                                                                                                                                                                                                                                                                      • PPARα activation leading to impaired fertility in adult male rodents
                                                                                                                                                                                                                                                                                                                                      3517 Reduction, Cholesterol transport in mitochondria Decreased, Pregnenolone levels Apr 8, 2025 Apr 8, 2025
                                                                                                                                                                                                                                                                                                                                        3216 Suppression, VLDL secretion Increased, Liver Steatosis May 9, 2024 May 9, 2024
                                                                                                                                                                                                                                                                                                                                        • AhR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                        475 Inhibition, Mitochondrial fatty acid beta-oxidation Accumulation, Fatty acid Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                        • AhR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                        • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                        538 Inhibition, Mitochondrial fatty acid beta-oxidation Increased, Liver Steatosis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                        • NFE2L2/FXR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                        486 Increased, Triglyceride formation Increased, Liver Steatosis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                        • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                        • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                        476 Suppression, Constitutive androstane receptor, NR1l3 Activation, LXR Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                        • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                        477 Suppression, Constitutive androstane receptor, NR1l3 demethylation, PPARg promoter Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                        • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                        482 Activation, SREBF1 Increased, De Novo FA synthesis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                          489 Activation, SREBF1 Up Regulation, SCD-1 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                          • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                          1662 Activation, SREBF1 Increased, Liver Steatosis Aug 31, 2017 Aug 31, 2017
                                                                                                                                                                                                                                                                                                                                          • AKT2 activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                          1607 Increased, De Novo FA synthesis Increased, Liver Steatosis Jul 18, 2017 Jul 18, 2017
                                                                                                                                                                                                                                                                                                                                          • NFE2L2/FXR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                          484 Increased, De Novo FA synthesis Increased, Triglyceride formation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                            512 Increased, De Novo FA synthesis Accumulation, Fatty acid Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                            • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                            1695 Increased, Liver Steatosis Increase, ROS Nov 14, 2017 Nov 14, 2017
                                                                                                                                                                                                                                                                                                                                            • Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)
                                                                                                                                                                                                                                                                                                                                            3218 Increased, Liver Steatosis Cell injury/death May 14, 2024 Jan 30, 2025
                                                                                                                                                                                                                                                                                                                                            • AhR activation leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                            2263 Increased, Fatty acid uptake Increased, Liver Steatosis Jan 15, 2021 Jan 15, 2021
                                                                                                                                                                                                                                                                                                                                              1657 Up Regulation, SCD-1 Accumulation, Triglyceride Aug 31, 2017 Aug 31, 2017
                                                                                                                                                                                                                                                                                                                                              • AhR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                              493 Up Regulation, SCD-1 Increased, Triglyceride formation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                              • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                              • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                              492 Up Regulation, FAS Increased, De Novo FA synthesis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                              • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                              504 Increased, FA Influx Accumulation, Triglyceride Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                505 Increased, FA Influx Accumulation, Fatty acid Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                • AhR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                1658 Increased, FA Influx Increased, Triglyceride formation Aug 31, 2017 Aug 31, 2017
                                                                                                                                                                                                                                                                                                                                                • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                507 Up Regulation, LDLR (low density lipoprotein receptor) Increased, LDL uptake Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                • AhR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                508 Increased, LDL uptake Accumulation, Fatty acid Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                • AhR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                3443 Increased, LDL uptake Foam cell formation Nov 25, 2024 Nov 25, 2024
                                                                                                                                                                                                                                                                                                                                                • Activation of reactive oxygen species leading the atherosclerosis
                                                                                                                                                                                                                                                                                                                                                511 Inhibition, PPAR alpha Inhibition, Mitochondrial fatty acid beta-oxidation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                517 Up Regulation, Acetyl-CoA carboxylase-1 (ACC-1) Increased, De Novo FA synthesis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                519 Inhibition, FoxA2 Down Regulation, CPT1A Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                523 Inhibition, FoxA2 Down Regulation, HMGCS2 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                520 Down Regulation, CPT1A Decreased, Mitochondrial fatty acid beta-oxidation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                524 Down Regulation, HMGCS2 Decreased, Ketogenesis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                1660 Decreased, Ketogenesis Accumulation, Fatty acid Aug 31, 2017 Aug 31, 2017
                                                                                                                                                                                                                                                                                                                                                • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                1406 Activation, NRF2 Activation, FXR Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                  532 Activation, NRF2 Activation, NR1H4 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                  • NFE2L2/FXR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                  533 Activation, NR1H4 Activation, SHP Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                  • NFE2L2/FXR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                  534 Activation, NR1H4 Activation, PPARα Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                  • NFE2L2/FXR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                  896 Activation, SHP Inhibition, SREBP1c Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                  • NFE2L2/FXR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                  1409 Activation, SHP Activation, PPARα Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                    1412 Activation, SHP Inhibition, LXR Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                      1414 Activation, SHP Inhibition, LRH-1 Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                        537 Decreased, DHB4/HSD17B4 Inhibition, Mitochondrial fatty acid beta-oxidation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                        • NFE2L2/FXR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                        1606 Activation, LXR alpha Increased, De Novo FA synthesis Jul 18, 2017 Jul 18, 2017
                                                                                                                                                                                                                                                                                                                                                        • NFE2L2/FXR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                        1661 Activation, AKT2 Activation, SREBF1 Aug 31, 2017 Aug 31, 2017
                                                                                                                                                                                                                                                                                                                                                        • AKT2 activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                        541 inflammation Activation, AKT2 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                        • AKT2 activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                        544 Decrease, Ovulation Reduction, Cumulative fecundity and spawning Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                          687 Decrease, Ovulation Reduced, Reproductive Success Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                          1753 Decrease, Ovulation Decrease, Fecundity Jun 12, 2018 Jun 12, 2018
                                                                                                                                                                                                                                                                                                                                                            1471 Decrease, Ovulation Decrease, Fertility Apr 15, 2017 Apr 15, 2017
                                                                                                                                                                                                                                                                                                                                                              550 Clonal Expansion/Cell Proliferation, to form Altered Hepatic Foci (AHF) Tumorigenesis, Hepatocellular carcinoma Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                              • AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
                                                                                                                                                                                                                                                                                                                                                              547 Increased, Insufficient repair or mis-repair of pro-mutagenic DNA adducts Increased, Induced Mutations in Critical Genes Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                              • AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
                                                                                                                                                                                                                                                                                                                                                              1645 GR Agonist, Activation Decreased Leydig Cells Aug 11, 2017 Aug 11, 2017
                                                                                                                                                                                                                                                                                                                                                              • Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
                                                                                                                                                                                                                                                                                                                                                              1646 GR Agonist, Activation Repressed expression of steroidogenic enzymes Aug 11, 2017 Aug 11, 2017
                                                                                                                                                                                                                                                                                                                                                              • Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
                                                                                                                                                                                                                                                                                                                                                              1648 Repressed expression of steroidogenic enzymes Reduction, Testosterone synthesis in Leydig cells Aug 11, 2017 Aug 11, 2017
                                                                                                                                                                                                                                                                                                                                                              • Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
                                                                                                                                                                                                                                                                                                                                                              1647 Decreased Leydig Cells Reduction, Testosterone synthesis in Leydig cells Aug 11, 2017 Aug 11, 2017
                                                                                                                                                                                                                                                                                                                                                              • Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
                                                                                                                                                                                                                                                                                                                                                              1650 Decreased sperm quantity or quality in the adult, Decreased fertility decreased, Fertility Aug 11, 2017 Aug 11, 2017
                                                                                                                                                                                                                                                                                                                                                              • Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
                                                                                                                                                                                                                                                                                                                                                              3465 Decreased, GnRH pulsatility/release Decreased, LH Surge Jan 3, 2025 Jan 3, 2025
                                                                                                                                                                                                                                                                                                                                                              • Decreased, GnRH pulsatility/release leading to estradiol availability, increased via impaired ovulation
                                                                                                                                                                                                                                                                                                                                                              3469 Decreased, LH Surge Impaired ovulation Jan 10, 2025 Jan 10, 2025
                                                                                                                                                                                                                                                                                                                                                              • Decreased, GnRH pulsatility/release leading to estradiol availability, increased via impaired ovulation
                                                                                                                                                                                                                                                                                                                                                              1146 Activation, Nicotinic acetylcholine receptor Impairment, Learning and memory Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                              • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1
                                                                                                                                                                                                                                                                                                                                                              • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                              • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within caste
                                                                                                                                                                                                                                                                                                                                                              • Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                              1147 Activation, Nicotinic acetylcholine receptor Abnormal, Foraging activity and behavior Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                581 Activation, Nicotinic acetylcholine receptor Mitochondrial dysfunction Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1
                                                                                                                                                                                                                                                                                                                                                                • Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                • Nicotinic acetylcholine receptor activation contributes to impaired hive thermoregulation and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                • Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1
                                                                                                                                                                                                                                                                                                                                                                658 Activation, Nicotinic acetylcholine receptor Desensitization, Nicotinic acetylcholine receptor Nov 29, 2016 Jun 7, 2018
                                                                                                                                                                                                                                                                                                                                                                • Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within caste
                                                                                                                                                                                                                                                                                                                                                                • Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2
                                                                                                                                                                                                                                                                                                                                                                569 Abnormal, Foraging activity and behavior Decrease, Number of worker bees Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                • Increased metabolic stress contributes to abnormal foraging and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                • Suppression of immune system contributes to abnormal foraging and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                584 Abnormal, Foraging activity and behavior Reduced, Food storage Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                  1144 Abnormal, Foraging activity and behavior Weakened, Colony Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                  • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1
                                                                                                                                                                                                                                                                                                                                                                  • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within caste
                                                                                                                                                                                                                                                                                                                                                                  • Varroa mite infestation contributes to abnormal foraging leading to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                  • Weather event contributes abnormal foraging leading to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                  • Nosema infection increases energetic demands leading to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                  1148 Abnormal, Foraging activity and behavior Abnormal, Roll change within caste Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                    1150 Abnormal, Foraging activity and behavior Abnormal, Role change within caste Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                    • Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                    • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                    558 Reduced, Food storage Decrease, Number of worker bees Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                      562 Reduced, Food storage impaired, Larval development Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                      • Decrease Glucose oxidase activity contributes to reduction of antiseptic in food and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                      565 Abnormal, Roll change within caste Reduced, Brood care Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                      • Abnormal role change in worker caste contributes to reduced brood care and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                      • Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2
                                                                                                                                                                                                                                                                                                                                                                      • Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1
                                                                                                                                                                                                                                                                                                                                                                      579 Abnormal, Roll change within caste Reduced, Food storage Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                      • Decrease Glucose oxidase activity contributes to reduction of antiseptic in food and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                      580 Abnormal, Roll change within caste Decrease, Number of worker bees Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                        1149 Abnormal, Roll change within caste Weakened, Colony Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                          566 Reduced, Brood care impaired, Larval development Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                          • Abnormal role change in worker caste contributes to reduced brood care and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                          • Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2
                                                                                                                                                                                                                                                                                                                                                                          • Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1
                                                                                                                                                                                                                                                                                                                                                                          563 impaired, Larval development Death/Failure, Colony Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                          • Abnormal role change in worker caste contributes to reduced brood care and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                          • Decrease Glucose oxidase activity contributes to reduction of antiseptic in food and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                          • Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2
                                                                                                                                                                                                                                                                                                                                                                          • Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1
                                                                                                                                                                                                                                                                                                                                                                          3460 impaired, Larval development Increase, Malformations Dec 24, 2024 Dec 24, 2024
                                                                                                                                                                                                                                                                                                                                                                          • DBDPE-induced inhibition of mitochondrial complex Ⅰ leading to population decline via neurotoxicity and metabotoxicity.
                                                                                                                                                                                                                                                                                                                                                                          574 impaired, Hive thermoregulation Death/Failure, Colony Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                          • Suppression of immune system contributes to impaired development and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                          • Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                          1153 impaired, Hive thermoregulation Weakened, Colony Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                          • Nicotinic acetylcholine receptor activation contributes to impaired hive thermoregulation and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                          662 Accumulation, Damaged mitochondrial DNA Accelerated, Aging Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                          • Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                          663 Accelerated, Aging Decrease, Number of worker bees Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                          • Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                          559 Decrease, Number of worker bees Death/Failure, Colony Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                          • Increased metabolic stress contributes to abnormal foraging and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                          • Suppression of immune system contributes to abnormal foraging and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                          573 Decrease, Number of worker bees impaired, Hive thermoregulation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                          • Suppression of immune system contributes to impaired development and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                          • Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                          567 Increase, Energetic demands and therefore metabolic stress Increased, Appetite and hunger Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                          • Increased metabolic stress contributes to abnormal foraging and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                          568 Increased, Appetite and hunger Abnormal, Foraging activity and behavior Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                          • Increased metabolic stress contributes to abnormal foraging and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                          571 Increased, Viral susceptibility impaired, Development Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                          • Suppression of immune system contributes to impaired development and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                          575 Increased, Viral susceptibility Abnormal, Foraging activity and behavior Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                          • Suppression of immune system contributes to abnormal foraging and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                          572 impaired, Development Decrease, Number of worker bees Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                          • Suppression of immune system contributes to impaired development and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                          576 Decreased, Glucose oxidase enzyme activity Decreased, Hydrogen peroxide production Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                          • Decrease Glucose oxidase activity contributes to reduction of antiseptic in food and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                          577 Decreased, Hydrogen peroxide production Reduced, Antiseptic incorporated in food Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                          • Decrease Glucose oxidase activity contributes to reduction of antiseptic in food and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                          578 Reduced, Antiseptic incorporated in food Abnormal, Roll change within caste Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                          • Decrease Glucose oxidase activity contributes to reduction of antiseptic in food and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                          665 impaired, Thoracic shivering impaired, Hive thermoregulation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                            585 Inhibition, sodium channel Decreased, Sodium conductance 1 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                            • Sodium channel inhibition leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                            • sodium channel inhibition leading to increased predation
                                                                                                                                                                                                                                                                                                                                                                            • Sodium channel inhibition leading to congenital malformations
                                                                                                                                                                                                                                                                                                                                                                            590 Inhibition, sodium channel Increased, Atrioventricular block and bradycardia Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                              1242 Inhibition, sodium channel Decreased, sodium conductance 2 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                              • Sodium channel (Nav1.1) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                              3414 Inhibition, sodium channel Altered, Action Potential Nov 21, 2024 Nov 21, 2024
                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure
                                                                                                                                                                                                                                                                                                                                                                              586 Decreased, Sodium conductance 1 Reduced, swimming speed Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                              • Sodium channel inhibition leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                              • sodium channel inhibition leading to increased predation
                                                                                                                                                                                                                                                                                                                                                                              • Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                              594 Decreased, Sodium conductance 1 Increased, Atrioventricular block and bradycardia Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                              • Sodium channel inhibition leading to congenital malformations
                                                                                                                                                                                                                                                                                                                                                                              587 Reduced, swimming speed Reduced, feeding 1 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                              • Sodium channel inhibition leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                              • Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                              588 Reduced, swimming speed Increased, predation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                              • Sodium channel inhibition leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                              • Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                              • sodium channel inhibition leading to increased predation
                                                                                                                                                                                                                                                                                                                                                                              589 Reduced, feeding 1 Increased, predation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                              • Sodium channel inhibition leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                              • Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                              596 Reduced, feeding 1 Reduced, survival Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                              • Sodium channel inhibition leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                              595 Increased, predation Reduced, survival Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                              • Sodium channel inhibition leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                              • Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                              654 Increased, predation Decreased, survival Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                              • Histamine (H2) receptor antagonism leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                              593 N/A, hypoxia Increased, amputations Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                              • Sodium channel inhibition leading to congenital malformations
                                                                                                                                                                                                                                                                                                                                                                              3307 N/A, hypoxia Increase, angiogenesis Jul 18, 2024 Jul 18, 2024
                                                                                                                                                                                                                                                                                                                                                                                3370 N/A, hypoxia Increase, Cancer Oct 25, 2024 Oct 25, 2024
                                                                                                                                                                                                                                                                                                                                                                                • Succinate dehydrogenase inactivation leads to cancer through hypoxic-like mechanisms
                                                                                                                                                                                                                                                                                                                                                                                3419 Inhibition, Ether-a-go-go (ERG) voltage-gated potassium channel Prolongation of Action Potential Nov 21, 2024 Nov 21, 2024
                                                                                                                                                                                                                                                                                                                                                                                • Inhibition, Ether-a-go-go (ERG) Voltage-Gated Potassium Channel leading to heart failure
                                                                                                                                                                                                                                                                                                                                                                                597 Inhibition, Ether-a-go-go (ERG) voltage-gated potassium channel Decreased, Sodium conductance 1 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                • Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                                603 modulation, sodium channel prolonged, Depolarization of neuronal membrane Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                • Axonal sodium channel modulation leading to acute mortality
                                                                                                                                                                                                                                                                                                                                                                                604 prolonged, Depolarization of neuronal membrane Overactivation, Neuronotransmitter release Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                • Axonal sodium channel modulation leading to acute mortality
                                                                                                                                                                                                                                                                                                                                                                                605 Overactivation, Neuronotransmitter release Overactivation, muscle contraction Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                • Axonal sodium channel modulation leading to acute mortality
                                                                                                                                                                                                                                                                                                                                                                                606 Overactivation, muscle contraction Increased, Ataxia, paralysis, or hyperactivity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                • Axonal sodium channel modulation leading to acute mortality
                                                                                                                                                                                                                                                                                                                                                                                607 Increased, Ataxia, paralysis, or hyperactivity Increased Mortality Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                • Axonal sodium channel modulation leading to acute mortality
                                                                                                                                                                                                                                                                                                                                                                                1999 Occurrence, Epileptic seizure Overactivation, NMDARs Nov 13, 2019 Nov 13, 2019
                                                                                                                                                                                                                                                                                                                                                                                  1861 Occurrence, Epileptic seizure Increased, glutamate Feb 13, 2019 Feb 13, 2019
                                                                                                                                                                                                                                                                                                                                                                                    630 Occurrence, A paroxysmal depolarizing shift Occurrence, Epileptic seizure Nov 29, 2016 May 22, 2018
                                                                                                                                                                                                                                                                                                                                                                                    • Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain
                                                                                                                                                                                                                                                                                                                                                                                    634 Decreased, Neuronal network function in adult brain Impairment, Learning and memory Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                    • Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.
                                                                                                                                                                                                                                                                                                                                                                                    2656 Decreased, Neuronal network function in adult brain Sensory axonal peripheral neuropathy May 16, 2022 May 16, 2022
                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality
                                                                                                                                                                                                                                                                                                                                                                                    3072 Decreased, Neuronal network function in adult brain Neurological disorder Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                    • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                    3073 Decreased, Neuronal network function in adult brain Neuroinflammation Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                    • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                    3074 Decreased, Neuronal network function in adult brain Degeneration of dopaminergic neurons of the nigrostriatal pathway Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                      3076 Decreased, Neuronal network function in adult brain impaired, Learning and memory Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                      • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                      1208 Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) Increased, cilia movement Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                        1316 Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) Increased, muscular waves in foot Jan 13, 2017 Jan 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                        • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                        1317 Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) Increased, valve movement Jan 13, 2017 Jan 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                        • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                        • 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline
                                                                                                                                                                                                                                                                                                                                                                                        • 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
                                                                                                                                                                                                                                                                                                                                                                                        1318 Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) Increase, cilia movement Jan 13, 2017 Jan 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                        • 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline
                                                                                                                                                                                                                                                                                                                                                                                        • 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
                                                                                                                                                                                                                                                                                                                                                                                        • 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
                                                                                                                                                                                                                                                                                                                                                                                        1319 Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) increased mantel display Jan 13, 2017 Jan 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                        • 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline
                                                                                                                                                                                                                                                                                                                                                                                        • 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
                                                                                                                                                                                                                                                                                                                                                                                        1337 Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) Increased, oocyte maturation Jan 30, 2017 Jan 30, 2017
                                                                                                                                                                                                                                                                                                                                                                                        • 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
                                                                                                                                                                                                                                                                                                                                                                                        3474 Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) Increased, extracellular serotonin Jan 14, 2025 Feb 13, 2025
                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) leads to Inhibition, Feeding
                                                                                                                                                                                                                                                                                                                                                                                        635 Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) Increased, serotonin (5-HT) 1 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                          643 Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) Increased, serotonin (5-HT) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                          • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to decreased shelter seeking and increased predation
                                                                                                                                                                                                                                                                                                                                                                                          • 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
                                                                                                                                                                                                                                                                                                                                                                                          • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                          • 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
                                                                                                                                                                                                                                                                                                                                                                                          • 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline
                                                                                                                                                                                                                                                                                                                                                                                          636 Increased, serotonin (5-HT) 1 Increase, cilia movement Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                            640 Increased, serotonin (5-HT) 1 Increased, muscular waves in foot Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                              1172 Increased, serotonin (5-HT) 1 Increased, valve movement Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                1186 Increased, serotonin (5-HT) 1 Decreased, gametogenesis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                  1189 Increased, serotonin (5-HT) 1 Increased, locomotion Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                    1192 Increased, serotonin (5-HT) 1 increased or inappropriate, mantel display Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                      1178 Increase, cilia movement premature, spawning 1 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                        1187 Increase, cilia movement premature, Spawning Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                          1217 Increase, cilia movement Increased, water pumping Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                            1218 Increase, cilia movement Depletion, energy reserves Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                              1321 Increase, cilia movement induced spawning Jan 13, 2017 Jan 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                              • 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
                                                                                                                                                                                                                                                                                                                                                                                                              1335 Increase, cilia movement Induced parturition Jan 30, 2017 Jan 30, 2017
                                                                                                                                                                                                                                                                                                                                                                                                              • 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
                                                                                                                                                                                                                                                                                                                                                                                                              • 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline
                                                                                                                                                                                                                                                                                                                                                                                                              637 Increase, cilia movement Increased, locomotion Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                639 Increase, cilia movement Increased, foot detachment Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                  638 Increased, locomotion Increase, predation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                  • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                  1177 Increased, locomotion Depletion, energy reserves Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                  • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                  2634 Increase, predation Decrease, Population growth rate Apr 6, 2022 Apr 6, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                  • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                  1176 Increased, foot detachment Depletion, energy reserves Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                  • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                  1183 Increased, foot detachment Increase, predation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                    1228 Increased, muscular waves in foot Depletion, energy reserves Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                      641 Increased, muscular waves in foot Increased, locomotion Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                      • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                      642 Increased, muscular waves in foot Increased, foot detachment Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                      • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                      644 Increased, serotonin (5-HT) Decreased, anxiety Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                      • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to decreased shelter seeking and increased predation
                                                                                                                                                                                                                                                                                                                                                                                                                      1207 Increased, serotonin (5-HT) Increased, mantel display Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                        1209 Increased, serotonin (5-HT) Increased, cilia movement Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          1212 Increased, serotonin (5-HT) Increased, oocyte maturation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          • 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
                                                                                                                                                                                                                                                                                                                                                                                                                          1327 Increased, serotonin (5-HT) Increased, valve movement Jan 17, 2017 Jan 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                          • 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
                                                                                                                                                                                                                                                                                                                                                                                                                          • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                          • 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
                                                                                                                                                                                                                                                                                                                                                                                                                          • 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline
                                                                                                                                                                                                                                                                                                                                                                                                                          1332 Increased, serotonin (5-HT) Increased, muscular waves in foot Jan 30, 2017 Jan 30, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                          • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                          1333 Increased, serotonin (5-HT) Increase, cilia movement Jan 30, 2017 Jan 30, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                          • 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
                                                                                                                                                                                                                                                                                                                                                                                                                          • 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
                                                                                                                                                                                                                                                                                                                                                                                                                          • 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline
                                                                                                                                                                                                                                                                                                                                                                                                                          1336 Increased, serotonin (5-HT) increased mantel display Jan 30, 2017 Jan 30, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                          • 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
                                                                                                                                                                                                                                                                                                                                                                                                                          • 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline
                                                                                                                                                                                                                                                                                                                                                                                                                          645 Decreased, anxiety Decreased, sheltering Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to decreased shelter seeking and increased predation
                                                                                                                                                                                                                                                                                                                                                                                                                          646 Decreased, sheltering Increased, predation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to decreased shelter seeking and increased predation
                                                                                                                                                                                                                                                                                                                                                                                                                          649 Decrease, histaminergic neuron excitation N/A, sedation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          • Histamine (H2) receptor antagonism leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                                                                          1643 Decrease, histaminergic neuron excitation Impairment, Learning and memory Aug 11, 2017 Aug 11, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                          • Histamine (H2) receptor antagonism leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                                                                          650 N/A, sedation Decreased, locomotion Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          • Histamine (H2) receptor antagonism leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                                                                          651 Decreased, locomotion Increased, predation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          • Histamine (H2) receptor antagonism leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                                                                          3079 impaired, Learning and memory Parkinsonian motor deficits Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                          • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                          1061 Antagonism, Histamine Receptor (H2) Decrease, histaminergic neuron excitation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          • Histamine (H2) receptor antagonism leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                                                                          3168 Decreased, steroidogenic protein expression Decrease, circulating testosterone levels Mar 20, 2024 Dec 3, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                          • Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Impaired, Spermatogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                          3171 Decreased, steroidogenic protein expression Decrease, DHT level Mar 20, 2024 Dec 3, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                          • Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Hypospadias, increased
                                                                                                                                                                                                                                                                                                                                                                                                                          3167 Decreased COUP-TFII in Leydig cells Decreased, steroidogenic protein expression Mar 20, 2024 Dec 3, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                          • Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Impaired, Spermatogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                          • Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Hypospadias, increased
                                                                                                                                                                                                                                                                                                                                                                                                                          659 Desensitization, Nicotinic acetylcholine receptor Neuronal network function, Decreased Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          • Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2
                                                                                                                                                                                                                                                                                                                                                                                                                          1309 Desensitization, Nicotinic acetylcholine receptor Altered, Ca2+-calmodulin activated signal transduction Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          • Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                          • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within caste
                                                                                                                                                                                                                                                                                                                                                                                                                          661 Overwhelmed, Mitochondrial DNA repair mechanisms Accumulation, Damaged mitochondrial DNA Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          • Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                          666 Binding at picrotoxin site, iGABAR chloride channel Reduction, Ionotropic GABA receptor chloride channel conductance Nov 29, 2016 Apr 29, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                          • Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain
                                                                                                                                                                                                                                                                                                                                                                                                                          683 Reduction, Neuronal synaptic inhibition Generation, Amplified excitatory postsynaptic potential (EPSP) Nov 29, 2016 May 15, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                          • Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain
                                                                                                                                                                                                                                                                                                                                                                                                                          672 Reduced, Prostaglandin F2alpha concentration, plasma Reduced, Spawning behavior Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior
                                                                                                                                                                                                                                                                                                                                                                                                                          678 Reduced, Prostaglandin F2alpha concentration, plasma Reduced, Pheromone release Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release
                                                                                                                                                                                                                                                                                                                                                                                                                          671 Reduced, Prostaglandin F2alpha synthesis, ovary Reduced, Prostaglandin F2alpha concentration, plasma Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior
                                                                                                                                                                                                                                                                                                                                                                                                                          673 Reduced, Spawning behavior Reduced, Ability to attract spawning mates Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior
                                                                                                                                                                                                                                                                                                                                                                                                                          674 Reduced, Ability to attract spawning mates Reduced, Reproductive Success Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior
                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release
                                                                                                                                                                                                                                                                                                                                                                                                                          675 Reduced, Reproductive Success Decrease, Population growth rate Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior
                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release
                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition
                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
                                                                                                                                                                                                                                                                                                                                                                                                                          679 Reduced, Pheromone release Reduced, Ability to attract spawning mates Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release
                                                                                                                                                                                                                                                                                                                                                                                                                          682 Decreased, Prostaglandin F2alpha synthesis, ovary Reduced, Prostaglandin F2alpha concentration, plasma Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release
                                                                                                                                                                                                                                                                                                                                                                                                                          684 Generation, Amplified excitatory postsynaptic potential (EPSP) Occurrence, A paroxysmal depolarizing shift Nov 29, 2016 May 15, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                          • Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain
                                                                                                                                                                                                                                                                                                                                                                                                                          685 Reduced, Prostaglandins, ovary Decrease, Ovulation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                          690 Reduced, Prostaglandin E2 concentration, hypothalamus Reduced, Gonadotropin releasing hormone, hypothalamus Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition
                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
                                                                                                                                                                                                                                                                                                                                                                                                                          691 Reduced, Gonadotropin releasing hormone, hypothalamus Reduced, Luteinizing hormone (LH), plasma Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition
                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
                                                                                                                                                                                                                                                                                                                                                                                                                          692 Reduced, Luteinizing hormone (LH), plasma Reduced, Maturation inducing steroid, plasma Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition
                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
                                                                                                                                                                                                                                                                                                                                                                                                                          693 Reduced, Maturation inducing steroid, plasma Reduced, Maturation inducing steroid receptor signalling, oocyte Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition
                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
                                                                                                                                                                                                                                                                                                                                                                                                                          694 Reduced, Maturation inducing steroid receptor signalling, oocyte Increased, cyclic adenosine monophosphate Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition
                                                                                                                                                                                                                                                                                                                                                                                                                          698 Reduced, Maturation inducing steroid receptor signalling, oocyte Upregulated, Spindle assembly checkpoint protein Mad2-oocyte Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
                                                                                                                                                                                                                                                                                                                                                                                                                          695 Increased, cyclic adenosine monophosphate Reduced, Reproductive Success Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                            696 Increased, cyclic adenosine monophosphate Reduced, Meiotic prophase I/metaphase I transition, oocyte Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                            • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition
                                                                                                                                                                                                                                                                                                                                                                                                                            3446 Increased, cyclic adenosine monophosphate RyR2 hyperphosphorylation Nov 26, 2024 Nov 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                            • Phosphodiesterase inhibition leading to heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                            697 Reduced, Meiotic prophase I/metaphase I transition, oocyte Reduced, Reproductive Success Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                            • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition
                                                                                                                                                                                                                                                                                                                                                                                                                            699 Upregulated, Spindle assembly checkpoint protein Mad2-oocyte Increased, Chromosome misseggregation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                            • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
                                                                                                                                                                                                                                                                                                                                                                                                                            700 Increased, Chromosome misseggregation Reduced, Reproductive Success Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                            • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
                                                                                                                                                                                                                                                                                                                                                                                                                            701 impaired, ion channels Altered, Action Potential Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                            • Altered ion channel activity leading impaired heart function
                                                                                                                                                                                                                                                                                                                                                                                                                            702 Altered, Action Potential Increased, cardiac arrthymia Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                            • Altered ion channel activity leading impaired heart function
                                                                                                                                                                                                                                                                                                                                                                                                                            3415 Altered, Action Potential Decrease, Cardiac contractility Nov 21, 2024 Nov 21, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                            3407 Altered, Action Potential Prolongation of QT interval Nov 20, 2024 Nov 20, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibiton of L-Type Calcium Channels leading to heart failure via QT interval prolongation and Torsades de Pointes (TdP)
                                                                                                                                                                                                                                                                                                                                                                                                                            3432 Altered, Action Potential Prolonged atrioventricular (AV) Nov 22, 2024 Nov 22, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of acetylcholinesterase (AChE) leading to arrhythmias
                                                                                                                                                                                                                                                                                                                                                                                                                            703 Increased, cardiac arrthymia Increased Mortality Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                            • Altered ion channel activity leading impaired heart function
                                                                                                                                                                                                                                                                                                                                                                                                                            707 Increased, Accumulation of alpha2u microglobulin (proximal tubular epithelium) Increase, Cytotoxicity (renal tubular cell) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                            • Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
                                                                                                                                                                                                                                                                                                                                                                                                                            708 Increase, Cytotoxicity (renal tubular cell) Increase, Regenerative cell proliferation (tubular epithelial cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                            • Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
                                                                                                                                                                                                                                                                                                                                                                                                                            1676 Increase, Cytotoxicity (renal tubular cell) Occurrence, Kidney toxicity Oct 25, 2017 Mar 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                            • Receptor mediated endocytosis and lysosomal overload leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                            • Renal protein alkylation leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                            760 Increase, Regenerative cell proliferation (tubular epithelial cells) Increase, Hyperplasia (renal tubular cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                            • Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
                                                                                                                                                                                                                                                                                                                                                                                                                            785 Increase, Regenerative cell proliferation (tubular epithelial cells) Increase, Hyperplasia (tubular epithelial cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                            • Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
                                                                                                                                                                                                                                                                                                                                                                                                                            706 Increased, Binding of chemicals to 2u (serum) Increased, Accumulation of alpha2u microglobulin (proximal tubular epithelium) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                            • Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
                                                                                                                                                                                                                                                                                                                                                                                                                            711 Activation, Constitutive androstane receptor Increase, cell proliferation (hepatocytes) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                              1268 Activation, Constitutive androstane receptor Altered expression of hepatic CAR-dependent genes Nov 29, 2016 Dec 21, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                              • Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat
                                                                                                                                                                                                                                                                                                                                                                                                                              1239 Increase, cell proliferation (hepatocytes) Increase, Clonal Expansion of Altered Hepatic Foci Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                              • PPARα activation leading to hepatocellular adenomas and carcinomas in rodents
                                                                                                                                                                                                                                                                                                                                                                                                                              2254 Increase, cell proliferation (hepatocytes) Increase, hepatocellular adenomas and carcinomas Dec 31, 2020 Dec 31, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                              • PPARα activation leading to hepatocellular adenomas and carcinomas in rodents
                                                                                                                                                                                                                                                                                                                                                                                                                              773 Increase, cell proliferation (hepatocytes) Increase, Preneoplastic foci (hepatocytes) Nov 29, 2016 Feb 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                              • Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat
                                                                                                                                                                                                                                                                                                                                                                                                                              • Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                              714 Binding, Tubulin Disruption, Microtubule dynamics Nov 29, 2016 May 27, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                              • Chemical binding to tubulin in oocytes leading to aneuploid offspring
                                                                                                                                                                                                                                                                                                                                                                                                                              724 Binding, Tubulin Altered, Chromosome number Nov 29, 2016 Dec 13, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                              • Chemical binding to tubulin in oocytes leading to aneuploid offspring
                                                                                                                                                                                                                                                                                                                                                                                                                              715 Disruption, Microtubule dynamics Disorganization, Meiotic Spindle Nov 29, 2016 Dec 13, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                              • Chemical binding to tubulin in oocytes leading to aneuploid offspring
                                                                                                                                                                                                                                                                                                                                                                                                                              737 Disorganization, Meiotic Spindle Altered, Meiotic chromosome dynamics Nov 29, 2016 Dec 13, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                              • Chemical binding to tubulin in oocytes leading to aneuploid offspring
                                                                                                                                                                                                                                                                                                                                                                                                                              723 Altered, Chromosome number Increase, Aneuploid offspring Nov 29, 2016 Dec 13, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                              • Chemical binding to tubulin in oocytes leading to aneuploid offspring
                                                                                                                                                                                                                                                                                                                                                                                                                              716 Inhibition, Pyruvate dehydrogenase kinase (PDK) enzyme Increased, Induction of pyruvate dehydrogenase (PDH) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                              762 Increased, Induction of pyruvate dehydrogenase (PDH) Increase, Oxidative metabolism Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                              726 Increase, Necrosis (terminal bronchiolar cells) Increase, Regenerative cell proliferation (terminal bronchiolar epithelial cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                              • Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)
                                                                                                                                                                                                                                                                                                                                                                                                                              727 Increase, Regenerative cell proliferation (terminal bronchiolar epithelial cells) Increase, Hyperplasia (terminal bronchiolar cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                              • Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)
                                                                                                                                                                                                                                                                                                                                                                                                                              728 Increase, Hyperplasia (terminal bronchiolar cells) Increase, Adenomas/carcinomas (bronchioloalveolar) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                              • Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)
                                                                                                                                                                                                                                                                                                                                                                                                                              768 Decreased, Uptake of inorganic iodide Decrease, Serum thyroid hormone (T4/T3) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                2421 Decreased, Uptake of inorganic iodide TH synthesis, Decreased Jul 7, 2021 Jul 7, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                  742 Increase, Hypertrophy and proliferation (follicular cell) Increase, Hyperplasia (follicular cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse)
                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)
                                                                                                                                                                                                                                                                                                                                                                                                                                  • Enhanced hepatic clearance of thyroid hormones leading to thyroid follicular cell adenomas and carcinomas in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                  743 Increase, Hyperplasia (follicular cells) Increase, Adenomas/carcinomas (follicular cell) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse)
                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)
                                                                                                                                                                                                                                                                                                                                                                                                                                  • Enhanced hepatic clearance of thyroid hormones leading to thyroid follicular cell adenomas and carcinomas in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                  730 Decreased, Testosterone binding to androgen receptor (hypothalamus) Increase, Hyperplasia (Leydig cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                    744 Decreased, Testosterone binding to androgen receptor (hypothalamus) Increased, Luteinizing hormone (LH) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                    • Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                    731 Increase, Hyperplasia (Leydig cells) Increase, Leydig cell tumors Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                    • Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                    732 Increase, Dopaminergic activity Decreased, Prolactin Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                    770 Increase, Dopaminergic activity Increase, Endometrial adenocarcinomas Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                      3524 Decreased, Prolactin Agonism, Estrogen receptor Apr 17, 2025 Apr 17, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                      • Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                      2737 Increased, Estrogen receptor (ER) activity Increase, Vitellogenin mRNA Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                      • Alcohol dehydrogenase leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                      772 Decreased, Progesterone from corpus luteum Increase, Hyperplasia (glandular epithelial cells of endometrium) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                      • Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                      738 Altered, Meiotic chromosome dynamics Altered, Chromosome number Nov 29, 2016 Dec 13, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                      • Chemical binding to tubulin in oocytes leading to aneuploid offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                      2554 Altered, Meiotic chromosome dynamics Increase, Pollen abnormal Jan 21, 2022 Jan 21, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                      • Deposition of ionising energy leads to population decline via pollen abnormal
                                                                                                                                                                                                                                                                                                                                                                                                                                      2384 Altered, Meiotic chromosome dynamics Decreased spermatogenesis May 12, 2021 May 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                      • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                      2383 Altered, Meiotic chromosome dynamics Increase, Oocyte apoptosis May 12, 2021 May 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                      • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                      2391 Altered, Meiotic chromosome dynamics Ionizing Energy May 12, 2021 May 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                        741 Increase, Thyroid-stimulating hormone (TSH) Increase, Hypertrophy and proliferation (follicular cell) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                          745 Increased, Luteinizing hormone (LH) Increase, Hyperplasia (Leydig cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                          • Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                          747 Hippocampal gene expression, Altered Hippocampal anatomy, Altered Nov 29, 2016 Aug 11, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                          • Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                          • Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                          • Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                          • Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                          2886 Hippocampal gene expression, Altered Hippocampal Physiology, Altered Apr 12, 2023 Apr 12, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                          • AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                          • AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                          749 Hippocampal anatomy, Altered Hippocampal Physiology, Altered Nov 29, 2016 Jul 25, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                          • Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                          • Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                          • Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                          • Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                          • Binding to voltage gate sodium channels during development leads to cognitive impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                          748 Hippocampal Physiology, Altered Cognitive function, decreased Nov 29, 2016 Jul 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                          • Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                          • Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                          • Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                          • AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                          • AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                          • Binding to voltage gate sodium channels during development leads to cognitive impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                          2864 Hippocampal Physiology, Altered Impairment, Learning and memory Apr 3, 2023 Apr 3, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                          • Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms
                                                                                                                                                                                                                                                                                                                                                                                                                                          2484 Hippocampal Physiology, Altered Loss, Cochlear function Sep 14, 2021 Sep 14, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                          • Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                          2466 Increased, Kidney Failure Increased Mortality Aug 11, 2021 Aug 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                          • Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure
                                                                                                                                                                                                                                                                                                                                                                                                                                          2462 Increased, Kidney Failure Increase, Mortality Aug 5, 2021 Aug 5, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                            752 Activation, Glutamate-gated chloride channel Increased, Chloride conductance Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                            • Glutamate-gated chloride channel activation leading to acute mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                            758 Increased, Chloride conductance hyperpolarisation, neuron Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                            • Glutamate-gated chloride channel activation leading to acute mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                            1052 Increased, Chloride conductance Increased, Neuronal synaptic inhibition Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                            • Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                            • Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                            1051 Activation, ionotropic GABA Receptor chloride channel Increased, Chloride conductance Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                            • Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                            1566 hyperpolarisation, neuron Analgesia Jun 8, 2017 Jun 8, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                            • Mu Opioid Receptor Agonism leading to Analgesia via K Channel Opening
                                                                                                                                                                                                                                                                                                                                                                                                                                            1572 hyperpolarisation, neuron Anti-depressant Activity Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                            • Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via K Channel Opening
                                                                                                                                                                                                                                                                                                                                                                                                                                            755 hyperpolarisation, neuron N/A, Ataxia, paralysis, or hyperactivity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                            • Glutamate-gated chloride channel activation leading to acute mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                            757 N/A, Ataxia, paralysis, or hyperactivity Increased Mortality Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                            • Glutamate-gated chloride channel activation leading to acute mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                            775 Inhibition, 4-hydroxyphenyl-pyruvate dioxygenase (HPPD) enzyme Increased, Plasma tyrosine Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                            • HPPD inhibition leading to corneal papillomas and carcinomas (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                            761 Increase, Hyperplasia (renal tubular cells) Increase, Adenomas/carcinomas (renal tubular) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                            • Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                            766 Increase, Cytotoxicity Increase, hepatocellular adenomas and carcinomas Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                            887 Increase, Cytotoxicity Increase, Tissue Degeneration, Necrosis & Atrophy Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                            • Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                            763 Increase, Oxidative metabolism Peptide Oxidation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                            767 Increase, Cytotoxicity (club cells) Increase, Necrosis (terminal bronchiolar cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                            • Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)
                                                                                                                                                                                                                                                                                                                                                                                                                                            769 Decrease, Serum thyroid hormone (T4/T3) Increase, Thyroid-stimulating hormone (TSH) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                              771 Increase, Hyperplasia (glandular epithelial cells of endometrium) Increase, Endometrial adenocarcinomas Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                              • Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                              2972 Increase, Hyperplasia (glandular epithelial cells of endometrium) Genomic instability Jul 27, 2023 Mar 27, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                              • Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulation
                                                                                                                                                                                                                                                                                                                                                                                                                                              774 Increase, Preneoplastic foci (hepatocytes) Increase, hepatocellular adenomas and carcinomas Nov 29, 2016 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                              • Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat
                                                                                                                                                                                                                                                                                                                                                                                                                                              • Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                              • Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                              776 Increased, Plasma tyrosine Increase, Cytotoxicity (corneal cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                              • HPPD inhibition leading to corneal papillomas and carcinomas (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                              777 Increase, Cytotoxicity (corneal cells) Increase, Inflammation (corneal cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                              • HPPD inhibition leading to corneal papillomas and carcinomas (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                              778 Increase, Inflammation (corneal cells) Increase, Regenerative cell proliferation (corneal cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                              • HPPD inhibition leading to corneal papillomas and carcinomas (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                              779 Increase, Regenerative cell proliferation (corneal cells) Increase, Papillomas/carcinomas (squamous cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                              • HPPD inhibition leading to corneal papillomas and carcinomas (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                              780 Increase, Cytotoxicity (epithelial cells) Increase, Inflammation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                              • Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                              2659 Increase, Cytotoxicity (epithelial cells) Increase, ROS May 25, 2022 May 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                              • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                              2664 Increase, Cytotoxicity (epithelial cells) Secondary genotoxicity May 25, 2022 May 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                              • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                              782 Increase, Regenerative cell proliferation (forestomach epithelial cells) Increase, Hyperplasia (forestomach epithelial cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                              • Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                              783 Increase, Hyperplasia (forestomach epithelial cells) Increase, Papillomas/carcinomas (squamous cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                              • Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                              784 Increase, Cytotoxicity (tubular epithelial cells) Increase, Regenerative cell proliferation (tubular epithelial cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                              • Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                              786 Increase, Hyperplasia (tubular epithelial cells) Increase, Adenomas/carcinomas (renal tubular) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                              • Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                              788 Increase, Cytotoxicity (hepatocytes) Increase, Regenerative cell proliferation (hepatocytes) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                              • Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                              789 Increase, Regenerative cell proliferation (hepatocytes) Increase, Preneoplastic foci (hepatocytes) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                              • Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                              791 Decrease, Incorporation of active iodide into iodotyrosines Decrease, Serum thyroid hormone (T4/T3) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                794 Increased, Leutinizing hormone (LH) Increase, Hyperplasia (Leydig cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                795 Increase, Urinary bladder calculi Increase, Cytotoxicity (urothelial cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                796 Increase, Cytotoxicity (urothelial cells) Increase, Regenerative cell proliferation (urothelial cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                797 Increase, Regenerative cell proliferation (urothelial cells) Increase, Hyperplasia (urothelial) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                • AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                798 Increase, Hyperplasia (urothelial) Increase, Adenomas/carcinomas (urothelial) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                2085 Increase, Hyperplasia (urothelial) carcinogenicity Apr 21, 2020 Apr 21, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                • AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                799 Inhibition, Prolyl hydroxylases Increased, HIF-1 heterodimer Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                3369 Inhibition, Prolyl hydroxylases N/A, hypoxia Oct 25, 2024 Oct 25, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Succinate dehydrogenase inactivation leads to cancer through hypoxic-like mechanisms
                                                                                                                                                                                                                                                                                                                                                                                                                                                800 Increased, HIF-1 heterodimer Decreased, Aromatase (Cyp19a1) mRNA Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
                                                                                                                                                                                                                                                                                                                                                                                                                                                801 Decreased, Aromatase (Cyp19a1) mRNA Reduction, 17beta-estradiol synthesis by ovarian granulosa cells Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
                                                                                                                                                                                                                                                                                                                                                                                                                                                802 modulation, Unknown Increased, HIF-1 alpha transcription Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
                                                                                                                                                                                                                                                                                                                                                                                                                                                803 Increased, HIF-1 alpha transcription Increased, HIF-1 heterodimer Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
                                                                                                                                                                                                                                                                                                                                                                                                                                                804 Inhibition, HMG-CoA reductase Decreased, mevalonate Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • HMG-CoA reductase inhibition leading to decreased fertility
                                                                                                                                                                                                                                                                                                                                                                                                                                                805 Decreased, mevalonate Decreased, cholesterol Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • HMG-CoA reductase inhibition leading to decreased fertility
                                                                                                                                                                                                                                                                                                                                                                                                                                                3201 Decreased, cholesterol Decrease, circulating testosterone levels Apr 25, 2024 Apr 25, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                • HMG-CoA reductase inhibition leading to decreased fertility
                                                                                                                                                                                                                                                                                                                                                                                                                                                2072 Decreased, cholesterol Decreased, 11KT Mar 23, 2020 May 6, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                • PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone
                                                                                                                                                                                                                                                                                                                                                                                                                                                808 malformed, Male reproductive tract Decrease, Fertility Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • HMG-CoA reductase inhibition leading to decreased fertility
                                                                                                                                                                                                                                                                                                                                                                                                                                                813 Increased, Serum creatinine Occurrence, Cytoplasmic vacuolization (Renal tubule) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                814 Increased, Serum creatinine Occurrence, Cystic dilatation (renal tubule) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                816 Increased, Serum creatinine Occurrence, Cytoplasmic vacuolization (podocyte) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                2648 Occurrence, Kidney toxicity Increased, Kidney Failure Apr 8, 2022 Apr 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                                                                                                                                                                                                817 Occurrence, Cytoplasmic vacuolization (Renal tubule) Decreased, Glomerular filtration Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                818 Occurrence, Cytoplasmic vacuolization (Renal tubule) Decreased, Renal plasma flow Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                819 Occurrence, Cytoplasmic vacuolization (Renal tubule) Decreased, Sodium reabsorption Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                820 Occurrence, Cytoplasmic vacuolization (Renal tubule) Decreased, Renal ability to dilute urine Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                829 Decreased, Glomerular filtration Occurrence, Kidney toxicity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                830 Decreased, Renal plasma flow Occurrence, Kidney toxicity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                831 Decreased, Sodium reabsorption Occurrence, Kidney toxicity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                821 Occurrence, Cystic dilatation (renal tubule) Decreased, Glomerular filtration Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                822 Occurrence, Cystic dilatation (renal tubule) Decreased, Renal plasma flow Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                823 Occurrence, Cystic dilatation (renal tubule) Decreased, Sodium reabsorption Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                824 Occurrence, Cystic dilatation (renal tubule) Decreased, Renal ability to dilute urine Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                825 Occurrence, Cytoplasmic vacuolization (podocyte) Decreased, Glomerular filtration Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                826 Occurrence, Cytoplasmic vacuolization (podocyte) Decreased, Renal plasma flow Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                827 Occurrence, Cytoplasmic vacuolization (podocyte) Decreased, Sodium reabsorption Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                828 Occurrence, Cytoplasmic vacuolization (podocyte) Decreased, Renal ability to dilute urine Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                832 Decreased, Renal ability to dilute urine Occurrence, Kidney toxicity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                834 Activation, Keratinocytes Activation, Dendritic Cells Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Covalent Protein binding leading to Skin Sensitisation
                                                                                                                                                                                                                                                                                                                                                                                                                                                836 Inhibition, Phospholipase A Damage, Lipid bilayer Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                837 Inhibition, Phospholipase A Disturbance, Lysosomal function Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                3154 Inhibition, Phospholipase A Mitochondrial dysfunction Mar 13, 2024 Mar 13, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                839 Damage, Lipid bilayer Occurrence, Cytoplasmic vacuolization (hepatocyte) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                840 Damage, Lipid bilayer Occurrence, Ballooning degeneration (hepatocyte) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                841 Damage, Lipid bilayer Occurrence, Cytoplasmic vacuolization (Bile duct cell) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                842 Damage, Lipid bilayer Occurrence, Cytoplasmic vacuolization (kupffer cell) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                843 Disturbance, Lysosomal function Occurrence, Cytoplasmic vacuolization (hepatocyte) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                844 Disturbance, Lysosomal function Occurrence, Ballooning degeneration (hepatocyte) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                845 Disturbance, Lysosomal function Occurrence, Cytoplasmic vacuolization (Bile duct cell) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                846 Disturbance, Lysosomal function Occurrence, Cytoplasmic vacuolization (kupffer cell) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                1678 Disturbance, Lysosomal function Disruption, Lysosome Oct 25, 2017 Oct 25, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Receptor mediated endocytosis and lysosomal overload leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                851 Occurrence, Cytoplasmic vacuolization (hepatocyte) Induction, Microvesicular fat Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                852 Occurrence, Cytoplasmic vacuolization (hepatocyte) Formation, Mallory body Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                853 Occurrence, Ballooning degeneration (hepatocyte) Induction, Microvesicular fat Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                854 Occurrence, Ballooning degeneration (hepatocyte) Formation, Mallory body Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                855 Occurrence, Cytoplasmic vacuolization (Bile duct cell) Induction, Microvesicular fat Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                856 Occurrence, Cytoplasmic vacuolization (Bile duct cell) Formation, Mallory body Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                857 Occurrence, Cytoplasmic vacuolization (kupffer cell) Induction, Microvesicular fat Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                858 Occurrence, Cytoplasmic vacuolization (kupffer cell) Formation, Mallory body Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                859 Induction, Microvesicular fat Formation, Liver fibrosis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                860 Formation, Mallory body Formation, Liver fibrosis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                864 Oxidation, Uroporphyrinogen Accumulation, Highly carboxylated porphyrins Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                  865 Oxidation, Uroporphyrinogen Inhibition, UROD Nov 29, 2016 May 30, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Aryl hydrocarbon receptor activation leading to uroporphyria
                                                                                                                                                                                                                                                                                                                                                                                                                                                  867 Inhibition, UROD Oxidation, Uroporphyrinogen Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                    1070 Inhibition, UROD Accumulation, Highly carboxylated porphyrins Nov 29, 2016 May 30, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Aryl hydrocarbon receptor activation leading to uroporphyria
                                                                                                                                                                                                                                                                                                                                                                                                                                                    866 Accumulation, Highly carboxylated porphyrins Uroporphyria Nov 29, 2016 May 7, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Aryl hydrocarbon receptor activation leading to uroporphyria
                                                                                                                                                                                                                                                                                                                                                                                                                                                    868 Induction, CYP1A2/CYP1A5 Oxidation, Uroporphyrinogen Nov 29, 2016 May 31, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Aryl hydrocarbon receptor activation leading to uroporphyria
                                                                                                                                                                                                                                                                                                                                                                                                                                                    3275 Induction, CYP1A2/CYP1A5 Oxidative Stress Jul 4, 2024 Jul 4, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                    • AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                    871 GABAergic interneurons, Decreased Synaptogenesis, Decreased Nov 29, 2016 Jan 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                    995 Changes/Inhibition, Cellular Homeostasis and Apoptosis N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects Nov 29, 2016 Dec 2, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Sustained AhR Activation leading to Rodent Liver Tumours
                                                                                                                                                                                                                                                                                                                                                                                                                                                    997 Alterations, Cellular proliferation / hyperplasia Formation, Hepatocellular and Bile duct tumors Nov 29, 2016 Dec 2, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Sustained AhR Activation leading to Rodent Liver Tumours
                                                                                                                                                                                                                                                                                                                                                                                                                                                    2911 Alterations, Cellular proliferation / hyperplasia prostatic intraepithelial neoplasia May 11, 2023 May 11, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Androgen receptor activation leading to prostate cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                    877 Binding as antagonist, Antagonist binding to PPARalpha ligand binding domain Decreased, PPARalpha transactivation of gene expression Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                      880 Decreased, PPARalpha transactivation of gene expression Decreased, Ketogenesis (production of ketone bodies) Nov 29, 2016 Jun 11, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Antagonist binding to PPARα leading to body-weight loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                      879 Decreased, PPARalpha transactivation of gene expression Decreased, Mitochondrial Fatty Acid Beta Oxidation Nov 29, 2016 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                        878 Decreased, PPARalpha transactivation of gene expression Decreased, Peroxisomal Fatty Acid Beta Oxidation of Fatty Acids Nov 29, 2016 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                          1748 Decreased, PPARalpha transactivation of gene expression Fatty Acid Beta Oxidation, Decreased Jun 11, 2018 Jun 11, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Antagonist binding to PPARα leading to body-weight loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                          881 Decreased, Peroxisomal Fatty Acid Beta Oxidation of Fatty Acids Decreased, Mitochondrial Fatty Acid Beta Oxidation Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                            882 Decreased, Mitochondrial Fatty Acid Beta Oxidation Decreased, Ketogenesis (production of ketone bodies) Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                              2264 Decreased, Mitochondrial Fatty Acid Beta Oxidation Accumulation, Triglyceride Jan 15, 2021 Jan 15, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Glucocorticoid Receptor activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                              2040 Decreased, Mitochondrial Fatty Acid Beta Oxidation Increased, Liver Steatosis Feb 22, 2020 Feb 22, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                883 Decreased, Ketogenesis (production of ketone bodies) Not Increased, Circulating Ketone Bodies Nov 29, 2016 Jun 11, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Antagonist binding to PPARα leading to body-weight loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                884 Not Increased, Circulating Ketone Bodies Increased, Catabolism of Muscle Protein Nov 29, 2016 Jun 11, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Antagonist binding to PPARα leading to body-weight loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                885 Increased, Catabolism of Muscle Protein Decreased, Body Weight Nov 29, 2016 Jun 11, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Antagonist binding to PPARα leading to body-weight loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                886 Decrease, Intracellular pH Increase, Cytotoxicity Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                                                888 Increase, Tissue Degeneration, Necrosis & Atrophy Increase, Respiratory or Squamous Metaplasia Nov 29, 2016 Dec 1, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                                                889 Increase, Respiratory or Squamous Metaplasia Increase, Cell Proliferation Nov 29, 2016 Dec 1, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                                                890 Increase, Cell Proliferation Increased, Induced Mutations in Critical Genes Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  893 Increase, Cell Proliferation Increase, Mutations in Critical Genes Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  895 Increase, Cell Proliferation Increase, Site of Contact Nasal Tumors Nov 29, 2016 Dec 1, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1967 Increase, Cell Proliferation Lung cancer Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Frustrated phagocytosis-induced lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1980 Increase, Cell Proliferation Increase, lung cancer Aug 29, 2019 Jan 10, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of energy leading to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2819 Increase, Cell Proliferation Cataracts Dec 18, 2022 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2419 Increase, Cell Proliferation Increased, mesotheliomas Jul 6, 2021 Jul 6, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Frustrated phagocytosis leads to malignant mesothelioma
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  919 Binding of agonist, Ionotropic glutamate receptors Overactivation, NMDARs Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3506 Binding of agonist, Ionotropic glutamate receptors Loss of drebrin Mar 9, 2025 Mar 9, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  894 Increase, Mutations in Critical Genes Increase, Site of Contact Nasal Tumors Nov 29, 2016 Dec 1, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1131 Inhibition, organic anion transporter 1 (OAT1) Increased, blood uric acid concentration Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Organic anion transporter (OAT1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  934 Inhibition, NADH-ubiquinone oxidoreductase (complex I) Mitochondrial dysfunction Nov 29, 2016 Aug 25, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1940 Inhibition, NADH-ubiquinone oxidoreductase (complex I) Decrease in mitochondrial oxidative phosphorylation Jun 7, 2019 Jun 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1809 Inhibition, NADH-ubiquinone oxidoreductase (complex I) Decrease, OXPHOS Dec 20, 2018 Dec 20, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndrome
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  933 Binding of inhibitor, NADH-ubiquinone oxidoreductase (complex I) Inhibition, NADH-ubiquinone oxidoreductase (complex I) Nov 29, 2016 Aug 25, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndrome
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  905 Impaired, Proteostasis Degeneration of dopaminergic neurons of the nigrostriatal pathway Nov 29, 2016 Aug 25, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1943 Impaired, Proteostasis Cell injury/death Jun 7, 2019 Jun 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  907 Degeneration of dopaminergic neurons of the nigrostriatal pathway Neuroinflammation Nov 29, 2016 Oct 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  910 Degeneration of dopaminergic neurons of the nigrostriatal pathway Parkinsonian motor deficits Nov 29, 2016 Aug 25, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3077 Degeneration of dopaminergic neurons of the nigrostriatal pathway impaired, Learning and memory Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3083 Parkinsonian motor deficits Increase, Mortality Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1679 Disruption, Lysosome Increase, Cytotoxicity (renal tubular cell) Oct 25, 2017 Oct 25, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Receptor mediated endocytosis and lysosomal overload leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  921 Disruption, Lysosome Peptide Oxidation Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                    993 Disruption, Lysosome Mitochondrial dysfunction Nov 29, 2016 Nov 12, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Endocytic lysosomal uptake leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Endocytotic lysosomal uptake leads to intestinal barrier disruption
                                                                                                                                                                                                                                                                                                                                                                                                                                                                    916 Infiltration, Inflammatory cells Inflammation, Liver Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3374 Infiltration, Inflammatory cells Activation, Macrophages Oct 30, 2024 Oct 30, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Activation of reactive oxygen species leading the atherosclerosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      926 Infiltration, Inflammatory cytokines Inflammation, Liver Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                        936 Activation, Epidermal Growth Factor Receptor Decreased ciliated cell apoptosis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                          946 Activation, Epidermal Growth Factor Receptor Activation, Sp1 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                            939 Activation, Epidermal Growth Factor Receptor Increased goblet cell proliferation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              942 Activation, Epidermal Growth Factor Receptor Occurrence, Transdifferentiation of ciliated epithelial cells Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                961 Decreased ciliated cell apoptosis Occurrence, Transdifferentiation of ciliated epithelial cells Nov 29, 2016 Aug 25, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2470 Decreased ciliated cell apoptosis Goblet cell metaplasia Aug 25, 2021 Aug 25, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    943 Occurrence, Transdifferentiation of ciliated epithelial cells Goblet cell metaplasia Nov 29, 2016 Aug 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      990 Goblet cell metaplasia Hypersecretion, Mucus Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2471 Goblet cell metaplasia Chronic, Mucus hypersecretion Aug 26, 2021 Aug 27, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1313 Goblet cell metaplasia Increase, Mucin production Nov 29, 2016 Aug 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1312 Goblet cell hyperplasia Increase, Mucin production Nov 29, 2016 Aug 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              989 Goblet cell hyperplasia Hypersecretion, Mucus Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2472 Goblet cell hyperplasia Chronic, Mucus hypersecretion Aug 26, 2021 Aug 30, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  944 Increased goblet cell proliferation Goblet cell hyperplasia Nov 29, 2016 Aug 27, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    987 Activation, Sp1 Increase, Mucin production Nov 29, 2016 Aug 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      954 Oxidation, Glutathione S-Glutathionylation, eNOS Nov 29, 2016 Sep 28, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2459 Oxidation, Glutathione Increase, ROS Aug 5, 2021 Aug 5, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        955 S-Glutathionylation, eNOS Uncoupling, eNOS Nov 29, 2016 Oct 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        956 Uncoupling, eNOS Depletion, Nitric Oxide Nov 29, 2016 Oct 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3014 Uncoupling, eNOS Increase, Vascular disrupting effects Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3023 Uncoupling, eNOS increased,Vascular endothelial dysfunction Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          958 Depletion, Nitric Oxide Impaired, Vasodilation Nov 29, 2016 Oct 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          953 Decrease, Tetrahydrobiopterin Uncoupling, eNOS Nov 29, 2016 Oct 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          952 Decrease, GTPCH-1 Decrease, Tetrahydrobiopterin Nov 29, 2016 Oct 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          982 Impaired, Vasodilation Increase, Vascular Resistance Nov 29, 2016 Oct 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          986 Activation, EGFR Increase, Mucin production Nov 29, 2016 Mar 9, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • EGFR Activation Leading to Decreased Lung Function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          962 Activation, EGFR Decreased ciliated cell apoptosis Nov 29, 2016 Aug 27, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            964 Activation, EGFR Activation, Sp1 Nov 29, 2016 Aug 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              965 Activation, EGFR Occurrence, Transdifferentiation of ciliated epithelial cells Nov 29, 2016 Aug 25, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                970 Activation, EGFR Increased goblet cell proliferation Nov 29, 2016 Aug 27, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2857 Activation, EGFR Increase, goblet cell number Mar 15, 2023 Mar 16, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • EGFR Activation Leading to Decreased Lung Function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2469 Activation, EGFR Goblet cell metaplasia Aug 25, 2021 Aug 27, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    973 dimerization, AHR/ARNT reduced dimerization, ARNT/HIF1-alpha Nov 29, 2016 Mar 23, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • AhR activation leading to preeclampsia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1350 dimerization, AHR/ARNT Increase, COX-2 expression Feb 9, 2017 May 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1996 dimerization, AHR/ARNT Increase, DNMT expression Oct 30, 2019 Oct 30, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2683 dimerization, AHR/ARNT Increase, slincR expression Jun 30, 2022 Sep 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2682 dimerization, AHR/ARNT Decrease, sox9 expression Jun 30, 2022 Jun 30, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3466 dimerization, AHR/ARNT increased, Bax Jan 4, 2025 Apr 19, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      974 reduced dimerization, ARNT/HIF1-alpha reduced production, VEGF Nov 29, 2016 Mar 23, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • AhR activation leading to preeclampsia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      975 reduced production, VEGF Impairment, Endothelial network Nov 29, 2016 Mar 23, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2407 reduced production, VEGF abnormal, placental labyrinth vasculature morphology May 31, 2021 May 31, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • AhR activation leading to preeclampsia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      983 Increase, Vascular Resistance Hypertension Nov 29, 2016 Oct 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2269 Binding, Transthyretin in serum Increased, Clearance of thyroxine from serum Jan 26, 2021 Jan 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2248 Binding, Transthyretin in serum Displacement, Serum thyroxine (T4) from carrier protein Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2245 Binding, Transthyretin in serum Displacement, Serum thyroxine (T4) from transthyretin Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2271 Binding, Transthyretin in serum Increased, Free serum thyroxine (T4) Jan 26, 2021 Jan 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2246 Displacement, Serum thyroxine (T4) from transthyretin Increased, Free serum thyroxine (T4) Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2268 Increased, Free serum thyroxine (T4) Increased, Uptake of thyroxine into tissue Jan 26, 2021 Jan 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2247 Increased, Free serum thyroxine (T4) Increased, Hepatic thyroid hormone uptake/transport Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2272 Increased, Free serum thyroxine (T4) Increased, Clearance of thyroxine from serum Jan 26, 2021 Jan 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2270 Increased, Clearance of thyroxine from serum T4 in serum, Decreased Jan 26, 2021 Jan 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Hepatic nuclear receptor activation leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Enhanced hepatic clearance of thyroid hormones leading to thyroid follicular cell adenomas and carcinomas in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            991 Increase, Mucin production Hypersecretion, Mucus Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1315 Increase, Mucin production Chronic, Mucus hypersecretion Nov 29, 2016 Aug 30, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2859 Increase, Mucin production Decreased lung function Mar 15, 2023 Mar 16, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • EGFR Activation Leading to Decreased Lung Function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                988 Decrease, AKT/eNOS activity Depletion, Nitric Oxide Nov 29, 2016 Oct 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1062 Formation, The binding of FK506 with FKBP12 Inhibition, Calcineurin Activity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1016 Activation, Suppression of NFAT activation and hindrance of nuclear localization Interference, nuclear localization of NFAT Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1017 Interference, nuclear localization of NFAT Reduction, NFAT/AP-1 complex formation Nov 29, 2016 Jul 2, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of Calcineurin Activity Leading to Impaired T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1015 Inhibition, Calcineurin Activity Activation, Suppression of NFAT activation and hindrance of nuclear localization Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1508 Inhibition, Calcineurin Activity Interference, nuclear localization of NFAT May 19, 2017 Jun 27, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of Calcineurin Activity Leading to Impaired T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1254 Inhibition, Calcineurin Activity Suppression, IL-2 and IL-4 production Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1256 Reduction, NFAT/AP-1 complex formation Suppression, Suppression of production of cytotoxic T-cells Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1257 Reduction, NFAT/AP-1 complex formation Suppression, Suppression of T-cell dependent antibody production Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1509 Reduction, NFAT/AP-1 complex formation Suppression, IL-2 and IL-4 production May 19, 2017 Jun 27, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of Calcineurin Activity Leading to Impaired T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1018 Reduction, NFAT/AP-1 complex formation Suppression, Suppression in mixed lymphocyte reaction (MLR) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1019 Reduction, NFAT/AP-1 complex formation Suppression, Suppression of T-cell dependent antibody response (TDAR) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1020 Reduction, NFAT/AP-1 complex formation Impairment, T-cell dependent antibody response Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1021 Reduction, NFAT/AP-1 complex formation Relief, Relief of atopic dermatitis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1022 Reduction, NFAT/AP-1 complex formation Impairment of TDAR Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1823 Suppression, Suppression of T-cell dependent antibody response (TDAR) Impairment of TDAR Dec 25, 2018 Dec 25, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1000 Decrease, Circulating ETH Increase, Incomplete ecdysis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1008 Decrease, Circulating ETH Decrease, Abdominal muscle contraction Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1346 Decrease, Circulating ETH Decrease, Circulating CCAP Feb 9, 2017 Feb 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1001 Decreased, synthesis and secretion of molting fluid proteases Increase, Incomplete ecdysis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1002 Increase, Incomplete ecdysis Increase, Mortality Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Doda decarboxylase leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1190 Increase, Incomplete ecdysis Increased Mortality Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2759 Increase, Incomplete ecdysis Increase, developmental abnormalities Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Knickkopf leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2751 Increase, Incomplete ecdysis Decrease, hatching of egg Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Doda decarboxylase leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2750 Increase, Incomplete ecdysis Increase, delay in oviposition Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Doda decarboxylase leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1010 Decrease, Abdominal muscle contraction Increase, Incomplete ecdysis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1009 Decreased, Synthesis of molting fluid proteases Decrease, Digestion of old cuticle Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1011 Decrease, Digestion of old cuticle Increase, Incomplete ecdysis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2171 Decrease, Digestion of old cuticle Increase, Premature molting Oct 21, 2020 Oct 21, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Chitinase inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Chitobiase inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1023 Binding of antagonist, PPAR alpha stabilization, PPAR alpha co-repressor Nov 29, 2016 Jun 11, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Antagonist binding to PPARα leading to body-weight loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1024 stabilization, PPAR alpha co-repressor Decreased, PPARalpha transactivation of gene expression Nov 29, 2016 Jun 11, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Antagonist binding to PPARα leading to body-weight loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1199 Inhibition, Deiodinase 2 Decreased, Triiodothyronine (T3) in tissues Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1026 Inhibition, Deiodinase 2 Decreased, Triiodothyronine (T3) Nov 29, 2016 Oct 7, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1042 Inhibition, Deiodinase 2 Reduced, Posterior swim bladder inflation Nov 29, 2016 Oct 7, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1043 Inhibition, Deiodinase 2 Reduced, Anterior swim bladder inflation Nov 29, 2016 Mar 8, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1027 Decreased, Triiodothyronine (T3) Reduced, Posterior swim bladder inflation Nov 29, 2016 Oct 7, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1035 Decreased, Triiodothyronine (T3) Reduced, Anterior swim bladder inflation Nov 29, 2016 Oct 7, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2378 Decreased, Triiodothyronine (T3) Altered, Photoreceptor patterning May 11, 2021 Oct 17, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2376 Decreased, Triiodothyronine (T3) Decreased, Eye size May 11, 2021 Jun 16, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to altered visual function via decreased eye size
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2373 Decreased, Triiodothyronine (T3) Altered, retinal layer structure May 11, 2021 Jul 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2213 Reduced, Posterior swim bladder inflation Increased Mortality Nov 30, 2020 Sep 8, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1031 Reduced, Posterior swim bladder inflation Reduced, Anterior swim bladder inflation Nov 29, 2016 Nov 20, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1028 Reduced, Posterior swim bladder inflation Reduced, Swimming performance Nov 29, 2016 Sep 3, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1642 Reduced, Swimming performance Decreased, survival Aug 3, 2017 Aug 3, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1641 Reduced, Swimming performance Growth, reduction Aug 3, 2017 Aug 3, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2212 Reduced, Swimming performance Increased Mortality Nov 30, 2020 Sep 8, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2081 Reduced, Swimming performance Decrease, Population growth rate Apr 21, 2020 Jun 4, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1032 Reduced, Anterior swim bladder inflation Reduced, Hearing Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1034 Reduced, Anterior swim bladder inflation Reduced, Swimming performance Nov 29, 2016 Oct 7, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2231 Reduced, Hearing Increased Mortality Dec 8, 2020 Dec 8, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • GSK3beta inactivation leading to increased mortality via defects in developing inner ear
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1045 Inhibition, Deiodinase 1 Reduced, Anterior swim bladder inflation Nov 29, 2016 Mar 8, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1044 Inhibition, Deiodinase 1 Reduced, Posterior swim bladder inflation Nov 29, 2016 Oct 10, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1037 Inhibition, Deiodinase 1 Decreased, Triiodothyronine (T3) Nov 29, 2016 Oct 10, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1198 Inhibition, Deiodinase 1 Decreased, Triiodothyronine (T3) in tissues Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Type I iodothyronine deiodinase (DIO1) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1047 Increased, Chloride influx Increased, Inhibitory postsynaptic potential Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1054 Increased, Inhibitory postsynaptic potential Induction, Somatic muscle paralysis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1048 Increased, Inhibitory postsynaptic potential Inhibition, Motor neuron activity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1058 Increased, Inhibitory postsynaptic potential Induction, pharyngeal muscle paralysis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1049 Inhibition, Motor neuron activity Induction, Somatic muscle paralysis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1055 Induction, Somatic muscle paralysis Inhibition, Feeding Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1050 Induction, Somatic muscle paralysis Increased Mortality Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3089 Induction, Somatic muscle paralysis Increased, Neuronal synaptic inhibition Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3090 Increased, Neuronal synaptic inhibition Inhibition, Feeding Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1053 Increased, Neuronal synaptic inhibition Increased, Inhibitory postsynaptic potential Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1056 Inhibition, Feeding Increased Mortality Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3087 Inhibition, Feeding Increase, Mortality Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3084 Activation, Glutamate-gated chloride channels Overactivation, NMDARs Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3085 Activation, Glutamate-gated chloride channels Increase, CNS Neural cell death Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1057 Activation, Glutamate-gated chloride channels Increased, Chloride conductance Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1059 Induction, pharyngeal muscle paralysis Inhibition, Feeding Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1063 Increased, induction of UDPGT's in liver Increased, T4/T3 catabolism Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1064 Increased, T4/T3 catabolism Decreased, serum T4/T3 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2423 Increased, T4/T3 catabolism T4 in serum, Decreased Jul 7, 2021 Jul 7, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1065 Decreased, serum T4/T3 Increased, Thyroid-stimulating hormone (TSH) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1066 Increased, Thyroid-stimulating hormone (TSH) Increased, Hypertrophy and proliferation (follicular cell) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2425 Increased, Thyroid-stimulating hormone (TSH) Increase, Thyroid-stimulating hormone (TSH) Jul 7, 2021 Jul 7, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2424 Increased, Thyroid-stimulating hormone (TSH) Increase, Hypertrophy and proliferation (follicular cell) Jul 7, 2021 Jul 7, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Enhanced hepatic clearance of thyroid hormones leading to thyroid follicular cell adenomas and carcinomas in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2240 Increased, Thyroid-stimulating hormone (TSH) Increased, Thyroxine (T4) in serum Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2427 Increased, Hypertrophy and proliferation (follicular cell) Increase, Hyperplasia (follicular cells) Jul 7, 2021 Jul 7, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1067 Increased, Hypertrophy and proliferation (follicular cell) Increased, Hyperplasia (follicular cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1068 Increased, Hyperplasia (follicular cells) Increased Apoptosis, Adenomas/carcinomas (follicular cell) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2426 Increased, Hyperplasia (follicular cells) Increase, Adenomas/carcinomas (follicular cell) Jul 7, 2021 Jul 7, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1071 Activation of specific nuclear receptors, PPAR-gamma activation Increased, adipogenesis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • PPARgamma activation leading to sarcomas in rats, mice, and hamsters
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1072 Activation of specific nuclear receptors, PPAR-gamma activation Increased, secretion of local growth factors Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • PPARgamma activation leading to sarcomas in rats, mice, and hamsters
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1609 Activation of specific nuclear receptors, PPAR-gamma activation increased adipogenesis Jul 24, 2017 Jul 24, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1073 Increased, adipogenesis Increased, secretion of local growth factors Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • PPARgamma activation leading to sarcomas in rats, mice, and hamsters
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1074 Increased, secretion of local growth factors Increased, proliferation of mesenchymal cells Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • PPARgamma activation leading to sarcomas in rats, mice, and hamsters
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1075 Increased, secretion of local growth factors Increased, IGF-1 (mouse) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • PPARgamma activation leading to sarcomas in rats, mice, and hamsters
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1624 Increased, secretion of local growth factors Differentiation of fibroblasts Jul 26, 2017 Jul 26, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1625 Increased, secretion of local growth factors EMT Jul 26, 2017 Jul 26, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1129 Increased, secretion of local growth factors Increased, Cell Proliferation (mesothelium) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1076 Increased, proliferation of mesenchymal cells Increased, Firbrosarcoma Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • PPARgamma activation leading to sarcomas in rats, mice, and hamsters
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1077 Increased, proliferation of mesenchymal cells Increased, liposarcoma Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • PPARgamma activation leading to sarcomas in rats, mice, and hamsters
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1078 Increased, proliferation of mesenchymal cells Increased, hemagiosarcoma Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • PPARgamma activation leading to sarcomas in rats, mice, and hamsters
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1079 Activation, beta-2 adrenergic receptor Increased activity, beta-2 adrenergic receptor Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3416 Activation, beta-2 adrenergic receptor Intracellular cAMP Nov 21, 2024 Nov 21, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • β-adrenergic receptor agonists leading to arrhythmias.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1080 Increased activity, beta-2 adrenergic receptor relaxation, smooth muscle Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1081 relaxation, smooth muscle Proliferation/Clonal Expansion, smooth muscle Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1082 Proliferation/Clonal Expansion, smooth muscle Hypertrophy/hyperplasia, smooth muscle Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1083 Hypertrophy/hyperplasia, smooth muscle Promotion, mesovarian leiomyomas Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1084 Decreased, Ovarian E2 Increased, secretion of GnRH from hypothalamus Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1085 Decreased, Ovarian E2 Decrease, E2 blood concentrations at hypothalamus Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1086 Suppression, Estrogen receptor (ER) activity Decrease, E2 blood concentrations at hypothalamus Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2580 Suppression, Estrogen receptor (ER) activity Increased, secretion of GnRH from hypothalamus Feb 26, 2022 Mar 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1088 Increased, secretion of GnRH from hypothalamus Increased, secrection of FSH from anterior pituitary Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1089 Increased, secretion of GnRH from hypothalamus Increased, secretion of LH from anterior pituitary Nov 29, 2016 Mar 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1090 Increased, secrection of FSH from anterior pituitary Hyperplasia, ovarian stromal cells Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1091 Increased, secrection of FSH from anterior pituitary Hyperplasia, ovarian epithelium Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1092 Increased, secretion of LH from anterior pituitary Hyperplasia, ovarian stromal cells Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2581 Increased, secretion of LH from anterior pituitary Increased, Steroidogenic acute regulatory protein (StAR) Feb 26, 2022 Mar 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1094 Hyperplasia, ovarian stromal cells Promotion, ovarian granular cell tumors Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1093 Hyperplasia, ovarian epithelium Promotion, ovarian adenomas Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2829 Promotion, ovarian adenomas Promotion, Ovarian Cancer Jan 13, 2023 Mar 11, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2830 Promotion, ovarian granular cell tumors Promotion, Ovarian Cancer Jan 13, 2023 Jan 13, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1087 Decrease, E2 blood concentrations at hypothalamus Increased, secretion of GnRH from hypothalamus Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1095 Increased, PPAR-alpha activation Decreased, bile flow Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1096 Increased, PPAR-alpha activation Increased, cholestasis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1097 Increased, PPAR-alpha activation Alteration, lipid metabolism Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1101 Decreased, bile flow Increased, cholestasis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1100 Increased, cholestasis prolonged, elevation of serun CCK Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3094 Alteration, lipid metabolism General Apoptosis Oct 18, 2023 Oct 19, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1098 prolonged, elevation of serun CCK Increased, Cellular proliferation / hyperplasia of acinar cells Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1099 Increased, Cellular proliferation / hyperplasia of acinar cells Increased, Pancreatic acinar tumors Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1103 Activation, estrogen receptor alpha Promotion, SIX-1 postive basal-type progenitor cells Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2969 Activation, estrogen receptor alpha Epigenetic modification process Jul 27, 2023 Mar 27, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2730 Activation, estrogen receptor alpha Impaired, Reproduction Aug 15, 2022 Aug 15, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2666 Activation, estrogen receptor alpha Decreased, Gonadotropins Jun 6, 2022 Aug 15, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2665 Activation, estrogen receptor alpha Increased, Kisspeptin signalling Jun 6, 2022 Aug 15, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1104 Promotion, SIX-1 postive basal-type progenitor cells Proliferation/Clonal Expansion, aberrant basal cells Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1105 Proliferation/Clonal Expansion, aberrant basal cells squamous metaplasia, aberrant basal cells Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1106 squamous metaplasia, aberrant basal cells Increased, Hyperplasia (glandular epithelial cells of endometrium) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1107 Increased, Hyperplasia (glandular epithelial cells of endometrium) Increased, adenosquamous carcinomas of endometrium Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1108 Decreased, GnRH pulsatility/release in hypothalamus Decreased, LH Surge from anterior pituitary Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • GnRH pulse disruption leading to pituitary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1109 Decreased, LH Surge from anterior pituitary interruption, Ovulation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • GnRH pulse disruption leading to pituitary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1110 Decreased, LH Surge from anterior pituitary prolonged, estrus Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • GnRH pulse disruption leading to pituitary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1118 interruption, Ovulation Increased, circulating estrogen levels Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • GnRH pulse disruption leading to pituitary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1111 prolonged, estrus Increased, circulating estrogen levels Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • GnRH pulse disruption leading to pituitary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1112 prolonged, estrus Increased, prolactin exposure Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1113 Increased, circulating estrogen levels Hyperplasia, Mammary gland Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1119 Increased, circulating estrogen levels Increased, lactotroph hyperplasia and hypertrophy Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • GnRH pulse disruption leading to pituitary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2585 Increased, circulating estrogen levels Hyperplasia, ovarian epithelium Feb 26, 2022 Mar 2, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2584 Increased, circulating estrogen levels Hyperplasia, ovarian stromal cells Feb 26, 2022 Mar 2, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3439 Increased, circulating estrogen levels Increased E2 availability Nov 22, 2024 Nov 22, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Aromatase induction leading to estrogen receptor alpha activation via increased estradiol
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3437 Increased, circulating estrogen levels Plasma E2, increased Nov 22, 2024 Nov 22, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Aromatase induction leading to estrogen receptor alpha activation via increased estradiol
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1114 Increased, prolactin exposure Hyperplasia, Mammary gland Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1115 Hyperplasia, Mammary gland Increased, latency period Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1116 Hyperplasia, Mammary gland Increased, Adenomas/carcinomas (mammary) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1117 Increased, latency period Increased, Adenomas/carcinomas (mammary) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Anti-dopaminergic activity leading to mammary adenomas and carcinomas in the SD rat
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1120 Increased, lactotroph hyperplasia and hypertrophy Increased, adenomas (pituitary) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • GnRH pulse disruption leading to pituitary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1121 Decreased, Dopaminergic activity Increased, prolactin secretion Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Anti-dopaminergic activity leading to mammary adenomas and carcinomas in the SD rat
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1122 Increased, prolactin secretion Increased, hyperplasia (mammary gland) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Anti-dopaminergic activity leading to mammary adenomas and carcinomas in the SD rat
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1123 Increased, hyperplasia (mammary gland) Increased, latency period Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Anti-dopaminergic activity leading to mammary adenomas and carcinomas in the SD rat
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1124 Increased, hyperplasia (mammary gland) Increased, Adenomas/carcinomas (mammary) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Anti-dopaminergic activity leading to mammary adenomas and carcinomas in the SD rat
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1125 persistent, cytotoxicity (pleura or peritoneum) Increased, inflammation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3261 persistent, cytotoxicity (pleura or peritoneum) Oxidative Stress Jul 3, 2024 Jul 3, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1127 Increased, inflammation Increased, secretion of local growth factors Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1130 Increased, Cell Proliferation (mesothelium) Increased, mesotheliomas Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1142 Decreased, Thyroxine (T4) in tissues Altered, Amphibian metamorphosis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1163 Decreased, Thyroxine (T4) in tissues Decreased, Triiodothyronine (T3) in tissues Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1132 Increased, blood uric acid concentration Occurrence, tophi (urate) deposition Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Organic anion transporter (OAT1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3263 Increased, blood uric acid concentration Oxidative Stress Jul 3, 2024 Jul 3, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Organic anion transporter (OAT1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1134 Occurrence, renal proximal tubular necrosis Increased, blood potassium concentration Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Organic anion transporter (OAT1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • unknown MIE leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1156 Occurrence, renal proximal tubular necrosis Increased, blood uric acid concentration Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Organic anion transporter (OAT1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2647 Occurrence, renal proximal tubular necrosis Occurrence, Kidney toxicity Apr 8, 2022 Apr 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1135 Increased, blood potassium concentration Occurrence, cardiac arrthymia Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1140 Increased, blood potassium concentration Occurrence, cardiac arrhythmia Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Organic anion transporter (OAT1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • unknown MIE leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3403 Increased, blood potassium concentration Disruption in action potential generation Nov 20, 2024 Nov 20, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Increased Muscarinic M2 Receptor leading to Arrhythmia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1136 Occurrence, cardiac arrthymia Increased Mortality Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1133 Occurrence, tophi (urate) deposition Occurrence, renal proximal tubular necrosis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Organic anion transporter (OAT1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1137 Inhibition, Cyclooxygenase 1 activity Decreased, Prostaglandin F2alpha concentration, plasma Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1138 Decreased, Prostaglandin F2alpha concentration, plasma Occurrence, renal ischemia Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1139 Occurrence, renal ischemia Occurrence, renal proximal tubular necrosis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3265 Occurrence, renal ischemia Oxidative Stress Jul 3, 2024 Jul 3, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1141 Occurrence, cardiac arrhythmia Increased Mortality Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Organic anion transporter (OAT1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • unknown MIE leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2854 Occurrence, cardiac arrhythmia Increased,Cardiac dysfunction Jan 29, 2023 Jan 29, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1145 Weakened, Colony Death/Failure, Colony Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within caste
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Nicotinic acetylcholine receptor activation contributes to impaired hive thermoregulation and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Nicotinic acetylcholine receptor activation contributes to mitochondrial dysfunction and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Varroa mite infestation increases virus levels leading to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Varroa mite infestation contributes to abnormal foraging leading to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Weather event contributes to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Weather event contributes abnormal foraging leading to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Nosema infection increases energetic demands leading to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Nosema infection causes abnormal role change that leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Queen egg-laying decrease leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1151 Abnormal, Role change within caste Weakened, Colony Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Nosema infection causes abnormal role change that leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1155 Increased, Deformed Wing Virus levels Weakened, Colony Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Varroa mite infestation increases virus levels leading to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1157 Increased, Energetic demands and therefore metabolic stress Abnormal, Foraging activity and behavior Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Nosema infection increases energetic demands leading to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1161 Unknown, MIE Increase, ROS Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • unknown MIE leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2035 Unknown, MIE Unknown, Jan 26, 2020 Jan 26, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2036 Unknown, MIE N/A, Unknown Jan 26, 2020 Jan 26, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2033 Increase, ROS β-catenin activation Jan 19, 2020 Jan 19, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2009 Increase, ROS Oxidative Stress Dec 3, 2019 Aug 2, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Essential element imbalance leads to reproductive failure via oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • unknown MIE leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Activation of reactive oxygen species leading the atherosclerosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Calcium-mediated neuronal ROS production and energy imbalance
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1696 Increase, ROS increased, oncotic necrosis Nov 14, 2017 Nov 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3492 Increase, ROS Decrease, Coupling of OXPHOS Feb 25, 2025 Feb 25, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3494 Increase, ROS Decreased, Nitric Oxide Feb 25, 2025 Feb 25, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Calcium-mediated neuronal ROS production and energy imbalance
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3496 Increase, ROS Mitochondrial dysfunction Feb 25, 2025 Feb 25, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3514 Increase, ROS Oxidation/denatuation of membrane proteins Apr 4, 2025 Apr 4, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Adverse outcome pathway on photochemical toxicity initiated by light exposure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3505 Increase, ROS Porcupine-induced Wnt secretion and Wnt signaling activation Mar 6, 2025 Mar 14, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Increase in reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3509 Increase, ROS Peptide Oxidation Apr 3, 2025 Apr 3, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3513 Increase, ROS Oxidation of membrane lipids Apr 4, 2025 Apr 4, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Adverse outcome pathway on photochemical toxicity initiated by light exposure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3490 Increase, ROS Increase, Oxidative DNA damage Feb 25, 2025 Feb 25, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of energy leading to population decline via DNA oxidation and follicular atresia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and cell death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and reduced cell proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Excessive reactive oxygen species production leading to mortality (4)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3491 Increase, ROS Increase, Protein oxidation Feb 25, 2025 Feb 25, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Excessive reactive oxygen species production leading to mortality (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2328 Increase, ROS Increased Sodium-sensitive hypertension Apr 10, 2021 Apr 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2324 Increase, ROS Increased extracellular matrix deposition Apr 10, 2021 Apr 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2320 Increase, ROS Increased activation, Nuclear factor kappa B (NF-kB) Apr 10, 2021 Apr 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Binding to ACE2 leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1965 Increase, ROS Increased, DNA damage and mutation Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Frustrated phagocytosis-induced lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Frustrated phagocytosis leads to malignant mesothelioma
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2660 Increase, ROS Secondary genotoxicity May 25, 2022 May 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3092 Increase, ROS Decreased, PPAR-gamma activation Oct 18, 2023 Oct 19, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2966 Increase, ROS Apoptosis Jul 18, 2023 Apr 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2594 Increase, ROS Accumulation, Collagen Mar 3, 2022 Mar 3, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2460 Increase, ROS Increase, LPO Aug 5, 2021 Apr 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Glutathione conjugation leading to reproductive dysfunction via oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Essential element imbalance leads to reproductive failure via oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and cell death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Excessive reactive oxygen species production leading to mortality (3)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2550 Increase, ROS Decrease, MMP Jan 21, 2022 Jan 21, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of ionising energy leading to population decline via mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Excessive reactive oxygen species production leading to mortality (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2549 Increase, ROS D1 protein deactivation Jan 21, 2022 Jan 21, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of ionizing energy leading to population decline via inhibition of photosynthesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1164 Decreased, Triiodothyronine (T3) in tissues Altered, Amphibian metamorphosis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Type I iodothyronine deiodinase (DIO1) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2239 Decreased, Triiodothyronine (T3) in tissues Altered, TH-dependent gene expression Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2238 Decreased, Triiodothyronine (T3) in tissues Increased, Thyroid-stimulating hormone (TSH) Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1168 Under carboxylated clotting factors will not assemble on cell surfaces to form clot, Failur Failure in vascular repair mechanisms, Unresolved blood loss (hemorrhage) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1169 Failure in vascular repair mechanisms, Unresolved blood loss (hemorrhage) Blood loss and development of anemia, Impaired oxygen delivery and nutrient delivery to tis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1165 Failure in gamma-glutamyl carboxylation of clotting factors II, VII, IX and X, Under carbo Hemostasis, Depletion from blood of fully functional carboxylated clotting factors Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1170 Blood loss and development of anemia, Impaired oxygen delivery and nutrient delivery to tis Reduced fitness or even mortality, Acidosis, hypovolemic shock and organ dysfunction Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1166 Hemostasis, Depletion from blood of fully functional carboxylated clotting factors Under carboxylated clotting factors will not assemble on cell surfaces to form clot, Failur Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1167 Irreversible inhibition of hepatic VKOR by binding of AR at tyrosine 139, Failure to cycle Failure in gamma-glutamyl carboxylation of clotting factors II, VII, IX and X, Under carbo Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1171 Reduced fitness or even mortality, Acidosis, hypovolemic shock and organ dysfunction Impaired recruitment , Population trajectory Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1175 Increased, water retention in foot Increased, foot detachment Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1223 Increased, water retention in foot Increased, valve movement Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1182 Delayed, Sexual maturity Decreased, Reproductive Success Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2635 Decreased, Reproductive Success Decrease, Population growth rate Apr 6, 2022 Apr 6, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1173 Increased, valve movement Depletion, energy reserves Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1174 Increased, valve movement Increased, water retention in foot Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1216 Increased, valve movement Increased, water pumping Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1227 Increased, valve movement Increase, predation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1320 Increased, valve movement induced spawning Jan 13, 2017 Jan 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1334 Increased, valve movement Induced parturition Jan 30, 2017 Jan 30, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1181 Depletion, energy reserves Delayed, Sexual maturity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1185 Depletion, energy reserves Increase, predation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1179 premature, spawning 1 Decreased, Reproductive Success Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1188 Decreased, gametogenesis Decreased, Reproductive Success Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1211 premature, Spawning Increased, Population Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1222 premature, Spawning Decreased, Reproductive Success Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1193 increased or inappropriate, mantel display Decreased, Reproductive Success Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1219 increased or inappropriate, mantel display Depletion, energy reserves Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1220 increased or inappropriate, mantel display induced, parturition Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1194 Anticoagulant rodenticide interferes with gamma-carboxyglutamate formation, Inhibition of p Calcium cannot bind to the hydroxyapatite matrix of bone, Osteocalcin and other bone protei Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1195 Calcium cannot bind to the hydroxyapatite matrix of bone, Osteocalcin and other bone protei Uncarboxylated osteocalcin not incorporated into bone matrix, decreasing bone strength, Imp Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1196 Uncarboxylated osteocalcin not incorporated into bone matrix, decreasing bone strength, Imp Osteoporosis and vascular calcification, Bone deterioration Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1197 Inhibition, Iodotyrosine deiodinase (IYD) Thyroidal Iodide, Decreased Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2476 Inhibition, Iodotyrosine deiodinase (IYD) T4 in serum, Decreased Sep 9, 2021 Sep 9, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1200 Inhibition, Deiodinase 3 Increased, Triiodothyronine (T3) in tissues Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Type III iodotyrosine deiodinase (DIO3) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1201 Increased, Triiodothyronine (T3) in tissues Altered, Amphibian metamorphosis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2243 Increased, Triiodothyronine (T3) in tissues Altered, TH-dependent gene expression Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Type III iodotyrosine deiodinase (DIO3) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1202 Inhibition, Pendrin TH synthesis, Decreased Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Pendrin inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1203 Inhibition, Dual oxidase TH synthesis, Decreased Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Dual oxidase (DUOX) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1204 Activation, Hepatic nuclear receptor(s) Increased, Hepatic thyroid hormone uptake/transport Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Hepatic nuclear receptor activation leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1205 Activation, Hepatic nuclear receptor(s) Induction, Upregulation of glucuronyltransferase activity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Hepatic nuclear receptor activation leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1206 Increased, Hepatic thyroid hormone uptake/transport Increase, Biliary excretion TH glucuronide Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2237 Increased, Hepatic thyroid hormone uptake/transport T4 in serum, Decreased Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Hepatic nuclear receptor activation leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2479 Increased, Hepatic thyroid hormone uptake/transport Increased, Clearance of thyroxine from serum Sep 10, 2021 Sep 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Hepatic nuclear receptor activation leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1214 Increased, mantel display Increased, Reproductive Success Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1213 Increased, oocyte maturation Increased, Reproductive Success Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1328 Increased, oocyte maturation induced spawning Jan 17, 2017 Jan 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1210 Increased, cilia movement premature, Spawning Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1329 Increased, cilia movement induced spawning Jan 17, 2017 Jan 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1215 Increased, Reproductive Success Increased, Population Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1224 Increased, water pumping Increased, water retention in foot Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1225 Increased, water pumping premature, Spawning Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1226 Increased, water pumping induced, parturition Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1221 induced, parturition Decreased, Reproductive Success Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1230 Increase, Phenotypic enzyme activity Increase, cell proliferation (hepatocytes) Nov 29, 2016 Dec 31, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • PPARα activation leading to hepatocellular adenomas and carcinomas in rodents
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1231 Increase, Phenotypic enzyme activity Increase, Clonal Expansion of Altered Hepatic Foci Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1232 Increase, Clonal Expansion of Altered Hepatic Foci Increase, hepatocellular adenomas and carcinomas Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • PPARα activation leading to hepatocellular adenomas and carcinomas in rodents
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1238 Increased activation, Nuclear factor kappa B (NF-kB) Increase, Phenotypic enzyme activity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2432 Increased activation, Nuclear factor kappa B (NF-kB) Increased pro-inflammatory mediators Jul 8, 2021 Jul 8, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2431 Increased activation, Nuclear factor kappa B (NF-kB) Release, Cytokine Jul 8, 2021 Jul 8, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2309 Increased activation, Nuclear factor kappa B (NF-kB) Increased proinflammatory mediators Mar 30, 2021 Mar 30, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding to ACE2 leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2612 Increased activation, Nuclear factor kappa B (NF-kB) Antagonism, Estrogen receptor Mar 22, 2022 Aug 27, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1241 Increase, Peroxisomal Fatty Acid Beta Oxidation of Fatty Acids Peptide Oxidation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1235 Activation, NADPH Oxidase Peptide Oxidation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3511 Activation, NADPH Oxidase Increase, ROS Apr 3, 2025 Apr 3, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1234 Increase, Genes involved in fatty acid oxidation Peptide Oxidation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1240 Increase, Genes involved in fatty acid oxidation Increase, Peroxisomal Fatty Acid Beta Oxidation of Fatty Acids Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1243 Decreased, sodium conductance 2 Decreased, Ionotropic GABA receptor chloride channel conductance Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1244 Decreased, sodium conductance 2 Decreased, GABA release Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Sodium channel (Nav1.1) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1245 Decreased, GABA release Decreased, Chloride conductance Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1246 Activation, Estrogen receptor Increased, ER binding to DNA (classical pathway) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1249 Activation, Estrogen receptor Increased, ER binding to T.F. to DNA (non-classical pathway) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1294 Activation, Estrogen receptor Increased, Non-genomic signaling Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1307 Activation, Estrogen receptor Increased, Second Messenger Production Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1247 Increase, Cell Proliferation (Epithelial Cells) Increased, Ductal Hyperplasia Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1907 Increase, Cell Proliferation (Epithelial Cells) Increase, Mutations May 8, 2019 May 8, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1248 Decreased, Apoptosis (Epithelial Cells) Increased, Ductal Hyperplasia Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2914 Decreased, Apoptosis (Epithelial Cells) Alterations, Cellular proliferation / hyperplasia May 11, 2023 May 11, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Androgen receptor activation leading to prostate cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1250 Increased, ER binding to DNA (classical pathway) Increase, Cell Proliferation (Epithelial Cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1296 Increased, ER binding to DNA (classical pathway) Altered, Gene Expression Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1251 Increased, ER binding to T.F. to DNA (non-classical pathway) Increase, Cell Proliferation (Epithelial Cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1297 Increased, ER binding to T.F. to DNA (non-classical pathway) Altered, Gene Expression Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1266 Increased, Proliferation (Endothelial cells) Increased, Angiogenesis Nov 29, 2016 Dec 20, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1267 Increased, Migration (Endothelial Cells) Increased, Angiogenesis Nov 29, 2016 Dec 20, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2575 Increased, Migration (Endothelial Cells) Increase, angiogenesis Feb 15, 2022 Mar 5, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Activation of the AhR leading to metastatic breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1295 Increased, Non-genomic signaling Increased, ER binding to T.F. to DNA (non-classical pathway) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1302 Increased, Non-genomic signaling Altered, Gene Expression Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1252 Increased, Ductal Hyperplasia N/A, Breast Cancer Nov 29, 2016 May 8, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1301 Increase, DNA Damage Altered, Gene Expression Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1468 Increase, DNA Damage Increase, Apoptosis Apr 15, 2017 Apr 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2595 Increase, DNA Damage Activation of TP53 Mar 9, 2022 Mar 9, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2622 Increase, DNA Damage Decreased spermatogenesis Mar 28, 2022 Mar 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2790 Increase, DNA Damage Cell cycle, disrupted Oct 25, 2022 Oct 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1899 Increase, DNA Damage Increase mutations May 7, 2019 May 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1898 Increase, DNA Damage Tissue resident cell activation May 7, 2019 May 10, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1897 Increase, DNA Damage Increase, Mutations May 7, 2019 May 8, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2338 Increase, DNA Damage Increase, Programmed cell death Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of ionising energy leading to population decline via programmed cell death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2382 Increase, DNA Damage Increase, Oocyte apoptosis May 12, 2021 May 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2381 Increase, DNA Damage Altered, Meiotic chromosome dynamics May 12, 2021 May 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of ionising energy leads to population decline via pollen abnormal
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2576 Increased, Invasion N/A, Breast Cancer Feb 15, 2022 Feb 15, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3138 Increased, Invasion Metastasis, Breast Cancer Mar 5, 2024 Mar 5, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Activation of the AhR leading to metastatic breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3376 Activation, Macrophages Foam cell formation Oct 30, 2024 Oct 30, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Activation of reactive oxygen species leading the atherosclerosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1253 Binding, Immunophilins Inhibition, Calcineurin Activity Nov 29, 2016 Oct 25, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1255 Suppression, IL-2 and IL-4 production Interference, nuclear localization of NFAT Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1510 Suppression, IL-2 and IL-4 production Impairment, T-cell dependent antibody response May 19, 2017 Jun 27, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Inhibition of Calcineurin Activity Leading to Impaired T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1258 Suppression, Suppression of production of cytotoxic T-cells Impairment, T-cell dependent antibody response Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1260 Suppression, Suppression of production of cytotoxic T-cells Impairment of TDAR Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1259 Suppression, Suppression of T-cell dependent antibody production Impairment of TDAR Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1261 Activation, Juvenile hormone receptor Induction, Doublesex1 gene Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Juvenile hormone receptor agonism leading to male offspring induction associated population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1262 Induction, Doublesex1 gene Induction, Male reproductive tract Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Juvenile hormone receptor agonism leading to male offspring induction associated population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1264 Increased, Male offspring Decline, Population Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Juvenile hormone receptor agonism leading to male offspring induction associated population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1263 Induction, Male reproductive tract Increased, Male offspring Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Juvenile hormone receptor agonism leading to male offspring induction associated population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1269 Altered expression of hepatic CAR-dependent genes Increase, cell proliferation (hepatocytes) Nov 29, 2016 Dec 21, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1271 TRPA1 activation, TRPA1 Receptor Opening of calcium channel, Calcium influx Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1284 TRPA1 activation, TRPA1 Receptor Non-neuronal production of IL-8/CXCL1, Epithelial irritation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1576 TRPA1 activation, TRPA1 Receptor Generation of novel epitopes , Antigen presentation Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1273 Sensory Airway Irritation Cough, Dyspnea, Sneezing, Acute respiratory effect Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1272 Opening of calcium channel, Calcium influx Sensory Airway Irritation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1274 Opening of calcium channel, Calcium influx Excitation, Trigeminal nerve excitation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1280 Opening of calcium channel, Calcium influx SP (Substance P) release, Local increase of SP Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1275 Excitation, Trigeminal nerve excitation Cough, Dyspnea, Sneezing, Acute respiratory effect Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1276 Excitation, Trigeminal nerve excitation Increased Airway Hyper-responsiveness,Cough, Dyspnea Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1575 Excitation, Trigeminal nerve excitation SP (Substance P) release, Local increase of SP Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1578 Excitation, Trigeminal nerve excitation Increased CGRP Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1582 Excitation, Trigeminal nerve excitation Irritation induced sneezing Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1583 Excitation, Trigeminal nerve excitation Increased NKA Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1574 SP (Substance P) release, Local increase of SP Increased Airway Hyper-responsiveness,Cough, Dyspnea Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1577 SP (Substance P) release, Local increase of SP Leukocyte infiltration Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1279 SP (Substance P) release, Local increase of SP Non-neuronal production of TNF, Epithelial irritation Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1772 SP (Substance P) release, Local increase of SP Respiratory irritability Sep 24, 2018 Sep 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1771 Increased Airway Hyper-responsiveness,Cough, Dyspnea Respiratory irritability Sep 24, 2018 Sep 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1277 Non-neuronal production of TNF, Epithelial irritation Leukocyte infiltration Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1288 Non-neuronal production of TNF, Epithelial irritation Opening of calcium channel, Calcium influx Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1278 Leukocyte infiltration Respiratory irritability Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1290 Leukocyte infiltration Sensitization, Immune system Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1770 Respiratory irritability Increased Airway Hyper-responsiveness,Cough, Dyspnea Sep 24, 2018 Sep 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1281 TRPV1 activation, TRPV1 Opening of calcium channel, Calcium influx Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1282 Oxidization of biomolecules, Lipid bilayer and cellular proteins TRPA1 activation, TRPA1 Receptor Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1285 Oxidization of biomolecules, Lipid bilayer and cellular proteins Generation of novel epitopes , Antigen presentation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1286 Oxidization of biomolecules, Lipid bilayer and cellular proteins Production of nerve growth factor , Epithelial irritation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1283 Production of nerve growth factor , Epithelial irritation SP (Substance P) release, Local increase of SP Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1287 Non-neuronal production of IL-8/CXCL1, Epithelial irritation Opening of calcium channel, Calcium influx Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1289 Generation of novel epitopes , Antigen presentation Sensitization, Immune system Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1291 Oxidation Generation of novel epitopes , Antigen presentation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1292 Oxidation TRPA1 activation, TRPA1 Receptor Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1293 Oxidation Production of nerve growth factor , Epithelial irritation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1298 Altered, Gene Expression Altered, Protein Production Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1807 Altered, Gene Expression Altered differentiation Dec 20, 2018 Dec 20, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Histone deacetylase inhibition leads to neural tube defects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3266 Altered, Protein Production Oxidative Stress Jul 4, 2024 Jul 4, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1303 Altered, Protein Production Increased, Proliferation (Endothelial cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1304 Altered, Protein Production Decreased, Apoptosis (Epithelial Cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1305 Altered, Protein Production Increased, Motility Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1306 Increased, Motility Increased, Invasion Nov 29, 2016 Feb 29, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Activation of the AhR leading to metastatic breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1308 Increased, Second Messenger Production Increased, Non-genomic signaling Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1310 Altered, Ca2+-calmodulin activated signal transduction Impairment, Learning and memory Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within caste
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1314 Chronic, Mucus hypersecretion Decreased lung function Nov 29, 2016 Aug 30, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1330 Binding, topoisomerase II MLL translocation Jan 20, 2017 Apr 26, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1634 Binding, topoisomerase II Increase, DSB Aug 2, 2017 Aug 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibitor binding to topoisomerase II leading to infant leukaemia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1331 MLL translocation IFL Jan 20, 2017 Aug 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibitor binding to topoisomerase II leading to infant leukaemia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1324 induced spawning Decreased, Reproductive Success Jan 13, 2017 Jan 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1325 induced spawning Increased, Reproductive Success Jan 13, 2017 Jan 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1322 increased mantel display Induced parturition Jan 13, 2017 Jan 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1323 Induced parturition Decreased, Reproductive Success Jan 13, 2017 Jan 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1326 Induced parturition Increased, Reproductive Success Jan 13, 2017 Jan 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3147 Decompartmentalization Mitochondrial dysfunction Mar 13, 2024 Mar 13, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • AOP from chemical insult to cell death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3148 narcosis Mitochondrial dysfunction Mar 13, 2024 Mar 13, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • AOP from chemical insult to cell death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3145 Direct mitochondrial inhibition Mitochondrial dysfunction Mar 13, 2024 Mar 13, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • AOP from chemical insult to cell death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3468 Apoptosis Decreased, ovarian reserve Jan 4, 2025 Apr 19, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3257 Apoptosis Neuroinflammation Jun 19, 2024 Jun 19, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Binding and activation of GPER leading to learning and memory impairments
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3251 Apoptosis Disruption, neurotransmitter release Jun 19, 2024 Jun 19, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Binding and activation of GPER leading to learning and memory impairments
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3250 Apoptosis Aberrant, synaptic formation and plasticity Jun 19, 2024 Jun 19, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Binding and activation of GPER leading to learning and memory impairments
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3327 Apoptosis Reduction, 17beta-estradiol synthesis by ovarian granulosa cells Jul 26, 2024 Jul 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1869 Apoptosis Liver Injury Mar 6, 2019 Mar 6, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of N-linked glycosylation leads to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1867 Apoptosis Activation, hepatic stellate cells Mar 6, 2019 Mar 6, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of N-linked glycosylation leads to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3106 Apoptosis decline, neural progenitor cells Jan 10, 2024 Jan 10, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2967 Apoptosis N/A, Neurodegeneration Jul 18, 2023 Apr 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2191 Apoptosis Increase, Tissue/organ damage Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2792 Apoptosis Decrease, facial prominence outgrowth Oct 27, 2022 Apr 4, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Decrease, GLI1/2 target gene expression leads to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2675 Apoptosis Emphysema Jun 17, 2022 Jun 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1735 Apoptosis Spermatocyte depletion May 22, 2018 Jul 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Histone deacetylase inhibition leading to testicular atrophy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1713 Apoptosis Testicular atrophy Jan 21, 2018 Jan 21, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1368 Apoptosis Reproductive failure Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2577 Apoptosis tumor growth Feb 15, 2022 Mar 5, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Activation of the AhR leading to metastatic breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1344 Increase, E75b expression Increase, Ftz-f1 expression Feb 9, 2017 Feb 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1345 Increase, Ftz-f1 expression Decrease, Circulating ETH Feb 9, 2017 Feb 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1347 Decrease, Circulating CCAP Decrease, Ecdysis motoneuron bursts Feb 9, 2017 Feb 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1348 Decrease, Ecdysis motoneuron bursts Decrease, Excitatory postsynaptic potential Feb 9, 2017 Feb 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1349 Decrease, Excitatory postsynaptic potential Decrease, Abdominal muscle contraction Feb 9, 2017 Feb 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1351 Increase, COX-2 expression Altered, Cardiovascular development/function Feb 9, 2017 Mar 28, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1353 Inactivation of PPARγ Activation of TGF-β signaling Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2156 Inactivation of PPARγ Activation, TGF-beta pathway Jul 9, 2020 Jul 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1354 Activation of TGF-β signaling Differentiation of Myofibroblast Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1355 Activation of TGF-β signaling Expression of Collagen Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1721 Activation of TGF-β signaling Increase, Inflammation Mar 18, 2018 Mar 18, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1723 Activation of TGF-β signaling EMT Mar 18, 2018 Mar 18, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1356 Differentiation of Myofibroblast Production of α-smooth muscle actin Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1357 Expression of Collagen Collagen Deposition Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1358 Production of α-smooth muscle actin Lung fibrosis Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1359 Collagen Deposition Lung fibrosis Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1628 Collagen Deposition Accumulation, Collagen Jul 26, 2017 Jul 26, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1362 Increase, Oxidative Stress / Activation, PMK-1 P38 MAPK Increased, DNA Damage-Repair Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1364 Increase, Oxidative Stress / Activation, PMK-1 P38 MAPK Activation, HIF-1 Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3166 Increase, Oxidative Stress / Activation, PMK-1 P38 MAPK Mitochondrial dysfunction Mar 14, 2024 Mar 14, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3512 Increase, Oxidative Stress / Activation, PMK-1 P38 MAPK Increase, ROS Apr 3, 2025 Apr 3, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1365 Activation, HIF-1 Apoptosis Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1366 Increased, DNA Damage-Repair Apoptosis Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1369 Activation, JAK/STAT pathway Activation, TGF-beta pathway Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) and Transforming growth factor (TGF)-beta pathways activation leading to reproductive failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1370 Activation, TGF-beta pathway Reproductive failure Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) and Transforming growth factor (TGF)-beta pathways activation leading to reproductive failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2153 Activation, TGF-beta pathway EMT Jul 9, 2020 Jul 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1371 Up Regulation, SREBF2 Up Regulation, Unsaturated fatty acid Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1372 Up Regulation, Unsaturated fatty acid Perturbation of cholesterol Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1373 Down Regulation, GSS and GSTs gene Glutathione synthesis Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1376 Down Regulation, GSS and GSTs gene Glutathione homeostasis Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1374 Glutathione synthesis Activation, 3-hydroxy-3-methylglutaryl-CoA reductase gene Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1375 Activation, 3-hydroxy-3-methylglutaryl-CoA reductase gene Perturbation of cholesterol Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1377 Perturbation of cholesterol Hepatotoxicity Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1378 Glutathione homeostasis Hepatotoxicity Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1380 Activation, JNK Activation, FOXO Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Activation of c-Jun N-terminal kinase (JNK) and Forkhead box O (FOXO) and reduction of WNT pathways leading to reproductive failure: Integrated multi-OMICS approach for AOP building
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2149 Activation, JNK AP-1 activation Jul 9, 2020 Jul 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2150 Activation, JNK Pin-1 activation Jul 9, 2020 Jul 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1381 Activation, FOXO Inhibition, Wnt pathway Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Activation of c-Jun N-terminal kinase (JNK) and Forkhead box O (FOXO) and reduction of WNT pathways leading to reproductive failure: Integrated multi-OMICS approach for AOP building
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1382 Inhibition, Wnt pathway Defect of Embryogenesis Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Activation of c-Jun N-terminal kinase (JNK) and Forkhead box O (FOXO) and reduction of WNT pathways leading to reproductive failure: Integrated multi-OMICS approach for AOP building
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1383 Defect of Embryogenesis Reproductive failure Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Activation of c-Jun N-terminal kinase (JNK) and Forkhead box O (FOXO) and reduction of WNT pathways leading to reproductive failure: Integrated multi-OMICS approach for AOP building
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1390 Increase, insulin Activation, insulin receptor Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1391 Activation, insulin receptor Activation, mTORC2 Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1392 Activation, mTORC2 Activation, AKT Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1393 Activation, mTORC2 Activation, mTORC1 Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1394 Activation, AKT Activation, SREBP-1 Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1398 Activation, AKT Activation, mTORC1 Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1400 Activation, AKT Activation, L-FABP Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1395 Activation, mTORC1 Activation, L-FABP Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1396 Activation, mTORC1 Activation, HSD17B4 Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1399 Activation, mTORC1 Activation, SREBP-1 Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1397 Activation, SREBP-1 Activation, FXR Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1403 Activation, SREBP-1 Activation, SCD-1 Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1401 Activation, L-FABP Increase, cytosolic fatty acid Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1423 Activation, L-FABP demethylation, PPARg promoter Apr 13, 2017 Apr 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1411 Activation, HSD17B4 Inhibition, Mitochondrial fatty acid beta-oxidation Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1415 Activation, HSD17B4 Increase, Fatty acid β-oxidation Apr 13, 2017 Apr 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1407 Activation, FXR Activation, SHP Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1408 Activation, FXR Activation, PPARα Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1693 Increase, cytosolic fatty acid steatohepatitis Nov 13, 2017 Nov 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1694 Increase, cytosolic fatty acid Increased, Liver Steatosis Nov 14, 2017 Nov 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1405 Increased, lipogenesis Increase, cytosolic fatty acid Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1413 Inhibition, LXR Inhibition, PPAR alpha Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1421 Activation, aPKC Activation, SREBP-1 Apr 13, 2017 Apr 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1418 Activation, PI3K Activation, AKT Apr 13, 2017 Apr 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1419 Activation, PI3K Activation, L-FABP Apr 13, 2017 Apr 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1420 Activation, PI3K Activation, aPKC Apr 13, 2017 Apr 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1417 Increase, Fatty acid β-oxidation Decrease, cytosolic fatty acid Apr 13, 2017 Apr 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1425 Activation, LRH-1 Activation, FAS Apr 13, 2017 Apr 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1520 Inhibit, serotonin transporter activity Decreased, serotonin transporter activity May 30, 2017 May 30, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1426 Decreased, serotonin transporter activity Increased, intracellular sodium (Na+) Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1427 Decreased, serotonin transporter activity Increased, intracellular chloride (Cl-) Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1428 Decreased, serotonin transporter activity Decreased, extracellular Na+ Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1429 Decreased, serotonin transporter activity Decreased, extracellular chloride (Cl-) Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1430 Decreased, serotonin transporter activity Increased, extracellular serotonin Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Mental stress to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Mental stress to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1431 Decreased, serotonin transporter activity Decreased, intracellular serotonin Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Mental stress to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Mental stress to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1521 Increased, extracellular serotonin Decreased, extracellular serotonin May 30, 2017 May 30, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1529 Increased, extracellular serotonin Decreased, 5-HT3 Jun 1, 2017 Jun 1, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Serotonin transporter activation to seizure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1531 Increased, extracellular serotonin Activation, 5-HT2A Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3475 Increased, extracellular serotonin Increased, stimulation of brain serotonin 5-HT1a, 5-HT2c receptors Jan 14, 2025 Feb 20, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) leads to Inhibition, Feeding
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3489 Increased, extracellular serotonin Inhibition, Feeding Feb 20, 2025 Feb 20, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) leads to Inhibition, Feeding
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3424 Increased, intracellular sodium (Na+) Impaired Sodium-Calcium Exchange Nov 21, 2024 Nov 21, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Decreased Na/K ATPase activity leading to heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1455 Increased, intracellular sodium (Na+) Activated, voltage-gated sodium channel Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • presynaptic neuron 1 activation to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1465 Increased, intracellular chloride (Cl-) Inactive, membrane depolarization Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1432 Decreased, intracellular serotonin Decreased, packaged serotonin Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Mental stress to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Mental stress to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1433 Decreased, packaged serotonin Decreased, synaptic release Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Mental stress to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Mental stress to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1434 Decreased, synaptic release Decreased, extracellular serotonin Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Mental stress to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Mental stress to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1445 Increased, 5-HT3 Increased, seizure Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1446 Inactivated, 5-HTR Reduce expression, BDNF Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Serotonin transporter activation to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Serotonin transporter activation to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1511 Inactivated, 5-HTR Reduced, BDNF May 30, 2017 May 30, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Mental stress to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1447 Reduce expression, BDNF Decreased, neuroplasticity Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Mental stress to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Serotonin transporter activation to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Serotonin transporter activation to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1448 Decreased, neuroplasticity Increased, agitation Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Mental stress to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Serotonin transporter activation to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1449 Decreased, neuroplasticity Increased, depression Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Mental stress to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Serotonin transporter activation to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1450 Increase, cortisone Activation, Glucocorticoid Receptor Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1523 Reduced, BDNF Decreased, neuroplasticity May 31, 2017 May 31, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Mental stress to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1438 Activation, 5-HT2A Activate, PLC Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1439 Activate, PLC Increase, inositol triphosphate Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1440 Increase, inositol triphosphate Increase, intracellular calcium Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1441 Increase, intracellular calcium Activate, calmodulin Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2968 Increase, intracellular calcium Apoptosis Jul 18, 2023 Apr 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2954 Increase, intracellular calcium Disruption, neurotransmitter release Jun 27, 2023 Apr 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via disrupted neurotransmitter release
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3140 Increase, intracellular calcium Mitochondrial dysfunction Mar 6, 2024 Apr 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1442 Activate, calmodulin Increase, myosin light chain phosphorylation Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1443 Increase, myosin light chain phosphorylation Increase, vascular smooth muscle contraction Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1444 Increase, vascular smooth muscle contraction Increase, hypertension Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1581 Increase, hypertension Respiratory irritability Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1550 Increased, seizure Increased, epilepsy Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • presynaptic neuron 1 activation to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • presynaptic neuron 2 repression to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1519 Decreased, extracellular serotonin Decreased, synaptic release May 30, 2017 May 30, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1435 Decreased, extracellular serotonin Increased, 5-HT3 Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1436 Decreased, extracellular serotonin Inactivated, 5-HTR Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Mental stress to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Mental stress to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Serotonin transporter activation to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Serotonin transporter activation to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1437 Decreased, extracellular serotonin Activation, 5-HT2A Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1460 Increase, seizure Increased, epilepsy Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1452 Activated, presynaptic neuron 1 Increased, glutamate Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • presynaptic neuron 1 activation to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3086 Activated, presynaptic neuron 1 Activation, Glutamate-gated chloride channels Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3088 Activated, presynaptic neuron 1 Decreased, Ionotropic GABA receptor chloride channel conductance Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2868 Increased, glutamate decreased, Bcl-2 Apr 4, 2023 Apr 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2869 Increased, glutamate increased, Bax Apr 4, 2023 Apr 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2861 Increased, glutamate Microglia activation Apr 3, 2023 Apr 3, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1453 Increased, glutamate Activated, NMDA receptor Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • presynaptic neuron 1 activation to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1859 Increased, glutamate Overactivation, NMDARs Feb 13, 2019 Sep 3, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Acetylcholinesterase Inhibition Leading to Neurodegeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1454 Activated, NMDA receptor Increased, intracellular sodium (Na+) Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • presynaptic neuron 1 activation to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1457 Activated, voltage-gated sodium channel Activated, membrane depolarization Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • presynaptic neuron 1 activation to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2605 Binding to VGSC Altered kinetics of sodium channel Mar 21, 2022 Jul 31, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Binding to voltage gate sodium channels during development leads to cognitive impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1456 Treat, carbamazepine Binding to VGSC Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • presynaptic neuron 1 activation to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1458 Activated, membrane depolarization Increased, hippocampal hyperdepolarization Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • presynaptic neuron 1 activation to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • presynaptic neuron 2 repression to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1463 Increased, RDX dose Activate, GABA-A receptor Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1555 Increased, RDX dose Reduced, GABA-A receptor activation Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • presynaptic neuron 2 repression to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1464 Activate, GABA-A receptor Increased, intracellular chloride (Cl-) Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1461 Activate, presynaptic neuron 2 Increase, GABA Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1462 Increase, GABA Activate, GABA-A receptor Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1459 Increased, hippocampal hyperdepolarization Increase, seizure Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1549 Increased, hippocampal hyperdepolarization Increased, seizure Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • presynaptic neuron 1 activation to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • presynaptic neuron 2 repression to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3082 Increased, epilepsy Increase, Mortality Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3034 Increase, Apoptosis increased,Vascular endothelial dysfunction Aug 28, 2023 Aug 28, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2948 Increase, Apoptosis Inhibition of neurotransmitter release Jun 20, 2023 Jun 20, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1596 Increase, Apoptosis Increase, Follicular atresia Jun 29, 2017 Jun 29, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1469 Increase, Apoptosis Decrease, Oogenesis Apr 15, 2017 Apr 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1741 Increase, Apoptosis Decrease, Growth May 24, 2018 May 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1751 Increase, Apoptosis Increase, Mortality Jun 12, 2018 Jun 12, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Excessive reactive oxygen species production leading to mortality (4)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2075 Increase, Apoptosis Reduce, Sperm count Apr 6, 2020 Apr 6, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Alkylation of DNA leading to reduced sperm count
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2185 Increase, Apoptosis Increase, Tissue/organ damage Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2602 Increase, Apoptosis Microcephaly Mar 17, 2022 Mar 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2461 Increase, Apoptosis Increased, Kidney Failure Aug 5, 2021 Aug 5, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2645 Increase, Apoptosis Occurrence, renal proximal tubular necrosis Apr 8, 2022 Apr 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2619 Increase, Apoptosis Decreased spermatogenesis Mar 28, 2022 Mar 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2725 Increase, Apoptosis Decrease, facial prominence outgrowth Jul 28, 2022 Jul 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1752 Decrease, Oogenesis Decrease, Fecundity Jun 12, 2018 Jun 12, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • DNA methyltransferase inhibition leading to population decline (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • DNA methyltransferase inhibition leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • DNA methyltransferase inhibition leading to population decline (3)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1470 Decrease, Oogenesis Decrease, Ovulation Apr 15, 2017 Apr 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2588 Decrease, Oogenesis Reduction, Cumulative fecundity and spawning Mar 1, 2022 Mar 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of energy leading to population decline via DNA strand breaks and follicular atresia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of energy leading to population decline via DNA strand breaks and oocyte apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of energy leading to population decline via DNA oxidation and follicular atresia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2586 Decrease, Oogenesis Decrease, Reproduction Mar 1, 2022 Mar 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1480 Activation, PTGS-1 Increase, platelet aggregation Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1481 Activation, PTGS-1 Increase, mucosal blood flow Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1482 Activation, PTGS-1 Increase, mucous Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1483 Activation, PTGS-1 Increase, bicarbonate Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1478 Activation, PTGS-2 Decrease, leukocyte adherence Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1479 Activation, PTGS-2 Increase, angiogenesis Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1484 Increase, bicarbonate Activate, mucosal defense Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1485 Increase, mucous Activate, mucosal defense Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1486 Increase, mucosal blood flow Activate, mucosal defense Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1474 Increase, platelet aggregation Inhibit, gastric ulcer formation Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1473 Increase, angiogenesis Inhibit, gastric ulcer formation Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3137 Increase, angiogenesis Metastasis, Breast Cancer Mar 5, 2024 Mar 5, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Activation of the AhR leading to metastatic breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3308 Increase, angiogenesis Increase, Cancer Jul 18, 2024 Jul 18, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2578 Increase, angiogenesis N/A, Breast Cancer Feb 15, 2022 Feb 15, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1477 Increase, leukocyte adherence Activate, leukocyte Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1476 Activate, leukocyte Activated, gastric ulcer formation Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1475 Activate, mucosal defense Inhibit, gastric ulcer formation Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1489 Increase, surfactant Activate, mucosal defense Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1547 Decrease, surfactant Reduced, mucosal defense Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Helicobacter pylori to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1488 Activate, phospholipase Decrease, surfactant Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Helicobacter pylori to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1487 Increase, ammonium (NH4+) Decrease, surfactant Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Helicobacter pylori to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1493 CYP7B activity, inhibition 7α-hydroxypregnenolone synthesis in the brain, decreased May 2, 2017 May 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1494 CYP7B activity, inhibition Locomotor activity, decreased May 2, 2017 May 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1495 7α-hydroxypregnenolone synthesis in the brain, decreased Locomotor activity, decreased May 2, 2017 May 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1496 7α-hydroxypregnenolone synthesis in the brain, decreased Dopamine release in the brain, decreased May 2, 2017 May 25, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1498 7α-hydroxypregnenolone synthesis in the brain, decreased Sexual behavior, decreased May 3, 2017 May 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1497 Dopamine release in the brain, decreased Locomotor activity, decreased May 2, 2017 May 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1502 Dopamine release in the brain, decreased Sexual behavior, decreased May 9, 2017 May 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1500 Locomotor activity, decreased Decreased, Reproductive Success May 8, 2017 Jun 26, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1499 Sexual behavior, decreased Decreased, Reproductive Success May 8, 2017 May 8, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1512 Activation of Cyp2E1 Oxidative Stress May 30, 2017 Jul 1, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Cyp2E1 Activation Leading to Liver Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1515 Activation of Cyp2E1 Hepatocytotoxicity May 30, 2017 Dec 6, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Cyp2E1 Activation Leading to Liver Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1513 Oxidative Stress Hepatocytotoxicity May 30, 2017 Jun 19, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Cyp2E1 Activation Leading to Liver Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1516 Oxidative Stress Liver Cancer May 30, 2017 Jun 19, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Cyp2E1 Activation Leading to Liver Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1685 Oxidative Stress Glutamate dyshomeostasis Nov 9, 2017 Feb 6, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1690 Oxidative Stress Cell injury/death Nov 9, 2017 Feb 7, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2451 Oxidative Stress CBF, Decreased Aug 2, 2021 Mar 24, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Oxidative stress Leading to Decreased Lung Function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2450 Oxidative Stress FOXJ1 Protein, Decreased Aug 2, 2021 Sep 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2449 Oxidative Stress CFTR Function, Decreased Jul 30, 2021 Sep 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2505 Oxidative Stress p-Tau Oct 26, 2021 Oct 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2716 Oxidative Stress Increase, Cell death Jul 25, 2022 Aug 23, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Deposition of energy leading to occurrence of bone loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2674 Oxidative Stress Pulmonary inflammation Jun 17, 2022 Jun 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2714 Oxidative Stress Mitochondrial Injury Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2771 Oxidative Stress Altered Signaling Sep 28, 2022 Feb 13, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2772 Oxidative Stress Increased pro-inflammatory mediators Sep 28, 2022 Aug 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of energy leads to abnormal vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2774 Oxidative Stress Altered, Nitric Oxide Levels Sep 28, 2022 Nov 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of energy leads to abnormal vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2776 Oxidative Stress Increase, Endothelial Dysfunction Sep 28, 2022 Aug 27, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of energy leads to abnormal vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Activation of reactive oxygen species leading the atherosclerosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2008 Oxidative Stress Wnt ligand stimulation Dec 3, 2019 Dec 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3116 Oxidative Stress Increase, LPO Jan 24, 2024 Apr 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Essential element imbalance leads to reproductive failure via oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3129 Oxidative Stress Mitochondrial dysfunction Feb 17, 2024 May 31, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2975 Oxidative Stress Increase, Inflammation Jul 31, 2023 Oct 19, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3047 Oxidative Stress Accumulation, misfolded proteins Sep 14, 2023 Sep 14, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3048 Oxidative Stress Proteasomal dysfunction Sep 14, 2023 Sep 14, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3277 Oxidative Stress Activation, inflammation pathway Jul 4, 2024 Jul 4, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3311 Oxidative Stress Unfolded Protein Response Jul 23, 2024 Jul 23, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • CYP2E1 activation and formation of protein adducts leading to neurodegeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3279 Oxidative Stress Abnormal expression of NO Jul 4, 2024 Jul 4, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Demethylation of PPAR promotor leading to vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3281 Oxidative Stress Activation, Dll4-Notch pathway Jul 4, 2024 Jul 4, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3282 Oxidative Stress Activated BMP/TGF-beta pathway Jul 4, 2024 Jul 4, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3283 Oxidative Stress Activated Wnt/Frizzled pathway Jul 4, 2024 Jul 4, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3284 Oxidative Stress Uncoupling, eNOS Jul 4, 2024 Jul 4, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3285 Oxidative Stress Activated AKT/ERK/PI3K pathway Jul 4, 2024 Jul 4, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3286 Oxidative Stress Inhibition VEGF/VEGFR pathway Jul 4, 2024 Jul 4, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3293 Oxidative Stress The NO synthase pathway activation Jul 9, 2024 Jul 9, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Adverse outcome pathway of PFAS-induced vascular disrupting effects via activating oxidative stress related pathways
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3294 Oxidative Stress Ferroptosis related pathways activation Jul 9, 2024 Jul 9, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Adverse outcome pathway of PFAS-induced vascular disrupting effects via activating oxidative stress related pathways
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3312 Oxidative Stress N/A, Neurodegeneration Jul 23, 2024 Jul 23, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3280 Oxidative Stress Activated ANG/Tie2 pathway Jul 4, 2024 Jul 4, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3310 Oxidative Stress Lipid Peroxidation Jul 23, 2024 Jul 23, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • CYP2E1 activation and formation of protein adducts leading to neurodegeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3314 Oxidative Stress Neuronal network function, Decreased Jul 23, 2024 Jul 23, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Excessive iron accumulation leading to neurological disorders
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3274 Oxidative Stress TH synthesis, Decreased Jul 4, 2024 Jul 4, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3272 Oxidative Stress Impaired insulin signaling Jul 4, 2024 Jul 4, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3252 Oxidative Stress Neuroinflammation Jun 19, 2024 Jun 19, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Binding and activation of GPER leading to learning and memory impairments
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3270 Oxidative Stress Increase, Apoptosis Jul 4, 2024 Jul 4, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3249 Oxidative Stress Apoptosis Jun 19, 2024 Jun 19, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Binding and activation of GPER leading to learning and memory impairments
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3267 Oxidative Stress Increase, DNA Damage Jul 4, 2024 Jul 4, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3262 Oxidative Stress Increased, secretion of local growth factors Jul 3, 2024 Jul 3, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3264 Oxidative Stress Occurrence, renal proximal tubular necrosis Jul 3, 2024 Jul 3, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Organic anion transporter (OAT1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • unknown MIE leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3322 Oxidative Stress Decreased, Neuronal network function in adult brain Jul 24, 2024 Jul 24, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3324 Oxidative Stress Down Regulation, Gulcose-6-phosphate dehydrogenase Jul 24, 2024 Jul 24, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3325 Oxidative Stress Damaging, Red blood cells; hemolysis Jul 24, 2024 Jul 24, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3316 Oxidative Stress Altered Stress Response Signaling Jul 24, 2024 Aug 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of energy leads to abnormal vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3319 Oxidative Stress Altered cell differentiation signaling Jul 24, 2024 Aug 23, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of energy leading to occurrence of bone loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3382 Oxidative Stress Increase mutations Nov 6, 2024 Nov 6, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3442 Oxidative Stress Increased, LDL uptake Nov 25, 2024 Nov 25, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Activation of reactive oxygen species leading the atherosclerosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3239 Oxidative Stress Increase, Oocyte apoptosis May 31, 2024 May 31, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2289 Oxidative Stress Coagulation Mar 25, 2021 Mar 25, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2827 Oxidative Stress Mitochondrial dysfunction EMPTY Jan 9, 2023 Jan 9, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2833 Oxidative Stress Tissue resident cell activation Jan 25, 2023 Jul 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2810 Oxidative Stress Increase, Oxidative DNA damage Dec 16, 2022 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2811 Oxidative Stress Increase, DNA strand breaks Dec 16, 2022 Jul 29, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leads to abnormal vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2812 Oxidative Stress Modified Proteins Dec 16, 2022 Mar 30, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2818 Oxidative Stress Cataracts Dec 18, 2022 Mar 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2846 Oxidative Stress Altered Bone Cell Homeostasis Jan 25, 2023 Aug 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to occurrence of bone loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1514 Hepatocytotoxicity Sustained proliferation May 30, 2017 Jun 19, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Cyp2E1 Activation Leading to Liver Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1517 Hepatocytotoxicity Liver Cancer May 30, 2017 May 1, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Cyp2E1 Activation Leading to Liver Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1518 Sustained proliferation Liver Cancer May 30, 2017 Oct 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Cyp2E1 Activation Leading to Liver Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1522 Increased, glucocorticoid receptor activity Reduced, BDNF May 31, 2017 May 31, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Mental stress to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Mental stress to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1524 Increased, serotonin transporter activity Increased, intracellular serotonin Jun 1, 2017 Jun 1, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Serotonin transporter activation to seizure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Serotonin transporter activation to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Serotonin transporter activation to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1528 Increased, serotonin transporter activity Decreased, extracellular serotonin Jun 1, 2017 Jun 1, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Serotonin transporter activation to seizure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Serotonin transporter activation to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Serotonin transporter activation to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1525 Increased, intracellular serotonin Increased, packaged serotonin Jun 1, 2017 Jun 1, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Serotonin transporter activation to seizure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Serotonin transporter activation to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Serotonin transporter activation to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1526 Increased, packaged serotonin Increased, synaptic release Jun 1, 2017 Jun 1, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Serotonin transporter activation to seizure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Serotonin transporter activation to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Serotonin transporter activation to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1527 Increased, synaptic release Increased, extracellular serotonin Jun 1, 2017 Jun 1, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Serotonin transporter activation to seizure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Serotonin transporter activation to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Serotonin transporter activation to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1530 Decreased, 5-HT3 Increased, seizure Jun 1, 2017 Jun 1, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Serotonin transporter activation to seizure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1532 Reduced, PTGS1 function Reduced, platelet aggregation Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • NSAID induced PTGS1 inactivation to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1534 Reduced, PTGS1 function Decreased, mucosal blood flow Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • NSAID induced PTGS1 inactivation to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1537 Reduced, PTGS1 function Decreased, mucous Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • NSAID induced PTGS1 inactivation to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1539 Reduced, PTGS1 function Decreased, bicarbonate Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • NSAID induced PTGS1 inactivation to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1533 Reduced, platelet aggregation Activated, gastric ulcer formation Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • NSAID induced PTGS1 inactivation to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1535 Decreased, mucosal blood flow Reduced, mucosal defense Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • NSAID induced PTGS1 inactivation to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1536 Reduced, mucosal defense Activated, gastric ulcer formation Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • NSAID induced PTGS1 inactivation to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Helicobacter pylori to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1548 Reduced, mucosal defense Helicobacter pylori infection Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1538 Decreased, mucous Reduced, mucosal defense Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • NSAID induced PTGS1 inactivation to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1540 Decreased, bicarbonate Reduced, mucosal defense Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • NSAID induced PTGS1 inactivation to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1541 Reduced, PTGS2 function Decreased, angiogenesis Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • NSAID induced PTGS2 inactivation to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1543 Reduced, PTGS2 function Increased, leukocyte adherence Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • NSAID induced PTGS2 inactivation to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1542 Decreased, angiogenesis Activated, gastric ulcer formation Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • NSAID induced PTGS2 inactivation to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1544 Increased, leukocyte adherence Increased, leukocyte activation Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • NSAID induced PTGS2 inactivation to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1545 Increased, leukocyte activation Activated, gastric ulcer formation Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • NSAID induced PTGS2 inactivation to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1546 Helicobacter pylori infection Increase, ammonium (NH4+) Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Helicobacter pylori to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1551 Reduced, presynaptic neuron 2 activity Decreased, GABA Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • presynaptic neuron 2 repression to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1552 Decreased, GABA Reduced, GABA-A receptor activation Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • presynaptic neuron 2 repression to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1553 Reduced, GABA-A receptor activation Decreased, intracellular chloride Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • presynaptic neuron 2 repression to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1554 Decreased, intracellular chloride Activated, membrane depolarization Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • presynaptic neuron 2 repression to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1556 NFE2/Nrf2 repression Reduced, FXR activity Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • NFE2/Nrf2 repression to steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2984 NFE2/Nrf2 repression Activation, HIF1α Aug 20, 2023 Aug 20, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Nrf2 inhibition leading to vascular disrupting effects through activating HIF1α, Semaphorin 6A, and Dll4-Notch pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3035 NFE2/Nrf2 repression Activation, inflammation pathway Aug 28, 2023 Aug 28, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3276 NFE2/Nrf2 repression Oxidative Stress Jul 4, 2024 Jul 4, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1557 Reduced, FXR activity Reduced, SHP activity Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • NFE2/Nrf2 repression to steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1558 Reduced, SHP activity Activated, LXR Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • NFE2/Nrf2 repression to steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1559 Activated, LXR Reduced, PPARalpha Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • NFE2/Nrf2 repression to steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1560 Reduced, PPARalpha Reduced, HSD17B4 activity Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • NFE2/Nrf2 repression to steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1561 Reduced, HSD17B4 activity Reduced, fatty acid beta oxidation Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • NFE2/Nrf2 repression to steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3215 Reduced, fatty acid beta oxidation Increased, Liver Steatosis May 9, 2024 May 9, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • NFE2/Nrf2 repression to steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1563 Mu Opioid Receptor Agonism Release of G Proteins Jun 8, 2017 Jun 8, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Mu Opioid Receptor Agonism leading to Analgesia via K Channel Opening
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Mu Opioid Receptor Agonism leading to Analgesia via Ca Channel Inhibition
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1564 Release of G Proteins Opening of GIRK channels Jun 8, 2017 Jun 8, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Mu Opioid Receptor Agonism leading to Analgesia via K Channel Opening
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via K Channel Opening
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1568 Release of G Proteins Inhibition of Ca Channels Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Mu Opioid Receptor Agonism leading to Analgesia via Ca Channel Inhibition
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via Ca Channel Inhibition
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1565 Opening of GIRK channels hyperpolarisation, neuron Jun 8, 2017 Jun 8, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Mu Opioid Receptor Agonism leading to Analgesia via K Channel Opening
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via K Channel Opening
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1569 Inhibition of Ca Channels Inhibition of neurotransmitter release Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Mu Opioid Receptor Agonism leading to Analgesia via Ca Channel Inhibition
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via Ca Channel Inhibition
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1570 Inhibition of neurotransmitter release Analgesia Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Mu Opioid Receptor Agonism leading to Analgesia via Ca Channel Inhibition
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1573 Inhibition of neurotransmitter release Anti-depressant Activity Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via Ca Channel Inhibition
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1571 Serotonin 1A Receptor Agonism Release of G Proteins Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via K Channel Opening
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via Ca Channel Inhibition
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1579 Increased CGRP Increased Airway Hyper-responsiveness,Cough, Dyspnea Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1580 Increased CGRP Increase, hypertension Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1586 Increased CGRP Leukocyte infiltration Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1587 Increased CGRP Respiratory irritability Jun 27, 2017 Jun 27, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1774 Irritation induced sneezing Increased Airway Hyper-responsiveness,Cough, Dyspnea Sep 24, 2018 Sep 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1773 Increased NKA Respiratory irritability Sep 24, 2018 Sep 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1584 Increased NKA Increased Airway Hyper-responsiveness,Cough, Dyspnea Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1585 Increased NKA Leukocyte infiltration Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1588 Sensing of the stressor Increased transcription of genes encoding acute phase proteins Jun 29, 2017 Jun 29, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1589 Increased transcription of genes encoding acute phase proteins Systemic acute phase response Jun 29, 2017 Jan 17, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Substance interaction with lung resident cell membrane components leading to atherosclerosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1590 Systemic acute phase response HDL-SAA formation Jun 29, 2017 Jun 29, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2860 Systemic acute phase response Atherosclerosis Mar 28, 2023 Jan 20, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Substance interaction with lung resident cell membrane components leading to atherosclerosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1591 HDL-SAA formation Systemic cholesterol increased Jun 29, 2017 Jun 29, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1593 HDL-SAA formation Foam cell formation Jun 29, 2017 Jun 29, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1592 Systemic cholesterol increased Foam cell formation Jun 29, 2017 Jun 29, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1594 Foam cell formation Atherosclerosis Jun 29, 2017 Jun 29, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1597 Increase, Follicular atresia Decrease, Oogenesis Jun 29, 2017 Jun 29, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of energy leading to population decline via DNA strand breaks and follicular atresia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of energy leading to population decline via DNA oxidation and follicular atresia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2211 Increase, Follicular atresia Decrease, Fecundity Nov 25, 2020 Nov 25, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2210 Increase, LPO Increase, Apoptosis Nov 25, 2020 Nov 25, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2222 Increase, LPO Increase, Cell death Dec 4, 2020 Dec 4, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2097 Increase, LPO Decrease, TAG Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Excessive reactive oxygen species production leading to mortality (3)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2464 Increase, LPO Increase, Necrosis Aug 11, 2021 Aug 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1599 Increase, LPO Decrease, Coupling of OXPHOS Jun 29, 2017 Jun 29, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2879 Increase, LPO decreased, Fertility Apr 5, 2023 Sep 14, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Glutathione conjugation leading to reproductive dysfunction via oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3117 Increase, LPO Increased, histomorphological alteration of testis Jan 24, 2024 Apr 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Essential element imbalance leads to reproductive failure via oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3360 Increase, LPO Cell injury/death Oct 8, 2024 Oct 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and cell death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3364 Increase, LPO Cell cycle, disrupted Oct 8, 2024 Oct 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3495 Decrease, Coupling of OXPHOS Increase, ROS Feb 25, 2025 Feb 25, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2203 Decrease, Coupling of OXPHOS Decrease, ATP pool Nov 12, 2020 Jul 6, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2182 Decrease, Coupling of OXPHOS Increase, Complex III dysfunction Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2188 Decrease, Coupling of OXPHOS Increase, Complex I dysfunction Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2175 Decrease, Coupling of OXPHOS Decrease, ATP synthase activity Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2219 Decrease, Coupling of OXPHOS Increase, Oxygen consumption Dec 4, 2020 Dec 4, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2763 Decrease, Coupling of OXPHOS Increase, Cytosolic Ca Sep 13, 2022 Sep 13, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calcium
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2796 Decrease, Coupling of OXPHOS Increase, Mitochondrial swelling Nov 1, 2022 Nov 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swelling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2793 Decrease, Coupling of OXPHOS Increase, Glycolysis Nov 1, 2022 Nov 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1600 Decrease, Coupling of OXPHOS Decrease, Mitochondrial ATP production Jun 29, 2017 Jun 29, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1610 activation of CEBPA Activation of specific nuclear receptors, PPAR-gamma activation Jul 24, 2017 Jul 24, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1611 activation of CEBPA increased adipogenesis Jul 24, 2017 Jul 24, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1612 increased adipogenesis obesity Jul 24, 2017 Jul 24, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1614 decreased dopamine decreased reward Jul 24, 2017 Jul 24, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1615 decreased reward decreased DNA methylation of tyrosine hydroxylase Jul 24, 2017 Jul 24, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1616 decreased reward decreased methylation of dopamine transporter promoter Jul 24, 2017 Jul 24, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1617 decreased reward decreased dopamine Jul 24, 2017 Jul 24, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1618 decreased DNA methylation of tyrosine hydroxylase obesity Jul 24, 2017 Jul 24, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1620 decreased DNA methylation of tyrosine hydroxylase decreased dopamine Jul 24, 2017 Jul 24, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1619 decreased methylation of dopamine transporter promoter obesity Jul 24, 2017 Jul 24, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1621 decreased methylation of dopamine transporter promoter decreased dopamine Jul 24, 2017 Jul 24, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1613 chronic high fat diet decreased dopamine Jul 24, 2017 Jul 24, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1622 Sustained inflammatory cytokine release Increased, secretion of local growth factors Jul 26, 2017 Jul 26, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1633 Sustained inflammatory cytokine release Differentiation of fibroblasts Jul 26, 2017 Jul 26, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1654 Differentiation of fibroblasts Accumulation, Collagen Aug 16, 2017 Aug 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1626 Differentiation of fibroblasts Expression of Collagen Jul 26, 2017 Jul 26, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1627 EMT Expression of Collagen Jul 26, 2017 Jul 26, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1655 EMT Accumulation, Collagen Aug 16, 2017 Aug 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1725 EMT Lung fibrosis Mar 18, 2018 Mar 18, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2154 EMT Pulmonary fibrosis Jul 9, 2020 Jul 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1779 EMT Collagen Deposition Nov 20, 2018 Nov 20, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1840 EMT Fibroproliferative airway lesions Jan 30, 2019 Jan 30, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • α-diketone-induced bronchiolitis obliterans
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3306 EMT Increase, Cancer Jul 18, 2024 Jul 18, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Succinate dehydrogenase inactivation leads to cancer by promoting EMT
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3200 EMT Resistant gastric cancer Apr 23, 2024 Apr 23, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Increase in reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3204 EMT Airway remodeling May 1, 2024 May 1, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2614 EMT Metastasis, Breast Cancer Mar 22, 2022 Sep 26, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1630 Cell damage sensing Sustained inflammatory cytokine release Jul 26, 2017 Jul 26, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1632 Cell damage sensing Increased, secretion of local growth factors Jul 26, 2017 Jul 26, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1635 Increase, DSB MLL translocation Aug 2, 2017 Aug 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibitor binding to topoisomerase II leading to infant leukaemia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3096 Increase, DSB Increase, Apoptosis Nov 16, 2023 Nov 16, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Excessive reactive oxygen species production leading to mortality (4)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3099 Increase, DSB Increase, Casp transcription Nov 16, 2023 Nov 16, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • DNA methyltransferase inhibition leading to population decline (3)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1636 Thiol protein adducts Inhibition of lysyl oxidase Aug 3, 2017 Aug 3, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1637 Inhibition of lysyl oxidase Reduction of collagen crosslinking Aug 3, 2017 Aug 3, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1638 Reduction of collagen crosslinking Weak collagen matrix Aug 3, 2017 Aug 3, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1639 Weak collagen matrix Notochord malformation Aug 3, 2017 Aug 3, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1640 Notochord malformation Reduced, Swimming performance Aug 3, 2017 Aug 3, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1651 TGFbeta1 activation TGFbeta pathway activation Aug 16, 2017 Aug 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1653 TGFbeta pathway activation EMT Aug 16, 2017 Aug 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1652 TGFbeta pathway activation Differentiation of fibroblasts Aug 16, 2017 Aug 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1663 Increase, Uncoupling of photophosphorylation Decrease, ATP production Oct 10, 2017 Oct 10, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1664 Decrease, ATP production Decrease, Chlorophyll synthesis Oct 10, 2017 Oct 10, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2341 Decrease, ATP production Decrease, Leaf development Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2547 Decrease, ATP production Decrease, Reproduction Jan 21, 2022 Jan 21, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of ionizing energy leading to population decline via inhibition of photosynthesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1665 Decrease, Chlorophyll synthesis Decrease, Light harvest capacity Oct 10, 2017 Oct 10, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1666 Decrease, Light harvest capacity Decrease, Photosynthesis Oct 10, 2017 Oct 10, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1667 Decrease, Photosynthesis Decrease, Glycolysis Oct 10, 2017 Oct 10, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2334 Decrease, Photosynthesis Decrease, ATP production Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of ionizing energy leading to population decline via inhibition of photosynthesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2343 Decrease, Photosynthesis Decrease, ATP synthase activity Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1668 Decrease, Glycolysis Decrease, OXPHOS Oct 10, 2017 Oct 10, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1738 Decrease, Glycolysis Decrease, Mitochondrial ATP production May 24, 2018 May 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1669 Decrease, OXPHOS Decrease, Mitochondrial ATP production Oct 10, 2017 Oct 10, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Deposition of ionising energy leading to population decline via mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1810 Decrease, OXPHOS Decreased Na/K ATPase activity Dec 20, 2018 Dec 20, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndrome
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2095 Decrease, OXPHOS Decrease, ATP pool Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Excessive reactive oxygen species production leading to mortality (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2713 Decrease, OXPHOS Oxidative Stress Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2346 Decrease, OXPHOS Decrease, ATP synthase activity Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1671 Decrease, Leaf cell mitosis Decrease, Leaf development Oct 10, 2017 Oct 10, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1672 Decrease, Leaf development Increase, Growth hormone Oct 10, 2017 Oct 10, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2335 Decrease, Leaf development Decrease, Reproduction Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2283 Decrease, Leaf development Decrease, Growth Feb 16, 2021 Feb 16, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1673 Inhibition, mitochondrial DNA polymerase gamma (Pol gamma) Depletion, mtDNA Oct 25, 2017 Oct 25, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3133 Depletion, mtDNA Mitochondrial dysfunction Feb 28, 2024 Feb 28, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1677 Binding of substrate, endocytic receptor Disturbance, Lysosomal function Oct 25, 2017 Oct 25, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Receptor mediated endocytosis and lysosomal overload leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1683 Binding, SH/SeH proteins involved in protection against oxidative stress Mitochondrial dysfunction Nov 9, 2017 Nov 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1689 Binding, SH/SeH proteins involved in protection against oxidative stress Oxidative Stress Nov 9, 2017 Feb 7, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1765 Binding, SH/SeH proteins involved in protection against oxidative stress Protection against oxidative stress, decreased Sep 13, 2018 Feb 10, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1691 Glutamate dyshomeostasis Neuronal network function, Decreased Nov 9, 2017 Nov 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1686 Glutamate dyshomeostasis Cell injury/death Nov 9, 2017 Feb 6, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1692 Inhibition of fatty acid beta oxidation Increase, cytosolic fatty acid Nov 13, 2017 Nov 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1697 increased, oncotic necrosis steatohepatitis Nov 14, 2017 Nov 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1763 Tissue resident cell activation Increased pro-inflammatory mediators Aug 2, 2018 Aug 2, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Protein Alkylation leading to Liver Fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2834 Tissue resident cell activation Increase, Pro-Inflammatory Mediators Jan 25, 2023 Jul 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1719 Increased pro-inflammatory mediators Cell injury/death Feb 1, 2018 Feb 12, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1777 Increased pro-inflammatory mediators Leukocyte recruitment/activation Nov 12, 2018 Nov 12, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Endocytic lysosomal uptake leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1764 Increased pro-inflammatory mediators Activation, Stellate cells Aug 2, 2018 Aug 2, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Protein Alkylation leading to Liver Fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1908 Increased pro-inflammatory mediators Increase, Cell Proliferation (Epithelial Cells) May 10, 2019 May 10, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1903 Increased pro-inflammatory mediators Increase in RONS May 7, 2019 May 9, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1902 Increased pro-inflammatory mediators N/A, Breast Cancer May 7, 2019 May 10, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2777 Increased pro-inflammatory mediators Increase, Endothelial Dysfunction Sep 28, 2022 Aug 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of energy leads to abnormal vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1901 Leukocyte recruitment/activation Increase, Cell Proliferation (Epithelial Cells) May 7, 2019 May 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1778 Leukocyte recruitment/activation Activation, Stellate cells Nov 12, 2018 Nov 12, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Endocytic lysosomal uptake leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1905 Leukocyte recruitment/activation Increase in RONS May 7, 2019 May 9, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2891 Leukocyte recruitment/activation Increased extracellular matrix deposition Apr 13, 2023 Apr 13, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2960 Interaction with the lung cell membrane Atherosclerosis Jul 4, 2023 Feb 19, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Substance interaction with lung resident cell membrane components leading to atherosclerosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2958 Interaction with the lung cell membrane Increased transcription of genes encoding acute phase proteins Jul 4, 2023 Jan 20, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Substance interaction with lung resident cell membrane components leading to atherosclerosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2959 Interaction with the lung cell membrane Systemic acute phase response Jul 4, 2023 Jan 20, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Substance interaction with lung resident cell membrane components leading to atherosclerosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1702 Interaction with the lung cell membrane Increased proinflammatory mediators Jan 5, 2018 Feb 20, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Substance interaction with lung resident cell membrane components leading to atherosclerosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2662 Interaction with the lung cell membrane Increase, ROS May 25, 2022 May 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2663 Interaction with the lung cell membrane Increased, DNA damage and mutation May 25, 2022 May 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2651 Increased proinflammatory mediators Activation, Dendritic Cells Apr 28, 2022 Aug 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3052 Increased proinflammatory mediators Systemic acute phase response Sep 19, 2023 Jan 20, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Substance interaction with lung resident cell membrane components leading to atherosclerosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2061 Increased proinflammatory mediators Increased inflammatory immune responses Mar 10, 2020 Mar 10, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2053 Increased proinflammatory mediators Increased transcription of genes encoding acute phase proteins Mar 1, 2020 Jan 20, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Substance interaction with lung resident cell membrane components leading to atherosclerosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2301 Increased proinflammatory mediators Impaired gustatory nerve Mar 28, 2021 Mar 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2307 Increased proinflammatory mediators Accumulation, Collagen Mar 30, 2021 Mar 30, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Binding to ACE2 leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1703 Increased proinflammatory mediators Recruitment of inflammatory cells Jan 5, 2018 May 18, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Frustrated phagocytosis leads to malignant mesothelioma
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1704 Recruitment of inflammatory cells Loss of alveolar capillary membrane integrity Jan 5, 2018 May 18, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2658 Recruitment of inflammatory cells Increase, Cytotoxicity (epithelial cells) May 25, 2022 May 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2761 Recruitment of inflammatory cells Increased proinflammatory mediators Sep 1, 2022 Sep 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2543 Recruitment of inflammatory cells Gut dysbiosis Dec 15, 2021 Dec 15, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2492 Recruitment of inflammatory cells GI disorders Oct 19, 2021 Oct 19, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2491 Recruitment of inflammatory cells Disruption of the intestinal barrier Oct 19, 2021 Oct 19, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2903 Recruitment of inflammatory cells Increase in inflammation May 4, 2023 May 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2354 Recruitment of inflammatory cells Hyperinflammation Apr 20, 2021 Feb 8, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1964 Recruitment of inflammatory cells Increase, ROS Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Frustrated phagocytosis-induced lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Frustrated phagocytosis leads to malignant mesothelioma
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1705 Loss of alveolar capillary membrane integrity Activation of Th2 cells Jan 5, 2018 May 16, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2368 Loss of alveolar capillary membrane integrity Inhibition of LS function. Apr 27, 2021 Apr 27, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Lung surfactant function inhibition leading to decreased lung function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2369 Loss of alveolar capillary membrane integrity Reduced tidal volume Apr 27, 2021 Apr 27, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Lung surfactant function inhibition leading to decreased lung function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2372 Loss of alveolar capillary membrane integrity Decreased lung function Apr 27, 2021 Apr 27, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Lung surfactant function inhibition leading to decreased lung function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2174 Loss of alveolar capillary membrane integrity Blood extravasation into the lungs Oct 22, 2020 Oct 22, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2259 Loss of alveolar capillary membrane integrity Substance - LS interaction Jan 8, 2021 Jan 8, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2258 Loss of alveolar capillary membrane integrity Impaired lung function Jan 8, 2021 Jan 8, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1706 Activation of Th2 cells Increased cellular proliferation and differentiation Jan 5, 2018 May 18, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1707 Increased cellular proliferation and differentiation Increased extracellular matrix deposition Jan 5, 2018 Dec 7, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2652 Increased cellular proliferation and differentiation Accumulation, Collagen May 4, 2022 May 18, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1708 Increased extracellular matrix deposition Pulmonary fibrosis Jan 16, 2018 Dec 6, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2325 Increased extracellular matrix deposition N/A, Liver fibrosis Apr 10, 2021 Feb 1, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • AhR activation leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2699 Histone deacetylase inhibition Neural tube defects Jul 19, 2022 Jul 19, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Ceramide synthase inhibition leading to neural tube defects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2010 Histone deacetylase inhibition Spermatocyte depletion Dec 11, 2019 Jul 1, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Histone deacetylase inhibition leading to testicular atrophy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1802 Histone deacetylase inhibition Reduced neural crest cell migration Dec 20, 2018 Dec 20, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Histone deacetylase inhibition leads to impeded craniofacial development
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1805 Histone deacetylase inhibition Reduced collagen production Dec 20, 2018 Dec 20, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Histone deacetylase inhibition leads to impeded craniofacial development
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1709 Histone deacetylase inhibition Histone acetylation, increase Jan 21, 2018 Aug 5, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Histone deacetylase inhibition leading to testicular atrophy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Histone deacetylase inhibition leads to neural tube defects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1714 Histone deacetylase inhibition p21 (CDKN1A) expression, increase Jan 21, 2018 Jul 25, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1715 Histone deacetylase inhibition Cell cycle, disrupted Jan 21, 2018 Jul 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Histone deacetylase inhibition leading to testicular atrophy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1717 Histone deacetylase inhibition Testicular atrophy Jan 21, 2018 Jul 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Histone deacetylase inhibition leading to testicular atrophy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1716 Histone deacetylase inhibition Apoptosis Jan 21, 2018 Jul 1, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Histone deacetylase inhibition leading to testicular atrophy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1710 Histone acetylation, increase p21 (CDKN1A) expression, increase Jan 21, 2018 Jul 25, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1997 Histone acetylation, increase Cell cycle, disrupted Nov 11, 2019 Jul 1, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Histone deacetylase inhibition leading to testicular atrophy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1806 Histone acetylation, increase Altered, Gene Expression Dec 20, 2018 Dec 20, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Histone deacetylase inhibition leads to neural tube defects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1711 p21 (CDKN1A) expression, increase Cell cycle, disrupted Jan 21, 2018 Jul 25, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1712 Cell cycle, disrupted Apoptosis Jan 21, 2018 Jul 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Histone deacetylase inhibition leading to testicular atrophy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2791 Cell cycle, disrupted Altered, Meiotic chromosome dynamics Oct 25, 2022 Oct 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3363 Cell cycle, disrupted Decrease, Cell proliferation Oct 8, 2024 Oct 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and reduced cell proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1720 Activation of PPARγ Increase, Inflammation Mar 18, 2018 Mar 18, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3309 CYP2E1 Activation Oxidative Stress Jul 23, 2024 Jul 23, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • CYP2E1 activation and formation of protein adducts leading to neurodegeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1729 Protein Adduct Formation Unfolded Protein Response Apr 4, 2018 Apr 5, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • CYP2E1 activation and formation of protein adducts leading to neurodegeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1731 Lipid Peroxidation General Apoptosis Apr 4, 2018 Apr 5, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • CYP2E1 activation and formation of protein adducts leading to neurodegeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1728 Lipid Peroxidation Protein Adduct Formation Apr 4, 2018 Apr 5, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • CYP2E1 activation and formation of protein adducts leading to neurodegeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3377 Lipid Peroxidation Foam cell formation Oct 30, 2024 Oct 30, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1732 Unfolded Protein Response General Apoptosis Apr 4, 2018 Apr 5, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • CYP2E1 activation and formation of protein adducts leading to neurodegeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1866 Unfolded Protein Response Apoptosis Mar 6, 2019 Mar 6, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of N-linked glycosylation leads to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2712 Unfolded Protein Response Increase, Cell death Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3041 Unfolded Protein Response Caspase activation Sep 14, 2023 Sep 14, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2977 General Apoptosis Increase, Cancer Jul 31, 2023 Oct 19, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1733 General Apoptosis Neurodegeneration Apr 4, 2018 Apr 5, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • CYP2E1 activation and formation of protein adducts leading to neurodegeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1734 Spermatocyte depletion Testicular atrophy May 22, 2018 Jul 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Histone deacetylase inhibition leading to testicular atrophy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1736 Increase, D1 protein antagonism Decrease, PSII activity May 24, 2018 May 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1737 Decrease, PSII activity Decrease, Photosynthesis May 24, 2018 May 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2169 Decrease, Growth Decrease, Population growth rate Oct 8, 2020 Oct 8, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2804 Decrease, Growth Decreased, Reproductive Success Nov 16, 2022 Nov 16, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1742 Inhibition, CHS-1 Decrease, Cuticular chitin content May 24, 2018 Feb 17, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • S-adenosylmethionine depletion leading to population decline (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Chitin synthase 1 inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1743 Decrease, Cuticular chitin content Increase, Premature molting May 24, 2018 Feb 17, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • S-adenosylmethionine depletion leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • S-adenosylmethionine depletion leading to population decline (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Chitin synthase 1 inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Sulfonylureareceptor binding leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1744 Increase, Premature molting Increase, Mortality May 24, 2018 Feb 17, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • S-adenosylmethionine depletion leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • S-adenosylmethionine depletion leading to population decline (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Chitinase inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Chitobiase inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Chitin synthase 1 inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Sulfonylureareceptor binding leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1745 Increase, SUR binding Increase, Cell membrane depolarization May 24, 2018 May 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • S-adenosylmethionine depletion leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Sulfonylureareceptor binding leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1747 Increase, Opening of voltage-dependent calcium channel Decrease, Cuticular chitin content May 24, 2018 May 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • S-adenosylmethionine depletion leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Sulfonylureareceptor binding leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1746 Increase, Cell membrane depolarization Increase, Opening of voltage-dependent calcium channel May 24, 2018 May 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • S-adenosylmethionine depletion leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Sulfonylureareceptor binding leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2788 Increase, Cell membrane depolarization Cell injury/death Oct 19, 2022 Oct 19, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2708 Increase, Cell membrane depolarization Increased, Intracellular Calcium overload Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3039 Increase, Cell membrane depolarization Opening VGCCs Sep 14, 2023 Sep 14, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1749 Fatty Acid Beta Oxidation, Decreased Decreased, Ketogenesis (production of ketone bodies) Jun 11, 2018 Jun 11, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Antagonist binding to PPARα leading to body-weight loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1755 Blockade, L-Type Calcium Channels Decrease, Calcium currents Jun 19, 2018 Jun 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3406 Blockade, L-Type Calcium Channels Altered, Action Potential Nov 20, 2024 Nov 20, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibiton of L-Type Calcium Channels leading to heart failure via QT interval prolongation and Torsades de Pointes (TdP)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1756 Decrease, Calcium currents Decrease, Calcium binding to Troponin C Jun 19, 2018 Jun 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1760 Decrease, Calcium currents Disruption, Intracellular calcium mobilization Jun 21, 2018 Jun 21, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1757 Decrease, Calcium binding to Troponin C Decrease, Cardiac contractility Jun 19, 2018 Jun 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1758 Decrease, Cardiac contractility Decrease, Cardiac ejection fraction Jun 19, 2018 Jun 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3176 Decrease, Cardiac contractility Decrease LV function Apr 3, 2024 Apr 3, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Mitochondrial complexes inhibition leading to heart failure via decreased ATP production
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2824 Decrease, Cardiac contractility Heart failure Jan 5, 2023 Jan 5, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Decreased Na/K ATPase activity leading to heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Phosphodiesterase inhibition leading to heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1759 Decrease, Cardiac ejection fraction Heart failure Jun 19, 2018 Jun 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2825 Heart failure Increase, Mortality Jan 5, 2023 Jan 5, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2514 Heart failure Altered mechanotransduction properties of pericytes Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2508 Heart failure Upregulation of ACE2 Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1761 Disruption, Intracellular calcium mobilization Disruption, Sarcomere assembly Jun 21, 2018 Jun 21, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1762 Disruption, Sarcomere assembly Decrease, Cardiac contractility Jun 21, 2018 Jun 21, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1766 Protection against oxidative stress, decreased Oxidative Stress Sep 13, 2018 Feb 7, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1775 Endocytosis Disruption, Lysosome Nov 12, 2018 Nov 12, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Endocytic lysosomal uptake leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Endocytotic lysosomal uptake leads to intestinal barrier disruption
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1780 Mitochondrial Complex I inhibition Decrease in mitochondrial oxidative phosphorylation Dec 19, 2018 Mar 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3453 Mitochondrial Complex I inhibition Altered, Redox Homeostasis Dec 24, 2024 Dec 24, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • DBDPE-induced inhibition of mitochondrial complex Ⅰ leading to population decline via neurotoxicity and metabotoxicity.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1781 Increase, Mitochondrial complex III antagonism Decrease in mitochondrial oxidative phosphorylation Dec 19, 2018 Mar 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1872 Increase, Mitochondrial complex III antagonism Decrease, OXPHOS Mar 19, 2019 Mar 19, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2230 Increase, Mitochondrial complex III antagonism Decrease, ATP pool Dec 4, 2020 Dec 4, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Mitochondrial complex III antagonism leading to growth inhibition (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1782 Mitochondrial Complex IV inhibition Decrease in mitochondrial oxidative phosphorylation Dec 19, 2018 Mar 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1783 Mitochondrial Complex V inhibition Decrease in mitochondrial oxidative phosphorylation Dec 19, 2018 Mar 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1787 Decrease in mitochondrial oxidative phosphorylation Mitochondrial Injury Dec 19, 2018 Mar 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1956 Decrease in mitochondrial oxidative phosphorylation Mitochondrial dysfunction Jun 15, 2019 Jun 15, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1942 Mitochondrial Injury Impaired, Proteostasis Jun 7, 2019 Jun 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2715 Mitochondrial Injury Increase, Cell death Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3049 Mitochondrial Injury Increase, Cyt c release Sep 14, 2023 Sep 14, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1789 Necrotic Tissue Liver Injury Dec 19, 2018 Mar 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • IKK complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1798 Ionizing Energy Increase mutations Dec 19, 2018 Dec 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1799 Ionizing Energy Increase chromosomal aberrations Dec 19, 2018 Dec 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3240 Ionizing Energy Oxidative Stress May 31, 2024 May 31, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2392 Ionizing Energy Altered, Meiotic chromosome dynamics May 14, 2021 May 14, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2394 Ionizing Energy decreased, Fertility May 14, 2021 May 14, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2397 Ionizing Energy Increase, Oocyte apoptosis May 14, 2021 May 14, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2396 Ionizing Energy Decreased, Population size May 14, 2021 May 14, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2380 Ionizing Energy Increase, DNA Damage May 12, 2021 May 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2395 Ionizing Energy Decrease of egg production and cummulative fecundity May 14, 2021 May 14, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2379 Ionizing Energy Increase, ROS May 12, 2021 May 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2393 Ionizing Energy Decreased spermatogenesis May 14, 2021 May 14, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1793 DNA repair Increase mutations Dec 19, 2018 Dec 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1794 DNA repair Increase chromosomal aberrations Dec 19, 2018 Dec 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1795 Increase mutations Increase cell proliferation Dec 19, 2018 Dec 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1800 Increase mutations Increase, lung cancer Dec 19, 2018 Dec 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1900 Increase mutations Increase, Cell Proliferation (Epithelial Cells) May 7, 2019 May 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3237 Increase mutations Increase, Cancer May 28, 2024 May 28, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2729 Increase chromosomal aberrations Increase,miRNA levels Aug 14, 2022 Aug 27, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1796 Increase chromosomal aberrations Increase cell proliferation Dec 19, 2018 Dec 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1801 Increase chromosomal aberrations Increase, lung cancer Dec 19, 2018 Dec 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1797 Increase cell proliferation Increase, lung cancer Dec 19, 2018 Dec 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1803 Reduced neural crest cell migration Reduced collagen production Dec 20, 2018 Dec 20, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Histone deacetylase inhibition leads to impeded craniofacial development
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2563 Reduced neural crest cell migration Transposition of the great arteries Feb 8, 2022 Feb 15, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of RALDH2 causes reduced all-trans retinoic acid levels, leading to transposition of the great arteries
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1804 Reduced collagen production Smaller and morphologically distorted facial cartilage structures Dec 20, 2018 Dec 20, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Histone deacetylase inhibition leads to impeded craniofacial development
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2686 Smaller and morphologically distorted facial cartilage structures Increase, Early Life Stage Mortality Jun 30, 2022 Apr 13, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2603 Altered differentiation Microcephaly Mar 17, 2022 Mar 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1808 Altered differentiation Neural tube defects Dec 20, 2018 Dec 20, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Histone deacetylase inhibition leads to neural tube defects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1811 Decreased Na/K ATPase activity Decreased proximal tubular vectorial transport Dec 20, 2018 Dec 20, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndrome
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2787 Decreased Na/K ATPase activity Increase, Cell membrane depolarization Oct 19, 2022 Oct 19, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3444 Decreased Na/K ATPase activity Increased, intracellular sodium (Na+) Nov 26, 2024 Nov 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Decreased Na/K ATPase activity leading to heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3287 Decreased Na/K ATPase activity Decreased, sodium uptake in gills Jul 8, 2024 Dec 3, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Decreased Sodium/Potassium ATPase activity leads to Heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1812 Decreased proximal tubular vectorial transport Chemical induced Fanconi syndrome Dec 20, 2018 Dec 20, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndrome
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1817 Suppressed AP-1 Suppressed DC activation Dec 25, 2018 Dec 25, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1818 Suppressed NF-kB Suppressed DC activation Dec 25, 2018 Dec 25, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1819 Suppressed DC activation Impaired antigen presentation Dec 25, 2018 Dec 25, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1820 Impaired antigen presentation Impaired T cell activation Dec 25, 2018 Dec 25, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1822 Impaired T cell activation Impairment of TDAR Dec 25, 2018 Jun 1, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1821 Impaired T cell activation Suppression, Suppression of T-cell dependent antibody response (TDAR) Dec 25, 2018 Dec 25, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1922 Impaired T cell activation Impaired Ab production May 23, 2019 Jun 25, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1813 Blocking of IL-1R Impaired IL-1 signaling Dec 24, 2018 Jun 25, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1814 Decreased IL-1 production Impaired IL-1 signaling Dec 25, 2018 Jun 25, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1824 Decreased IL-1 production Suppressed MyD88 Jan 6, 2019 Jan 6, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1816 Impaired IL-1 signaling Suppressed NF-kB Dec 25, 2018 Dec 25, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1815 Impaired IL-1 signaling Suppressed AP-1 Dec 25, 2018 Dec 25, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1825 Impaired IL-1 signaling Suppressed MyD88 Jan 6, 2019 Mar 14, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1920 Impaired IL-1 signaling Inhibition, Nuclear factor kappa B (NF-kB) May 23, 2019 Jun 25, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1870 Suppressed MyD88 Inhibition, Nuclear factor kappa B (NF-kB) Mar 12, 2019 Mar 12, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1826 Suppressed MyD88 Impairment of TDAR Jan 6, 2019 Jan 6, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1827 Inhibition, IKK complex Inhibition, Nuclear factor kappa B (NF-kB) Jan 7, 2019 Mar 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • IKK complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1829 Activation, Caspase 8 pathway Cell injury/death Jan 7, 2019 Mar 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • IKK complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1832 Activation, Tissue resident cells (Kuppfer cells) Increase, proinflammatory mediators (TNFalpha) Jan 7, 2019 Jan 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • IKK complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1833 Binding of MSAs to microtubules Disturbance in microtubule dynamic instability Jan 29, 2019 Jan 29, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Microtubule interacting drugs lead to peripheral neuropathy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1834 Disturbance in microtubule dynamic instability Impaired axonial transport Jan 29, 2019 Jan 29, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Microtubule interacting drugs lead to peripheral neuropathy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1835 Impaired axonial transport Sensory axonal peripheral neuropathy Jan 29, 2019 Jan 29, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Microtubule interacting drugs lead to peripheral neuropathy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2506 Impaired axonial transport Dysfunctional synapses Oct 26, 2021 Oct 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2657 Sensory axonal peripheral neuropathy Increased Mortality May 16, 2022 May 16, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3066 Sensory axonal peripheral neuropathy Decreased, Neuronal network function in adult brain Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3067 Sensory axonal peripheral neuropathy Overactivation, NMDARs Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1836 Interaction of α-diketones with arginine residues Proteasomal dysfunction Jan 30, 2019 Jan 30, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • α-diketone-induced bronchiolitis obliterans
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1837 Proteasomal dysfunction Airway epithelial injury Jan 30, 2019 Jan 30, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • α-diketone-induced bronchiolitis obliterans
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3044 Proteasomal dysfunction Accumulation, misfolded proteins Sep 14, 2023 Sep 14, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1838 Airway epithelial injury Increase, Inflammation Jan 30, 2019 Jan 30, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • α-diketone-induced bronchiolitis obliterans
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1841 Fibroproliferative airway lesions Bronchiolitis obliterans Jan 30, 2019 Jan 30, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • α-diketone-induced bronchiolitis obliterans
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1842 Distribution of chemicals Absorption of photon energy Feb 4, 2019 Feb 4, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1844 Absorption of photon energy Radical generation Feb 4, 2019 Feb 4, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1848 Radical generation DNA photo-adducts Feb 4, 2019 Feb 4, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1849 Radical generation Protein photo-adducts Feb 4, 2019 Feb 4, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1850 Oxidation of membrane lipids Inflammatory events Feb 4, 2019 Jul 9, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Adverse outcome pathway on photochemical toxicity initiated by light exposure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1851 Oxidation/denatuation of membrane proteins Inflammatory events Feb 4, 2019 Jul 9, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Adverse outcome pathway on photochemical toxicity initiated by light exposure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1852 Oxidation of DNA Inflammatory events Feb 4, 2019 Feb 4, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1853 DNA photo-adducts Inflammatory events Feb 4, 2019 Feb 4, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1854 Protein photo-adducts Inflammatory events Feb 4, 2019 Feb 4, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1855 Inflammatory events Eczematous eruption Feb 4, 2019 Feb 4, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2916 Inflammatory events Increased, Invasion May 11, 2023 May 11, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Androgen receptor activation leading to prostate cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2917 Inflammatory events prostatic intraepithelial neoplasia May 11, 2023 May 11, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Androgen receptor activation leading to prostate cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1856 Eczematous eruption Scaling, Lichenification Feb 4, 2019 Feb 4, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1858 Activation, Muscarinic Acetylcholine Receptors Increased, glutamate Feb 13, 2019 Feb 13, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1889 Activation, Muscarinic Acetylcholine Receptors Occurrence, Focal Seizure Apr 22, 2019 Sep 3, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Acetylcholinesterase Inhibition Leading to Neurodegeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3402 Activation, Muscarinic Acetylcholine Receptors Increased, blood potassium concentration Nov 20, 2024 Nov 20, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Increased Muscarinic M2 Receptor leading to Arrhythmia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3431 Activation, Muscarinic Acetylcholine Receptors Altered, Action Potential Nov 22, 2024 Nov 22, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of acetylcholinesterase (AChE) leading to arrhythmias
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1864 Inhibition of N-linked glycosylation Accumulation, misfolded proteins Mar 6, 2019 Mar 6, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of N-linked glycosylation leads to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1865 Accumulation, misfolded proteins Unfolded Protein Response Mar 6, 2019 Mar 6, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of N-linked glycosylation leads to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3045 Accumulation, misfolded proteins Endoplasmic reticulum stress Sep 14, 2023 Sep 14, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3046 Accumulation, misfolded proteins Caspase activation Sep 14, 2023 Sep 14, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1868 Activation, hepatic stellate cells Liver Injury Mar 6, 2019 Mar 6, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of N-linked glycosylation leads to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1874 Increase, Necrosis Increase, Mortality Mar 19, 2019 Mar 19, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2465 Increase, Necrosis Increased, Kidney Failure Aug 11, 2021 Aug 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2177 Increase, Necrosis Increase, Tissue/organ damage Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2122 Increase, Necrosis Increase, Ovarian follicle breakdown May 8, 2020 May 8, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1878 Inhibition of Cyp17A1 activity Reduction, DHEA Apr 10, 2019 Apr 8, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1879 Inhibition of Cyp17A1 activity Reduction, androstenedione Apr 10, 2019 Apr 8, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3228 Reduction, DHEA Decrease, circulating testosterone levels May 24, 2024 Apr 8, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3229 Reduction, androstenedione Decrease, circulating testosterone levels May 24, 2024 Apr 8, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3172 Decrease, DHT level Impaired, urethral tube closure Mar 20, 2024 Dec 3, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Hypospadias, increased
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1881 Decrease, DHT level Reduction, Plasma 17beta-estradiol concentrations Apr 18, 2019 Apr 18, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of 5α-reductase leading to impaired fecundity in female fish
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1935 Decrease, DHT level Decrease, AR activation Jun 3, 2019 Apr 5, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • 5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • 5α-reductase inhibition leading to hypospadias in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • 5α-reductase inhibition leading to increased nipple retention (NR) in male (rodent) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1937 Decrease, AR activation Impaired inguinoscrotal phase Jun 3, 2019 Jun 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3348 Decrease, AR activation nipple retention, increased Sep 26, 2024 Sep 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • 5α-reductase inhibition leading to increased nipple retention (NR) in male (rodent) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3451 Decrease, AR activation Decreased, Testosterone binding to androgen receptor (hypothalamus) Dec 23, 2024 Dec 23, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2124 Decrease, AR activation Altered, Transcription of genes by the AR May 11, 2020 Apr 5, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Androgen receptor (AR) antagonism leading to decreased fertility in females
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • 5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Decreased testosterone synthesis leading to hypospadias in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • 5α-reductase inhibition leading to hypospadias in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • 5α-reductase inhibition leading to increased nipple retention (NR) in male (rodent) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2820 Decrease, AR activation AGD, decreased Dec 22, 2022 Aug 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • 5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2828 Decrease, AR activation Hypospadias Jan 11, 2023 Jan 11, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Androgen receptor (AR) antagonism leading to hypospadias in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Decreased testosterone synthesis leading to hypospadias in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • 5α-reductase inhibition leading to hypospadias in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1938 Impaired inguinoscrotal phase Malformation, cryptorchidism Jun 3, 2019 Dec 3, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Decreased Insulin-like peptide 3 (INSL3) leads to Malformation, cryptorchidism - maldescended testis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1880 Inhibition, 5α-reductase Decrease, DHT level Apr 18, 2019 Apr 5, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of 5α-reductase leading to impaired fecundity in female fish
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • 5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • 5α-reductase inhibition leading to hypospadias in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • 5α-reductase inhibition leading to increased nipple retention (NR) in male (rodent) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3452 Inhibition, 5α-reductase Decrease, circulating testosterone levels Dec 23, 2024 Dec 23, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3305 Increase, DNMT inhibition EMT Jul 18, 2024 Jul 18, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Succinate dehydrogenase inactivation leads to cancer by promoting EMT
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1883 Increase, DNMT inhibition Increase, DNA hypomethylation Apr 22, 2019 Apr 22, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2101 Increase, DNMT inhibition Decrease, Global DNA methylation Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • DNA methyltransferase inhibition leading to population decline (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • DNA methyltransferase inhibition leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • DNA methyltransferase inhibition leading to transgenerational effects (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • DNA methyltransferase inhibition leading to transgenerational effects (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3098 Increase, DNMT inhibition Increase, DSB Nov 16, 2023 Nov 16, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • DNA methyltransferase inhibition leading to population decline (3)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1887 Increase, DNA hypomethylation Decrease, Transgenerational DNA methylation Apr 22, 2019 Apr 22, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1884 Increase, DNA hypomethylation Increase, Gene expression Apr 22, 2019 Apr 22, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1885 Increase, Gene expression Decrease, Fecundity Apr 22, 2019 Apr 22, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1888 Decrease, Transgenerational DNA methylation Increase, Gene expression Apr 22, 2019 Apr 22, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1890 Occurrence, Focal Seizure Increased, glutamate Apr 22, 2019 Sep 3, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Acetylcholinesterase Inhibition Leading to Neurodegeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1998 Occurrence, Focal Seizure Overactivation, NMDARs Nov 13, 2019 Nov 13, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1891 tyrosinase Reduction of L-Dopaquinone May 3, 2019 May 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Inhibition of tyrosinase leads to decreased population in fish
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1892 Reduction of L-Dopaquinone Reduction in melanin level May 3, 2019 May 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Inhibition of tyrosinase leads to decreased population in fish
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1893 Reduction in melanin level Reduction of melanosome level May 3, 2019 May 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Inhibition of tyrosinase leads to decreased population in fish
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1894 Reduction of melanosome level Reduction fo Pigmentation pattern May 3, 2019 May 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Inhibition of tyrosinase leads to decreased population in fish
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1895 Reduction fo Pigmentation pattern Decrease, Population growth rate May 3, 2019 May 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Inhibition of tyrosinase leads to decreased population in fish
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1904 Increase in RONS Increase, DNA Damage May 7, 2019 May 8, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1906 Increase in RONS Tissue resident cell activation May 7, 2019 May 9, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3268 Increase in RONS Oxidative Stress Jul 4, 2024 Jul 4, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2798 Increase in RONS methemocyanin formation (decrease overall oxygen binding capacity) Nov 16, 2022 Nov 16, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2331 Increase in RONS D1 protein deactivation Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2337 Increase in RONS Decrease, MMP Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2199 Increase in inflammation hepatitis Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Immune mediated hepatitis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3177 Increase in inflammation Insulin resistance, increased Apr 9, 2024 Apr 9, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2646 Increase in inflammation Occurrence, renal proximal tubular necrosis Apr 8, 2022 Apr 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1909 Increase, Oxidative DNA damage Inadequate DNA repair May 19, 2019 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Oxidative DNA damage leading to chromosomal aberrations and mutations
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1914 Increase, Oxidative DNA damage Increase, Mutations May 19, 2019 Jan 9, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Oxidative DNA damage leading to chromosomal aberrations and mutations
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1913 Increase, Oxidative DNA damage Increase, DNA strand breaks May 19, 2019 Dec 17, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Oxidative DNA damage leading to chromosomal aberrations and mutations
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2591 Increase, Oxidative DNA damage Increase, Follicular atresia Mar 1, 2022 Mar 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of energy leading to population decline via DNA oxidation and follicular atresia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2592 Increase, Oxidative DNA damage Increase, Oocyte apoptosis Mar 1, 2022 Mar 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3362 Increase, Oxidative DNA damage Cell cycle, disrupted Oct 8, 2024 Oct 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and reduced cell proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3359 Increase, Oxidative DNA damage Cell injury/death Oct 8, 2024 Oct 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and cell death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3230 Increase, Oxidative DNA damage Increase, DSB May 27, 2024 May 27, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Excessive reactive oxygen species production leading to mortality (4)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3232 Increase, Oxidative DNA damage Increase, Apoptosis May 27, 2024 May 27, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3315 Increase, DNA strand breaks Altered Stress Response Signaling Jul 24, 2024 Aug 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Deposition of energy leads to abnormal vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3480 Increase, DNA strand breaks Cell cycle, disrupted Jan 20, 2025 Jan 20, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1931 Increase, DNA strand breaks Increase, Mutations Jun 2, 2019 Jan 9, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Oxidative DNA damage leading to chromosomal aberrations and mutations
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of energy leading to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1911 Increase, DNA strand breaks Inadequate DNA repair May 19, 2019 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Oxidative DNA damage leading to chromosomal aberrations and mutations
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of energy leading to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1939 Increase, DNA strand breaks Increase, Chromosomal aberrations Jun 3, 2019 Jan 9, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Oxidative DNA damage leading to chromosomal aberrations and mutations
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of energy leading to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2841 Increase, DNA strand breaks Abnormal Neural Remodeling Jan 25, 2023 Jul 29, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2589 Increase, DNA strand breaks Increase, Oocyte apoptosis Mar 1, 2022 Mar 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of energy leading to population decline via DNA strand breaks and oocyte apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2587 Increase, DNA strand breaks Increase, Follicular atresia Mar 1, 2022 Mar 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of energy leading to population decline via DNA strand breaks and follicular atresia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2074 Increase, DNA strand breaks Increase, Apoptosis Apr 6, 2020 Apr 6, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Alkylation of DNA leading to reduced sperm count
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2856 Increase, DNA strand breaks Altered Signaling Mar 10, 2023 Mar 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1979 Increase, Chromosomal aberrations Increase, Cell Proliferation Aug 29, 2019 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of energy leading to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1985 Increase, Chromosomal aberrations Increase, lung cancer Aug 29, 2019 Jan 10, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of energy leading to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1915 Retinaldehyde dehydrogenase retinoic acid May 22, 2019 May 22, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of retinaldehyde dehydrogenase leads to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1918 Altered, Photoreceptor patterning Altered, Visual function May 22, 2019 Jun 16, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of retinaldehyde dehydrogenase leads to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1916 retinoic acid plasma retionic acid May 22, 2019 May 22, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of retinaldehyde dehydrogenase leads to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1917 plasma retionic acid Altered, Photoreceptor patterning May 22, 2019 May 22, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of retinaldehyde dehydrogenase leads to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1919 Altered, Visual function Decline, Population May 22, 2019 May 22, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2375 Altered, Visual function Increased Mortality May 11, 2021 Jul 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to altered visual function via decreased eye size
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2143 Altered, Visual function Decrease, Population growth rate May 25, 2020 May 25, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of retinaldehyde dehydrogenase leads to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1923 Impaired Ab production Impairment of TDAR May 23, 2019 Jun 25, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1924 Wnt ligand stimulation Frizzled activation May 29, 2019 May 29, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1925 Frizzled activation GSK3beta inactivation May 29, 2019 May 29, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1926 GSK3beta inactivation β-catenin activation May 29, 2019 May 29, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2485 GSK3beta inactivation Repression of Gbx2 expression Oct 3, 2021 Dec 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • GSK3beta inactivation leading to increased mortality via defects in developing inner ear
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1927 β-catenin activation Snail, Zeb, Twist activation May 29, 2019 May 29, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1930 Increase, SAM depletion Increase, DNA hypomethylation May 30, 2019 May 30, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1944 Binding of inhibitor, mitochondrial complex III Increase, Mitochondrial complex III antagonism Jun 7, 2019 Jun 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1945 Binding of inhibitor, mitochondrial complex IV Mitochondrial Complex IV inhibition Jun 7, 2019 Jun 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1946 Binding of inhibitor, mitochondrial complex V Mitochondrial Complex V inhibition Jun 7, 2019 Jun 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1947 TR Antagnoism Hippocampal gene expression, Altered Jun 8, 2019 Jun 8, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1948 TR Antagnoism Cognitive function, decreased Jun 8, 2019 Jun 8, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3186 TR Antagnoism Reduced number of oligodendrocytes Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3193 TR Antagnoism Hypomyelination Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1949 CBS inhibition Homocysteine increases Jun 14, 2019 Jun 14, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of Cystathionine Beta synthase leading to impaired the early development of anterior-posterior axis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1951 Methionine synthase Homocysteine increases Jun 14, 2019 Jun 14, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1950 MTHFR inhibition Homocysteine increases Jun 14, 2019 Jun 14, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1952 betaine-homocysteine methyltransferase inhibition Homocysteine increases Jun 14, 2019 Jun 14, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1953 Homocysteine increases plasma homocysteine increases Jun 14, 2019 Jun 14, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1959 Homocysteine increases Plasma HCY level Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Inhibition of Cystathionine Beta synthase leading to impaired the early development of anterior-posterior axis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1954 plasma homocysteine increases brain Homocysteine level increases Jun 14, 2019 Jun 14, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1955 brain Homocysteine level increases Neuronal dysfunctions induction Jun 14, 2019 Jun 14, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1960 Plasma HCY level dysfunction of microcirculation Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of Cystathionine Beta synthase leading to impaired the early development of anterior-posterior axis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1961 dysfunction of microcirculation anterior-posterior axis development Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of Cystathionine Beta synthase leading to impaired the early development of anterior-posterior axis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2512 dysfunction of microcirculation Increased inflammatory immune responses Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2415 Frustrated phagocytosis Increased proinflammatory mediators Jul 6, 2021 Jul 6, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Frustrated phagocytosis leads to malignant mesothelioma
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2416 Frustrated phagocytosis Increase, ROS Jul 6, 2021 Jul 6, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Frustrated phagocytosis leads to malignant mesothelioma
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1962 Frustrated phagocytosis Release, Cytokine Jul 3, 2019 Aug 13, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Frustrated phagocytosis-induced lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1966 Increased, DNA damage and mutation Increase, Cell Proliferation Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Frustrated phagocytosis-induced lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2608 Increased, DNA damage and mutation Inadequate DNA repair Mar 22, 2022 Aug 27, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2728 Increased, DNA damage and mutation Increase chromosomal aberrations Aug 14, 2022 Aug 27, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2417 Increased, DNA damage and mutation Genomic instability Jul 6, 2021 Jul 6, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Frustrated phagocytosis leads to malignant mesothelioma
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1968 Substance - LS interaction Inhibition of LS function. Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1969 Inhibition of LS function. Alveolar collapse Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Lung surfactant function inhibition leading to decreased lung function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2370 Inhibition of LS function. Decreased lung function Apr 27, 2021 Apr 27, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Lung surfactant function inhibition leading to decreased lung function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2256 Inhibition of LS function. Reduced tidal volume Jan 8, 2021 Jan 8, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2255 Inhibition of LS function. Loss of alveolar capillary membrane integrity Jan 8, 2021 Jan 8, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2371 Alveolar collapse Decreased lung function Apr 27, 2021 Apr 27, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Lung surfactant function inhibition leading to decreased lung function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2284 Alveolar collapse Loss of alveolar capillary membrane integrity Feb 16, 2021 Feb 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Lung surfactant function inhibition leading to decreased lung function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2285 Alveolar collapse Impaired lung function Feb 16, 2021 Feb 16, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1970 Alveolar collapse Alveolar reopening Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1974 Alveolar collapse Reduced tidal volume Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Lung surfactant function inhibition leading to decreased lung function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1971 Alveolar reopening Loss of barrier function Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2173 Alveolar reopening Loss of alveolar capillary membrane integrity Oct 22, 2020 Oct 22, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1972 Loss of barrier function Blood extravasation into the lungs Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1973 Blood extravasation into the lungs Acute inhalation toxicity Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1975 Reduced tidal volume Impaired oxygenation of the blood Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2257 Reduced tidal volume Impaired lung function Jan 8, 2021 Jan 8, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2367 Reduced tidal volume Decreased lung function Apr 27, 2021 Apr 27, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Lung surfactant function inhibition leading to decreased lung function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1976 Impaired oxygenation of the blood Acute inhalation toxicity Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2562 Disruption, Progenitor cells of second heart field Reduced neural crest cell migration Feb 8, 2022 Feb 10, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of RALDH2 causes reduced all-trans retinoic acid levels, leading to transposition of the great arteries
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2552 Energy Deposition Increase, DNA Damage Jan 21, 2022 Jan 21, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of ionising energy leading to population decline via programmed cell death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of ionising energy leads to population decline via pollen abnormal
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2548 Energy Deposition Increase, ROS Jan 21, 2022 Jan 21, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of ionizing energy leading to population decline via inhibition of photosynthesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of ionising energy leading to population decline via mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to population decline via DNA oxidation and follicular atresia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2604 Energy Deposition Microcephaly Mar 17, 2022 Mar 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1977 Energy Deposition Increase, DNA strand breaks Aug 26, 2019 Jul 29, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to population decline via DNA strand breaks and follicular atresia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to population decline via DNA strand breaks and oocyte apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leads to abnormal vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1981 Energy Deposition Increase, Mutations Aug 29, 2019 Dec 17, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3484 Energy Deposition Increased, ROS Jan 28, 2025 Jan 28, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2847 Energy Deposition Altered Bone Cell Homeostasis Jan 25, 2023 Aug 9, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of energy leading to occurrence of bone loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2848 Energy Deposition Bone Remodeling Jan 25, 2023 Aug 9, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of energy leading to occurrence of bone loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2849 Energy Deposition Bone Loss Jan 25, 2023 Aug 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of energy leading to occurrence of bone loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2616 Energy Deposition Increase in RONS Mar 28, 2022 Mar 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2779 Energy Deposition Altered, Nitric Oxide Levels Sep 28, 2022 Aug 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of energy leads to abnormal vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2785 Energy Deposition Occurrence, Abnormal Vascular Remodeling Oct 17, 2022 Aug 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of energy leads to abnormal vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2780 Energy Deposition Increase, Endothelial Dysfunction Sep 28, 2022 Aug 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of energy leads to abnormal vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2769 Energy Deposition Oxidative Stress Sep 28, 2022 Aug 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of energy leads to abnormal vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of energy leading to occurrence of bone loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2770 Energy Deposition Vascular remodeling Sep 28, 2022 Sep 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2832 Energy Deposition Tissue resident cell activation Jan 25, 2023 Jul 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2837 Energy Deposition Abnormal Neural Remodeling Jan 25, 2023 Jul 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2838 Energy Deposition Impairment, Learning and memory Jan 25, 2023 Jul 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2809 Energy Deposition Modified Proteins Dec 16, 2022 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2813 Energy Deposition Increase, Oxidative DNA damage Dec 18, 2022 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2814 Energy Deposition Increase, Cell Proliferation Dec 18, 2022 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2815 Energy Deposition Cataracts Dec 18, 2022 Mar 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1982 Energy Deposition Increase, Chromosomal aberrations Aug 29, 2019 Dec 17, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of energy leading to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1983 Energy Deposition Increase, lung cancer Aug 29, 2019 Jul 5, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of energy leading to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3486 Decrease, circulating testosterone levels nipple retention, increased Jan 30, 2025 Jan 30, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3225 Decrease, circulating testosterone levels Decreased sperm quantity or quality in the adult, Decreased fertility May 24, 2024 May 24, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3227 Decrease, circulating testosterone levels Increased, Leutinizing hormone (LH) May 24, 2024 May 24, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3214 Decrease, circulating testosterone levels Reduction, the ratio of E2/11-KT in plasma May 8, 2024 May 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3213 Decrease, circulating testosterone levels Reduction, Plasma 17beta-estradiol concentrations May 8, 2024 May 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3205 Decrease, circulating testosterone levels Malformation, Male reproductive tract May 1, 2024 May 1, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • PPARα activation in utero leading to impaired fertility in males
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3206 Decrease, circulating testosterone levels Increase, Luteinizing hormone (LH) May 1, 2024 May 1, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • PPARα activation leading to impaired fertility in adult male rodents
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3202 Decrease, circulating testosterone levels malformed, Male reproductive tract Apr 25, 2024 Apr 25, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • HMG-CoA reductase inhibition leading to decreased fertility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3169 Decrease, circulating testosterone levels Epididymal agenesis Mar 20, 2024 Dec 3, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Impaired, Spermatogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3350 Decrease, circulating testosterone levels Hypospadias Oct 1, 2024 Oct 1, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Decreased testosterone synthesis leading to hypospadias in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3349 Decrease, circulating testosterone levels AGD, decreased Oct 1, 2024 Jan 31, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2126 Decrease, circulating testosterone levels Decrease, DHT level May 11, 2020 Oct 19, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2131 Decrease, circulating testosterone levels Decrease, AR activation May 11, 2020 Apr 5, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Decreased testosterone synthesis leading to hypospadias in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1986 Antagonism,LH receptor Reduction, Progesterone synthesis Oct 3, 2019 Oct 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Luteinizing hormone receptor antagonism leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1987 Reduction, Progesterone synthesis Decreased, Progesterone levels Oct 3, 2019 Oct 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Luteinizing hormone receptor antagonism leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1988 Decreased, Progesterone levels Reduction, progesterone uptake, decresed maturation Oct 3, 2019 Oct 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Luteinizing hormone receptor antagonism leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3521 Decreased, Progesterone levels Reduction, androstenedione Apr 8, 2025 Apr 8, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1989 Reduction, progesterone uptake, decresed maturation Impaired ovulation Oct 3, 2019 Oct 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Luteinizing hormone receptor antagonism leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1990 Impaired ovulation Decrease of egg production and cummulative fecundity Oct 3, 2019 Oct 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Luteinizing hormone receptor antagonism leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3470 Impaired ovulation Plasma estradiol/progesterone ratio, increase Jan 10, 2025 Jan 14, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Decreased, GnRH pulsatility/release leading to estradiol availability, increased via impaired ovulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1991 Decrease of egg production and cummulative fecundity Decline, Population trajectory Oct 3, 2019 Oct 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Luteinizing hormone receptor antagonism leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2389 Decrease of egg production and cummulative fecundity Decreased, Population size May 12, 2021 May 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1993 Increase, DNMT expression Increase, hypermethylation of the promotor region of GnRHR Oct 30, 2019 Oct 30, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1994 Increase, hypermethylation of the promotor region of GnRHR Decease, expression of GnRHR Oct 30, 2019 Oct 30, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1995 Decease, expression of GnRHR Reduction, 17beta-estradiol synthesis by ovarian granulosa cells Oct 30, 2019 Oct 30, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2002 Impaired IL-1R1 signaling Inhibition, Nuclear factor kappa B (NF-kB) Nov 17, 2019 Sep 29, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Impaired IL-1R1 signaling leading to Impaired T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2000 Impaired IL-1R1 signaling Suppression of T cell activation Nov 17, 2019 Nov 17, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2001 Suppression of T cell activation Inhibition, Nuclear factor kappa B (NF-kB) Nov 17, 2019 Nov 17, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2004 Suppression of T cell activation Impairment of TDAR Nov 17, 2019 Mar 2, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2927 Suppression of T cell activation Impaired IL-1R1 signaling May 24, 2023 May 24, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2928 Suppression of T cell activation Impairment, T-cell dependent antibody response May 24, 2023 May 25, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Impaired IL-1R1 signaling leading to Impaired T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2006 Cardiovascular dysregulation Respiratory distress/arrest Nov 25, 2019 Dec 19, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Acetylcholinesterase inhibition leading to acute mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2037 test N/A, Unknown Jan 26, 2020 Jan 26, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2034 test Unknown, MIE Jan 26, 2020 Jan 26, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2012 Impaired coordination and movement Increased Mortality Dec 20, 2019 Dec 20, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement​
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2015 Impaired coordination and movement Decrease, Population growth rate Dec 20, 2019 Dec 20, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement​
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2017 Stimulation of TLR7/8 Increase of IL-23 Dec 27, 2019 Dec 27, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Stimulation of TLR7/8 in dendric cells leading to Psoriatic skin disease
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2018 Increase of IL-23 Th17 cell migration and inflammation induction Dec 27, 2019 Dec 27, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Stimulation of TLR7/8 in dendric cells leading to Psoriatic skin disease
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2019 Th17 cell migration and inflammation induction Skin disease Dec 27, 2019 Dec 27, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Stimulation of TLR7/8 in dendric cells leading to Psoriatic skin disease
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2020 Binding to estrogen receptor (ER)-α Induction of GATA3 expression Dec 29, 2019 Aug 14, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2021 Induction of GATA3 expression Increase of Th2 cells producing IL-4 Dec 29, 2019 Aug 14, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2022 Increase of Th2 cells producing IL-4 Increase of autoantibody production Dec 29, 2019 Aug 14, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2023 Increase of autoantibody production Exacerbation of SLE Dec 29, 2019 Aug 14, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2024 Inhibition of JAK3 STAT5 inhibition Jan 5, 2020 Nov 3, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2025 STAT5 inhibition Suppression of STAT5 binding to cytokine gene promoters Jan 5, 2020 Nov 3, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2026 Suppression of STAT5 binding to cytokine gene promoters Suppression of IL-4 production Jan 5, 2020 Mar 30, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2027 Suppression of IL-4 production Impairment, TDAR Jan 5, 2020 Apr 4, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2028 Inhibition, trypsin Increased monitor peptide Jan 8, 2020 Jan 8, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Trypsin inhibition leading to pancreatic acinar cell tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2029 Increased monitor peptide Increased blood CCK level Jan 8, 2020 Jan 8, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Trypsin inhibition leading to pancreatic acinar cell tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2030 Increased blood CCK level Increased acinar cell exocrine secretion Jan 8, 2020 Jan 8, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Trypsin inhibition leading to pancreatic acinar cell tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2031 Increased acinar cell exocrine secretion Acinar cell proliferation Jan 8, 2020 Jan 8, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Trypsin inhibition leading to pancreatic acinar cell tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2032 Acinar cell proliferation Acinar cell tumors Jan 8, 2020 Jan 8, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Trypsin inhibition leading to pancreatic acinar cell tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2052 SARS-CoV-2 cell entry Increased proinflammatory mediators Mar 1, 2020 Mar 1, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2361 SARS-CoV-2 cell entry Sustentacular cells, decrease Apr 26, 2021 Apr 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2302 SARS-CoV-2 cell entry TLR Activation/Dysregulation Mar 29, 2021 Mar 29, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2314 SARS-CoV-2 cell entry Increased viral transcription and replication Apr 9, 2021 Apr 9, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2310 SARS-CoV-2 cell entry SARS-CoV-2 production Mar 30, 2021 Feb 7, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • SARS-CoV-2 infection leading to hyperinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2510 SARS-CoV-2 cell entry Endothelial cell dysfunction Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2496 SARS-CoV-2 cell entry IFN-I response, antagonized Oct 24, 2021 Dec 12, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding of SARS-CoV-2 to ACE2 in enterocytes leads to intestinal barrier disruption
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2522 Binding to ACE2 ADAM17 induction Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2452 Binding to ACE2 Endothelial cell dysfunction Aug 4, 2021 Aug 4, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2312 Binding to ACE2 Downregulation of ACE2 Mar 31, 2021 Nov 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Viral spike protein interaction with ACE2 leads to microvascular dysfunction, via ACE2 dysregulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2311 Binding to ACE2 ACE2 dysregulation Mar 31, 2021 Feb 7, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Viral spike protein interaction with ACE2 leads to microvascular dysfunction, via ACE2 dysregulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Binding of S-protein to ACE2 in enterocytes induces ACE2 dysregulation leading to gut dysbiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2294 Binding to ACE2 Induced, Angiotensin (Ang) II accumulation Mar 28, 2021 Mar 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2297 Binding to ACE2 Increased AngII Mar 28, 2021 Mar 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2286 Binding to ACE2 Neuroinflammation Feb 23, 2021 Feb 23, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on brain cells (neuronal and non-neuronal) leads to neuroinflammation resulting in encephalitis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2299 Binding to ACE2 ACE2 enzymatic inhibition Mar 28, 2021 Mar 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2056 Binding to ACE2 SARS-CoV-2 cell entry Mar 2, 2020 Oct 21, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • SARS-CoV-2 infection leading to hyperinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Binding of SARS-CoV-2 to ACE2 in enterocytes leads to intestinal barrier disruption
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2065 ACE2 enzymatic inhibition Increased AngII Mar 17, 2020 Mar 17, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Binding to ACE2 leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2321 ACE2 enzymatic inhibition Induced, Angiotensin (Ang) II accumulation Apr 10, 2021 Apr 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2434 ACE2 enzymatic inhibition Increase plasma Ang II Jul 13, 2021 Jul 13, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2322 Induced, Angiotensin (Ang) II accumulation Increased Ang II type 1 receptor (AT1R) Apr 10, 2021 Apr 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2295 Induced, Angiotensin (Ang) II accumulation Impaired gustatory nerve Mar 28, 2021 Mar 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2520 Induced, Angiotensin (Ang) II accumulation Hyperactivation of ACE/Ang-II/AT1R axis Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2435 Increase plasma Ang II Increased Ang II type 1 receptor (AT1R) Jul 13, 2021 Jul 13, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2138 Increase plasma Ang II Accumulation, Collagen May 15, 2020 May 15, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2067 Increase plasma Ang II Increase,collagen synthesis Mar 17, 2020 Mar 17, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2068 Increase,collagen synthesis Induction lung fibrosis Mar 17, 2020 Mar 17, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2064 Increase, the risk of acute respiratory failure Decreased mortality Mar 17, 2020 Mar 17, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2135 Increase, the risk of acute respiratory failure Increased Mortality May 13, 2020 May 13, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2062 Increased inflammatory immune responses Increase, the risk of acute respiratory failure Mar 10, 2020 Mar 10, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2513 Increased inflammatory immune responses Heart attack Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2593 Increased AngII Binding of agonist, Angiotensin II receptor type 1 receptor (AT1R) Mar 3, 2022 Mar 3, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Binding to ACE2 leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2066 Increased AngII Increase plasma Ang II Mar 17, 2020 Mar 17, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2298 Increased AngII Impaired gustatory nerve Mar 28, 2021 Mar 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2300 Increased AngII Increased proinflammatory mediators Mar 28, 2021 Mar 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2327 Increased AngII Increased Ang II type 1 receptor (AT1R) Apr 10, 2021 Apr 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2317 Increased AngII Sodium inhibition, Sweet enhancement Apr 10, 2021 Apr 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2069 Chronic ROS Porcupine-induced Wnt secretion and Wnt signaling activation Mar 23, 2020 May 13, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Increase in reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2070 Porcupine-induced Wnt secretion and Wnt signaling activation beta-catenin activation Mar 23, 2020 Nov 9, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Increase in reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3199 beta-catenin activation EMT Apr 23, 2024 Apr 23, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Increase in reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2076 Decreased, 11KT Impaired, Spermatogenesis Apr 16, 2020 Apr 19, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2165 Decreased, 11KT Decrease, Fertility Jul 21, 2020 Jul 21, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2166 Decreased, 11KT Decreased spermatogenesis Jul 21, 2020 Jul 21, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Inhibition of 11β-hydroxylase leading to decresed population trajectory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2164 Impaired, Spermatogenesis Decrease, Fertility Jul 13, 2020 Jul 13, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2274 Impaired, Spermatogenesis decreased, Fertility Jan 29, 2021 Aug 15, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2937 Impaired, Spermatogenesis Decreased, Viable Offspring Jun 2, 2023 Sep 29, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Essential element imbalance leads to reproductive failure via oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2692 Impaired, Spermatogenesis Viable offspring, decreased Jul 18, 2022 Jul 18, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2080 Inhibition, Fin regeneration Reduced, Swimming performance Apr 21, 2020 Jul 10, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2084 cell injury Increase, Regenerative cell proliferation (urothelial cells) Apr 21, 2020 Apr 21, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3097 Increase, Formation of DNA photoproducts Increase, DSB Nov 16, 2023 Nov 16, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3361 Increase, Protein oxidation Cell injury/death Oct 8, 2024 Oct 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2090 Increase, Protein oxidation Increase, Abnormal osmoregulation Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Excessive reactive oxygen species production leading to mortality (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2223 Increase, Protein oxidation Increase, Cell death Dec 4, 2020 Dec 4, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2181 Increase, Abnormal osmoregulation Increase, Tissue/organ damage Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2091 Increase, Abnormal osmoregulation Increase, Body fluid overload Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Excessive reactive oxygen species production leading to mortality (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3290 Increase, Abnormal osmoregulation Increased, Blood viscosity Jul 8, 2024 Dec 3, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2092 Increase, Body fluid overload Increase, Mortality Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Excessive reactive oxygen species production leading to mortality (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2094 Decrease, MMP Decrease, OXPHOS Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Deposition of ionising energy leading to population decline via mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Excessive reactive oxygen species production leading to mortality (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3163 Decrease, MMP Mitochondrial dysfunction Mar 14, 2024 Mar 14, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2347 Decrease, MMP Increase, Programmed cell death Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2179 Decrease, ATP pool Decrease, ATPase activity Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2204 Decrease, ATP pool Decrease, Cell proliferation Nov 12, 2020 Dec 7, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Mitochondrial ATP synthase antagonism leading to growth inhibition (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Mitochondrial complex III antagonism leading to growth inhibition (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2216 Decrease, ATP pool Increase, Fatty acid β-oxidation Dec 4, 2020 Dec 4, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2214 Decrease, ATP pool Increase, Cell death Dec 4, 2020 Dec 4, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Mitochondrial ATP synthase antagonism leading to growth inhibition (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2209 Decrease, ATP pool Decrease, Oogenesis Nov 25, 2020 Nov 25, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2768 Decrease, ATP pool Cell injury/death Sep 27, 2022 Sep 27, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2786 Decrease, ATP pool Decreased Na/K ATPase activity Oct 19, 2022 Oct 19, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2096 Decrease, ATP pool Increase, Mortality Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Excessive reactive oxygen species production leading to mortality (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Excessive reactive oxygen species production leading to mortality (3)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2121 Decrease, ATP pool Increase, Necrosis May 8, 2020 May 8, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2120 Decrease, ATP pool Increase, Oocyte apoptosis May 8, 2020 May 8, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2098 Decrease, TAG Decrease, ATP pool Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Excessive reactive oxygen species production leading to mortality (3)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2110 Decrease, Global DNA methylation Decrease, Heritable DNA methylation (F3) Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • DNA methyltransferase inhibition leading to transgenerational effects (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • DNA methyltransferase inhibition leading to transgenerational effects (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2102 Decrease, Global DNA methylation Increase, Casp transcription Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • DNA methyltransferase inhibition leading to population decline (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • DNA methyltransferase inhibition leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2105 Increase, Casp transcription Increase, Ovarian somatic cell apoptosis Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • DNA methyltransferase inhibition leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2103 Increase, Casp transcription Increase, Oocyte apoptosis Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • DNA methyltransferase inhibition leading to population decline (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • DNA methyltransferase inhibition leading to population decline (3)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2104 Increase, Oocyte apoptosis Decrease, Oogenesis Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • DNA methyltransferase inhibition leading to population decline (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • DNA methyltransferase inhibition leading to population decline (3)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of energy leading to population decline via DNA strand breaks and oocyte apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2386 Increase, Oocyte apoptosis decreased, Fertility May 12, 2021 May 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2400 Increase, Oocyte apoptosis Decrease of egg production and cummulative fecundity May 18, 2021 May 18, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2106 Increase, Ovarian somatic cell apoptosis Increase, Ovarian follicle breakdown Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • DNA methyltransferase inhibition leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2107 Increase, Ovarian follicle breakdown Decrease, Oogenesis Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • DNA methyltransferase inhibition leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2560 Increase, Ovarian follicle breakdown Decrease, Fecundity Feb 4, 2022 Feb 4, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2111 Decrease, Heritable DNA methylation (F3) Increase, Casp transcription (F3) Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • DNA methyltransferase inhibition leading to transgenerational effects (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • DNA methyltransferase inhibition leading to transgenerational effects (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2112 Increase, Casp transcription (F3) Increase, Oocyte apoptosis (F3) Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • DNA methyltransferase inhibition leading to transgenerational effects (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2116 Increase, Casp transcription (F3) Increase, Ovarian somatic cell apoptosis (F3) Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • DNA methyltransferase inhibition leading to transgenerational effects (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2113 Increase, Oocyte apoptosis (F3) Decrease, Oogenesis (F3) Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • DNA methyltransferase inhibition leading to transgenerational effects (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2115 Decrease, Fecundity (F3) Decrease, Population growth rate Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • DNA methyltransferase inhibition leading to transgenerational effects (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • DNA methyltransferase inhibition leading to transgenerational effects (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2114 Decrease, Oogenesis (F3) Decrease, Fecundity (F3) Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • DNA methyltransferase inhibition leading to transgenerational effects (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • DNA methyltransferase inhibition leading to transgenerational effects (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2117 Increase, Ovarian somatic cell apoptosis (F3) Increase, Ovarian follicle breakdown (F3) Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • DNA methyltransferase inhibition leading to transgenerational effects (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2118 Increase, Ovarian follicle breakdown (F3) Decrease, Oogenesis (F3) Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • DNA methyltransferase inhibition leading to transgenerational effects (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2119 Increase, Mitochondrial ATP synthase antagonism Decrease, OXPHOS May 8, 2020 May 8, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2229 Increase, Mitochondrial ATP synthase antagonism Decrease, ATP pool Dec 4, 2020 Dec 4, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Mitochondrial ATP synthase antagonism leading to growth inhibition (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Mitochondrial ATP synthase antagonism leading to growth inhibition (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2137 Downregulation of ACE2 Increased AngII May 15, 2020 May 15, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2136 Downregulation of ACE2 Increase plasma Ang II May 15, 2020 May 15, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2517 Downregulation of ACE2 Ang (1-7) levels reduced Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2141 Status epilepticus Overactivation, NMDARs May 21, 2020 May 21, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2783 Status epilepticus Increased, Intracellular Calcium overload Oct 12, 2022 Jul 24, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Acetylcholinesterase Inhibition Leading to Neurodegeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2782 Status epilepticus Increased, glutamate Oct 12, 2022 Sep 3, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Acetylcholinesterase Inhibition Leading to Neurodegeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2145 Reduction, E2 Synthesis by the undifferentiated gonad Increased, Differentiation to Testis Jun 15, 2020 Jul 11, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2146 Increased, Differentiation to Testis Increased, Male Biased Sex Ratio Jun 15, 2020 Jan 3, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Androgen receptor agonism leading to male-biased sex ratio
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2147 Increased, Male Biased Sex Ratio Decrease, Population growth rate Jun 15, 2020 Jan 3, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Androgen receptor agonism leading to male-biased sex ratio
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2148 TLR4 activation Activation, JNK Jul 9, 2020 Jul 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2155 TLR4 activation Activation, TGF-beta pathway Jul 9, 2020 Jul 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2251 TLR4 activation AP-1 activation Dec 23, 2020 Dec 23, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2157 AP-1 activation TGFbeta expression Jul 9, 2020 Jul 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2151 Pin-1 activation TGFbeta expression Jul 9, 2020 Jul 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2152 TGFbeta expression Activation, TGF-beta pathway Jul 9, 2020 Jul 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2158 11β-hydroxylase inhibition Decreased, 11KT Jul 13, 2020 Jul 13, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2275 11β-hydroxylase inhibition Cortisol and 11β-(OH) testosterone decreased Feb 9, 2021 Feb 9, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of 11β-hydroxylase leading to decresed population trajectory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2161 Decreased spermatogenesis decreased, Fertility Jul 13, 2020 Jul 13, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of 11β-hydroxylase leading to decresed population trajectory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2388 Decreased spermatogenesis Decrease of egg production and cummulative fecundity May 12, 2021 May 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2620 Decreased spermatogenesis Decrease, Fecundity Mar 28, 2022 Mar 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2623 Decreased spermatogenesis Decrease, Reproduction Mar 28, 2022 Mar 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2624 Decreased spermatogenesis Decrease, Population growth rate Mar 28, 2022 Mar 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2162 Inhibition of 11β-HSD Decreased, 11KT Jul 13, 2020 Jul 13, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3142 Reduced granulosa cell proliferation disrupted, ovarian cycle Mar 7, 2024 Mar 18, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Androgen receptor (AR) antagonism leading to decreased fertility in females
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2170 Inhibition, Chitinase Decrease, Digestion of old cuticle Oct 21, 2020 Oct 21, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Chitinase inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2172 Inhibition, Chitobiase Decrease, Digestion of old cuticle Oct 21, 2020 Oct 21, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Chitobiase inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2176 Decrease, ATP synthase activity Decrease, ATP pool Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2344 Decrease, ATP synthase activity Decrease, Leaf development Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2178 Increase, Tissue/organ damage Decrease, Growth Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2180 Decrease, ATPase activity Increase, Abnormal osmoregulation Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2183 Increase, Complex III dysfunction Increase, Cyt c release Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2184 Increase, Cyt c release Increase, Apoptosis Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3050 Increase, Cyt c release Caspase activation Sep 14, 2023 Sep 14, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2194 Reactive Metabolite Immune cell activation Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Immune mediated hepatitis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2192 Reactive Metabolite Mitochondrial dysfunction EMPTY Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3151 Reactive Metabolite Mitochondrial dysfunction Mar 13, 2024 Mar 13, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Immune mediated hepatitis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2200 ER stress Apoptotic cell death Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Immune mediated hepatitis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2643 ER stress Increase, Apoptosis Apr 8, 2022 Apr 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2499 Mitochondrial dysfunction EMPTY Oxidative Stress Oct 26, 2021 Oct 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3043 Mitochondrial dysfunction EMPTY Proteasomal dysfunction Sep 14, 2023 Sep 14, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2932 Mitochondrial dysfunction EMPTY Impaired insulin signaling May 25, 2023 May 25, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2195 Mitochondrial dysfunction EMPTY ER stress Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2193 Mitochondrial dysfunction EMPTY Apoptotic cell death Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2198 Apoptotic cell death Increase in inflammation Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Immune mediated hepatitis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2196 Immune cell activation IFNγ signaling Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Immune mediated hepatitis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2197 IFNγ signaling Increase in inflammation Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Immune mediated hepatitis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2205 Decrease, Cell proliferation Decrease, Growth Nov 12, 2020 Jul 6, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Mitochondrial ATP synthase antagonism leading to growth inhibition (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Mitochondrial complex III antagonism leading to growth inhibition (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and reduced cell proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2405 Decrease, Cell proliferation Decreased, Eye size May 28, 2021 Aug 7, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2724 Decrease, Cell proliferation Decrease, facial prominence outgrowth Jul 28, 2022 Apr 2, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Decrease, GLI1/2 target gene expression leads to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2208 Decrease, FAO Decrease, ATP pool Nov 25, 2020 Nov 25, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2215 Increase, Cell death Decrease, Growth Dec 4, 2020 Dec 4, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Mitochondrial ATP synthase antagonism leading to growth inhibition (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2718 Increase, Cell death Neuroinflammation Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2706 Increase, Cell death Parkinsonian motor deficits Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2760 Increase, Cell death Increased proinflammatory mediators Sep 1, 2022 Sep 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3504 Increase, Cell death Increased, nasal lesions Mar 5, 2025 Mar 19, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Cytochrome oxidase inhibition leading to increased nasal lesions
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3507 Increase, Cell death Increased, pulmonary edema Mar 12, 2025 Mar 24, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition, cytochrome oxidase leads to Increased, pulmonary edema
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3508 Increase, Cell death Loss of olfactory function Mar 13, 2025 Mar 25, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition, cytochrome oxidase leads to Loss of olfactory function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2467 Increase, Cell death Altered, inner ear development Aug 23, 2021 Aug 29, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • GSK3beta inactivation leading to increased mortality via defects in developing inner ear
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2489 Increase, Cell death Disruption of the intestinal barrier Oct 19, 2021 Oct 19, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2863 Increase, Cell death Hippocampal Physiology, Altered Apr 3, 2023 Apr 3, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2842 Increase, Cell death Altered Bone Cell Homeostasis Jan 25, 2023 Nov 6, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Deposition of energy leading to occurrence of bone loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2226 Increase, Global methylation Increase, Apoptosis Dec 4, 2020 Dec 4, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2242 Increased, Thyroxine (T4) in serum Altered, TH-dependent gene expression Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2241 Increased, Thyroxine (T4) in serum Altered, Amphibian metamorphosis Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2244 Altered, TH-dependent gene expression Altered, Amphibian metamorphosis Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Type III iodotyrosine deiodinase (DIO3) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2249 Displacement, Serum thyroxine (T4) from carrier protein Increased, Free serum thyroxine (T4) Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2250 Binding, Thyroid binding globulin in serum Displacement, Serum thyroxine (T4) from carrier protein Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2267 Decrease, ACAD Decreased, Mitochondrial Fatty Acid Beta Oxidation Jan 15, 2021 Jan 15, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Glucocorticoid Receptor activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2277 Cortisol and 11β-(OH) testosterone decreased Decreased, 11KT Feb 9, 2021 Feb 9, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of 11β-hydroxylase leading to decresed population trajectory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2276 Cortisol and 11β-(OH) testosterone decreased Decreased plasma Cortisol level Feb 9, 2021 Feb 9, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of 11β-hydroxylase leading to decresed population trajectory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2278 Decreased plasma Cortisol level decreased oocyte maturation Feb 9, 2021 Feb 9, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of 11β-hydroxylase leading to decresed population trajectory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2293 decreased oocyte maturation decreased, Fertility Mar 26, 2021 Mar 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of 11β-hydroxylase leading to decresed population trajectory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3503 Inhibition, cytochrome oxidase Increase, Cell death Mar 5, 2025 Mar 18, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Cytochrome oxidase inhibition leading to increased nasal lesions
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition, cytochrome oxidase leads to Increased, pulmonary edema
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition, cytochrome oxidase leads to Loss of olfactory function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2429 TLR9 activation MyD88 activation Jul 8, 2021 Jul 8, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2433 TLR9 activation inflammasome activity, increased Jul 8, 2021 Jul 8, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2290 Coagulation Thrombosis and DIC Mar 25, 2021 Jun 23, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2360 Coagulation Diminished Protective Response to ROS Apr 20, 2021 Jun 21, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2313 Coagulation Oxidative Stress Apr 8, 2021 Apr 8, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2351 SARS-CoV-2 production TLR Activation/Dysregulation Apr 16, 2021 Apr 16, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2291 SARS-CoV-2 production Oxidative Stress Mar 25, 2021 Mar 25, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2358 SARS-CoV-2 production Diminished Protective Response to ROS Apr 20, 2021 Sep 26, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • SARS-CoV-2 infection leading to hyperinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2488 SARS-CoV-2 production Increase, Cell death Oct 19, 2021 Oct 19, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2546 SARS-CoV-2 production Disruption of the intestinal barrier Jan 5, 2022 Jun 14, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding of SARS-CoV-2 to ACE2 in enterocytes leads to intestinal barrier disruption
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2545 SARS-CoV-2 production Sustentacular cells, decrease Jan 5, 2022 Jan 5, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2498 SARS-CoV-2 production Viral infection, proliferated Oct 24, 2021 Jun 29, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2303 TLR Activation/Dysregulation Increased proinflammatory mediators Mar 29, 2021 Feb 7, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2296 Impaired gustatory nerve taste impairment Mar 28, 2021 Mar 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2319 Binding of agonist, Angiotensin II receptor type 1 receptor (AT1R) Increase, ROS Apr 10, 2021 Apr 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding to ACE2 leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2323 Increased Ang II type 1 receptor (AT1R) Increase, ROS Apr 10, 2021 Apr 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2326 Hyperactivation of ACE/Ang-II/AT1R axis Increased AngII Apr 10, 2021 Apr 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2521 Hyperactivation of ACE/Ang-II/AT1R axis Heart failure Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2493 ACE2 dysregulation Recruitment of inflammatory cells Oct 19, 2021 Oct 19, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2532 ACE2 dysregulation Gut dysbiosis Dec 2, 2021 Dec 2, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Binding of S-protein to ACE2 in enterocytes induces ACE2 dysregulation leading to gut dysbiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2831 ACE2 dysregulation (Micro)vascular dysfunction Jan 23, 2023 Feb 28, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Viral spike protein interaction with ACE2 leads to microvascular dysfunction, via ACE2 dysregulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2329 Increased Sodium-sensitive hypertension Chronic kidney disease Apr 10, 2021 Apr 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2318 Sodium inhibition, Sweet enhancement Impaired gustatory nerve Apr 10, 2021 Apr 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2458 Platelet-neutrophil interactions, Increased Thromboinflammation, Increased Aug 4, 2021 Aug 4, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Endothelial cell dysfunction leading to thromboinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2315 Increased viral transcription and replication Increased proinflammatory mediators Apr 9, 2021 Apr 9, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2316 Increased viral transcription and replication TLR Activation/Dysregulation Apr 9, 2021 Apr 9, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2330 Excitation of intracellular water Increase in RONS Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2332 D1 protein deactivation Decrease, Photosystem II efficiency Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2333 Decrease, Photosystem II efficiency Decrease, Photosynthesis Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of ionizing energy leading to population decline via inhibition of photosynthesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2336 Decrease, Reproduction Decrease, Population growth rate Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of ionizing energy leading to population decline via inhibition of photosynthesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of ionising energy leading to population decline via mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of ionising energy leading to population decline via programmed cell death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2556 Decrease, Reproduction Decreased, Population trajectory Jan 21, 2022 Jan 21, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of ionising energy leads to population decline via pollen abnormal
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2553 Increase, Programmed cell death Decrease, Reproduction Jan 21, 2022 Jan 21, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of ionising energy leading to population decline via programmed cell death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2339 Increase, Programmed cell death Decrease, Leaf development Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2340 Increase, OEC damage Decrease, Photosystem II efficiency Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2352 Hypofibrinolysis Bradykinin, activated Apr 20, 2021 Apr 20, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2356 Hypofibrinolysis Increased proinflammatory mediators Apr 20, 2021 Feb 7, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2355 Bradykinin, activated Hypofibrinolysis Apr 20, 2021 Jan 24, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2357 Bradykinin, activated Hyperinflammation Apr 20, 2021 Oct 19, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2353 Bradykinin, activated Increased proinflammatory mediators Apr 20, 2021 Jan 14, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2762 Hyperinflammation Increase, the risk of acute respiratory failure Sep 1, 2022 Sep 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2413 Diminished Protective Response to ROS inflammasome activity, increased Jun 25, 2021 Jun 25, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • SARS-CoV-2 infection leading to hyperinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2359 Diminished Protective Response to ROS Coagulation Apr 20, 2021 Jan 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2365 Sustentacular cells, decrease anosmia Apr 26, 2021 Apr 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2362 Sustentacular cells, decrease olfacotry neurons, decrease Apr 26, 2021 Apr 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2366 olfacotry neurons, decrease anosmia Apr 26, 2021 Apr 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2363 olfacotry neurons, decrease Olfactory epithelium degeneration Apr 26, 2021 Apr 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2364 Olfactory epithelium degeneration anosmia Apr 26, 2021 Apr 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2374 Altered, retinal layer structure Altered, Visual function May 11, 2021 Jul 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2377 Decreased, Eye size Altered, Visual function May 11, 2021 Jan 7, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to altered visual function via decreased eye size
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2406 Decreased, Eye size Increased Mortality May 28, 2021 May 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2399 Bulky DNA adducts, increase Increase, Mutations May 17, 2021 Sep 14, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Bulky DNA adducts leading to mutations
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2398 Bulky DNA adducts, increase Inadequate DNA repair May 17, 2021 May 17, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Bulky DNA adducts leading to mutations
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2401 Decreased, ALDH1A activity Decreased, atRA concentration May 24, 2021 Dec 18, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Decreased ALDH1A (RALDH) activity leading to decreased fertility via disrupted meiotic initiation of fetal oogonia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of RALDH2 causes reduced all-trans retinoic acid levels, leading to transposition of the great arteries
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2561 Decreased, atRA concentration Disruption, Progenitor cells of second heart field Feb 8, 2022 Feb 15, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of RALDH2 causes reduced all-trans retinoic acid levels, leading to transposition of the great arteries
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2477 Decreased, atRA concentration Disrupted, meiotic initiation in oocyte Sep 10, 2021 Dec 18, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Decreased ALDH1A (RALDH) activity leading to decreased fertility via disrupted meiotic initiation of fetal oogonia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2481 Disrupted, meiotic initiation in oocyte Decreased, ovarian reserve Sep 13, 2021 Dec 18, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Decreased ALDH1A (RALDH) activity leading to decreased fertility via disrupted meiotic initiation of fetal oogonia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2487 Decreased, ovarian reserve decreased, Fertility Oct 10, 2021 Oct 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2480 Decreased, ovarian reserve Decreased fertility, Reduced number of oocytes ovulated Sep 12, 2021 Sep 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2525 Decreased, ovarian reserve disrupted, ovarian cycle Oct 29, 2021 Dec 18, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Decreased ALDH1A (RALDH) activity leading to decreased fertility via disrupted meiotic initiation of fetal oogonia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3483 Decreased, ovarian reserve POI Jan 22, 2025 Apr 10, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2402 Inhibition of Fyna Inhibition of Plxna2 May 28, 2021 Dec 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2403 Inhibition of Plxna2 Overexpression of rasl11b May 28, 2021 Dec 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2404 Overexpression of rasl11b Decrease, Cell proliferation May 28, 2021 Dec 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2527 increased atRA concentration premature meiosis, male germ cells Nov 10, 2021 Nov 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Increased (ectopic) concentration of all-trans retinoic acid (ATRA) if fetal testis leading to reduced sperm count, males
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2408 abnormal, placental labyrinth vasculature morphology increase, placental insufficiency May 31, 2021 May 31, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • AhR activation leading to preeclampsia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2409 increase, placental insufficiency increase, Preeclampsia May 31, 2021 May 31, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • AhR activation leading to preeclampsia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2414 inflammasome activity, increased Hyperinflammation Jun 25, 2021 Jun 25, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • SARS-CoV-2 infection leading to hyperinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2418 Genomic instability Increase, Cell Proliferation Jul 6, 2021 Jul 6, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Frustrated phagocytosis leads to malignant mesothelioma
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2973 Genomic instability endometrioid adenocarcinoma Type I Jul 27, 2023 Mar 27, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2430 MyD88 activation Increased activation, Nuclear factor kappa B (NF-kB) Jul 8, 2021 Jul 8, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2497 IFN-I response, antagonized SARS-CoV-2 production Oct 24, 2021 Dec 14, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Binding of SARS-CoV-2 to ACE2 in enterocytes leads to intestinal barrier disruption
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2436 Repression of Gbx2 expression foxi1 expression, increased Jul 14, 2021 Aug 13, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • GSK3beta inactivation leading to increased mortality via defects in developing inner ear
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2437 foxi1 expression, increased six1b expression, increased Jul 14, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • GSK3beta inactivation leading to increased mortality via defects in developing inner ear
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2438 six1b expression, increased eya1 expression, inhibited Jul 14, 2021 Aug 13, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • GSK3beta inactivation leading to increased mortality via defects in developing inner ear
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2439 eya1 expression, inhibited Increase, Cell death Jul 14, 2021 Aug 22, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • GSK3beta inactivation leading to increased mortality via defects in developing inner ear
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2440 CFTR Function, Decreased ASL Height, Decreased Jul 19, 2021 Sep 7, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2441 ASL Height, Decreased CBF, Decreased Jul 19, 2021 Sep 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2444 ASL Height, Decreased Mucus Viscosity, Increased Jul 19, 2021 Aug 2, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2442 CBF, Decreased MCC, Decreased Jul 19, 2021 Mar 24, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Oxidative stress Leading to Decreased Lung Function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2443 MCC, Decreased Decreased lung function Jul 19, 2021 Mar 24, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Oxidative stress Leading to Decreased Lung Function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2446 Mucus Viscosity, Increased MCC, Decreased Jul 19, 2021 Aug 2, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2445 Mucus Viscosity, Increased CBF, Decreased Jul 19, 2021 Aug 2, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2447 FOXJ1 Protein, Decreased Motile Cilia Number/Length, Decreased Jul 23, 2021 Aug 2, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2448 Motile Cilia Number/Length, Decreased CBF, Decreased Jul 23, 2021 Sep 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2453 Endothelial cell dysfunction Release, Cytokine Aug 4, 2021 Aug 4, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Endothelial cell dysfunction leading to thromboinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2511 Endothelial cell dysfunction dysfunction of microcirculation Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2456 Platelet activation, Increased Platelet-neutrophil interactions, Increased Aug 4, 2021 Aug 4, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Endothelial cell dysfunction leading to thromboinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2457 Neutrophil activation, Increased Platelet-neutrophil interactions, Increased Aug 4, 2021 Aug 4, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Endothelial cell dysfunction leading to thromboinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3271 Altered expression of NRF2 pathway-dependent genes Oxidative Stress Jul 4, 2024 Jul 4, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2641 Altered expression of NRF2 pathway-dependent genes ER stress Apr 8, 2022 Apr 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2855 Increased,Cardiac dysfunction Increased Mortality Jan 29, 2023 Jan 29, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3413 Increased,Cardiac fibrosis Heart failure Nov 21, 2024 Nov 21, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Increased LMNA gene mutation leading to heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3401 Increased,Cardiac fibrosis Increased incidence of cardiovascular morbidity and mortality Nov 20, 2024 Nov 20, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3297 increased,Vascular endothelial dysfunction Increase, Vascular disrupting effects Jul 9, 2024 Jul 9, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Adverse outcome pathway of PFAS-induced vascular disrupting effects via activating oxidative stress related pathways
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2982 increased,Vascular endothelial dysfunction Angiogenesis disfunction Aug 19, 2023 Aug 19, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3019 increased,Vascular endothelial dysfunction Impaired Platelet Aggregation Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3027 increased,Vascular endothelial dysfunction Vascular barrier disruption Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3031 increased,Vascular endothelial dysfunction Angiogenesis dysfunction Aug 28, 2023 Aug 28, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Demethylation of PPAR promotor leading to vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Nrf2 inhibition leading to vascular disrupting effects through activating HIF1α, Semaphorin 6A, and Dll4-Notch pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2468 Altered, inner ear development Reduced, Hearing Aug 23, 2021 Aug 23, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • GSK3beta inactivation leading to increased mortality via defects in developing inner ear
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2490 Disruption of the intestinal barrier Recruitment of inflammatory cells Oct 19, 2021 Oct 19, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2494 Disruption of the intestinal barrier GI disorders Oct 19, 2021 Oct 19, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2495 Disruption of the intestinal barrier Hyperinflammation Oct 19, 2021 Feb 8, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3335 Disruption of the intestinal barrier Celiac disease Aug 13, 2024 Feb 27, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Gluten-driven immune activation leading to celiac disease in genetically predisposed individuals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2518 Ang (1-7) levels reduced Degradation of Ang-II reduced Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2519 Degradation of Ang-II reduced Induced, Angiotensin (Ang) II accumulation Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2523 ADAM17 induction ACE2 increased shedding Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2524 ACE2 increased shedding Ang (1-7) levels reduced Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2526 Increased, ROS Porcupine-induced Wnt secretion and Wnt signaling activation Oct 31, 2021 Apr 27, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3500 Increased, ROS Increase, CNS Neural cell death Mar 2, 2025 Mar 2, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Decreased DNA methylation of FAM50B/PTCHD3 leading to IQ loss of children via PI3K-Akt pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3481 Increased, ROS Decrease, Coupling of OXPHOS Jan 20, 2025 Jan 20, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3479 Increased, ROS Increase, Protein oxidation Jan 20, 2025 Jan 20, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3478 Increased, ROS Increase, Oxidative DNA damage Jan 20, 2025 Jan 20, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3477 Increased, ROS Increase, LPO Jan 20, 2025 Jan 20, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3485 Increased, ROS Decrease, MMP Jan 28, 2025 Jan 28, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2507 Accumulation, Toxic Tau oligomers Neuroinflammation Oct 26, 2021 Oct 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2503 Accumulation, Toxic Tau oligomers Impaired axonial transport Oct 26, 2021 Oct 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2504 Dysfunctional synapses Neuronal network function, Decreased Oct 26, 2021 Oct 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3065 Dysfunctional synapses Impaired axonial transport Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3078 Dysfunctional synapses impaired, Learning and memory Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2808 Dysfunctional synapses Impairment, Learning and memory Dec 11, 2022 Dec 11, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2676 Dysfunctional autophagy Emphysema Jun 17, 2022 Jun 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2502 Dysfunctional autophagy Accumulation, Toxic Tau oligomers Oct 26, 2021 Oct 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2515 Altered mechanotransduction properties of pericytes Pericyte dysfunction Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2516 Pericyte dysfunction Endothelial cell dysfunction Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2509 Upregulation of ACE2 SARS-CoV-2 cell entry Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2529 Decrease, GLUT4 Decrease, Glucose uptake Nov 18, 2021 Nov 18, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2528 Increase, TNF Decrease, GLUT4 Nov 18, 2021 Nov 18, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2530 Decrease, Glucose uptake Abnormal, Glucose homeostasis Nov 18, 2021 Nov 18, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2531 Abnormal, Glucose homeostasis GDM Nov 18, 2021 Nov 18, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2533 Gut dysbiosis Disruption of the intestinal barrier Dec 2, 2021 Dec 2, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2544 Gut dysbiosis Recruitment of inflammatory cells Dec 15, 2021 Dec 15, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2534 Binding to hERG channel Direct hERG channel blockage Dec 13, 2021 Dec 13, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2535 hERG channel biogenesis interference Direct hERG channel blockage Dec 13, 2021 Dec 13, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2536 hERG channel biogenesis interference Induction of hERG trafficking defects Dec 13, 2021 Dec 13, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2537 Direct hERG channel blockage Inhibition of Ikr Dec 13, 2021 Dec 13, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2538 Induction of hERG trafficking defects Inhibition of Ikr Dec 13, 2021 Dec 13, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2539 Inhibition of Ikr Prolongation of Action Potential Dec 13, 2021 Dec 13, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2540 Prolongation of Action Potential Prolongation of QT interval Dec 13, 2021 Dec 13, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • hERG channel blockade leading to sudden cardiac death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition, Ether-a-go-go (ERG) Voltage-Gated Potassium Channel leading to heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3411 Prolongation of Action Potential Early premature depolarizations Nov 21, 2024 Nov 21, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Cardiac ion channels blockade leading to increased incidence of cardiovascular morbidity and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3420 Prolongation of QT interval Early premature depolarizations Nov 21, 2024 Nov 21, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition, Ether-a-go-go (ERG) Voltage-Gated Potassium Channel leading to heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2541 Prolongation of QT interval Torsades de Pointes Dec 13, 2021 Dec 13, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • hERG channel blockade leading to sudden cardiac death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibiton of L-Type Calcium Channels leading to heart failure via QT interval prolongation and Torsades de Pointes (TdP)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2853 Prolongation of QT interval Occurrence, cardiac arrhythmia Jan 29, 2023 Jan 29, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2852 Torsades de Pointes Increased Mortality Jan 29, 2023 Jan 29, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3408 Torsades de Pointes uncoordinated cardiac contraction Nov 20, 2024 Nov 20, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibiton of L-Type Calcium Channels leading to heart failure via QT interval prolongation and Torsades de Pointes (TdP)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2542 Torsades de Pointes Sudden cardiac death Dec 13, 2021 Dec 13, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • hERG channel blockade leading to sudden cardiac death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2555 Increase, Pollen abnormal Decrease, Reproduction Jan 21, 2022 Jan 21, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Deposition of ionising energy leads to population decline via pollen abnormal
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2579 tumor growth N/A, Breast Cancer Feb 15, 2022 Feb 15, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3139 tumor growth Metastasis, Breast Cancer Mar 5, 2024 Mar 5, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Activation of the AhR leading to metastatic breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2582 Increased, Steroidogenic acute regulatory protein (StAR) Increased, estrogens Feb 26, 2022 Mar 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2583 Increased, estrogens Increased, circulating estrogen levels Feb 26, 2022 Mar 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2600 Activation of TP53 Increase, Apoptosis Mar 9, 2022 Mar 9, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2601 Activation of TP53 Altered differentiation Mar 17, 2022 Mar 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2606 Activation of TP53 Premature differentiation Mar 21, 2022 Mar 21, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3105 Activation of TP53 Apoptosis Jan 10, 2024 Jan 10, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2615 Altered kinetics of sodium channel Altered, Action Potential Mar 25, 2022 Mar 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2625 Altered kinetics of sodium channel Disruption in action potential generation Mar 31, 2022 Jul 25, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Binding to voltage gate sodium channels during development leads to cognitive impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3107 Premature differentiation decline, neural progenitor cells Jan 10, 2024 Jan 10, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2607 Premature differentiation Microcephaly Mar 21, 2022 Mar 21, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2610 Increase,miRNA levels Decrease,SIRT1(sirtuin 1) levels Mar 22, 2022 Aug 27, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2611 Decrease,SIRT1(sirtuin 1) levels Increased activation, Nuclear factor kappa B (NF-kB) Mar 22, 2022 Aug 27, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3404 Disruption in action potential generation Prolonged atrioventricular (AV) Nov 20, 2024 Nov 20, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Increased Muscarinic M2 Receptor leading to Arrhythmia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3242 Disruption in action potential generation neurotrasmission in development Jun 3, 2024 Jul 31, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Binding to voltage gate sodium channels during development leads to cognitive impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2626 Agonism, Estrogen Receptor alpha Increased, Kisspeptin signalling Apr 5, 2022 Apr 11, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2628 Agonism, Estrogen Receptor alpha Decreased, Gonadotropins Apr 5, 2022 Apr 5, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2627 Increased, Kisspeptin signalling Decreased, Gonadotropins Apr 5, 2022 Aug 15, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2629 Decreased, Gonadotropins Decreased , Androgen and Progestin Apr 5, 2022 Apr 5, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2630 Decreased , Androgen and Progestin Decreased, Maturation Inducing Steroids Surge by Granulosa cells Apr 5, 2022 Apr 5, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2631 Decreased, Maturation Inducing Steroids Surge by Granulosa cells Impaired, Oocyte maturation and ovulation Apr 5, 2022 Apr 5, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2632 Impaired, Oocyte maturation and ovulation Increased, Oocyte Atresia Apr 5, 2022 Apr 5, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2633 Increased, Oocyte Atresia Impaired, Reproduction Apr 5, 2022 Apr 5, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2862 Microglia activation Neuroinflammation Apr 3, 2023 Apr 3, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3243 neurotrasmission in development Hippocampal anatomy, Altered Jun 3, 2024 Jul 31, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Binding to voltage gate sodium channels during development leads to cognitive impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2661 Secondary genotoxicity Increased, DNA damage and mutation May 25, 2022 May 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2670 Non-coding RNA expression,alteration Fibroblast proliferation and differentiation Jun 17, 2022 Jun 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2668 Non-coding RNA expression,alteration Oxidative Stress Jun 17, 2022 Jun 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2671 Non-coding RNA expression,alteration Apoptosis Jun 17, 2022 Jun 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2672 Non-coding RNA expression,alteration Dysfunctional autophagy Jun 17, 2022 Jun 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2667 Non-coding RNA expression,alteration Activation, inflammation pathway Jun 17, 2022 Jun 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3203 Non-coding RNA expression,alteration EMT May 1, 2024 May 1, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2981 Activation, inflammation pathway increased,Vascular endothelial dysfunction Aug 19, 2023 Aug 19, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3006 Activation, inflammation pathway Endothelial cell death Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3007 Activation, inflammation pathway Decreased endothelial cell proliferation Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3008 Activation, inflammation pathway Decrease, ATP production Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3009 Activation, inflammation pathway Increase, Vascular disrupting effects Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2673 Activation, inflammation pathway Pulmonary inflammation Jun 17, 2022 Jun 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2679 Pulmonary inflammation Chronic obstructive pulmonary disease Jun 17, 2022 Jun 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2680 Emphysema Chronic obstructive pulmonary disease Jun 17, 2022 Jun 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2678 Fibroblast proliferation and differentiation Airway remodeling Jun 17, 2022 Jun 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2681 Airway remodeling Chronic obstructive pulmonary disease Jun 17, 2022 Jun 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2711 Endoplasmic reticulum stress Unfolded Protein Response Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2691 Decrease, sox9 expression Altered, Cardiovascular development/function Jun 30, 2022 Oct 20, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2685 Decrease, sox9 expression Smaller and morphologically distorted facial cartilage structures Jun 30, 2022 Oct 20, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2684 Increase, slincR expression Decrease, sox9 expression Jun 30, 2022 Sep 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2690 Increase, slincR expression Smaller and morphologically distorted facial cartilage structures Jun 30, 2022 Sep 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2727 Increase, slincR expression Altered, Cardiovascular development/function Aug 2, 2022 Sep 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2697 Inhibition CerS Increased S1-P Jul 19, 2022 Jul 19, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Ceramide synthase inhibition leading to neural tube defects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2694 Inhibition CerS Reduced complex sphingolipids Jul 19, 2022 Jul 20, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Ceramide synthase inhibition leading to neural tube defects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2695 Reduced complex sphingolipids Affected folate transporter Jul 19, 2022 Jul 20, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Ceramide synthase inhibition leading to neural tube defects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2696 Affected folate transporter decrease folate Jul 19, 2022 Jul 19, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Ceramide synthase inhibition leading to neural tube defects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2700 decrease folate Neural tube defects Jul 19, 2022 Jul 19, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Ceramide synthase inhibition leading to neural tube defects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2720 Antagonism Smoothened Decrease, GLI1/2 translocation Jul 28, 2022 Jul 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2734 Antagonism Smoothened Decrease, SMO relocation Aug 23, 2022 Apr 2, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2894 Antagonism Smoothened orofacial cleft Apr 14, 2023 Apr 4, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2721 Decrease, GLI1/2 translocation Decrease, GLI1/2 target gene expression Jul 28, 2022 Apr 2, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3247 GPER activation Decreased, ERαβ heterodimers Jun 19, 2024 Jun 19, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Binding and activation of GPER leading to learning and memory impairments
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3246 GPER activation Increased, Intracellular Calcium overload Jun 19, 2024 Jun 19, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Binding and activation of GPER leading to learning and memory impairments
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2719 PARP1 Mitochondrial dysfunction Jul 28, 2022 Jul 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2693 Viable offspring, decreased Decrease, Population growth rate Jul 18, 2022 Jul 18, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2698 Increased S1-P Histone deacetylase inhibition Jul 19, 2022 Jul 19, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Ceramide synthase inhibition leading to neural tube defects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2701 Activation, mGLUr Increased, Intracellular Calcium overload Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2703 Activation, mGLUr Activation, IP3R Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2702 Activation, IP3R Increased, Intracellular Calcium overload Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3037 Activation, IP3R Increased, glutamate Sep 8, 2023 Sep 8, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2705 Activation, calpain Increase, Cell death Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2707 Inhibition, GABAAr Increase, Cell membrane depolarization Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2722 Decrease, GLI1/2 target gene expression Decrease, Cell proliferation Jul 28, 2022 Nov 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2723 Decrease, GLI1/2 target gene expression Increase, Apoptosis Jul 28, 2022 Jul 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2805 Decrease, GLI1/2 target gene expression Decrease, facial prominence outgrowth Nov 17, 2022 Nov 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2731 Decrease, GLI1/2 target gene expression Decrease, SHH second messenger production Aug 23, 2022 Apr 3, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Decrease, GLI1/2 target gene expression leads to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2882 Decrease, GLI1/2 target gene expression Apoptosis Apr 6, 2023 Apr 4, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2726 Decrease, facial prominence outgrowth orofacial cleft Jul 28, 2022 May 22, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Decrease, GLI1/2 target gene expression leads to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2732 Decrease, SHH second messenger production Decrease, Cell proliferation Aug 23, 2022 Apr 3, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Decrease, GLI1/2 target gene expression leads to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2733 Decrease, SHH second messenger production Increase, Apoptosis Aug 23, 2022 Aug 23, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2957 Decrease, SHH second messenger production Apoptosis Jun 29, 2023 Jun 29, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Decrease, GLI1/2 target gene expression leads to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2735 Decrease, SMO relocation Decrease, GLI1/2 translocation Aug 23, 2022 Apr 2, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2736 Increase, Alcohol dehydrogenase Increased, Estrogen receptor (ER) activity Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Alcohol dehydrogenase leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2738 Increase, Vitellogenin mRNA Delay, Ovarian maturation Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Alcohol dehydrogenase leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2740 Delay, Ovarian maturation Increase, sex ratio (F/M) Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Alcohol dehydrogenase leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2739 Delay, Ovarian maturation Increase, Body volume of female adults Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Alcohol dehydrogenase leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2741 Increase, Body volume of female adults Increase, developmental abnormalities Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Alcohol dehydrogenase leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2742 Increase, sex ratio (F/M) Increase, developmental abnormalities Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Alcohol dehydrogenase leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2743 Increase, developmental abnormalities Increase, Mortality Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Alcohol dehydrogenase leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Knickkopf leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2744 Decrease, Tyrosine Decrease, dopa decarboxylase Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Doda decarboxylase leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2745 Decrease, dopa decarboxylase Increase, Defects in tanning of new cuticle Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Doda decarboxylase leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2746 Increase, Defects in tanning of new cuticle Increase, impairment of cuticle sclerotization Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Doda decarboxylase leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2747 Increase, Defects in tanning of new cuticle Increase, pigmentation Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Doda decarboxylase leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2748 Increase, impairment of cuticle sclerotization Increase, Incomplete ecdysis Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Doda decarboxylase leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2749 Increase, pigmentation Increase, Incomplete ecdysis Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Doda decarboxylase leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2752 Decrease, 20-hydroxyecdysone Decrease, knickkopf gene Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Knickkopf leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2754 Decrease, knickkopf gene Decrease, Prevent chitin degradation by chitinases Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Knickkopf leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2753 Decrease, knickkopf gene Decrease, Chitin laminar organization Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Knickkopf leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2755 Decrease, Chitin laminar organization Weak, Procuticle protection Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Knickkopf leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2756 Decrease, Prevent chitin degradation by chitinases Weak, Procuticle protection Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Knickkopf leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2757 Weak, Procuticle protection Decrease, New cuticle secretion Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Knickkopf leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2758 Decrease, New cuticle secretion Increase, Incomplete ecdysis Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Knickkopf leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2764 Increase, Cytosolic Ca Increase, Cell death Sep 13, 2022 Sep 13, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2766 Increase, Cytosolic Ca Cell injury/death Sep 27, 2022 Sep 27, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calcium
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2773 Altered Signaling Altered, Nitric Oxide Levels Sep 28, 2022 Mar 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2775 Altered Signaling Increase, Endothelial Dysfunction Sep 28, 2022 Mar 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3400 Altered Signaling Increased,Cardiac fibrosis Nov 20, 2024 Nov 20, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Increased LMNA gene mutation leading to heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2840 Altered Signaling Abnormal Neural Remodeling Jan 25, 2023 Mar 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2843 Altered Signaling Altered Bone Cell Homeostasis Jan 25, 2023 Mar 22, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2789 Altered, Nitric Oxide Levels Increase, Endothelial Dysfunction Oct 20, 2022 Aug 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of energy leads to abnormal vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2784 Increase, Endothelial Dysfunction Occurrence, Abnormal Vascular Remodeling Oct 17, 2022 Aug 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of energy leads to abnormal vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2778 Increase, Endothelial Dysfunction Vascular remodeling Sep 28, 2022 Sep 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3373 Increase, Endothelial Dysfunction Infiltration, Inflammatory cells Oct 30, 2024 Oct 30, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Activation of reactive oxygen species leading the atherosclerosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2794 Increase, Glycolysis Decrease, Glucose pool Nov 1, 2022 Nov 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2795 Decrease, Glucose pool Decrease, Cell proliferation Nov 1, 2022 Nov 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2797 Increase, Mitochondrial swelling Cell injury/death Nov 1, 2022 Nov 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swelling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2799 methemocyanin formation (decrease overall oxygen binding capacity) Decrease overall oxygen binding capacity (methemocyanin formation) Nov 16, 2022 Nov 16, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2800 methemocyanin formation (decrease overall oxygen binding capacity) Hemocyanin Bohr effect decrease Nov 16, 2022 Nov 16, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2803 Decrease overall oxygen binding capacity (methemocyanin formation) Increase, hemocyanin mRNA Nov 16, 2022 Nov 16, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2801 Hemocyanin Bohr effect decrease behavioral change leading to possible reduced feeding opportunity Nov 16, 2022 Nov 16, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2802 behavioral change leading to possible reduced feeding opportunity Decrease, Growth Nov 16, 2022 Nov 16, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2807 Loss of drebrin Dysfunctional synapses Dec 11, 2022 Apr 4, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3298 Loss of drebrin Dendritic spine abnormality Jul 14, 2024 Apr 4, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3300 Loss of drebrin Impairment, Learning and memory Jul 14, 2024 Mar 9, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2816 Modified Proteins Cataracts Dec 18, 2022 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3175 Increase, Cardiac remodelling Decrease LV function Apr 3, 2024 Apr 3, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3527 Altered Bone Cell Homeostasis Inhibition, Fin regeneration Apr 18, 2025 Apr 18, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2844 Altered Bone Cell Homeostasis Bone Remodeling Jan 25, 2023 Aug 9, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Deposition of energy leading to occurrence of bone loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2845 Bone Remodeling Bone Loss Jan 25, 2023 Aug 9, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Deposition of energy leading to occurrence of bone loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2835 Increase, Pro-Inflammatory Mediators Abnormal Neural Remodeling Jan 25, 2023 Sep 10, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2839 Increase, Pro-Inflammatory Mediators Impairment, Learning and memory Jan 25, 2023 Jul 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2836 Abnormal Neural Remodeling Impairment, Learning and memory Jan 25, 2023 Jul 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2850 hERG channel blockade Inhibition of rapid delayed rectifying potassium current Jan 29, 2023 Jan 29, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • hERG channel blockade leading to sudden cardiac death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2851 Inhibition of rapid delayed rectifying potassium current Prolongation of Action Potential Jan 29, 2023 Jan 29, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • hERG channel blockade leading to sudden cardiac death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3191 Hypomyelination Altered, white brain matter Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3192 Altered, white brain matter Impairment, Learning and memory Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3196 Cholesterol metabolism LXR activity, altered Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3189 Cholesterol metabolism Reduced number of oligodendrocytes Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2858 Increase, goblet cell number Increase, Mucin production Mar 15, 2023 Mar 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • EGFR Activation Leading to Decreased Lung Function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2866 SDH, inhibited Superoxide generation, increased Apr 3, 2023 May 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3302 SDH, inhibited Succinate Accumulation Jul 18, 2024 Jul 18, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Succinate dehydrogenase inactivation leads to cancer by promoting EMT
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Succinate dehydrogenase inactivation leads to cancer through hypoxic-like mechanisms
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3233 SDH, inhibited Decrease, Coupling of OXPHOS May 28, 2024 May 28, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3180 Insulin resistance, increased Metabolic syndrome Apr 9, 2024 Apr 9, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3178 Insulin resistance, increased Metabolically unhealthy Obesity Apr 9, 2024 Apr 9, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3273 Superoxide generation, increased Oxidative Stress Jul 4, 2024 Jul 4, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2867 decreased, IQ increased, Economic Burden Apr 4, 2023 Apr 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2873 decreased, Bcl-2 Increase, Cell death Apr 4, 2023 Apr 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2870 decreased, Bcl-2 Cell injury/death Apr 4, 2023 Apr 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2874 increased, Bax Increase, Cell death Apr 4, 2023 Apr 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2871 increased, Bax Cell injury/death Apr 4, 2023 Apr 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3467 increased, Bax Apoptosis Jan 4, 2025 Apr 19, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2876 Increased fat mass Recruitment of inflammatory cells Apr 5, 2023 Apr 5, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2901 Increased fat mass Increased cytokine expression May 4, 2023 May 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2906 ERa inactivation increased lipid accumulation May 4, 2023 May 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2929 ERa inactivation Decreased, Mitochondrial fatty acid beta-oxidation May 25, 2023 May 25, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2930 ERa inactivation Increase, ROS May 25, 2023 May 25, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2880 ERa inactivation Increased adipocyte size Apr 6, 2023 Apr 6, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2881 ERa inactivation Increased adipocyte numbers Apr 6, 2023 Apr 6, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2899 Increased adipocyte size Increased fat mass May 4, 2023 May 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2898 Increased adipocyte numbers Increased fat mass May 4, 2023 May 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2900 increased lipid accumulation Increased fat mass May 4, 2023 May 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2877 Conjugation, GSH Depletion, GSH Apr 5, 2023 Sep 14, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Glutathione conjugation leading to reproductive dysfunction via oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2902 Increased cytokine expression Increase in inflammation May 4, 2023 May 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2885 Increase, Glucuronidation of T4 Increased, Clearance of thyroxine from serum Apr 12, 2023 Apr 12, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2910 Increase, AR protein expression/abundance Alterations, Cellular proliferation / hyperplasia May 11, 2023 May 11, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Androgen receptor activation leading to prostate cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2912 prostatic intraepithelial neoplasia Prostate cancer May 11, 2023 May 11, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Androgen receptor activation leading to prostate cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3212 Increase, Gonadotropins concentration in plasma Decrease, circulating testosterone levels May 8, 2024 May 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3393 Reduction, the ratio of E2/11-KT in plasma Increase, Gonadotropins concentration in plasma Nov 16, 2024 Nov 16, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2923 Reduction, the ratio of E2/11-KT in plasma Reduction, Plasma vitellogenin concentrations May 22, 2023 May 22, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3179 Impaired insulin signaling Insulin resistance, increased Apr 9, 2024 Apr 9, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2942 Activation of MEK, ERK1/2 Increase, intracellular calcium Jun 20, 2023 Apr 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via disrupted neurotransmitter release
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2938 Decreased, Viable Offspring Decrease, Population growth rate Jun 2, 2023 Sep 29, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2939 Increased LCN2/iron complex Increased intracelluar Iron Jun 15, 2023 Jun 15, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Increased LCN2/iron complex leading to neurological disorders
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2940 Increased intracelluar Iron Neuronal dysfunction Jun 15, 2023 Jun 15, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Increased LCN2/iron complex leading to neurological disorders
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3313 Increased intracelluar Iron Oxidative Stress Jul 23, 2024 Jul 23, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Excessive iron accumulation leading to neurological disorders
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3458 Disruption, neurotransmitter release Abnormal, Behavior Dec 24, 2024 Dec 24, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • DBDPE-induced inhibition of mitochondrial complex Ⅰ leading to population decline via neurotoxicity and metabotoxicity.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2955 Disruption, neurotransmitter release Impairment, Learning and memory Jun 27, 2023 Apr 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via disrupted neurotransmitter release
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Binding and activation of GPER leading to learning and memory impairments
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3080 Disruption, neurotransmitter release impaired, Learning and memory Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2970 Epigenetic modification process Expression of factors ruling proliferation, modified Jul 27, 2023 Mar 27, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2971 Expression of factors ruling proliferation, modified Increase, Hyperplasia (glandular epithelial cells of endometrium) Jul 27, 2023 Mar 27, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2974 SULT1E1 inhibition Increased, estrogens Jul 28, 2023 Jul 28, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3390 SULT1E1 inhibition Increased E2 availability Nov 15, 2024 Feb 21, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • SULT1E1 inhibition leading to uterine adenocarcinoma via increased estrogen availability at target organ level
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2978 IAV binds receptor IAV cell entry Aug 11, 2023 Jan 18, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Binding of Influenza A Virus (IAV) to Sialic Acid Glycan Receptor leads to viral infection proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3030 IAV cell entry immune mechanisms antagonized Aug 23, 2023 Aug 23, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Binding of Influenza A Virus (IAV) to Sialic Acid Glycan Receptor leads to viral infection proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2983 Angiogenesis disfunction Increase, Vascular disrupting effects Aug 19, 2023 Aug 19, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3018 Increase, Vascular disrupting effects Angiogenesis disfunction Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2985 Activation, HIF1α Activation Sema6A Aug 20, 2023 Aug 20, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Nrf2 inhibition leading to vascular disrupting effects through activating HIF1α, Semaphorin 6A, and Dll4-Notch pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2986 Activation Sema6A Activation, Dll4-Notch pathway Aug 20, 2023 Aug 20, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Nrf2 inhibition leading to vascular disrupting effects through activating HIF1α, Semaphorin 6A, and Dll4-Notch pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2987 Activation, Dll4-Notch pathway increased,Vascular endothelial dysfunction Aug 20, 2023 Aug 20, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Nrf2 inhibition leading to vascular disrupting effects through activating HIF1α, Semaphorin 6A, and Dll4-Notch pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3011 Activation, Dll4-Notch pathway Increase, Vascular disrupting effects Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2990 Activation of PPAR Activation of MMP-2 MMP-9 Aug 20, 2023 Aug 20, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Demethylation of PPAR promotor leading to vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2991 Activation of PPAR Activation of angiopoietin like protein 4 Aug 20, 2023 Aug 20, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Demethylation of PPAR promotor leading to vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2992 Activation of PPAR Activation of Angiogenic cytokines Aug 20, 2023 Aug 20, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Demethylation of PPAR promotor leading to vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3278 Activation of PPAR Oxidative Stress Jul 4, 2024 Jul 4, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Demethylation of PPAR promotor leading to vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2997 Abnormal expression of NO increased,Vascular endothelial dysfunction Aug 20, 2023 Aug 20, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Demethylation of PPAR promotor leading to vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2994 Activation of MMP-2 MMP-9 increased,Vascular endothelial dysfunction Aug 20, 2023 Aug 20, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Demethylation of PPAR promotor leading to vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2995 Activation of angiopoietin like protein 4 increased,Vascular endothelial dysfunction Aug 20, 2023 Aug 20, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Demethylation of PPAR promotor leading to vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2996 Activation of Angiogenic cytokines increased,Vascular endothelial dysfunction Aug 20, 2023 Aug 20, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Demethylation of PPAR promotor leading to vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3010 Activated ANG/Tie2 pathway Increase, Vascular disrupting effects Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3020 Activated ANG/Tie2 pathway increased,Vascular endothelial dysfunction Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3012 Activated BMP/TGF-beta pathway Increase, Vascular disrupting effects Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3021 Activated BMP/TGF-beta pathway increased,Vascular endothelial dysfunction Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3013 Activated Wnt/Frizzled pathway Increase, Vascular disrupting effects Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3022 Activated Wnt/Frizzled pathway increased,Vascular endothelial dysfunction Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3015 Activated AKT/ERK/PI3K pathway Increase, Vascular disrupting effects Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3024 Activated AKT/ERK/PI3K pathway increased,Vascular endothelial dysfunction Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3016 Inhibition VEGF/VEGFR pathway Increase, Vascular disrupting effects Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3025 Inhibition VEGF/VEGFR pathway increased,Vascular endothelial dysfunction Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3028 Vascular barrier disruption Increase, Vascular disrupting effects Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3029 Impaired Platelet Aggregation Increase, Vascular disrupting effects Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3054 immune mechanisms antagonized IAV production increased Oct 3, 2023 Oct 3, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Binding of Influenza A Virus (IAV) to Sialic Acid Glycan Receptor leads to viral infection proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3032 Angiogenesis dysfunction Increase, Vascular disrupting effects Aug 28, 2023 Aug 28, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Demethylation of PPAR promotor leading to vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Nrf2 inhibition leading to vascular disrupting effects through activating HIF1α, Semaphorin 6A, and Dll4-Notch pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3036 Activation, RyR Increased, glutamate Sep 8, 2023 Sep 8, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3040 Opening VGCCs Increased, Intracellular Calcium overload Sep 14, 2023 Sep 14, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3051 Caspase activation Increase, Cell death Sep 14, 2023 Sep 14, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3053 IAV production increased IAV budding Oct 3, 2023 Oct 3, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Binding of Influenza A Virus (IAV) to Sialic Acid Glycan Receptor leads to viral infection proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3055 IAV budding infection proliferation Oct 3, 2023 Oct 3, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Binding of Influenza A Virus (IAV) to Sialic Acid Glycan Receptor leads to viral infection proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3056 Increase, CNS Neural cell death Decrease, elavl3 Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3057 Increase, CNS Neural cell death Decrease, sox10 Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3058 Increase, CNS Neural cell death Decrease, mbp Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3501 Increase, CNS Neural cell death decreased, IQ Mar 2, 2025 Mar 2, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Decreased DNA methylation of FAM50B/PTCHD3 leading to IQ loss of children via PI3K-Akt pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3059 Decrease, elavl3 N/A, Neurodegeneration Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3060 Decrease, sox10 N/A, Neurodegeneration Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3061 Decrease, mbp N/A, Neurodegeneration Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3104 Increased, Expression of LXR activated genes Synthesis, De Novo Fatty Acid (FA) Dec 7, 2023 Mar 29, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Liver X Receptor (LXR) activation leads to liver steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3108 decline, neural progenitor cells Microcephaly Jan 10, 2024 Jan 10, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3109 RAR agonism Altered expression of cell cycle genes Jan 14, 2024 Apr 18, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Retinoic acid receptor agonism during neurodevelopment leading to microcephaly
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3114 RAR agonism Impairment, Learning and memory Jan 14, 2024 Jan 14, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3128 RAR agonism Microcephalus Feb 2, 2024 Feb 2, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3113 RAR agonism Decreased proliferation of cortical NPCs Jan 14, 2024 Feb 14, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Retinoic acid receptor agonism during neurodevelopment leading to microcephaly
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3144 RAR agonism Microcephaly Mar 13, 2024 Mar 13, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Retinoic acid receptor agonism during neurodevelopment leading to microcephaly
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3110 Altered expression of cell cycle genes Decreased proliferation of cortical NPCs Jan 14, 2024 Jan 14, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Retinoic acid receptor agonism during neurodevelopment leading to microcephaly
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3111 Decreased proliferation of cortical NPCs Altered brain morphology Jan 14, 2024 Jan 14, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3126 Decreased proliferation of cortical NPCs Reduced cortical thickness Feb 2, 2024 Feb 2, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Retinoic acid receptor agonism during neurodevelopment leading to microcephaly
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3125 Decreased proliferation of cortical NPCs RAR agonism Feb 2, 2024 Feb 2, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3112 Altered brain morphology Impairment, Learning and memory Jan 14, 2024 Jan 14, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3115 Increased, essential element imbalance Increase, ROS Jan 24, 2024 Aug 2, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Essential element imbalance leads to reproductive failure via oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3118 Increased, histomorphological alteration of testis Impaired, Spermatogenesis Jan 24, 2024 Apr 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Essential element imbalance leads to reproductive failure via oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3121 inhibition, EKR1/2 signaling pathway Aberrant, synaptic formation and plasticity Jan 25, 2024 Jan 25, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Estrogen antagonism leading to increased risk of autism-like behavior
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3122 Aberrant, synaptic formation and plasticity Neuronal network function, Decreased Jan 25, 2024 Jan 25, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Estrogen antagonism leading to increased risk of autism-like behavior
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3253 Aberrant, synaptic formation and plasticity Impairment, Learning and memory Jun 19, 2024 Jun 19, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Binding and activation of GPER leading to learning and memory impairments
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3143 Reduced cortical thickness Microcephaly Mar 13, 2024 Mar 13, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Retinoic acid receptor agonism during neurodevelopment leading to microcephaly
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3127 Reduced cortical thickness Microcephalus Feb 2, 2024 Feb 2, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3170 Epididymal agenesis Impaired, Spermatogenesis Mar 20, 2024 Dec 3, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Impaired, Spermatogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3173 Impaired, urethral tube closure Hypospadias Mar 20, 2024 Dec 3, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Hypospadias, increased
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3174 Decreased, INSL3 Impaired inguinoscrotal phase Mar 20, 2024 Dec 3, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Decreased Insulin-like peptide 3 (INSL3) leads to Malformation, cryptorchidism - maldescended testis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3181 Binding of antagonist to thyroid hormone receptor TR Antagnoism Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3182 Binding of antagonist to glucocorticoid hormone receptor GR antagonism Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3187 Binding of (ant)agonist to liver X receptor Cholesterol metabolism Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3183 Binding of (ant)agonist to liver X receptor LXR activity, altered Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3188 Binding of (ant)agonist to PPAR alpha Cholesterol metabolism Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3195 Binding of (ant)agonist to PPAR alpha Reduced number of oligodendrocytes Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3185 Binding of (ant)agonist to PPAR alpha PPAR alpha activity, altered Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3184 Binding of (ant)agonist to PPAR alpha Binding of antagonist to thyroid hormone receptor Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3194 LXR activity, altered Reduced number of oligodendrocytes Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3190 Reduced number of oligodendrocytes Hypomyelination Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3224 Dysregulation of transcriptional expression within PPAR signaling network Disrupted Lipid Storage May 14, 2024 May 29, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3223 Dysregulation of transcriptional expression within PPAR signaling network Decreased, Mitochondrial fatty acid beta-oxidation May 14, 2024 May 24, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3211 Disrupted Lipid Storage Accumulation, Triglyceride May 8, 2024 May 29, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3210 Disrupted Lipid Storage Accumulation, Fatty acid May 8, 2024 May 28, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3220 Binding PPAR isoforms Disrupted PPAR isoform nuclear signaling May 14, 2024 May 23, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3208 Binding PPAR isoforms Decreased, Mitochondrial fatty acid beta-oxidation May 8, 2024 May 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3207 Binding PPAR isoforms Dysregulation of transcriptional expression within PPAR signaling network May 8, 2024 May 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3222 Disrupted PPAR isoform nuclear signaling Decreased, Mitochondrial fatty acid beta-oxidation May 14, 2024 May 14, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3221 Disrupted PPAR isoform nuclear signaling Dysregulation of transcriptional expression within PPAR signaling network May 14, 2024 May 23, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3254 Decreased, ERαβ heterodimers Apoptosis Jun 19, 2024 Jun 19, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Binding and activation of GPER leading to learning and memory impairments
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3288 Decreased, sodium uptake in gills Decreased, Plasma sodium concentrations Jul 8, 2024 Dec 3, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Decreased Sodium/Potassium ATPase activity leads to Heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3289 Decreased, Plasma sodium concentrations Increase, Abnormal osmoregulation Jul 8, 2024 Dec 3, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3346 Decreased, Plasma sodium concentrations Decreased, blood plasma volume Sep 20, 2024 Dec 3, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Decreased Sodium/Potassium ATPase activity leads to Heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3291 Increased, Blood viscosity Increased, Cardiac stress Jul 8, 2024 Dec 3, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Decreased Sodium/Potassium ATPase activity leads to Heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3292 Increased, Cardiac stress Heart failure Jul 8, 2024 Dec 3, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Decreased Sodium/Potassium ATPase activity leads to Heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3295 The NO synthase pathway activation increased,Vascular endothelial dysfunction Jul 9, 2024 Jul 9, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Adverse outcome pathway of PFAS-induced vascular disrupting effects via activating oxidative stress related pathways
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3296 Ferroptosis related pathways activation increased,Vascular endothelial dysfunction Jul 9, 2024 Jul 9, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Adverse outcome pathway of PFAS-induced vascular disrupting effects via activating oxidative stress related pathways
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3301 Dendritic spine abnormality Dysfunctional synapses Jul 17, 2024 Apr 3, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3299 Dendritic spine abnormality Impairment, Learning and memory Jul 14, 2024 Jul 14, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3304 Succinate Accumulation Inhibition, Prolyl hydroxylases Jul 18, 2024 Jul 18, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Succinate dehydrogenase inactivation leads to cancer through hypoxic-like mechanisms
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3303 Succinate Accumulation Increase, DNMT inhibition Jul 18, 2024 Jul 18, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Succinate dehydrogenase inactivation leads to cancer by promoting EMT
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3317 Altered Stress Response Signaling Altered, Nitric Oxide Levels Jul 24, 2024 Aug 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of energy leads to abnormal vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3318 Altered Stress Response Signaling Increase, Endothelial Dysfunction Jul 24, 2024 Aug 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of energy leads to abnormal vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3321 Altered Stress Response Signaling Abnormal Neural Remodeling Jul 24, 2024 Jul 25, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3320 Altered cell differentiation signaling Altered Bone Cell Homeostasis Jul 24, 2024 Aug 23, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of energy leading to occurrence of bone loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3464 HSD17B2 inhibition Increased E2 availability Jan 2, 2025 Jan 2, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • 17β-Hydroxysteroid dehydrogenase 2, inhibition leading to activation, estrogen receptor alpha
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3391 Increased E2 availability Activation, estrogen receptor alpha Nov 15, 2024 Nov 21, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • SULT1E1 inhibition leading to uterine adenocarcinoma via increased estrogen availability at target organ level
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Aromatase induction leading to estrogen receptor alpha activation via increased estradiol
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • 17β-Hydroxysteroid dehydrogenase 2, inhibition leading to activation, estrogen receptor alpha
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3383 Formation of HLA-DQ2/8-gluten complexes Co-localization of gluten reactive adaptive T-cells with APC Nov 12, 2024 Apr 8, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Gluten-driven immune activation leading to celiac disease in genetically predisposed individuals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3338 Formation of HLA-DQ2/8-gluten complexes Activation of gluten-reactive CD4+ T cells Sep 13, 2024 Sep 13, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3328 Formation of HLA-DQ2/8-gluten complexes Activation/Proliferation, T-cells Aug 13, 2024 Aug 13, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3339 Generation of gluten-reactive T cell receptors Activation of gluten-reactive CD4+ T cells Sep 13, 2024 Sep 13, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3329 Generation of gluten-reactive T cell receptors Activation/Proliferation, T-cells Aug 13, 2024 Aug 13, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3385 Generation of gluten-reactive T cell receptors Co-localization of gluten reactive adaptive T-cells with APC Nov 12, 2024 Apr 8, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Gluten-driven immune activation leading to celiac disease in genetically predisposed individuals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3384 Generation of gluten-reactive and TG2-reactive B cell receptors Co-localization of gluten reactive adaptive T-cells with APC Nov 12, 2024 Feb 27, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Gluten-driven immune activation leading to celiac disease in genetically predisposed individuals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3340 Generation of gluten-reactive and TG2-reactive B cell receptors Activation of gluten-reactive CD4+ T cells Sep 13, 2024 Sep 13, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3330 Generation of gluten-reactive and TG2-reactive B cell receptors Activation/Proliferation, T-cells Aug 13, 2024 Aug 13, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3341 Activation of the innate immune response Activation of gluten-reactive CD4+ T cells Sep 13, 2024 Apr 3, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Gluten-driven immune activation leading to celiac disease in genetically predisposed individuals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3331 Activation of the innate immune response Activation/Proliferation, T-cells Aug 13, 2024 Aug 13, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3333 Activation of gluten- and TG2-reactive B cells Disruption of the intestinal barrier Aug 13, 2024 Feb 27, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Gluten-driven immune activation leading to celiac disease in genetically predisposed individuals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3345 Activation of gluten- and TG2-reactive B cells Activation of gluten-reactive CD4+ T cells Sep 13, 2024 Sep 13, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3336 Activation of gluten- and TG2-reactive B cells Activation/Proliferation, T-cells Aug 13, 2024 Aug 13, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3344 Activation of gluten-reactive CD4+ T cells Formation of HLA-DQ2/8-gluten complexes Sep 13, 2024 Sep 13, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3343 Activation of gluten-reactive CD4+ T cells Disruption of the intestinal barrier Sep 13, 2024 Sep 13, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3342 Activation of gluten-reactive CD4+ T cells Activation of gluten- and TG2-reactive B cells Sep 13, 2024 Feb 27, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Gluten-driven immune activation leading to celiac disease in genetically predisposed individuals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3347 Decreased, blood plasma volume Increased, Blood viscosity Sep 20, 2024 Dec 3, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Decreased Sodium/Potassium ATPase activity leads to Heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3351 NTE, inhibited LPS, increased Oct 1, 2024 Oct 1, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of neuropathy target esterase leading to delayed neuropathy via lysolecithin cell membrane integration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of neuropathy target esterase leading to delayed neuropathy via increased inflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3352 LPS, increased LPS cell membrane integration, increased Oct 1, 2024 Oct 1, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of neuropathy target esterase leading to delayed neuropathy via lysolecithin cell membrane integration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3356 LPS, increased Increase, Inflammation Oct 1, 2024 Oct 1, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of neuropathy target esterase leading to delayed neuropathy via increased inflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3353 LPS cell membrane integration, increased Oligodendrocyte death, increased Oct 1, 2024 Oct 1, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of neuropathy target esterase leading to delayed neuropathy via lysolecithin cell membrane integration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3354 Oligodendrocyte death, increased Demyelination, increased Oct 1, 2024 Oct 1, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of neuropathy target esterase leading to delayed neuropathy via lysolecithin cell membrane integration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of neuropathy target esterase leading to delayed neuropathy via increased inflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3355 Demyelination, increased Delayed neuropathy, increased Oct 1, 2024 Oct 1, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of neuropathy target esterase leading to delayed neuropathy via lysolecithin cell membrane integration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of neuropathy target esterase leading to delayed neuropathy via increased inflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3366 Decreased, INSIG1 protein activity Increased, SREBP2 protein expression Oct 22, 2024 Feb 10, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Activation, Pregnane-X receptor, NR1l2 leads to increased plasma low-density lipoprotein (LDL) cholesterol via increased cholesterol synthesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Activation, Pregnane-X receptor, NR1l2 leads to increased plasma low-density lipoprotein (LDL) cholesterol via increased PCSK9 protein expression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3367 Increased, SREBP2 protein expression Increased, cholesterol synthesis enzymes Oct 22, 2024 Feb 10, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Activation, Pregnane-X receptor, NR1l2 leads to increased plasma low-density lipoprotein (LDL) cholesterol via increased cholesterol synthesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3388 Increased, SREBP2 protein expression Increased, PCSK9 protein expression Nov 13, 2024 Feb 13, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Activation, Pregnane-X receptor, NR1l2 leads to increased plasma low-density lipoprotein (LDL) cholesterol via increased PCSK9 protein expression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3368 Increased, cholesterol synthesis enzymes Increased, plasma LDL cholesterol Oct 22, 2024 Feb 10, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Activation, Pregnane-X receptor, NR1l2 leads to increased plasma low-density lipoprotein (LDL) cholesterol via increased cholesterol synthesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3380 Testosterone levels, increased Androgen receptor activation, increased Nov 2, 2024 Nov 24, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3381 Dihydrotestosterone (DHT) levels, increased Androgen receptor activation, increased Nov 2, 2024 Nov 24, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3379 Androgen receptor activation, increased Altered, Transcription of genes by the AR Nov 2, 2024 Nov 24, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Androgen receptor agonism leading to long anogenital distance in female offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3386 Co-localization of gluten reactive adaptive T-cells with APC Activation of the innate immune response Nov 12, 2024 Apr 3, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Gluten-driven immune activation leading to celiac disease in genetically predisposed individuals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3387 Co-localization of gluten reactive adaptive T-cells with APC Formation of HLA-DQ2/8-gluten complexes Nov 12, 2024 Nov 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3389 Increased, PCSK9 protein expression Increased, plasma LDL cholesterol Nov 13, 2024 Feb 10, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Activation, Pregnane-X receptor, NR1l2 leads to increased plasma low-density lipoprotein (LDL) cholesterol via increased PCSK9 protein expression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3395 Inhibition, plasma aromatase activity Reduction, Plasma 17beta-estradiol concentrations Nov 16, 2024 Nov 16, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Aromatase inhibition leads to reproductive toxicity (including growth and developmental toxicity) in adult female zebrafish
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3398 LMNA Mutation Structural changes in lamin A/C Nov 20, 2024 Nov 20, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Increased LMNA gene mutation leading to heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3399 Structural changes in lamin A/C Altered Signaling Nov 20, 2024 Nov 20, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Increased LMNA gene mutation leading to heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3405 Prolonged atrioventricular (AV) Occurrence, cardiac arrhythmia Nov 20, 2024 Nov 20, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Increased Muscarinic M2 Receptor leading to Arrhythmia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Inhibition of acetylcholinesterase (AChE) leading to arrhythmias
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3409 uncoordinated cardiac contraction Increased incidence of cardiovascular morbidity and mortality Nov 20, 2024 Nov 20, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3447 uncoordinated cardiac contraction Heart failure Nov 27, 2024 Nov 27, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibiton of L-Type Calcium Channels leading to heart failure via QT interval prolongation and Torsades de Pointes (TdP)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3410 Cardiac ion channels (e.g., potassium, sodium, calcium) Prolongation of Action Potential Nov 21, 2024 Nov 21, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Cardiac ion channels blockade leading to increased incidence of cardiovascular morbidity and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3421 Early premature depolarizations Heart failure Nov 21, 2024 Nov 21, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition, Ether-a-go-go (ERG) Voltage-Gated Potassium Channel leading to heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3412 Early premature depolarizations Increased incidence of cardiovascular morbidity and mortality Nov 21, 2024 Nov 21, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Cardiac ion channels blockade leading to increased incidence of cardiovascular morbidity and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3428 Intracellular cAMP RyR2 hyperphosphorylation Nov 22, 2024 Nov 22, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3417 Intracellular cAMP the delayed and early afterdepolarizations Nov 21, 2024 Nov 21, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • β-adrenergic receptor agonists leading to arrhythmias.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3418 the delayed and early afterdepolarizations Occurrence, cardiac arrhythmia Nov 21, 2024 Nov 21, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • β-adrenergic receptor agonists leading to arrhythmias.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3422 Na⁺/K⁺-ATPase Heart failure Nov 21, 2024 Nov 21, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3423 Na⁺/K⁺-ATPase Increased, intracellular sodium (Na+) Nov 21, 2024 Nov 21, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3425 Impaired Sodium-Calcium Exchange Increased, Intracellular Calcium overload Nov 21, 2024 Nov 21, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Decreased Na/K ATPase activity leading to heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3445 Phosphodiesterase (PDE) Increased, cyclic adenosine monophosphate Nov 26, 2024 Nov 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Phosphodiesterase inhibition leading to heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3427 Phosphodiesterase (PDE) Intracellular cAMP Nov 22, 2024 Nov 22, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3429 RyR2 hyperphosphorylation Increased, Intracellular Calcium overload Nov 22, 2024 Nov 22, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Phosphodiesterase inhibition leading to heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3433 if Bradycardia Nov 22, 2024 Nov 22, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of Funny current (If) leading to Arrhythmias
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3434 Bradycardia Altered Cardiac Electrical Conduction Nov 22, 2024 Nov 22, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of Funny current (If) leading to Arrhythmias
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • HCN Channel Inhibition leading to Arrhythmias
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3435 Altered Cardiac Electrical Conduction Occurrence, cardiac arrhythmia Nov 22, 2024 Nov 22, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of Funny current (If) leading to Arrhythmias
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • HCN Channel Inhibition leading to Arrhythmias
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3436 Aromatase, induction Increased, circulating estrogen levels Nov 22, 2024 Dec 16, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Aromatase induction leading to estrogen receptor alpha activation via increased estradiol
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3438 Plasma E2, increased Increased E2 availability Nov 22, 2024 Nov 22, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Aromatase induction leading to estrogen receptor alpha activation via increased estradiol
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3440 HCN Channel Inhibition Reduced Pacemaker Activity in SA Node Nov 24, 2024 Nov 24, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • HCN Channel Inhibition leading to Arrhythmias
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3441 Reduced Pacemaker Activity in SA Node Bradycardia Nov 24, 2024 Nov 24, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • HCN Channel Inhibition leading to Arrhythmias
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3448 Decrease, intratesticular testosterone Decrease, circulating testosterone levels Dec 12, 2024 Jan 31, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Decreased testosterone synthesis leading to hypospadias in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3449 Decrease, intratesticular testosterone AGD, decreased Dec 12, 2024 Jan 31, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3488 Decrease, intratesticular testosterone Hypospadias Feb 15, 2025 Feb 15, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Decreased testosterone synthesis leading to hypospadias in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3487 Decrease, intratesticular testosterone nipple retention, increased Jan 30, 2025 Jan 30, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3454 Altered, Redox Homeostasis Disruption, Mitochondrial electron transport chain Dec 24, 2024 Dec 24, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • DBDPE-induced inhibition of mitochondrial complex Ⅰ leading to population decline via neurotoxicity and metabotoxicity.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3457 Disruption, Glucolipid metabolism impaired, Larval development Dec 24, 2024 Dec 24, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • DBDPE-induced inhibition of mitochondrial complex Ⅰ leading to population decline via neurotoxicity and metabotoxicity.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3459 Abnormal, Behavior impaired, Larval development Dec 24, 2024 Dec 24, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • DBDPE-induced inhibition of mitochondrial complex Ⅰ leading to population decline via neurotoxicity and metabotoxicity.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3461 Increase, Malformations Increased Mortality Dec 24, 2024 Dec 24, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • DBDPE-induced inhibition of mitochondrial complex Ⅰ leading to population decline via neurotoxicity and metabotoxicity.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3471 Plasma estradiol/progesterone ratio, increase Increased E2 availability Jan 10, 2025 Jan 14, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Decreased, GnRH pulsatility/release leading to estradiol availability, increased via impaired ovulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3473 Plasma estradiol/progesterone ratio, increase PVC Jan 13, 2025 Jan 14, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Decreased, GnRH pulsatility/release leading to estradiol availability, increased via impaired ovulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3476 Increased, stimulation of brain serotonin 5-HT1a, 5-HT2c receptors Inhibition, Feeding Jan 14, 2025 Feb 20, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) leads to Inhibition, Feeding
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3502 FAM50B/PTCHD3 methylation decreased, IQ Mar 2, 2025 Mar 2, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Decreased DNA methylation of FAM50B/PTCHD3 leading to IQ loss of children via PI3K-Akt pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3497 FAM50B/PTCHD3 methylation FAM50B/PTCHD3 expression Mar 2, 2025 Mar 2, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Decreased DNA methylation of FAM50B/PTCHD3 leading to IQ loss of children via PI3K-Akt pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3498 FAM50B/PTCHD3 expression PI3K-Akt pathway Mar 2, 2025 Mar 2, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Decreased DNA methylation of FAM50B/PTCHD3 leading to IQ loss of children via PI3K-Akt pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3499 PI3K-Akt pathway Increased, ROS Mar 2, 2025 Mar 2, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Decreased DNA methylation of FAM50B/PTCHD3 leading to IQ loss of children via PI3K-Akt pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3515 Decreased 3βHSD activity Reduction, androstenedione Apr 8, 2025 Apr 8, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3516 Decreased 3βHSD activity Decreased, Progesterone levels Apr 8, 2025 Apr 8, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3520 Decreased, Pregnenolone levels Reduction, DHEA Apr 8, 2025 Apr 8, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3522 Decreased, Pregnenolone levels Decreased, Progesterone levels Apr 8, 2025 Apr 8, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3518 Decreased, 17βHSD3 activity Decrease, circulating testosterone levels Apr 8, 2025 Apr 8, 2025
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3519 Decreased, CYP11A1 activity Decreased, Pregnenolone levels Apr 8, 2025 Apr 8, 2025