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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 leading to Reproductive Failure
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 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
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
1750	Decrease, Mitochondrial ATP production	Increase, Apoptosis	Jun 12, 2018	Jun 12, 2018
1739	Decrease, Mitochondrial ATP production	Decrease, Growth	May 24, 2018	May 24, 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
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
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
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
1863	Cell injury/death	Neurodegeneration	Feb 19, 2019	Feb 19, 2019
1831	Cell injury/death	Activation, Tissue resident cells (Kuppfer cells)	Jan 7, 2019	Jan 7, 2019	IKK complex inhibition leading to liver injury
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
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
2887	Up Regulation, CYP1A1	Increase, ROS formation	Apr 13, 2023	Apr 13, 2023
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
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
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
2077	Activation, Glucocorticoid Receptor	Increase, Cripto-1 expression	Apr 20, 2020	Jul 10, 2020	Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
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
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
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
3158	Mitochondrial dysfunction	Occurrence, Cytoplasmic vacuolization (Bile duct cell)	Mar 13, 2024	Mar 13, 2024	Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
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
3152	Mitochondrial dysfunction	Apoptotic cell death	Mar 13, 2024	Mar 13, 2024	Immune mediated hepatitis
3153	Mitochondrial dysfunction	ER stress	Mar 13, 2024	Mar 13, 2024	Immune mediated hepatitis
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
3155	Mitochondrial dysfunction	Occurrence, Cytoplasmic vacuolization (hepatocyte)	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
3157	Mitochondrial dysfunction	Occurrence, Cytoplasmic vacuolization (kupffer cell)	Mar 13, 2024	Mar 13, 2024	Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
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
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
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
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
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
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
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
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
2224	Mitochondrial dysfunction	Increase, Excessive ROS	Dec 4, 2020	Dec 4, 2020
2227	Mitochondrial dysfunction	Increase, ROS formation	Dec 4, 2020	Dec 4, 2020
2228	Mitochondrial dysfunction	Decrease, ATP pool	Dec 4, 2020	Dec 4, 2020
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.
3493	Disruption, Mitochondrial electron transport chain	Increase, ROS	Feb 25, 2025	Feb 25, 2025	Calcium-mediated neuronal ROS production and energy imbalance
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
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
2931	Decreased, Mitochondrial fatty acid beta-oxidation	Mitochondrial dysfunction EMPTY	May 25, 2023	May 25, 2023
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
196	Abnormal, Morphogenesis	Increased, Lethality	Nov 29, 2016	Dec 3, 2016
197	Abnormal, Morphogenesis	Increased, Structural malformations	Nov 29, 2016	Dec 3, 2016
1025	Abnormal, Morphogenesis	Increased, Developmental Defects	Nov 29, 2016	Dec 3, 2016
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
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
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
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
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
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
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
2717	Neuroinflammation	Increase, Cell death	Jul 25, 2022	Jul 25, 2022
210	Neuronal dysfunction	Neuroinflammation	Nov 29, 2016	Nov 29, 2016
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
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
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
2306	Inhibition, Nuclear factor kappa B (NF-kB)	Increased proinflammatory mediators	Mar 30, 2021	Mar 30, 2021
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
932	Peptide Oxidation	Cholestasis, Pathology	Nov 29, 2016	Dec 3, 2016	Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
922	Peptide Oxidation	Mitochondrial dysfunction	Nov 29, 2016	Nov 29, 2016
923	Peptide Oxidation	Release, Cytokine	Nov 29, 2016	Dec 3, 2016
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
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
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
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)
930	Bile accumulation, Pathological condition	Production, Reactive oxygen species	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)
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
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
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）
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
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
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
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
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
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
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
2988	demethylation, PPARg promoter	Activation of PPAR	Aug 20, 2023	Aug 20, 2023	Demethylation of PPAR promotor leading to vascular disrupting effects
487	demethylation, PPARg promoter	Activation, SREBF1	Nov 29, 2016	Dec 3, 2016	NR1I3 (CAR) suppression leading to hepatic steatosis
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
276	Production, Reactive oxygen species	Peptide Oxidation	Nov 29, 2016	Dec 3, 2016	Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
931	Production, Reactive oxygen species	Cholestasis, Pathology	Nov 29, 2016	Dec 3, 2016
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
3238	Increase, Excessive ROS	Oxidative Stress	May 31, 2024	May 31, 2024	The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
912	Increase, Excessive ROS	Mitochondrial dysfunction	Nov 29, 2016	Dec 3, 2016
1602	Increase, Excessive ROS	Increase, DNA Damage	Jun 29, 2017	Jun 29, 2017
1603	Increase, Excessive ROS	Increase, LPO	Jun 29, 2017	Jun 29, 2017
1623	Increase, Excessive ROS	Increased, secretion of local growth factors	Jul 26, 2017	Jul 26, 2017
1754	Increase, Excessive ROS	Decrease, Coupling of OXPHOS	Jun 12, 2018	Jun 12, 2018
2590	Increase, Excessive ROS	Increase, Oxidative DNA damage	Mar 1, 2022	Mar 1, 2022
2225	Increase, Excessive ROS	Increase, Global methylation	Dec 4, 2020	Dec 4, 2020
2187	Increase, Excessive ROS	Increase, Apoptosis	Nov 2, 2020	Nov 2, 2020
2305	Increase, Excessive ROS	Inhibition, Nuclear factor kappa B (NF-kB)	Mar 30, 2021	Mar 30, 2021
2308	Increase, Excessive ROS	Increased activation, Nuclear factor kappa B (NF-kB)	Mar 30, 2021	Mar 30, 2021
2348	Increase, Excessive ROS	D1 protein deactivation	Apr 11, 2021	Apr 11, 2021
2093	Increase, Excessive ROS	Decrease, MMP	Apr 30, 2020	Apr 30, 2020
2089	Increase, Excessive ROS	Increase, Protein oxidation	Apr 30, 2020	Apr 30, 2020
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	Dec 2, 2016	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
835	Activation/Proliferation, T-cells	sensitisation, skin	Nov 29, 2016	Dec 3, 2016	Covalent Protein binding leading to Skin Sensitisation
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
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
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
1504	TH synthesis, Decreased	BDNF, Reduced	May 10, 2017	Apr 4, 2019	Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
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
810	TH synthesis, Decreased	Increased, Serum creatinine	Nov 29, 2016	Dec 3, 2016	Kidney dysfunction by decreased thyroid hormone
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
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
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
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
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
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
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
1143	T4 in serum, Decreased	Decreased, Thyroxine (T4) in tissues	Nov 29, 2016	Sep 3, 2020
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
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)
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
2884	Induction, Upregulation of glucuronyltransferase activity	Increase, Glucuronidation of T4	Apr 12, 2023	Apr 12, 2023
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
329	Insufficiency, Vascular	Abnormal, Morphogenesis	Nov 29, 2016	Dec 3, 2016
1036	Insufficiency, Vascular	Increased, Developmental Defects	Nov 29, 2016	Jan 18, 2022	Disruption of VEGFR Signaling Leading to Developmental Defects
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)
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
977	Altered, Cardiovascular development/function	Increase, Pericardial edema	Nov 29, 2016	Jun 9, 2017
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
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
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
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
2463	Increase, Mortality	Decrease, Population growth rate	Aug 5, 2021	Aug 5, 2021
1004	Increase, Mortality	Decreased, population 1	Nov 29, 2016	Dec 3, 2016
1013	Increase, Mortality	Decreased, Population size	Nov 29, 2016	Dec 3, 2016
756	Increased Mortality	Decreased, population 1	Nov 29, 2016	Dec 3, 2016	Glutamate-gated chloride channel activation leading to acute mortality
200	Increased Mortality	Decline, Population	Nov 29, 2016	Dec 3, 2016
428	Increased Mortality	Decreased, Population trajectory	Nov 29, 2016	Dec 20, 2019
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.
2486	Increased Mortality	Decline, Population trajectory	Oct 8, 2021	Oct 8, 2021
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
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
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
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
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
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
2953	Neuronal network function, Decreased	Neurological disorder	Jun 21, 2023	Jun 21, 2023	Excessive iron accumulation leading to neurological disorders
3123	Neuronal network function, Decreased	autism-like behavior	Jan 25, 2024	Jan 25, 2024	Estrogen antagonism leading to increased risk of autism-like behavior
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
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
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
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
892	Increased, Intracellular Calcium overload	Decreased, Neuronal network function in adult brain	Nov 29, 2016	Dec 3, 2016
1862	Increased, Intracellular Calcium overload	Cell injury/death	Feb 19, 2019	Sep 3, 2023	Acetylcholinesterase Inhibition Leading to Neurodegeneration
1860	Increased, Intracellular Calcium overload	Occurrence, Epileptic seizure	Feb 13, 2019	Feb 13, 2019
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	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
2140	Increased, Intracellular Calcium overload	Status epilepticus	May 21, 2020	May 21, 2020
2202	Covalent Binding, Protein	Activation, Inflammatory cytokines, chemokines, cytoprotective gene pathways	Nov 5, 2020	Feb 11, 2021
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
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
833	Covalent Binding, Protein	Activation, Keratinocytes	Nov 29, 2016	Dec 3, 2016	Covalent Protein binding leading to Skin Sensitisation
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
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
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)
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
591	Increased, Atrioventricular block and bradycardia	Respiratory distress/arrest	Nov 29, 2016	Dec 3, 2016	Sodium channel inhibition leading to congenital malformations
432	Increased, Atrioventricular block and bradycardia	Increased Mortality	Nov 29, 2016	Nov 29, 2016
433	Respiratory distress/arrest	Increased Mortality	Nov 29, 2016	Dec 20, 2019	Acetylcholinesterase inhibition leading to acute mortality
592	Respiratory distress/arrest	N/A, hypoxia	Nov 29, 2016	Dec 3, 2016	Sodium channel inhibition leading to congenital malformations
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
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
3218	Increased, Liver Steatosis	Cell injury/death	May 14, 2024	Jan 30, 2025	AhR activation leading to liver fibrosis
1695	Increased, Liver Steatosis	Increase, ROS	Nov 14, 2017	Nov 14, 2017	Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)
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
1471	Decrease, Ovulation	Decrease, Fertility	Apr 15, 2017	Apr 15, 2017
1753	Decrease, Ovulation	Decrease, Fecundity	Jun 12, 2018	Jun 12, 2018
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
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
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
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
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
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
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
1242	Inhibition, sodium channel	Decreased, sodium conductance 2	Nov 29, 2016	Dec 3, 2016	Sodium channel (Nav1.1) inhibition leading to population decline
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
3370	N/A, hypoxia	Increase, Cancer	Oct 25, 2024	Oct 25, 2024	Succinate dehydrogenase inactivation leads to cancer through hypoxic-like mechanisms
3307	N/A, hypoxia	Increase, angiogenesis	Jul 18, 2024	Jul 18, 2024
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
1861	Occurrence, Epileptic seizure	Increased, glutamate	Feb 13, 2019	Feb 13, 2019
1999	Occurrence, Epileptic seizure	Overactivation, NMDARs	Nov 13, 2019	Nov 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
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
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
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
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
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
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
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
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
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
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)
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
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
733	Decreased, Prolactin	Increased, Estrogen receptor (ER) activity	Nov 29, 2016	Dec 3, 2016	Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)
734	Increased, Estrogen receptor (ER) activity	Decreased, Progesterone from corpus luteum	Nov 29, 2016	Dec 3, 2016	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
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
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
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	Jul 27, 2023	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
2072	Decreased, cholesterol	Decreased, 11KT	Mar 23, 2020	May 6, 2020	PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone
3201	Decreased, cholesterol	Decrease, circulating testosterone levels	Apr 25, 2024	Apr 25, 2024	HMG-CoA reductase inhibition leading to decreased fertility
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
2893	Induction, CYP1A2/CYP1A5	Increase, Excessive ROS	Apr 13, 2023	Apr 13, 2023
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
2419	Increase, Cell Proliferation	Increased, mesotheliomas	Jul 6, 2021	Jul 6, 2021	Frustrated phagocytosis leads to malignant mesothelioma
2819	Increase, Cell Proliferation	Cataracts	Dec 18, 2022	Mar 8, 2024	Deposition of energy leading to occurrence of cataracts
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
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
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
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
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
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
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
911	Disruption, Lysosome	Increase, Excessive ROS	Nov 29, 2016	Dec 3, 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
3466	dimerization, AHR/ARNT	increased, Bax	Jan 4, 2025	Mar 10, 2025	Aryl hydrocarbon Receptor (AhR) activation causes Premature Ovarian Insufficiency leading to Reproductive Failure
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
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
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
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
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
2269	Binding, Transthyretin in serum	Increased, Clearance of thyroxine from serum	Jan 26, 2021	Jan 26, 2021
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
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
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
2268	Increased, Free serum thyroxine (T4)	Increased, Uptake of thyroxine into tissue	Jan 26, 2021	Jan 26, 2021
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
1254	Inhibition, Calcineurin Activity	Suppression, IL-2 and IL-4 production	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
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
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
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
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
1190	Increase, Incomplete ecdysis	Increased Mortality	Nov 29, 2016	Dec 3, 2016
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
2081	Reduced, Swimming performance	Decrease, Population growth rate	Apr 21, 2020	Jun 4, 2020	Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
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
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
1102	prepubertal increase, Estrogen receptor (ER) activity	Activation, estrogen receptor alpha	Nov 29, 2016	Dec 3, 2016	Early-life estrogen receptor activity leading to endometrial carcinoma in the 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	Jul 27, 2023	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
3403	Increased, blood potassium concentration	Disruption in action potential generation	Nov 20, 2024	Nov 20, 2024	Increased Muscarinic M2 Receptor leading to Arrhythmia
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
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
2660	Increase, ROS	Secondary genotoxicity	May 25, 2022	May 25, 2022	Interaction with lung resident cell membrane components leads to lung cancer
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
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
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
1696	Increase, ROS	increased, oncotic necrosis	Nov 14, 2017	Nov 14, 2017	Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)
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
3496	Increase, ROS	Mitochondrial dysfunction	Feb 25, 2025	Feb 25, 2025	Mitochondrial complex inhibition leading to liver injury
3494	Increase, ROS	Decreased, Nitric Oxide	Feb 25, 2025	Feb 25, 2025	Calcium-mediated neuronal ROS production and energy imbalance
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
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)
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)
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
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
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
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
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
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
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
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
1360	Activation, NADPH Oxidase	ROS formation	Feb 15, 2017	Feb 15, 2017	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
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
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
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
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
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
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
3266	Altered, Protein Production	Oxidative Stress	Jul 4, 2024	Jul 4, 2024	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
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
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
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
3468	Apoptosis	Decreased, ovarian reserve	Jan 4, 2025	Mar 10, 2025	Aryl hydrocarbon Receptor (AhR) activation causes Premature Ovarian Insufficiency leading to Reproductive Failure
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
2792	Apoptosis	Decrease, outgrowth	Oct 27, 2022	Apr 11, 2023	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
1867	Apoptosis	Activation, hepatic stellate cells	Mar 6, 2019	Mar 6, 2019	Inhibition of N-linked glycosylation leads to liver injury
1869	Apoptosis	Liver Injury	Mar 6, 2019	Mar 6, 2019	Inhibition of N-linked glycosylation leads to liver injury
1368	Apoptosis	Reproductive failure	Feb 15, 2017	Feb 15, 2017	NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
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
2577	Apoptosis	tumor growth	Feb 15, 2022	Mar 5, 2024	Activation of the AhR leading to metastatic breast cancer
2191	Apoptosis	Increase, Tissue/organ damage	Nov 2, 2020	Nov 2, 2020
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
1723	Activation of TGF-β signaling	EMT	Mar 18, 2018	Mar 18, 2018
1721	Activation of TGF-β signaling	Increase, Inflammation	Mar 18, 2018	Mar 18, 2018	Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis
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
1361	ROS formation	Increase, Oxidative Stress / Activation, PMK-1 P38 MAPK	Feb 15, 2017	Feb 15, 2017	NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
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
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
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
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
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
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
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
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
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
1595	Increase, ROS formation	Increase, DNA Damage	Jun 29, 2017	Jun 29, 2017
1598	Increase, ROS formation	Increase, LPO	Jun 29, 2017	Jun 29, 2017
1466	Increase, ROS formation	Peptide Oxidation	Apr 15, 2017	Apr 15, 2017
2826	Increase, ROS formation	Oxidative Stress	Jan 9, 2023	Jan 9, 2023	AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases.
3231	Increase, ROS formation	Increase, Oxidative DNA damage	May 27, 2024	May 27, 2024
2342	Increase, ROS formation	D1 protein deactivation	Apr 11, 2021	Apr 11, 2021
2345	Increase, ROS formation	Decrease, MMP	Apr 11, 2021	Apr 11, 2021
2185	Increase, Apoptosis	Increase, Tissue/organ damage	Nov 2, 2020	Nov 2, 2020
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
2075	Increase, Apoptosis	Reduce, Sperm count	Apr 6, 2020	Apr 6, 2020	Alkylation of DNA leading to reduced sperm count
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, outgrowth	Jul 28, 2022	Jul 28, 2022
1469	Increase, Apoptosis	Decrease, Oogenesis	Apr 15, 2017	Apr 15, 2017
1596	Increase, Apoptosis	Increase, Follicular atresia	Jun 29, 2017	Jun 29, 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)
2602	Increase, Apoptosis	Microcephaly	Mar 17, 2022	Mar 17, 2022
2461	Increase, Apoptosis	Increased, Kidney Failure	Aug 5, 2021	Aug 5, 2021
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
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
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
2578	Increase, angiogenesis	N/A, Breast Cancer	Feb 15, 2022	Feb 15, 2022
3308	Increase, angiogenesis	Increase, Cancer	Jul 18, 2024	Jul 18, 2024
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
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
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
3314	Oxidative Stress	Neuronal network function, Decreased	Jul 23, 2024	Jul 23, 2024	Excessive iron accumulation leading to neurological disorders
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
3311	Oxidative Stress	Unfolded Protein Response	Jul 23, 2024	Jul 23, 2024	CYP2E1 activation and formation of protein adducts leading to neurodegeneration
3310	Oxidative Stress	Lipid Peroxidation	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
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
3284	Oxidative Stress	Uncoupling, eNOS	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
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
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
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
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.
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
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
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
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
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
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
3252	Oxidative Stress	Neuroinflammation	Jun 19, 2024	Jun 19, 2024	Binding and activation of GPER leading to learning and memory impairments
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
3239	Oxidative Stress	Increase, Oocyte apoptosis	May 31, 2024	May 31, 2024	Deposition of ionizing energy leads to population decline via impaired meiosis
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
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
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
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
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
2289	Oxidative Stress	Coagulation	Mar 25, 2021	Mar 25, 2021
2008	Oxidative Stress	Wnt ligand stimulation	Dec 3, 2019	Dec 3, 2019
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
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
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
3116	Oxidative Stress	Increase, LPO	Jan 24, 2024	Apr 11, 2024	Essential element imbalance leads to reproductive failure via oxidative stress
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
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
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
1600	Decrease, Coupling of OXPHOS	Decrease, Mitochondrial ATP production	Jun 29, 2017	Jun 29, 2017
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
2175	Decrease, Coupling of OXPHOS	Decrease, ATP synthase activity	Nov 2, 2020	Nov 2, 2020
2182	Decrease, Coupling of OXPHOS	Increase, Complex III dysfunction	Nov 2, 2020	Nov 2, 2020
2219	Decrease, Coupling of OXPHOS	Increase, Oxygen consumption	Dec 4, 2020	Dec 4, 2020
2188	Decrease, Coupling of OXPHOS	Increase, Complex I dysfunction	Nov 2, 2020	Nov 2, 2020
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
3495	Decrease, Coupling of OXPHOS	Increase, ROS	Feb 25, 2025	Feb 25, 2025	Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress
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
1725	EMT	Lung fibrosis	Mar 18, 2018	Mar 18, 2018
1655	EMT	Accumulation, Collagen	Aug 16, 2017	Aug 16, 2017	Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis
3306	EMT	Increase, Cancer	Jul 18, 2024	Jul 18, 2024	Succinate dehydrogenase inactivation leads to cancer by promoting EMT
3204	EMT	Airway remodeling	May 1, 2024	May 1, 2024	Adverse outcome pathway of PM-induced respiratory toxicity
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
2614	EMT	Metastasis, Breast Cancer	Mar 22, 2022	Sep 26, 2023	DNA damage and mutations leading to Metastatic Breast Cancer
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
1630	Cell damage sensing	Sustained inflammatory cytokine release	Jul 26, 2017	Jul 26, 2017
1631	Cell damage sensing	Increase, Excessive ROS	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
3099	Increase, DSB	Increase, Casp transcription	Nov 16, 2023	Nov 16, 2023	DNA methyltransferase inhibition leading to population decline (3)
3096	Increase, DSB	Increase, Apoptosis	Nov 16, 2023	Nov 16, 2023	Excessive reactive oxygen species production leading to mortality (4)
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
1652	TGFbeta pathway activation	Differentiation of fibroblasts	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
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
2547	Decrease, ATP production	Decrease, Reproduction	Jan 21, 2022	Jan 21, 2022	Deposition of ionizing energy leading to population decline via inhibition of photosynthesis
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
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
2346	Decrease, OXPHOS	Decrease, ATP synthase activity	Apr 11, 2021	Apr 11, 2021
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
2713	Decrease, OXPHOS	Oxidative Stress	Jul 25, 2022	Jul 25, 2022
2095	Decrease, OXPHOS	Decrease, ATP pool	Apr 30, 2020	Apr 30, 2020	Excessive reactive oxygen species production leading to mortality (2)
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
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
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
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
2891	Leukocyte recruitment/activation	Increased extracellular matrix deposition	Apr 13, 2023	Apr 13, 2023
1901	Leukocyte recruitment/activation	Increase, Cell Proliferation (Epithelial Cells)	May 7, 2019	May 7, 2019
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
1778	Leukocyte recruitment/activation	Activation, Stellate cells	Nov 12, 2018	Nov 12, 2018	Endocytic lysosomal uptake leading to liver fibrosis
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
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
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)
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
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
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
2651	Increased proinflammatory mediators	Activation, Dendritic Cells	Apr 28, 2022	Aug 1, 2022	Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response
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)
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)
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
1964	Recruitment of inflammatory cells	Increase, ROS	Jul 3, 2019	Jul 3, 2019	Frustrated phagocytosis-induced lung cancer Frustrated phagocytosis leads to malignant mesothelioma
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
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
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
2258	Loss of alveolar capillary membrane integrity	Impaired lung function	Jan 8, 2021	Jan 8, 2021
2259	Loss of alveolar capillary membrane integrity	Substance - LS interaction	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
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
1717	Histone deacetylase inhibition	Testicular atrophy	Jan 21, 2018	Jul 28, 2021	Histone deacetylase inhibition leading to testicular atrophy
1715	Histone deacetylase inhibition	Cell cycle, disrupted	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
2699	Histone deacetylase inhibition	Neural tube defects	Jul 19, 2022	Jul 19, 2022	Ceramide synthase inhibition leading to neural tube defects
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
2010	Histone deacetylase inhibition	Spermatocyte depletion	Dec 11, 2019	Jul 1, 2021	Histone deacetylase inhibition leading to testicular atrophy
1997	Histone acetylation, increase	Cell cycle, disrupted	Nov 11, 2019	Jul 1, 2021	Histone deacetylase inhibition leading to testicular atrophy
1710	Histone acetylation, increase	p21 (CDKN1A) expression, increase	Jan 21, 2018	Jul 25, 2018
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
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
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
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
2712	Unfolded Protein Response	Increase, Cell death	Jul 25, 2022	Jul 25, 2022
1732	Unfolded Protein Response	General Apoptosis	Apr 4, 2018	Apr 5, 2018	CYP2E1 activation and formation of protein adducts leading to neurodegeneration
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
1866	Unfolded Protein Response	Apoptosis	Mar 6, 2019	Mar 6, 2019	Inhibition of N-linked glycosylation leads to liver injury
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
1740	Decrease, PSII activity	Increase, ROS formation	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
1875	Increase, Mitochondrial complex III antagonism	Increase, ROS formation	Mar 19, 2019	Mar 19, 2019
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
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
2715	Mitochondrial Injury	Increase, Cell death	Jul 25, 2022	Jul 25, 2022
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
1821	Impaired T cell activation	Suppression, Suppression of T-cell dependent antibody response (TDAR)	Dec 25, 2018	Dec 25, 2018
1822	Impaired T cell activation	Impairment of TDAR	Dec 25, 2018	Jun 1, 2019
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
1824	Decreased IL-1 production	Suppressed MyD88	Jan 6, 2019	Jan 6, 2019
1814	Decreased IL-1 production	Impaired IL-1 signaling	Dec 25, 2018	Jun 25, 2019
1825	Impaired IL-1 signaling	Suppressed MyD88	Jan 6, 2019	Mar 14, 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
1920	Impaired IL-1 signaling	Inhibition, Nuclear factor kappa B (NF-kB)	May 23, 2019	Jun 25, 2019
1826	Suppressed MyD88	Impairment of TDAR	Jan 6, 2019	Jan 6, 2019
1870	Suppressed MyD88	Inhibition, Nuclear factor kappa B (NF-kB)	Mar 12, 2019	Mar 12, 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
1843	Absorption of photon energy	ROS generation	Feb 4, 2019	Feb 4, 2019
1845	ROS generation	Oxidation of membrane lipids	Feb 4, 2019	Jul 9, 2019	Adverse outcome pathway on photochemical toxicity initiated by light exposure
1847	ROS generation	Oxidation of DNA	Feb 4, 2019	Feb 4, 2019
1846	ROS generation	Oxidation/denatuation of membrane proteins	Feb 4, 2019	Jul 9, 2019	Adverse outcome pathway on photochemical toxicity initiated by light exposure
1849	Radical generation	Protein photo-adducts	Feb 4, 2019	Feb 4, 2019
1848	Radical generation	DNA 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
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
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
1878	Inhibition of Cyp17A1 activity	Reduction, DHEA	Apr 10, 2019	Apr 10, 2019	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 10, 2019	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	May 24, 2024	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	May 24, 2024	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
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
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
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 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
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
2337	Increase in RONS	Decrease, MMP	Apr 11, 2021	Apr 11, 2021
2331	Increase in RONS	D1 protein deactivation	Apr 11, 2021	Apr 11, 2021
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
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
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
2199	Increase in inflammation	hepatitis	Nov 2, 2020	Nov 2, 2020	Immune mediated hepatitis
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
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
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
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
3480	Increase, DNA strand breaks	Cell cycle, disrupted	Jan 20, 2025	Jan 20, 2025
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
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
2841	Increase, DNA strand breaks	Abnormal Neural Remodeling	Jan 25, 2023	Jul 29, 2024	Deposition of Energy Leading to Learning and Memory Impairment
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
2856	Increase, DNA strand breaks	Altered Signaling	Mar 10, 2023	Mar 21, 2023
2074	Increase, DNA strand breaks	Increase, Apoptosis	Apr 6, 2020	Apr 6, 2020	Alkylation of DNA leading to reduced sperm count
1985	Increase, Chromosomal aberrations	Increase, lung cancer	Aug 29, 2019	Jan 10, 2023	Deposition of energy leading to lung cancer
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
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
2143	Altered, Visual function	Decrease, Population growth rate	May 25, 2020	May 25, 2020	Inhibition of retinaldehyde dehydrogenase leads to population decline
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
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
3193	TR Antagnoism	Hypomyelination	Apr 12, 2024	Apr 12, 2024	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
3186	TR Antagnoism	Reduced number of oligodendrocytes	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
1962	Frustrated phagocytosis	Release, Cytokine	Jul 3, 2019	Aug 13, 2019	Frustrated phagocytosis-induced lung cancer
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
2417	Increased, DNA damage and mutation	Genomic instability	Jul 6, 2021	Jul 6, 2021	Frustrated phagocytosis leads to malignant mesothelioma
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
2728	Increased, DNA damage and mutation	Increase chromosomal aberrations	Aug 14, 2022	Aug 27, 2023	DNA damage and mutations leading to Metastatic Breast 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
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
2255	Inhibition of LS function.	Loss of alveolar capillary membrane integrity	Jan 8, 2021	Jan 8, 2021
2256	Inhibition of LS function.	Reduced tidal volume	Jan 8, 2021	Jan 8, 2021
2370	Inhibition of LS function.	Decreased lung function	Apr 27, 2021	Apr 27, 2021	Lung surfactant function inhibition leading to decreased lung function
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
2557	Energy Deposition	Increase, Excessive ROS	Feb 4, 2022	Feb 4, 2022
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
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
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
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
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
3486	Decrease, circulating testosterone levels	nipple retention, increased	Jan 30, 2025	Jan 30, 2025
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)
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
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
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）
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
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
3202	Decrease, circulating testosterone levels	malformed, Male reproductive tract	Apr 25, 2024	Apr 25, 2024	HMG-CoA reductase inhibition leading to decreased fertility
3350	Decrease, circulating testosterone levels	Hypospadias	Oct 1, 2024	Oct 1, 2024
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
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	Reduction, Plasma progesterone concentration	Oct 3, 2019	Oct 3, 2019	Luteinizing hormone receptor antagonism leading to reproductive dysfunction
1988	Reduction, Plasma progesterone concentration	Reduction, progesterone uptake, decresed maturation	Oct 3, 2019	Oct 3, 2019	Luteinizing hormone receptor antagonism leading to reproductive dysfunction
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
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)
2361	SARS-CoV-2 cell entry	Sustentacular cells, decrease	Apr 26, 2021	Apr 26, 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)
2302	SARS-CoV-2 cell entry	TLR Activation/Dysregulation	Mar 29, 2021	Mar 29, 2021
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
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
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)
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
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
2065	ACE2 enzymatic inhibition	Increased AngII	Mar 17, 2020	Mar 17, 2020	Binding to ACE2 leading to lung fibrosis
2520	Induced, Angiotensin (Ang) II accumulation	Hyperactivation of ACE/Ang-II/AT1R axis	Oct 28, 2021	Oct 28, 2021
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
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
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
2066	Increased AngII	Increase plasma Ang II	Mar 17, 2020	Mar 17, 2020
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
2082	Increase, Cripto-1 expression	Inhibition, Fin regeneration	Apr 21, 2020	Jul 10, 2020	Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
2078	Increase, Cripto-1 expression	Inhibition, Activin signaling	Apr 21, 2020	Jul 7, 2020	Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
2079	Inhibition, Activin signaling	Inhibition, Fin regeneration	Apr 21, 2020	Jul 10, 2020	Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
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
2223	Increase, Protein oxidation	Increase, Cell death	Dec 4, 2020	Dec 4, 2020
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)
2091	Increase, Abnormal osmoregulation	Increase, Body fluid overload	Apr 30, 2020	Apr 30, 2020	Excessive reactive oxygen species production leading to mortality (1)
2181	Increase, Abnormal osmoregulation	Increase, Tissue/organ damage	Nov 2, 2020	Nov 2, 2020
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
2216	Decrease, ATP pool	Increase, Fatty acid β-oxidation	Dec 4, 2020	Dec 4, 2020
2179	Decrease, ATP pool	Decrease, ATPase activity	Nov 2, 2020	Nov 2, 2020
2214	Decrease, ATP pool	Increase, Cell death	Dec 4, 2020	Dec 4, 2020	Mitochondrial ATP synthase antagonism leading to growth inhibition (2)
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
2209	Decrease, ATP pool	Decrease, Oogenesis	Nov 25, 2020	Nov 25, 2020
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
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
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
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
2386	Increase, Oocyte apoptosis	decreased, Fertility	May 12, 2021	May 12, 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
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
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
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
2186	Increase, Complex III dysfunction	Increase, Excessive ROS	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
2189	Increase, Complex I dysfunction	Increase, Excessive ROS	Nov 2, 2020	Nov 2, 2020
2192	Reactive Metabolite	Mitochondrial dysfunction EMPTY	Nov 2, 2020	Nov 2, 2020
2194	Reactive Metabolite	Immune cell activation	Nov 2, 2020	Nov 2, 2020	Immune mediated hepatitis
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
2193	Mitochondrial dysfunction EMPTY	Apoptotic cell death	Nov 2, 2020	Nov 2, 2020
2195	Mitochondrial dysfunction EMPTY	ER stress	Nov 2, 2020	Nov 2, 2020
2932	Mitochondrial dysfunction EMPTY	Impaired insulin signaling	May 25, 2023	May 25, 2023
3043	Mitochondrial dysfunction EMPTY	Proteasomal dysfunction	Sep 14, 2023	Sep 14, 2023
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, outgrowth	Jul 28, 2022	May 22, 2023	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)
2842	Increase, Cell death	Altered Bone Cell Homeostasis	Jan 25, 2023	Nov 6, 2024	Deposition of energy leading to occurrence of bone loss
3508	Increase, Cell death	Loss of olfactory function	Mar 13, 2025	Mar 25, 2025	Inhibition, cytochrome oxidase leads to Loss of olfactory function
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
2863	Increase, Cell death	Hippocampal Physiology, Altered	Apr 3, 2023	Apr 3, 2023
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
2220	Increase, Oxygen consumption	Increase, Excessive ROS	Dec 4, 2020	Dec 4, 2020
2226	Increase, Global methylation	Increase, Apoptosis	Dec 4, 2020	Dec 4, 2020
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
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
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
2313	Coagulation	Oxidative Stress	Apr 8, 2021	Apr 8, 2021
2360	Coagulation	Diminished Protective Response to ROS	Apr 20, 2021	Jun 21, 2024	Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation
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
2291	SARS-CoV-2 production	Oxidative Stress	Mar 25, 2021	Mar 25, 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
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
2304	Binding of agonist, Angiotensin II receptor type 1 receptor (AT1R)	Increase, Excessive ROS	Mar 30, 2021	Mar 30, 2021
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
2316	Increased viral transcription and replication	TLR Activation/Dysregulation	Apr 9, 2021	Apr 9, 2021
2315	Increased viral transcription and replication	Increased proinflammatory mediators	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	Mar 8, 2025	Aryl hydrocarbon Receptor (AhR) activation causes Premature Ovarian Insufficiency leading to Reproductive Failure
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	Jul 27, 2023	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
3479	Increased, ROS	Increase, Protein oxidation	Jan 20, 2025	Jan 20, 2025
3481	Increased, ROS	Decrease, Coupling of OXPHOS	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
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
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	Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons
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
2536	hERG channel biogenesis interference	Induction of hERG trafficking defects	Dec 13, 2021	Dec 13, 2021
2535	hERG channel biogenesis interference	Direct hERG channel blockage	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
2601	Activation of TP53	Altered differentiation	Mar 17, 2022	Mar 17, 2022
2600	Activation of TP53	Increase, Apoptosis	Mar 9, 2022	Mar 9, 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	May 17, 2023	Antagonism of Smoothened receptor leading to orofacial clefting
2894	Antagonism Smoothened	OFC	Apr 14, 2023	May 12, 2023	Antagonism of Smoothened receptor leading to orofacial clefting
2721	Decrease, GLI1/2 translocation	Decrease, GLI1/2 target gene expression	Jul 28, 2022	Jun 13, 2023	Antagonism of Smoothened receptor leading to orofacial clefting
3246	GPER activation	Increased, Intracellular Calcium overload	Jun 19, 2024	Jun 19, 2024	Binding and activation of GPER leading to learning and memory impairments
3247	GPER activation	Decreased, ERαβ heterodimers	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, outgrowth	Nov 17, 2022	Nov 17, 2022
2731	Decrease, GLI1/2 target gene expression	Decrease, SHH second messenger production	Aug 23, 2022	May 22, 2023	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	May 1, 2023	Antagonism of Smoothened receptor leading to orofacial clefting
2726	Decrease, outgrowth	OFC	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	Nov 14, 2023	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	May 22, 2023	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	Dec 11, 2022	Various neuronal effects induced by elavl3, sox10, and mbp
3298	Loss of drebrin	Dendritic spine abnormality	Jul 14, 2024	Mar 12, 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
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
3189	Cholesterol metabolism	Reduced number of oligodendrocytes	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
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
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
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
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
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
2873	decreased, Bcl-2	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
2874	increased, Bax	Increase, Cell death	Apr 4, 2023	Apr 4, 2023
3467	increased, Bax	Apoptosis	Jan 4, 2025	Feb 21, 2025	Aryl hydrocarbon Receptor (AhR) activation causes Premature Ovarian Insufficiency leading to Reproductive Failure
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
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
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
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	Jul 27, 2023	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	Jul 27, 2023	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
3128	RAR agonism	Microcephalus	Feb 2, 2024	Feb 2, 2024
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
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
3125	Decreased proliferation of cortical NPCs	RAR agonism	Feb 2, 2024	Feb 2, 2024
3126	Decreased proliferation of cortical NPCs	Reduced cortical thickness	Feb 2, 2024	Feb 2, 2024	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
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
3127	Reduced cortical thickness	Microcephalus	Feb 2, 2024	Feb 2, 2024
3143	Reduced cortical thickness	Microcephaly	Mar 13, 2024	Mar 13, 2024	Retinoic acid receptor agonism during neurodevelopment leading to microcephaly
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
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
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
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
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
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
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
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
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
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
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	Jul 17, 2024	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	Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons
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
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	Feb 27, 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	Feb 27, 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	Feb 27, 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	Feb 27, 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
3487	Decrease, intratesticular testosterone	nipple retention, increased	Jan 30, 2025	Jan 30, 2025
3488	Decrease, intratesticular testosterone	Hypospadias	Feb 15, 2025	Feb 15, 2025
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
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