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KE Relationships

ID	Upstream Event	Downstream Event	Creation Date	Last Updated	AOPs
1927	β-catenin activation	Snail, Zeb, Twist activation	May 29, 2019	May 29, 2019
1924	Wnt ligand stimulation	Frizzled activation	May 29, 2019	May 29, 2019
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
2757	Weak, Procuticle protection	Decrease, New cuticle secretion	Aug 28, 2022	Aug 28, 2022	Knickkopf leading to mortality
1639	Weak collagen matrix	Notochord malformation	Aug 3, 2017	Aug 3, 2017	Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
2693	Viable offspring, decreased	Decrease, Population growth rate	Jul 18, 2022	Jul 18, 2022
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
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
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
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
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
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
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
1657	Up Regulation, SCD-1	Accumulation, Triglyceride	Aug 31, 2017	Aug 31, 2017	AhR 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
492	Up Regulation, FAS	Increased, De Novo FA synthesis	Nov 29, 2016	Dec 3, 2016	NR1I3 (CAR) suppression leading to hepatic steatosis
104	Up Regulation, CYP1B1	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells	Nov 29, 2016	Dec 3, 2016
96	Up Regulation, CYP1A1	Peptide Oxidation	Nov 29, 2016	Dec 3, 2016
2887	Up Regulation, CYP1A1	Increase, ROS	Apr 13, 2023	Apr 13, 2023	AhR activation leading to liver fibrosis
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
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
1161	Unknown, MIE	Increased, Reactive oxygen species	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
1732	Unfolded Protein Response	General Apoptosis	Apr 4, 2018	Apr 5, 2018	CYP2E1 activation and formation of protein adducts leading to neurodegeneration
1866	Unfolded Protein Response	Apoptosis	Mar 6, 2019	Mar 6, 2019	Inhibition of N-linked glycosylation leads to liver injury
2712	Unfolded Protein Response	Increase, Cell death	Jul 25, 2022	Jul 25, 2022
3041	Unfolded Protein Response	Caspase activation	Sep 14, 2023	Sep 14, 2023	Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
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
1196	Uncarboxylated osteocalcin not incorporated into bone matrix, decreasing bone strength, Imp	Osteoporosis and vascular calcification, Bone deterioration	Nov 29, 2016	Dec 3, 2016
2028	Inhibition, trypsin	Increased monitor peptide	Jan 8, 2020	Jan 8, 2020	Trypsin inhibition leading to pancreatic acinar cell tumors
1281	TRPV1 activation, TRPV1	Opening of calcium channel, Calcium influx	Nov 29, 2016	Nov 29, 2016
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
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
1771	Increased Airway Hyper-responsiveness,Cough, Dyspnea	Respiratory irritability	Sep 24, 2018	Sep 24, 2018
1456	Treat, carbamazepine	Binding to VGSC	Apr 14, 2017	Apr 14, 2017	Molecular events lead to epilepsy presynaptic neuron 1 activation to epilepsy
1589	Increased transcription of genes encoding acute phase proteins	Systemic acute phase response	Jun 29, 2017	Dec 19, 2023	Substance interaction with lung resident cell membrane components leading to atherosclerosis
2542	Torsades de Pointes	Sudden cardiac death	Dec 13, 2021	Dec 13, 2021	hERG channel blockade leading to sudden cardiac death
2852	Torsades de Pointes	Increased Mortality	Jan 29, 2023	Jan 29, 2023
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
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
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
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
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)
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
383	Thyroperoxidase, Inhibition	Cognitive function, decreased	Nov 29, 2016	Dec 3, 2016
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
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
810	TH synthesis, Decreased	Increased, Serum creatinine	Nov 29, 2016	Dec 3, 2016	Kidney dysfunction by decreased thyroid hormone
1504	TH synthesis, Decreased	BDNF, Reduced	May 10, 2017	Apr 4, 2019	Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
1505	TH synthesis, Decreased	GABAergic interneurons, Decreased	May 10, 2017	May 29, 2018	Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
1506	TH synthesis, Decreased	Impairment, Learning and memory	May 10, 2017	May 29, 2018	Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
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
1636	Thiol protein adducts	Inhibition of lysyl oxidase	Aug 3, 2017	Aug 3, 2017	Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
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
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
2034	test	Unknown, MIE	Jan 26, 2020	Jan 26, 2020
2037	test	N/A, Unknown	Jan 26, 2020	Jan 26, 2020
541	inflammation	Activation, AKT2	Nov 29, 2016	Dec 3, 2016	AKT2 activation leading to hepatic steatosis
1590	Systemic acute phase response	HDL-SAA formation	Jun 29, 2017	Jun 29, 2017
2860	Systemic acute phase response	Atherosclerosis	Mar 28, 2023	Dec 18, 2023	Substance interaction with lung resident cell membrane components leading to atherosclerosis
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
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
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
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
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)
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)
3216	Suppression, VLDL secretion	Increased, Liver Steatosis	May 9, 2024	May 9, 2024	AhR activation leading to hepatic steatosis
1823	Suppression, Suppression of T-cell dependent antibody response (TDAR)	Impairment of TDAR	Dec 25, 2018	Dec 25, 2018
1259	Suppression, Suppression of T-cell dependent antibody production	Impairment of TDAR	Nov 29, 2016	Dec 3, 2016
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
388	Suppression, Inflammatory cytokines	Decreased, Lymphocytes	Nov 29, 2016	Dec 3, 2016	Glucocorticoid Receptor Activation Leading to Increased Disease Susceptibility
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
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
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
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
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
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
1818	Suppressed NF-kB	Suppressed DC activation	Dec 25, 2018	Dec 25, 2018
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
1819	Suppressed DC activation	Impaired antigen presentation	Dec 25, 2018	Dec 25, 2018
1817	Suppressed AP-1	Suppressed DC activation	Dec 25, 2018	Dec 25, 2018
2896	Superoxide generation, increased	Increase, Oxidative Stress	Apr 24, 2023	Jun 1, 2023
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
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
2895	SDH, inhibited	Increase, Oxidative Stress	Apr 24, 2023	Apr 24, 2023
3233	SDH, inhibited	Decrease, Coupling of OXPHOS	May 28, 2024	May 28, 2024	Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress
3302	SDH, inhibited	Succinate Accumulation	Jul 18, 2024	Jul 18, 2024	Succinate dehydrogenase inactivation leading to cancer
3303	Succinate Accumulation	Increase, DNMT inhibition	Jul 18, 2024	Jul 18, 2024	Succinate dehydrogenase inactivation leading to cancer
3304	Succinate Accumulation	Inhibition, Prolyl hydroxylases	Jul 18, 2024	Jul 18, 2024	Succinate dehydrogenase inactivation leading to cancer
1702	Interaction with the lung cell membrane	Increased proinflammatory mediators	Jan 5, 2018	Aug 29, 2023	Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis Interaction with lung resident cell membrane components leads to lung cancer Substance interaction with lung resident cell membrane components leading to atherosclerosis
2662	Interaction with the lung cell membrane	Increased, Reactive oxygen species	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
2958	Interaction with the lung cell membrane	Increased transcription of genes encoding acute phase proteins	Jul 4, 2023	Dec 19, 2023	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	Dec 19, 2023	Substance interaction with lung resident cell membrane components leading to atherosclerosis
2960	Interaction with the lung cell membrane	Atherosclerosis	Jul 4, 2023	Dec 18, 2023	Substance interaction with lung resident cell membrane components leading to atherosclerosis
1968	Substance - LS interaction	Inhibition of LS function.	Jul 3, 2019	Jul 3, 2019
3207	Binding PPAR isoforms	Dysregulation of transcriptional expression within PPAR signaling network	May 8, 2024	May 8, 2024
3208	Binding PPAR isoforms	Decreased, Mitochondrial fatty acid beta-oxidation	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
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
2141	Status epilepticus	Overactivation, NMDARs	May 21, 2020	May 21, 2020
2782	Status epilepticus	Increased, glutamate	Oct 12, 2022	Sep 3, 2023	Acetylcholinesterase Inhibition Leading to Neurodegeneration
2783	Status epilepticus	Increased, Intracellular Calcium overload	Oct 12, 2022	Jul 24, 2023	Acetylcholinesterase Inhibition Leading to Neurodegeneration
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
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.
1734	Spermatocyte depletion	Testicular atrophy	May 22, 2018	Jul 28, 2021	Histone deacetylase inhibition leading to testicular atrophy
1279	SP (Substance P) release, Local increase of SP	Non-neuronal production of TNF, Epithelial irritation	Nov 29, 2016	Nov 29, 2016
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
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
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
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
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
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
1588	Sensing of the stressor	Increased transcription of genes encoding acute phase proteins	Jun 29, 2017	Jun 29, 2017
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
2052	SARS-CoV-2 cell entry	Increased proinflammatory mediators	Mar 1, 2020	Mar 1, 2020
2302	SARS-CoV-2 cell entry	TLR Activation/Dysregulation	Mar 29, 2021	Mar 29, 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)
2314	SARS-CoV-2 cell entry	Increased viral transcription and replication	Apr 9, 2021	Apr 9, 2021
2361	SARS-CoV-2 cell entry	Sustentacular cells, decrease	Apr 26, 2021	Apr 26, 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)
2510	SARS-CoV-2 cell entry	Endothelial cell dysfunction	Oct 28, 2021	Oct 28, 2021
3036	Activation, RyR	Increased, glutamate	Sep 8, 2023	Sep 8, 2023	Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
1845	ROS generation	Oxidation of membrane lipids	Feb 4, 2019	Jul 9, 2019	Adverse outcome pathway on photochemical toxicity initiated by light exposure
1846	ROS generation	Oxidation/denatuation of membrane proteins	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
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
1915	Retinaldehyde dehydrogenase	retinoic acid	May 22, 2019	May 22, 2019	Inhibition of retinaldehyde dehydrogenase leads to population decline
378	Response, Keratinocytes	Activation, Dendritic Cells	Nov 29, 2016	Nov 29, 2016
380	Response, Keratinocytes	Activation/Proliferation, T-cells	Nov 29, 2016	Dec 3, 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
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
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
108	Release, Cytokine	Increase, Inflammation	Nov 29, 2016	Dec 3, 2016	Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
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)
2454	Release, Cytokine	Platelet activation, Increased	Aug 4, 2021	Aug 4, 2021	Endothelial cell dysfunction leading to thromboinflammation
2455	Release, Cytokine	Neutrophil activation, Increased	Aug 4, 2021	Aug 4, 2021	Endothelial cell dysfunction leading to thromboinflammation
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
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
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
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
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）
439	Reduction, Testosterone synthesis in Leydig cells	Reduction of testosterone	Nov 29, 2016	Dec 2, 2016
2125	Reduction, Testosterone synthesis in Leydig cells	Decrease, 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
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)
268	Reduction, Prostaglandin E2 concentration	N/A, Gap	Nov 29, 2016	Dec 3, 2016	Cyclooxygenase inhibition leading reproductive failure
1989	Reduction, progesterone uptake, decresed maturation	Impaired ovulation	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
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
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
1882	Reduction, Plasma vitellogenin concentrations	Reduction, egg production and spawning	Apr 18, 2019	Apr 18, 2019
1988	Reduction, Plasma progesterone concentration	Reduction, progesterone uptake, decresed maturation	Oct 3, 2019	Oct 3, 2019	Luteinizing hormone receptor antagonism leading to reproductive dysfunction
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
253	Reduction, Plasma 17beta-estradiol concentrations	Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development	Nov 29, 2016	Nov 29, 2016
392	Reduction, Plasma 17beta-estradiol concentrations	irregularities, ovarian cycle	Nov 29, 2016	Dec 3, 2016	Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female
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）
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）
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
1256	Reduction, NFAT/AP-1 complex formation	Suppression, Suppression of production of cytotoxic T-cells	Nov 29, 2016	Dec 3, 2016
1257	Reduction, NFAT/AP-1 complex formation	Suppression, Suppression of T-cell dependent antibody production	Nov 29, 2016	Dec 3, 2016
1509	Reduction, NFAT/AP-1 complex formation	Suppression, IL-2 and IL-4 production	May 19, 2017	Jun 27, 2021	Inhibition of Calcineurin Activity Leading to Impaired T-Cell Dependent Antibody Response
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
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
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)
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
123	Reduction, Eggshell thickness	N/A, Reproductive failure	Nov 29, 2016	Dec 3, 2016	Cyclooxygenase inhibition leading reproductive failure
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 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 Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production
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）
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
59	Reduction, Ca and HCO3 transport to shell gland	Reduction, Eggshell thickness	Nov 29, 2016	Dec 3, 2016	Cyclooxygenase inhibition leading reproductive failure
36	Reduction, Angiogenesis	Impairment, Endothelial network	Nov 29, 2016	Jan 18, 2022	Disruption of VEGFR Signaling Leading to Developmental Defects
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
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
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
3229	Reduction, androstenedione	Decrease, 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)
3228	Reduction, DHEA	Decrease, 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)
1894	Reduction of melanosome level	Reduction fo Pigmentation pattern	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
1638	Reduction of collagen crosslinking	Weak collagen matrix	Aug 3, 2017	Aug 3, 2017	Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
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
1893	Reduction in melanin level	Reduction of melanosome level	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
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
1641	Reduced, Swimming performance	Growth, reduction	Aug 3, 2017	Aug 3, 2017	Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
1642	Reduced, Swimming performance	Decreased, survival	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
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
1558	Reduced, SHP activity	Activated, LXR	Jun 2, 2017	Jun 2, 2017	NFE2/Nrf2 repression to steatosis
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
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
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
685	Reduced, Prostaglandins, ovary	Decrease, Ovulation	Nov 29, 2016	Dec 3, 2016	Cyclooxygenase inhibition leading to reproductive dysfunction
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
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
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
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
1551	Reduced, presynaptic neuron 2 activity	Decreased, GABA	Jun 2, 2017	Jun 2, 2017	presynaptic neuron 2 repression to epilepsy
1560	Reduced, PPARalpha	Reduced, HSD17B4 activity	Jun 2, 2017	Jun 2, 2017	NFE2/Nrf2 repression to steatosis
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
1031	Reduced, Posterior swim bladder inflation	Reduced, Anterior swim bladder inflation	Nov 29, 2016	Nov 20, 2020
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
1533	Reduced, platelet aggregation	Activated, gastric ulcer formation	Jun 2, 2017	Jun 2, 2017	NSAID induced PTGS1 inactivation to gastric ulcer
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
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
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
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
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
1561	Reduced, HSD17B4 activity	Reduced, fatty acid beta oxidation	Jun 2, 2017	Jun 2, 2017	NFE2/Nrf2 repression to steatosis
2231	Reduced, Hearing	Increased Mortality	Dec 8, 2020	Dec 8, 2020	GSK3beta inactivation leading to increased mortality via defects in developing inner ear
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
1553	Reduced, GABA-A receptor activation	Decreased, intracellular chloride	Jun 2, 2017	Jun 2, 2017	presynaptic neuron 2 repression to epilepsy
1557	Reduced, FXR activity	Reduced, SHP activity	Jun 2, 2017	Jun 2, 2017	NFE2/Nrf2 repression to steatosis
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
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
3215	Reduced, fatty acid beta oxidation	Increased, Liver Steatosis	May 9, 2024	May 9, 2024	NFE2/Nrf2 repression to steatosis
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
1523	Reduced, BDNF	Decreased, neuroplasticity	May 31, 2017	May 31, 2017	Mental stress to depression
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
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
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
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
2480	Ovarian reserve, reduced	Decreased fertility, Reduced number of oocytes ovulated	Sep 12, 2021	Sep 12, 2021
2487	Ovarian reserve, reduced	impaired, Fertility	Oct 10, 2021	Oct 10, 2021
2525	Ovarian reserve, reduced	irregularities, ovarian cycle	Oct 29, 2021	Jul 9, 2024	Inhibition of ALDH1A (RALDH) leading to impaired fertility via disrupted meiotic initiation of fetal oogonia of the ovary
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
3190	Reduced number of oligodendrocytes	Hypomyelination	Apr 12, 2024	Apr 12, 2024	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
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
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
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
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
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
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
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
2695	Reduced complex sphingolipids	Affected folate transporter	Jul 19, 2022	Jul 20, 2022	Ceramide synthase inhibition leading to neural tube defects
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
1848	Radical generation	DNA photo-adducts	Feb 4, 2019	Feb 4, 2019
1849	Radical generation	Protein photo-adducts	Feb 4, 2019	Feb 4, 2019
2679	Pulmonary inflammation	Chronic obstructive pulmonary disease	Jun 17, 2022	Jun 17, 2022	Adverse outcome pathway of PM-induced respiratory toxicity
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
1729	Protein Adduct Formation	Unfolded Protein Response	Apr 4, 2018	Apr 5, 2018	CYP2E1 activation and formation of protein adducts leading to neurodegeneration
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
2912	prostatic intraepithelial neoplasia	Prostate cancer	May 11, 2023	May 11, 2023	Androgen receptor activation leading to prostate cancer
240	Propagation, Oxidative stress	Down Regulation, Gulcose-6-phosphate dehydrogenase	Nov 29, 2016	Dec 3, 2016
241	Propagation, Oxidative stress	Damaging, Red blood cells; hemolysis	Nov 29, 2016	Dec 3, 2016
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.
2830	Promotion, ovarian granular cell tumors	Promotion, Ovarian Cancer	Jan 13, 2023	Jan 13, 2023
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
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.
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
604	prolonged, Depolarization of neuronal membrane	Overactivation, Neuronotransmitter release	Nov 29, 2016	Dec 3, 2016	Axonal sodium channel modulation leading to acute mortality
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)
2541	Prolongation of QT interval	Torsades de Pointes	Dec 13, 2021	Dec 13, 2021	hERG channel blockade leading to sudden cardiac death
2853	Prolongation of QT interval	Occurrence, cardiac arrhythmia	Jan 29, 2023	Jan 29, 2023
2540	Prolongation of Action Potential	Prolongation of QT interval	Dec 13, 2021	Dec 13, 2021	hERG channel blockade leading to sudden cardiac death
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
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.
69	Proliferation, Cell proliferation in the absence of cytotoxicity	Hyperplasia, Hyperplasia	Nov 29, 2016	Dec 3, 2016	Uncharacterized liver damage leading to hepatocellular carcinoma
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
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
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
1358	Production of α-smooth muscle actin	Lung fibrosis	Feb 15, 2017	Feb 15, 2017
1283	Production of nerve growth factor , Epithelial irritation	SP (Substance P) release, Local increase of SP	Nov 29, 2016	Dec 3, 2016
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.
1179	premature, spawning 1	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
2607	Premature differentiation	Microcephaly	Mar 21, 2022	Mar 21, 2022
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
2070	Porcupine-induced Wnt secretion and Wnt signaling activation	beta-catenin activation	Mar 23, 2020	Nov 9, 2021	Increases in cellular reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer
2458	Platelet-neutrophil interactions, Increased	Thromboinflammation, Increased	Aug 4, 2021	Aug 4, 2021	Endothelial cell dysfunction leading to thromboinflammation
2456	Platelet activation, Increased	Platelet-neutrophil interactions, Increased	Aug 4, 2021	Aug 4, 2021	Endothelial cell dysfunction leading to thromboinflammation
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
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
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.
1126	persistent, cytotoxicity (pleura or peritoneum)	Increased, Oxidative Stress	Nov 29, 2016	Dec 3, 2016
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.
256	demethylation, PPARg promoter	Decrease, Aromatase (Cyp19a1)	Nov 29, 2016	Dec 3, 2016
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
487	demethylation, PPARg promoter	Activation, SREBF1	Nov 29, 2016	Dec 3, 2016	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
1659	demethylation, PPARg promoter	Increased, FA Influx	Aug 31, 2017	Aug 31, 2017	NR1I3 (CAR) suppression leading to hepatic steatosis
2988	demethylation, PPARg promoter	Activation of PPAR	Aug 20, 2023	Aug 20, 2023	Demethylation of PPAR promotor leading to vascular disrupting effects
2516	Pericyte dysfunction	Endothelial cell dysfunction	Oct 28, 2021	Oct 28, 2021
236	Peptide Oxidation	Increased, Activation and Recruitment of Hepatic macrophages (Kupffer Cells)	Nov 29, 2016	Dec 3, 2016
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)
922	Peptide Oxidation	Mitochondrial dysfunction	Nov 29, 2016	Nov 29, 2016
923	Peptide Oxidation	Release, Cytokine	Nov 29, 2016	Dec 3, 2016
932	Peptide Oxidation	Cholestasis, Pathology	Nov 29, 2016	Dec 3, 2016	Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
948	Peptide Oxidation	Oxidation, Glutathione	Nov 29, 2016	Nov 29, 2016
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
1237	Peptide Oxidation	Increased activation, Nuclear factor kappa B (NF-kB)	Nov 29, 2016	Dec 3, 2016
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
1698	Peptide Oxidation	S-Glutathionylation, eNOS	Nov 16, 2017	Nov 20, 2017	Peptide Oxidation Leading to Hypertension
3083	Parkinsonian motor deficits	Increase, Mortality	Oct 17, 2023	Oct 17, 2023	Various neuronal effects induced by elavl3, sox10, and mbp
1711	p21 (CDKN1A) expression, increase	Cell cycle, disrupted	Jan 21, 2018	Jul 25, 2018
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
1727	Oxidative Stress in Brain	Lipid Peroxidation	Apr 4, 2018	Apr 5, 2018
1730	Oxidative Stress in Brain	Unfolded Protein Response	Apr 4, 2018	Apr 5, 2018
2655	Oxidative Stress in Brain	N/A, Neurodegeneration	May 16, 2022	May 16, 2022
2952	Oxidative Stress in Brain	Neuronal network function, Decreased	Jun 21, 2023	Jun 21, 2023
3062	Oxidative Stress in Brain	Decreased, Neuronal network function in adult brain	Oct 17, 2023	Oct 17, 2023
1513	Oxidative Stress	Hepatocytotoxicity	May 30, 2017	Jun 19, 2021	Cyp2E1 Activation Leading to Liver Cancer
1516	Oxidative Stress	Liver Cancer	May 30, 2017	Jun 19, 2021	Cyp2E1 Activation Leading to Liver Cancer
1685	Oxidative Stress	Glutamate dyshomeostasis	Nov 9, 2017	Feb 6, 2020	Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory
1690	Oxidative Stress	Cell injury/death	Nov 9, 2017	Feb 7, 2020	Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress
2008	Oxidative Stress	Wnt ligand stimulation	Dec 3, 2019	Dec 3, 2019
2289	Oxidative Stress	Coagulation	Mar 25, 2021	Mar 25, 2021
2449	Oxidative Stress	CFTR Function, Decreased	Jul 30, 2021	Sep 28, 2021	Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction
2450	Oxidative Stress	FOXJ1 Protein, Decreased	Aug 2, 2021	Sep 28, 2021	Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1
2451	Oxidative Stress	CBF, Decreased	Aug 2, 2021	Mar 24, 2023	Oxidative stress Leading to Decreased Lung Function
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
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
2716	Oxidative Stress	Increase, Cell death	Jul 25, 2022	Aug 23, 2024	Deposition of energy leading to occurrence of bone loss
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 vascular remodeling
2774	Oxidative Stress	Altered, Nitric Oxide Levels	Sep 28, 2022	Aug 26, 2024	Deposition of energy leads to vascular remodeling
2776	Oxidative Stress	Increase, Endothelial Dysfunction	Sep 28, 2022	Aug 27, 2024	Deposition of energy leads to vascular remodeling
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 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
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
2846	Oxidative Stress	Altered Bone Cell Homeostasis	Jan 25, 2023	Aug 12, 2024	Deposition of energy leading to occurrence of bone loss
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
3116	Oxidative Stress	Increased, LPO	Jan 24, 2024	Apr 11, 2024	Essential element imbalance leads to reproductive failure via oxidative stress
3129	Oxidative Stress	Mitochondrial dysfunction	Feb 17, 2024	May 31, 2024	AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases. Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
3239	Oxidative Stress	Increase, Oocyte apoptosis	May 31, 2024	May 31, 2024	Deposition of ionizing energy leads to population decline via impaired meiosis
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
3252	Oxidative Stress	Neuroinflammation	Jun 19, 2024	Jun 19, 2024	Binding and activation of GPER leading to learning and memory impairments
3262	Oxidative Stress	Increased, secretion of local growth factors	Jul 3, 2024	Jul 3, 2024	Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat.
3264	Oxidative Stress	Occurrence, renal proximal tubular necrosis	Jul 3, 2024	Jul 3, 2024	Organic anion transporter (OAT1) inhibition leading to renal failure and mortality Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality unknown MIE leading to renal failure and mortality Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
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
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
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
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
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
3279	Oxidative Stress	Abnormal expression of NO	Jul 4, 2024	Jul 4, 2024	Demethylation of PPAR promotor leading to 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
3281	Oxidative Stress	Activation, Dll4-Notch pathway	Jul 4, 2024	Jul 4, 2024	The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
3282	Oxidative Stress	Activated BMP/TGF-beta pathway	Jul 4, 2024	Jul 4, 2024	The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
3283	Oxidative Stress	Activated Wnt/Frizzled pathway	Jul 4, 2024	Jul 4, 2024	The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
3284	Oxidative Stress	Uncoupling, eNOS	Jul 4, 2024	Jul 4, 2024	The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
3285	Oxidative Stress	Activated AKT/ERK/PI3K pathway	Jul 4, 2024	Jul 4, 2024	The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
3286	Oxidative Stress	Inhibition VEGF/VEGFR pathway	Jul 4, 2024	Jul 4, 2024	The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
3293	Oxidative Stress	The NO synthase pathway activation	Jul 9, 2024	Jul 9, 2024	Adverse outcome pathway of PFAS-induced vascular disrupting effects via activating oxidative stress related pathways
3294	Oxidative Stress	Ferroptosis related pathways activation	Jul 9, 2024	Jul 9, 2024	Adverse outcome pathway of PFAS-induced vascular disrupting effects via activating oxidative stress related pathways
3310	Oxidative Stress	Lipid Peroxidation	Jul 23, 2024	Jul 23, 2024	CYP2E1 activation and formation of protein adducts leading to neurodegeneration
3311	Oxidative Stress	Unfolded Protein Response	Jul 23, 2024	Jul 23, 2024	CYP2E1 activation and formation of protein adducts leading to neurodegeneration
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
3314	Oxidative Stress	Neuronal network function, Decreased	Jul 23, 2024	Jul 23, 2024	Excessive iron accumulation leading to neurological disorders
3316	Oxidative Stress	Altered Stress Response Signaling	Jul 24, 2024	Aug 26, 2024	Deposition of energy leads to 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
1851	Oxidation/denatuation of membrane proteins	Inflammatory events	Feb 4, 2019	Jul 9, 2019	Adverse outcome pathway on photochemical toxicity initiated by light exposure
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
954	Oxidation, Glutathione	S-Glutathionylation, eNOS	Nov 29, 2016	Sep 28, 2017
2459	Oxidation, Glutathione	Increased, Reactive oxygen species	Aug 5, 2021	Aug 5, 2021	Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure
1850	Oxidation of membrane lipids	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
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
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)
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
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	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
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
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
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
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
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)
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)
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)
943	Occurrence, Transdifferentiation of ciliated epithelial cells	Goblet cell metaplasia	Nov 29, 2016	Aug 11, 2021
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
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
1139	Occurrence, renal ischemia	Occurrence, renal proximal tubular necrosis	Nov 29, 2016	Dec 3, 2016
1159	Occurrence, renal ischemia	Increased, Oxidative Stress	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
990	Goblet cell metaplasia	Hypersecretion, Mucus	Nov 29, 2016	Nov 29, 2016
1313	Goblet cell metaplasia	Increase, Mucin production	Nov 29, 2016	Aug 11, 2021
2471	Goblet cell metaplasia	Chronic, Mucus hypersecretion	Aug 26, 2021	Aug 27, 2021
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
989	Goblet cell hyperplasia	Hypersecretion, Mucus	Nov 29, 2016	Nov 29, 2016
1312	Goblet cell hyperplasia	Increase, Mucin production	Nov 29, 2016	Aug 11, 2021
2472	Goblet cell hyperplasia	Chronic, Mucus hypersecretion	Aug 26, 2021	Aug 30, 2021
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
1861	Occurrence, Epileptic seizure	Increased, glutamate	Feb 13, 2019	Feb 13, 2019
1999	Occurrence, Epileptic seizure	Overactivation, NMDARs	Nov 13, 2019	Nov 13, 2019
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
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
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
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
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
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
1136	Occurrence, cardiac arrthymia	Increased Mortality	Nov 29, 2016	Dec 3, 2016
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
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
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
1640	Notochord malformation	Reduced, Swimming performance	Aug 3, 2017	Aug 3, 2017	Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
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
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
1287	Non-neuronal production of IL-8/CXCL1, Epithelial irritation	Opening of calcium channel, Calcium influx	Nov 29, 2016	Dec 3, 2016
2667	Non-coding RNA expression，alteration	Activation, inflammation pathway	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
2670	Non-coding RNA expression，alteration	Fibroblast proliferation and differentiation	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
3203	Non-coding RNA expression，alteration	EMT	May 1, 2024	May 1, 2024	Adverse outcome pathway of PM-induced respiratory toxicity
2414	inflammasome activity, increased	Hyperinflammation	Jun 25, 2021	Jun 25, 2021	SARS-CoV-2 infection leading to hyperinflammation
1556	NFE2/Nrf2 repression	Reduced, FXR activity	Jun 2, 2017	Jun 2, 2017	NFE2/Nrf2 repression to steatosis
2979	NFE2/Nrf2 repression	Increase, Oxidative Stress	Aug 19, 2023	Aug 19, 2023
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
2457	Neutrophil activation, Increased	Platelet-neutrophil interactions, Increased	Aug 4, 2021	Aug 4, 2021	Endothelial cell dysfunction leading to thromboinflammation
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
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
759	Neuroinflammation	Synaptogenesis, Decreased	Nov 29, 2016	Dec 3, 2016
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
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 socio-economic burden through reduced IQ and 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
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
2717	Neuroinflammation	Increase, Cell death	Jul 25, 2022	Jul 25, 2022
3255	Neuroinflammation	Impairment, Learning and memory	Jun 19, 2024	Jun 19, 2024	Binding and activation of GPER leading to learning and memory impairments
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
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
3148	narcosis	Mitochondrial dysfunction	Mar 13, 2024	Mar 13, 2024	AOP from chemical insult to cell death
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
650	N/A, sedation	Decreased, locomotion	Nov 29, 2016	Dec 3, 2016	Histamine (H2) receptor antagonism leading to reduced survival
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
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
244	N/A, Parent compound is converted to the reactive metabolite and forms free radicals leadin	Propagation, Oxidative stress	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
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
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
368	N/A, Neurodegeneration	Neuronal network function, Decreased	Nov 29, 2016	Dec 3, 2016
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
1069	N/A, Neurodegeneration	Impairment, Learning and memory	Nov 29, 2016	Apr 11, 2024	Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
2287	N/A, Neurodegeneration	Encephalitis	Feb 23, 2021	Feb 23, 2021	Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on brain cells (neuronal and non-neuronal) leads to neuroinflammation resulting in encephalitis Various neuronal effects induced by elavl3, sox10, and mbp
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
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
2889	N/A, Liver Steatosis	Cell injury/death	Apr 13, 2023	Apr 13, 2023
168	N/A, Interferences with SH-/selen-proteins	Depletion, GSH	Nov 29, 2016	Dec 3, 2016
593	N/A, hypoxia	Increased, amputations	Nov 29, 2016	Dec 3, 2016	Sodium channel inhibition leading to congenital malformations
3307	N/A, hypoxia	Increase, angiogenesis	Jul 18, 2024	Jul 18, 2024	Succinate dehydrogenase inactivation leading to cancer
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
136	N/A, Gap	Reduction, Ca and HCO3 transport to shell gland	Nov 29, 2016	Dec 3, 2016	Cyclooxygenase inhibition leading reproductive failure
88	N/A, Covalent binding to protein, possibly lysine residue	Activation, Inflammatory cytokines, chemokines, cytoprotective gene pathways	Nov 29, 2016	Sep 24, 2020
1700	N/A, Covalent binding to protein, possibly lysine residue	Activation, Dendritic Cells	Dec 7, 2017	Sep 24, 2020
757	N/A, Ataxia, paralysis, or hyperactivity	Increased Mortality	Nov 29, 2016	Dec 3, 2016	Glutamate-gated chloride channel activation leading to acute mortality
33	N/A, Androgen receptor, Antagonism	Altered, Transcription of genes by the AR	Nov 29, 2016	Dec 3, 2016	Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)
35	N/A, Androgen receptor, Antagonism	Alteration, Wnt pathway	Nov 29, 2016	Dec 3, 2016	Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)
2445	Mucus Viscosity, Increased	CBF, Decreased	Jul 19, 2021	Aug 2, 2021
2446	Mucus Viscosity, Increased	MCC, Decreased	Jul 19, 2021	Aug 2, 2021
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
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
2448	Motile Cilia Number/Length, Decreased	CBF, Decreased	Jul 23, 2021	Sep 28, 2021	Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1
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
603	modulation, sodium channel	prolonged, Depolarization of neuronal membrane	Nov 29, 2016	Dec 3, 2016	Axonal sodium channel modulation leading to acute mortality
1941	Mitochondrial Injury	Increased reactive oxygen species (in the mitochondria)	Jun 7, 2019	Jun 7, 2019
1942	Mitochondrial Injury	Impaired, Proteostasis	Jun 7, 2019	Jun 7, 2019
2715	Mitochondrial Injury	Increase, Cell death	Jul 25, 2022	Jul 25, 2022
3049	Mitochondrial Injury	Increase, Cyt c release	Sep 14, 2023	Sep 14, 2023	Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
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
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
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
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
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
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
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
1958	Mitochondrial dysfunction	Increased reactive oxygen species (in the mitochondria)	Jun 15, 2019	Jun 15, 2019	Mitochondrial complex inhibition leading to liver injury
2224	Mitochondrial dysfunction	Increase, ROS production	Dec 4, 2020	Dec 4, 2020	Thermal stress leading to population decline (3)
2227	Mitochondrial dysfunction	Increase, ROS	Dec 4, 2020	Dec 4, 2020	Thermal stress leading to population decline (2)
2228	Mitochondrial dysfunction	Decrease, ATP pool	Dec 4, 2020	Dec 4, 2020	Thermal stress leading to population decline (1)
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
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
3134	Mitochondrial dysfunction	Increase, Cytotoxicity (renal tubular cell)	Feb 28, 2024	Mar 6, 2024	Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity
3136	Mitochondrial dysfunction	Proteasomal dysfunction	Feb 29, 2024	Feb 29, 2024	Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
3141	Mitochondrial dysfunction	Increased, Reactive oxygen species	Mar 6, 2024	Apr 11, 2024	Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
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
3149	Mitochondrial dysfunction	Necrosis	Mar 13, 2024	Mar 13, 2024	AOP from chemical insult to cell death
3150	Mitochondrial dysfunction	cell injury	Mar 13, 2024	Mar 13, 2024	AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment
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
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
3158	Mitochondrial dysfunction	Occurrence, Cytoplasmic vacuolization (Bile duct cell)	Mar 13, 2024	Mar 13, 2024	Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
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
1783	Mitochondrial Complex V inhibition	Decrease in mitochondrial oxidative phosphorylation	Dec 19, 2018	Mar 7, 2019	Mitochondrial complex inhibition leading to liver injury
1786	Mitochondrial Complex V inhibition	Increased reactive oxygen species (in the mitochondria)	Dec 19, 2018	Dec 19, 2018
1782	Mitochondrial Complex IV inhibition	Decrease in mitochondrial oxidative phosphorylation	Dec 19, 2018	Mar 7, 2019	Mitochondrial complex inhibition leading to liver injury
1785	Mitochondrial Complex IV inhibition	Increased reactive oxygen species (in the mitochondria)	Dec 19, 2018	Mar 7, 2019
1780	Mitochondrial Complex I inhibition	Decrease in mitochondrial oxidative phosphorylation	Dec 19, 2018	Mar 7, 2019
1790	Mitochondrial Complex I inhibition	Increased reactive oxygen species (in the mitochondria)	Dec 19, 2018	Mar 7, 2019
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)
808	malformed, Male reproductive tract	Decrease, Fertility	Nov 29, 2016	Dec 3, 2016	HMG-CoA reductase inhibition leading to decreased fertility
405	Malformation, Male reproductive tract	impaired, Fertility	Nov 29, 2016	Dec 2, 2016	PPARα activation in utero leading to impaired fertility in males
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	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
3300	Loss of drebrin	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
1972	Loss of barrier function	Blood extravasation into the lungs	Jul 3, 2019	Jul 3, 2019
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
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
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
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
1728	Lipid Peroxidation	Protein Adduct Formation	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
1778	Leukocyte recruitment/activation	Activation, Stellate cells	Nov 12, 2018	Nov 12, 2018	Endocytic lysosomal uptake leading to liver fibrosis
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
2891	Leukocyte recruitment/activation	Increased extracellular matrix deposition	Apr 13, 2023	Apr 13, 2023	AhR activation leading to liver 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
983	Increase, Vascular Resistance	Hypertension	Nov 29, 2016	Oct 13, 2017	Peptide Oxidation Leading to Hypertension
982	Impaired, Vasodilation	Increase, Vascular Resistance	Nov 29, 2016	Oct 13, 2017	Peptide Oxidation Leading to Hypertension
958	Depletion, Nitric Oxide	Impaired, Vasodilation	Nov 29, 2016	Oct 12, 2017	Peptide Oxidation Leading to Hypertension
988	Decrease, AKT/eNOS activity	Depletion, Nitric Oxide	Nov 29, 2016	Oct 16, 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
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
955	S-Glutathionylation, eNOS	Uncoupling, eNOS	Nov 29, 2016	Oct 12, 2017	Peptide Oxidation Leading to Hypertension
1774	Irritation induced sneezing	Increased Airway Hyper-responsiveness,Cough, Dyspnea	Sep 24, 2018	Sep 24, 2018
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
393	irregularities, ovarian cycle	Decrease, Fertility	Nov 29, 2016	Dec 3, 2016
394	irregularities, ovarian cycle	impaired, Fertility	Nov 29, 2016	Dec 3, 2016	Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female Inhibition of ALDH1A (RALDH) leading to impaired fertility via disrupted meiotic initiation of fetal oogonia of the ovary Androgen receptor (AR) antagonism leading to decreased fertility in females
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	Aug 13, 2024	Gluten intake leading to celiac disease example test - under development
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.
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)
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
1836	Interaction of α-diketones with arginine residues	Proteasomal dysfunction	Jan 30, 2019	Jan 30, 2019	α-diketone-induced bronchiolitis obliterans
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
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
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 socio-economic burden through reduced IQ and non-cholinergic mechanisms
3331	Innate immune response, activation	Activation/Proliferation, T-cells	Aug 13, 2024	Aug 13, 2024	Gluten intake leading to celiac disease example test - under development
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
335	Inhibition, VegfR2	Reduction, Angiogenesis	Nov 29, 2016	Jul 20, 2022	Disruption of VEGFR Signaling Leading to Developmental Defects
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
585	Inhibition, sodium channel	Decreased, Sodium conductance 1	Nov 29, 2016	Dec 3, 2016	Sodium channel inhibition leading to reduced survival sodium channel inhibition leading to increased predation Sodium channel inhibition leading to congenital malformations
590	Inhibition, sodium channel	Increased, Atrioventricular block and bradycardia	Nov 29, 2016	Dec 3, 2016
1242	Inhibition, sodium channel	Decreased, sodium conductance 2	Nov 29, 2016	Dec 3, 2016	Sodium channel (Nav1.1) inhibition leading to population decline
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)
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
511	Inhibition, PPAR alpha	Inhibition, Mitochondrial fatty acid beta-oxidation	Nov 29, 2016	Dec 3, 2016	NR1I3 (CAR) suppression leading to hepatic steatosis
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
1202	Inhibition, Pendrin	TH synthesis, Decreased	Nov 29, 2016	Dec 3, 2016	Pendrin inhibition leading to altered amphibian metamorphosis
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
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
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
1921	Inhibition, Nuclear factor kappa B (NF-kB)	Impaired T cell activation	May 23, 2019	Jun 25, 2019
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
2306	Inhibition, Nuclear factor kappa B (NF-kB)	Increased proinflammatory mediators	Mar 30, 2021	Mar 30, 2021
2644	Inhibition, Nuclear factor kappa B (NF-kB)	Increase in inflammation	Apr 8, 2022	Apr 8, 2022	Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
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
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
442	Inhibition, Na+/I- symporter (NIS)	Thyroidal Iodide, Decreased	Nov 29, 2016	May 29, 2018	Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis
552	Inhibition, Na+/I- symporter (NIS)	TH synthesis, Decreased	Nov 29, 2016	Dec 3, 2016	XX Inhibition of Sodium Iodide Symporter and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse)
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
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
1049	Inhibition, Motor neuron activity	Induction, Somatic muscle paralysis	Nov 29, 2016	Dec 3, 2016
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
2565	Inhibition, ETC complexes of the respiratory chain	Increase, Oxidative Stress	Feb 8, 2022	Mar 7, 2022
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
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
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
1413	Inhibition, LXR	Inhibition, PPAR alpha	Apr 12, 2017	Apr 12, 2017
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
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
1827	Inhibition, IKK complex	Inhibition, Nuclear factor kappa B (NF-kB)	Jan 7, 2019	Mar 7, 2019	IKK complex inhibition leading to liver injury
804	Inhibition, HMG-CoA reductase	Decreased, mevalonate	Nov 29, 2016	Dec 3, 2016	HMG-CoA reductase inhibition leading to decreased fertility
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
2080	Inhibition, Fin regeneration	Reduced, Swimming performance	Apr 21, 2020	Jul 10, 2020	Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
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
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)
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
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
1203	Inhibition, Dual oxidase	TH synthesis, Decreased	Nov 29, 2016	Dec 3, 2016	Dual oxidase (DUOX) 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
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
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
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
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
1045	Inhibition, Deiodinase 1	Reduced, Anterior swim bladder inflation	Nov 29, 2016	Mar 8, 2019
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
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)
95	Inhibition, Cyclooxygenase activity	Reduction, Prostaglandin E2 concentration	Nov 29, 2016	Dec 3, 2016	Cyclooxygenase inhibition leading reproductive failure
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
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
2172	Inhibition, Chitobiase	Decrease, Digestion of old cuticle	Oct 21, 2020	Oct 21, 2020	Chitobiase inhibition leading to mortality
2170	Inhibition, Chitinase	Decrease, Digestion of old cuticle	Oct 21, 2020	Oct 21, 2020	Chitinase inhibition leading to mortality
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
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
61	Inhibition, Ca++ ATPase	Increase, Ca++ (intracellular)	Nov 29, 2016	Dec 3, 2016	Calcium-mediated neuronal ROS production and energy imbalance
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)
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
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
2079	Inhibition, Activin signaling	Inhibition, Fin regeneration	Apr 21, 2020	Jul 10, 2020	Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
3226	Inhibition, 5α-reductase activity	Decrease, testosterone levels	May 24, 2024	May 24, 2024	Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)
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
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
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)
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
1891	tyrosinase	Reduction of L-Dopaquinone	May 3, 2019	May 3, 2019	Inhibition of tyrosinase leads to decreased population in fish
2974	SULT1E1 inhibition	Increased, estrogens	Jul 28, 2023	Jul 28, 2023	SULT1E1 inhibition leading to uterine adenocarcinoma via increased estrogen availability at target organ level
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
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)
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
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
1864	Inhibition of N-linked glycosylation	Accumulation, misfolded proteins	Mar 6, 2019	Mar 6, 2019	Inhibition of N-linked glycosylation leads to liver injury
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
1950	MTHFR inhibition	Homocysteine increases	Jun 14, 2019	Jun 14, 2019
1951	Methionine synthase	Homocysteine increases	Jun 14, 2019	Jun 14, 2019
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
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
2024	Inhibition of JAK3	STAT5 inhibition	Jan 5, 2020	Nov 3, 2021	Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody Response
2539	Inhibition of Ikr	Prolongation of Action Potential	Dec 13, 2021	Dec 13, 2021
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)
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
2694	Inhibition CerS	Reduced complex sphingolipids	Jul 19, 2022	Jul 20, 2022	Ceramide synthase inhibition leading to neural tube defects
2697	Inhibition CerS	Increased S1-P	Jul 19, 2022	Jul 19, 2022	Ceramide synthase inhibition leading to neural tube defects
1952	betaine-homocysteine methyltransferase inhibition	Homocysteine increases	Jun 14, 2019	Jun 14, 2019
2401	ALDH1A (RALDH), inhibition	Decreased, atRA concentration	May 24, 2021	Nov 11, 2021	Inhibition of ALDH1A (RALDH) leading to impaired fertility via disrupted meiotic initiation of fetal oogonia of the ovary Inhibition of RALDH2 causes reduced all-trans retinoic acid levels, leading to transposition of the great arteries
2162	Inhibition of 11β-HSD	Decreased, 11KT	Jul 13, 2020	Jul 13, 2020	Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory
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
1520	Inhibit, serotonin transporter activity	Decreased, serotonin transporter activity	May 30, 2017	May 30, 2017
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
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
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
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
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
926	Infiltration, Inflammatory cytokines	Inflammation, Liver	Nov 29, 2016	Dec 3, 2016
916	Infiltration, Inflammatory cells	Inflammation, Liver	Nov 29, 2016	Nov 29, 2016
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
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
2483	Induction, Upregulation of glucuronyltransferase activity	T4 in serum, Decreased	Sep 14, 2021	Sep 14, 2021
2884	Induction, Upregulation of glucuronyltransferase activity	Increase, Glucuronidation of T4	Apr 12, 2023	Apr 12, 2023
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
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
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
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
3089	Induction, Somatic muscle paralysis	Increased, Neuronal synaptic inhibition	Oct 17, 2023	Oct 17, 2023	Various neuronal effects induced by elavl3, sox10, and mbp
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
1059	Induction, pharyngeal muscle paralysis	Inhibition, Feeding	Nov 29, 2016	Dec 3, 2016	Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality
1518	Sustained proliferation	Liver Cancer	May 30, 2017	Oct 9, 2020	Cyp2E1 Activation Leading to Liver Cancer
859	Induction, Microvesicular fat	Formation, Liver fibrosis	Nov 29, 2016	Dec 3, 2016	Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
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
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
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
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
868	Induction, CYP1A2/CYP1A5	Oxidation, Uroporphyrinogen	Nov 29, 2016	May 31, 2018	Aryl hydrocarbon receptor activation leading to uroporphyria
2893	Induction, CYP1A2/CYP1A5	Increase, ROS production	Apr 13, 2023	Apr 13, 2023
2907	Induction, CYP1A2/CYP1A5	Increase, Oxidative Stress	May 4, 2023	May 4, 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
70	Induction, Chitin degradation and resorption	Induction, Pre-mature molting	Nov 29, 2016	Dec 3, 2016
1630	Cell damage sensing	Sustained inflammatory cytokine release	Jul 26, 2017	Jul 26, 2017
1631	Cell damage sensing	Increase, ROS production	Jul 26, 2017	Jul 26, 2017
1632	Cell damage sensing	Increased, secretion of local growth factors	Jul 26, 2017	Jul 26, 2017
2538	Induction of hERG trafficking defects	Inhibition of Ikr	Dec 13, 2021	Dec 13, 2021
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)
1221	induced, parturition	Decreased, Reproductive Success	Nov 29, 2016	Dec 3, 2016
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
2295	Induced, Angiotensin (Ang) II accumulation	Impaired gustatory nerve	Mar 28, 2021	Mar 28, 2021
2322	Induced, Angiotensin (Ang) II accumulation	Increased Ang II type 1 receptor (AT1R)	Apr 10, 2021	Apr 10, 2021
2520	Induced, Angiotensin (Ang) II accumulation	Hyperactivation of ACE/Ang-II/AT1R axis	Oct 28, 2021	Oct 28, 2021
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
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
2065	ACE2 enzymatic inhibition	Increased AngII	Mar 17, 2020	Mar 17, 2020	Binding to ACE2 leading to lung fibrosis
2321	ACE2 enzymatic inhibition	Induced, Angiotensin (Ang) II accumulation	Apr 10, 2021	Apr 10, 2021
2434	ACE2 enzymatic inhibition	Increase plasma Ang II	Jul 13, 2021	Jul 13, 2021	Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis
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
2526	Increases in cellular ROS	Porcupine-induced Wnt secretion and Wnt signaling activation	Oct 31, 2021	Apr 27, 2022	Increases in cellular reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer
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
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
2855	Increased，Cardiac dysfunction	Increased Mortality	Jan 29, 2023	Jan 29, 2023
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
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
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
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
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
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
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
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
1066	Increased, Thyroid-stimulating hormone (TSH)	Increased, Hypertrophy and proliferation (follicular cell)	Nov 29, 2016	Dec 3, 2016
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
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
2425	Increased, Thyroid-stimulating hormone (TSH)	Increase, Thyroid-stimulating hormone (TSH)	Jul 7, 2021	Jul 7, 2021
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
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
296	Increased, Structural malformations	Increased, Lethality	Nov 29, 2016	Dec 3, 2016
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
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
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
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
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
1550	Increased, seizure	Increased, epilepsy	Jun 2, 2017	Jun 2, 2017	presynaptic neuron 1 activation to epilepsy presynaptic neuron 2 repression to epilepsy
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)
2053	Increased proinflammatory mediators	Increased transcription of genes encoding acute phase proteins	Mar 1, 2020	Dec 19, 2023	Substance interaction with lung resident cell membrane components leading to atherosclerosis
2061	Increased proinflammatory mediators	Increased inflammatory immune responses	Mar 10, 2020	Mar 10, 2020	Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality
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
2651	Increased proinflammatory mediators	Activation, Dendritic Cells	Apr 28, 2022	Aug 1, 2022	Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response
3052	Increased proinflammatory mediators	Systemic acute phase response	Sep 19, 2023	Dec 19, 2023	Substance interaction with lung resident cell membrane components leading to atherosclerosis
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
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.
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
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
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
1308	Increased, Second Messenger Production	Increased, Non-genomic signaling	Nov 29, 2016	Dec 3, 2016	Estrogen receptor activation leading to breast cancer
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
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	Increased, Reactive oxygen species	Jul 3, 2019	Jul 3, 2019	Frustrated phagocytosis-induced lung cancer Frustrated phagocytosis leads to malignant mesothelioma
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)
2491	Recruitment of inflammatory cells	Disruption of the intestinal barrier	Oct 19, 2021	Oct 19, 2021
2492	Recruitment of inflammatory cells	GI disorders	Oct 19, 2021	Oct 19, 2021
2543	Recruitment of inflammatory cells	Gut dysbiosis	Dec 15, 2021	Dec 15, 2021
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)
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
1162	Increased, Reactive oxygen species	Increased, Oxidative Stress	Nov 29, 2016	Jul 31, 2023
1696	Increased, Reactive oxygen species	increased, oncotic necrosis	Nov 14, 2017	Nov 14, 2017	Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)
1965	Increased, Reactive oxygen species	Increased, DNA damage and mutation	Jul 3, 2019	Jul 3, 2019	Frustrated phagocytosis-induced lung cancer Frustrated phagocytosis leads to malignant mesothelioma
2009	Increased, Reactive oxygen species	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 Deposition of ionizing energy leads to population decline via impaired meiosis 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
2033	Increased, Reactive oxygen species	β-catenin activation	Jan 19, 2020	Jan 19, 2020
2320	Increased, Reactive oxygen species	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
2324	Increased, Reactive oxygen species	Increased extracellular matrix deposition	Apr 10, 2021	Apr 10, 2021	Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis
2328	Increased, Reactive oxygen species	Increased Sodium-sensitive hypertension	Apr 10, 2021	Apr 10, 2021	Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease
2460	Increased, Reactive oxygen species	Increased, 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
2549	Increased, Reactive oxygen species	D1 protein deactivation	Jan 21, 2022	Jan 21, 2022	Deposition of ionizing energy leading to population decline via inhibition of photosynthesis
2550	Increased, Reactive oxygen species	Decrease, MMP	Jan 21, 2022	Jan 21, 2022	Deposition of ionising energy leading to population decline via mitochondrial dysfunction
2594	Increased, Reactive oxygen species	Accumulation, Collagen	Mar 3, 2022	Mar 3, 2022
2660	Increased, Reactive oxygen species	Secondary genotoxicity	May 25, 2022	May 25, 2022	Interaction with lung resident cell membrane components leads to lung cancer
2966	Increased, Reactive oxygen species	Apoptosis	Jul 18, 2023	Apr 11, 2024	Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
3092	Increased, Reactive oxygen species	Decreased, PPAR-gamma activation	Oct 18, 2023	Oct 19, 2023	Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway
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
343	Increased, Proliferation/Clonal Expansion of Mutant Cells (Pre-Neoplastic Lesions/Altered H	Tumorigenesis, Hepatocellular carcinoma	Nov 29, 2016	Nov 29, 2016
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
1266	Increased, Proliferation (Endothelial cells)	Increased, Angiogenesis	Nov 29, 2016	Dec 20, 2022	Estrogen receptor activation leading to breast cancer
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
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.
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
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
776	Increased, Plasma tyrosine	Increase, Cytotoxicity (corneal cells)	Nov 29, 2016	Dec 3, 2016	HPPD inhibition leading to corneal papillomas and carcinomas (in rat)
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
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
1128	Increased, Oxidative Stress	Increased, secretion of local growth factors	Nov 29, 2016	Dec 3, 2016
1160	Increased, Oxidative Stress	Occurrence, renal proximal tubular necrosis	Nov 29, 2016	Dec 3, 2016
1300	Increased, Oxidative Stress	Increase, DNA Damage	Nov 29, 2016	Dec 3, 2016
2385	Increased, Oxidative Stress	Increase, Oocyte apoptosis	May 12, 2021	May 12, 2021
2618	Increased, Oxidative Stress	Increase, Apoptosis	Mar 28, 2022	Mar 28, 2022
2933	Increased, Oxidative Stress	Impaired insulin signaling	May 25, 2023	May 25, 2023
2936	Increased, Oxidative Stress	Mitochondrial dysfunction EMPTY	May 26, 2023	May 26, 2023
3160	Increased, Oxidative Stress	Mitochondrial dysfunction	Mar 13, 2024	Mar 13, 2024
3236	Increased, Oxidative Stress	Increase mutations	May 28, 2024	May 28, 2024	Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress
3269	Increased, Oxidative Stress	Oxidative Stress	Jul 4, 2024	Jul 4, 2024
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
2633	Increased, Oocyte Atresia	Impaired, Reproduction	Apr 5, 2022	Apr 5, 2022	Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
1697	increased, oncotic necrosis	steatohepatitis	Nov 14, 2017	Nov 14, 2017	Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)
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
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
3090	Increased, Neuronal synaptic inhibition	Inhibition, Feeding	Oct 17, 2023	Oct 17, 2023	Various neuronal effects induced by elavl3, sox10, and mbp
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
1228	Increased, muscular waves in foot	Depletion, energy reserves	Nov 29, 2016	Dec 3, 2016
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
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
1214	Increased, mantel display	Increased, Reproductive Success	Nov 29, 2016	Dec 3, 2016
1264	Increased, Male offspring	Decline, Population	Nov 29, 2016	Dec 3, 2016	Juvenile hormone receptor agonism leading to male offspring induction associated population decline
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
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)
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
1695	Increased, Liver Steatosis	Increased, Reactive oxygen species	Nov 14, 2017	Nov 14, 2017	Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)
3218	Increased, Liver Steatosis	Cell injury/death	May 14, 2024	May 14, 2024	AhR activation leading to liver fibrosis
1405	Increased, lipogenesis	Increase, cytosolic fatty acid	Apr 12, 2017	Apr 12, 2017
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)
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
508	Increased, LDL uptake	Accumulation, Fatty acid	Nov 29, 2016	Dec 3, 2016	AhR activation leading to hepatic steatosis
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.
2627	Increased, Kisspeptin signalling	Decreased, Gonadotropins	Apr 5, 2022	Aug 15, 2022	Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
2462	Increased, Kidney Failure	Increase, Mortality	Aug 5, 2021	Aug 5, 2021
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
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
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
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
1465	Increased, intracellular chloride (Cl-)	Inactive, membrane depolarization	Apr 14, 2017	Apr 14, 2017	Molecular events lead to epilepsy
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
1860	Increased, Intracellular Calcium overload	Occurrence, Epileptic seizure	Feb 13, 2019	Feb 13, 2019
1862	Increased, Intracellular Calcium overload	Cell injury/death	Feb 19, 2019	Sep 3, 2023	Acetylcholinesterase Inhibition Leading to Neurodegeneration
2140	Increased, Intracellular Calcium overload	Status epilepticus	May 21, 2020	May 21, 2020
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
2709	Increased, Intracellular Calcium overload	Decrease, OXPHOS	Jul 25, 2022	Jul 25, 2022
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
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	Oct 18, 2023	Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons
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
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)
1048	Increased, Inhibitory postsynaptic potential	Inhibition, Motor neuron activity	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
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
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.
1063	Increased, induction of UDPGT's in liver	Increased, T4/T3 catabolism	Nov 29, 2016	Dec 3, 2016
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)
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
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
1067	Increased, Hypertrophy and proliferation (follicular cell)	Increased, Hyperplasia (follicular cells)	Nov 29, 2016	Dec 3, 2016
2427	Increased, Hypertrophy and proliferation (follicular cell)	Increase, Hyperplasia (follicular cells)	Jul 7, 2021	Jul 7, 2021
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
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.
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
3118	Increased, histomorphological alteration of testis	Impaired, Spermatogenesis	Jan 24, 2024	Apr 11, 2024	Essential element imbalance leads to reproductive failure via oxidative stress
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
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
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
1206	Increased, Hepatic thyroid hormone uptake/transport	Increase, Biliary excretion TH glucuronide	Nov 29, 2016	Dec 3, 2016
2237	Increased, Hepatic thyroid hormone uptake/transport	T4 in serum, Decreased	Dec 9, 2020	Dec 9, 2020	Hepatic nuclear receptor activation leading to altered amphibian metamorphosis Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis
2479	Increased, Hepatic thyroid hormone uptake/transport	Increased, Clearance of thyroxine from serum	Sep 10, 2021	Sep 10, 2021	Hepatic nuclear receptor activation leading to altered amphibian metamorphosis Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis
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
2861	Increased, glutamate	Microglia activation	Apr 3, 2023	Apr 3, 2023	Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
2868	Increased, glutamate	decreased, Bcl-2	Apr 4, 2023	Apr 4, 2023	Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
2869	Increased, glutamate	increased, Bax	Apr 4, 2023	Apr 4, 2023	Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
1522	Increased, glucocorticoid receptor activity	Reduced, BDNF	May 31, 2017	May 31, 2017	Mental stress to depression Mental stress to agitation
2919	Increased, gene expression of AR	Increase, Gonadotropins concentration in plasma	May 22, 2023	May 22, 2023	Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）
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
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
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
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
2263	Increased, Fatty acid uptake	Increased, Liver Steatosis	Jan 15, 2021	Jan 15, 2021
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
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
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	Apr 10, 2021	Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis AhR activation leading to liver fibrosis
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
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
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
3115	Increased, essential element imbalance	Increased, Reactive oxygen species	Jan 24, 2024	Aug 2, 2024	Essential element imbalance leads to reproductive failure via oxidative stress
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
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
3082	Increased, epilepsy	Increase, Mortality	Oct 17, 2023	Oct 17, 2023	Various neuronal effects induced by elavl3, sox10, and mbp
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
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
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
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
2417	Increased, DNA damage and mutation	Genomic instability	Jul 6, 2021	Jul 6, 2021	Frustrated phagocytosis leads to malignant mesothelioma
2608	Increased, DNA damage and mutation	Inadequate DNA repair	Mar 22, 2022	Aug 27, 2023	DNA damage and mutations leading to Metastatic Breast Cancer
2728	Increased, DNA damage and mutation	Increase chromosomal aberrations	Aug 14, 2022	Aug 27, 2023	DNA damage and mutations leading to Metastatic Breast Cancer
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
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
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
1607	Increased, De Novo FA synthesis	Increased, Liver Steatosis	Jul 18, 2017	Jul 18, 2017	NFE2L2/FXR activation leading to hepatic steatosis
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
350	Increased, Clonal Expansion / Cell Proliferatin to form Pre-Neoplastic Altered Hepatic Foci	Tumorigenesis, Hepatocellular carcinoma	Nov 29, 2016	Dec 3, 2016
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
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.
2584	Increased, circulating estrogen levels	Hyperplasia, ovarian stromal cells	Feb 26, 2022	Mar 2, 2022
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
1210	Increased, cilia movement	premature, Spawning	Nov 29, 2016	Dec 3, 2016
1329	Increased, cilia movement	induced spawning	Jan 17, 2017	Jan 17, 2017
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
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
1047	Increased, Chloride influx	Increased, Inhibitory postsynaptic potential	Nov 29, 2016	Dec 3, 2016
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
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
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.
885	Increased, Catabolism of Muscle Protein	Decreased, Body Weight	Nov 29, 2016	Jun 11, 2018	Antagonist binding to PPARα leading to body-weight loss
3292	Increased, Cardiac stress	Heart failure	Jul 8, 2024	Aug 6, 2024	Decreased Sodium/Potassium ATPase activity leads to Heart failure
703	Increased, cardiac arrthymia	Increased Mortality	Nov 29, 2016	Dec 3, 2016	Altered ion channel activity leading impaired heart function
3291	Increased, Blood viscosity	Increased, Cardiac stress	Jul 8, 2024	Aug 6, 2024	Decreased Sodium/Potassium ATPase activity leads to Heart failure
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
1158	Increased, blood uric acid concentration	Increased, Oxidative Stress	Nov 29, 2016	Dec 3, 2016
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
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
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)
2871	increased, Bax	Cell injury/death	Apr 4, 2023	Apr 4, 2023	Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
2874	increased, Bax	Increase, Cell death	Apr 4, 2023	Apr 4, 2023
432	Increased, Atrioventricular block and bradycardia	Increased Mortality	Nov 29, 2016	Nov 29, 2016
591	Increased, Atrioventricular block and bradycardia	Respiratory distress/arrest	Nov 29, 2016	Dec 3, 2016	Sodium channel inhibition leading to congenital malformations
607	Increased, Ataxia, paralysis, or hyperactivity	Increased Mortality	Nov 29, 2016	Dec 3, 2016	Axonal sodium channel modulation leading to acute mortality
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
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
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
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
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)
1445	Increased, 5-HT3	Increased, seizure	Apr 14, 2017	Apr 14, 2017	Network of SSRIs (selective serotonin reuptake inhibitors)
2315	Increased viral transcription and replication	Increased proinflammatory mediators	Apr 9, 2021	Apr 9, 2021
2316	Increased viral transcription and replication	TLR Activation/Dysregulation	Apr 9, 2021	Apr 9, 2021
1592	Systemic cholesterol increased	Foam cell formation	Jun 29, 2017	Jun 29, 2017
2698	Increased S1-P	Histone deacetylase inhibition	Jul 19, 2022	Jul 19, 2022	Ceramide synthase inhibition leading to neural tube defects
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
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
2358	SARS-CoV-2 production	Diminished Protective Response to ROS	Apr 20, 2021	Sep 26, 2023	Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation SARS-CoV-2 infection leading to hyperinflammation
2488	SARS-CoV-2 production	Increase, Cell death	Oct 19, 2021	Oct 19, 2021	Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
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
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)
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
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
1788	Increased reactive oxygen species (in the mitochondria)	Mitochondrial Injury	Dec 19, 2018	Mar 7, 2019
1957	Increased reactive oxygen species (in the mitochondria)	Mitochondrial dysfunction	Jun 15, 2019	Jun 15, 2019	Mitochondrial complex inhibition leading to liver injury
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
1764	Increased pro-inflammatory mediators	Activation, Stellate cells	Aug 2, 2018	Aug 2, 2018	Protein Alkylation leading to Liver Fibrosis
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
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
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
2777	Increased pro-inflammatory mediators	Increase, Endothelial Dysfunction	Sep 28, 2022	Aug 26, 2024	Deposition of energy leads to vascular remodeling
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
1954	plasma homocysteine increases	brain Homocysteine level increases	Jun 14, 2019	Jun 14, 2019
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
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
1773	Increased NKA	Respiratory irritability	Sep 24, 2018	Sep 24, 2018	Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
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)
200	Increased Mortality	Decline, Population	Nov 29, 2016	Dec 3, 2016
428	Increased Mortality	Decreased, Population trajectory	Nov 29, 2016	Dec 20, 2019
756	Increased Mortality	Decreased, population 1	Nov 29, 2016	Dec 3, 2016	Glutamate-gated chloride channel activation leading to acute mortality
1191	Increased Mortality	Decreased, Population size	Nov 29, 2016	Dec 3, 2016
2013	Increased Mortality	Decrease, Population growth rate	Dec 20, 2019	Jul 8, 2022	Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement Acetylcholinesterase inhibition leading to acute mortality Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure Thyroperoxidase inhibition leading to altered visual function via decreased eye size Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos) GSK3beta inactivation leading to increased mortality via defects in developing inner ear Estrogen receptor agonism leading to reduced survival and population growth due to renal failure
2486	Increased Mortality	Decline, Population trajectory	Oct 8, 2021	Oct 8, 2021
2816	Modified Proteins	Cataracts	Dec 18, 2022	Mar 8, 2024	Deposition of energy leading to occurrence of cataracts
2610	Increase,miRNA levels	Decrease,SIRT1(sirtuin 1) levels	Mar 22, 2022	Aug 27, 2023	DNA damage and mutations leading to Metastatic Breast Cancer
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
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
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
2951	Increased intracelluar Iron	Oxidative Stress in Brain	Jun 21, 2023	Jun 21, 2023
3313	Increased intracelluar Iron	Oxidative Stress	Jul 23, 2024	Jul 23, 2024	Excessive iron accumulation leading to neurological disorders
2029	Increased monitor peptide	Increased blood CCK level	Jan 8, 2020	Jan 8, 2020	Trypsin inhibition leading to pancreatic acinar cell tumors
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
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
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
2031	Increased acinar cell exocrine secretion	Acinar cell proliferation	Jan 8, 2020	Jan 8, 2020	Trypsin inhibition leading to pancreatic acinar cell tumors
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
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
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
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
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
1955	brain Homocysteine level increases	Neuronal dysfunctions induction	Jun 14, 2019	Jun 14, 2019
2030	Increased blood CCK level	Increased acinar cell exocrine secretion	Jan 8, 2020	Jan 8, 2020	Trypsin inhibition leading to pancreatic acinar cell tumors
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
2066	Increased AngII	Increase plasma Ang II	Mar 17, 2020	Mar 17, 2020
2298	Increased AngII	Impaired gustatory nerve	Mar 28, 2021	Mar 28, 2021
2300	Increased AngII	Increased proinflammatory mediators	Mar 28, 2021	Mar 28, 2021
2317	Increased AngII	Sodium inhibition, Sweet enhancement	Apr 10, 2021	Apr 10, 2021	Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia
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
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
2323	Increased Ang II type 1 receptor (AT1R)	Increased, Reactive oxygen species	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
1612	increased adipogenesis	obesity	Jul 24, 2017	Jul 24, 2017	Epigenetic modification of PPARG leading to adipogenesis
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
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
1238	Increased activation, Nuclear factor kappa B (NF-kB)	Increase, Phenotypic enzyme activity	Nov 29, 2016	Dec 3, 2016
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
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)
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)
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
2509	Upregulation of ACE2	SARS-CoV-2 cell entry	Oct 28, 2021	Oct 28, 2021
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
2068	Increase,collagen synthesis	Induction lung fibrosis	Mar 17, 2020	Mar 17, 2020
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
2738	Increase, Vitellogenin mRNA	Delay, Ovarian maturation	Aug 28, 2022	Aug 28, 2022	Alcohol dehydrogenase leading to reproductive dysfunction
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
3018	Increase, Vascular disrupting effects	Angiogenesis disfunction	Aug 21, 2023	Aug 21, 2023
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)
1663	Increase, Uncoupling of photophosphorylation	Decrease, ATP production	Oct 10, 2017	Oct 10, 2017	Reduction in photophosphorylation leading to growth inhibition in aquatic plants
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)
2178	Increase, Tissue/organ damage	Decrease, Growth	Nov 2, 2020	Nov 2, 2020
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
741	Increase, Thyroid-stimulating hormone (TSH)	Increase, Hypertrophy and proliferation (follicular cell)	Nov 29, 2016	Dec 3, 2016
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
1489	Increase, surfactant	Activate, mucosal defense	Apr 17, 2017	Apr 17, 2017	Gastric ulcer formation
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
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
2742	Increase, sex ratio (F/M)	Increase, developmental abnormalities	Aug 28, 2022	Aug 28, 2022	Alcohol dehydrogenase leading to reproductive dysfunction
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
1930	Increase, SAM depletion	Increase, DNA hypomethylation	May 30, 2019	May 30, 2019
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
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
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
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)
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)
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)
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)
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)
282	Increase, ROS production	Decreased, Nitric Oxide	Nov 29, 2016	Dec 3, 2016	Calcium-mediated neuronal ROS production and energy imbalance
283	Increase, ROS production	Increased, Oxidative damage	Nov 29, 2016	Dec 3, 2016
912	Increase, ROS production	Mitochondrial dysfunction	Nov 29, 2016	Dec 3, 2016
1602	Increase, ROS production	Increase, DNA Damage	Jun 29, 2017	Jun 29, 2017
1603	Increase, ROS production	Increased, LPO	Jun 29, 2017	Jun 29, 2017	Excessive reactive oxygen species production leading to mortality (3)
1623	Increase, ROS production	Increased, secretion of local growth factors	Jul 26, 2017	Jul 26, 2017
1754	Increase, ROS production	Decrease, Coupling of OXPHOS	Jun 12, 2018	Jun 12, 2018
2089	Increase, ROS production	Increase, Protein oxidation	Apr 30, 2020	Apr 30, 2020	Excessive reactive oxygen species production leading to mortality (1)
2093	Increase, ROS production	Decrease, MMP	Apr 30, 2020	Apr 30, 2020	Excessive reactive oxygen species production leading to mortality (2)
2187	Increase, ROS production	Increase, Apoptosis	Nov 2, 2020	Nov 2, 2020
2225	Increase, ROS production	Increase, Global methylation	Dec 4, 2020	Dec 4, 2020	Thermal stress leading to population decline (3)
2305	Increase, ROS production	Inhibition, Nuclear factor kappa B (NF-kB)	Mar 30, 2021	Mar 30, 2021
2308	Increase, ROS production	Increased activation, Nuclear factor kappa B (NF-kB)	Mar 30, 2021	Mar 30, 2021
2348	Increase, ROS production	D1 protein deactivation	Apr 11, 2021	Apr 11, 2021
2590	Increase, ROS production	Increase, Oxidative DNA damage	Mar 1, 2022	Mar 1, 2022	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 production leading to mortality (4)
2998	Increase, ROS production	Increase, Oxidative Stress	Aug 21, 2023	Aug 21, 2023
3235	Increase, ROS production	Increased, Oxidative Stress	May 28, 2024	May 28, 2024	Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress
3238	Increase, ROS production	Oxidative Stress	May 31, 2024	May 31, 2024	Calcium-mediated neuronal ROS production and energy imbalance The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
1466	Increase, ROS	Peptide Oxidation	Apr 15, 2017	Apr 15, 2017
1595	Increase, ROS	Increase, DNA Damage	Jun 29, 2017	Jun 29, 2017
1598	Increase, ROS	Increased, LPO	Jun 29, 2017	Jun 29, 2017
2342	Increase, ROS	D1 protein deactivation	Apr 11, 2021	Apr 11, 2021
2345	Increase, ROS	Decrease, MMP	Apr 11, 2021	Apr 11, 2021
2826	Increase, ROS	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	Increase, Oxidative DNA damage	May 27, 2024	May 27, 2024	Thermal stress leading to population decline (2)
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
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
2090	Increase, Protein oxidation	Increase, Abnormal osmoregulation	Apr 30, 2020	Apr 30, 2020	Excessive reactive oxygen species production leading to mortality (1)
2223	Increase, Protein oxidation	Increase, Cell death	Dec 4, 2020	Dec 4, 2020
944	Increased goblet cell proliferation	Goblet cell hyperplasia	Nov 29, 2016	Aug 27, 2021
2339	Increase, Programmed cell death	Decrease, Leaf development	Apr 11, 2021	Apr 11, 2021
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
2835	Increase, Pro-Inflammatory Mediators	Abnormal Neural Remodeling	Jan 25, 2023	Jul 26, 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
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)
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
2634	Increase, predation	Decrease, Population growth rate	Apr 6, 2022	Apr 6, 2022	5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
2555	Increase, Pollen abnormal	Decrease, Reproduction	Jan 21, 2022	Jan 21, 2022	Deposition of ionising energy leads to population decline via pollen abnormal
1474	Increase, platelet aggregation	Inhibit, gastric ulcer formation	Apr 17, 2017	Apr 17, 2017	Gastric ulcer formation
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
2409	increase, placental insufficiency	increase, Preeclampsia	May 31, 2021	May 31, 2021	AhR activation leading to preeclampsia
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
1241	Increase, Peroxisomal Fatty Acid Beta Oxidation of Fatty Acids	Peptide Oxidation	Nov 29, 2016	Dec 3, 2016
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
2220	Increase, Oxygen consumption	Increase, ROS production	Dec 4, 2020	Dec 4, 2020
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
2897	Increase, Oxidative Stress	TH synthesis, Decreased	Apr 24, 2023	May 23, 2023
2980	Increase, Oxidative Stress	Activation, inflammation pathway	Aug 19, 2023	Aug 19, 2023
2993	Increase, Oxidative Stress	Abnormal expression of NO	Aug 20, 2023	Aug 20, 2023
2999	Increase, Oxidative Stress	Activated ANG/Tie2 pathway	Aug 21, 2023	Aug 21, 2023
3000	Increase, Oxidative Stress	Activation, Dll4-Notch pathway	Aug 21, 2023	Aug 21, 2023
3001	Increase, Oxidative Stress	Activated BMP/TGF-beta pathway	Aug 21, 2023	Aug 21, 2023
3002	Increase, Oxidative Stress	Activated Wnt/Frizzled pathway	Aug 21, 2023	Aug 21, 2023
3003	Increase, Oxidative Stress	Uncoupling, eNOS	Aug 21, 2023	Aug 21, 2023
3004	Increase, Oxidative Stress	Activated AKT/ERK/PI3K pathway	Aug 21, 2023	Aug 21, 2023
3005	Increase, Oxidative Stress	Inhibition VEGF/VEGFR pathway	Aug 21, 2023	Aug 21, 2023
3033	Increase, Oxidative Stress	Increase, Apoptosis	Aug 28, 2023	Aug 28, 2023
3130	Increase, Oxidative Stress	Mitochondrial dysfunction	Feb 21, 2024	Feb 21, 2024
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)
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
1913	Increase, Oxidative DNA damage	Increase, DNA strand breaks	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
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
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	Thermal stress leading to population decline (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)
2106	Increase, Ovarian somatic cell apoptosis	Increase, Ovarian follicle breakdown	Apr 30, 2020	Apr 30, 2020	DNA methyltransferase inhibition leading to population decline (2)
2118	Increase, Ovarian follicle breakdown (F3)	Decrease, Oogenesis (F3)	Apr 30, 2020	Apr 30, 2020	DNA methyltransferase inhibition leading to transgenerational effects (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
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
2113	Increase, Oocyte apoptosis (F3)	Decrease, Oogenesis (F3)	Apr 30, 2020	Apr 30, 2020	DNA methyltransferase inhibition leading to transgenerational effects (1)
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 energy leading to population decline via DNA oxidation and oocyte apoptosis Deposition of ionizing energy leads to population decline via impaired meiosis
2386	Increase, Oocyte apoptosis	impaired, Fertility	May 12, 2021	May 12, 2021	Deposition of ionizing energy leads to population decline via impaired meiosis
2400	Increase, Oocyte apoptosis	Decrease of egg production and cummulative fecundity	May 18, 2021	May 18, 2021	Deposition of ionizing energy leads to population decline via impaired meiosis
1344	Increase, E75b expression	Increase, Ftz-f1 expression	Feb 9, 2017	Feb 9, 2017	Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
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)
1874	Increase, Necrosis	Increase, Mortality	Mar 19, 2019	Mar 19, 2019
2122	Increase, Necrosis	Increase, Ovarian follicle breakdown	May 8, 2020	May 8, 2020
2177	Increase, Necrosis	Increase, Tissue/organ damage	Nov 2, 2020	Nov 2, 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
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
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
202	Increase, Mutations	Increase, Heritable mutations in offspring	Nov 29, 2016	Nov 29, 2016	Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutations
899	Increase, Mutations	Increase, Cancer	Nov 29, 2016	Dec 3, 2016	Alkylation of DNA leading to cancer 2 Alkylation of DNA leading to cancer 1
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
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
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
198	Increase, Mortality	Decrease, Fecundity	Nov 29, 2016	Dec 3, 2016
199	Increase, Mortality	Decline, Population	Nov 29, 2016	Dec 3, 2016
1004	Increase, Mortality	Decreased, population 1	Nov 29, 2016	Dec 3, 2016
1013	Increase, Mortality	Decreased, Population size	Nov 29, 2016	Dec 3, 2016
2463	Increase, Mortality	Decrease, Population growth rate	Aug 5, 2021	Aug 5, 2021
2797	Increase, Mitochondrial swelling	Cell injury/death	Nov 1, 2022	Nov 1, 2022	Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swelling
2183	Increase, Complex III dysfunction	Increase, Cyt c release	Nov 2, 2020	Nov 2, 2020
2186	Increase, Complex III dysfunction	Increase, ROS production	Nov 2, 2020	Nov 2, 2020
1781	Increase, Mitochondrial complex III antagonism	Decrease in mitochondrial oxidative phosphorylation	Dec 19, 2018	Mar 7, 2019	Mitochondrial complex inhibition leading to liver injury
1784	Increase, Mitochondrial complex III antagonism	Increased reactive oxygen species (in the mitochondria)	Dec 19, 2018	Mar 7, 2019
1872	Increase, Mitochondrial complex III antagonism	Decrease, OXPHOS	Mar 19, 2019	Mar 19, 2019
1875	Increase, Mitochondrial complex III antagonism	Increase, ROS	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)
2189	Increase, Complex I dysfunction	Increase, ROS production	Nov 2, 2020	Nov 2, 2020
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)
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
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
1599	Increased, LPO	Decrease, Coupling of OXPHOS	Jun 29, 2017	Jun 29, 2017
2097	Increased, LPO	Decrease, TAG	Apr 30, 2020	Apr 30, 2020	Excessive reactive oxygen species production leading to mortality (3)
2210	Increased, LPO	Increase, Apoptosis	Nov 25, 2020	Nov 25, 2020
2222	Increased, LPO	Increase, Cell death	Dec 4, 2020	Dec 4, 2020
2464	Increased, LPO	Increase, Necrosis	Aug 11, 2021	Aug 11, 2021	Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure
2879	Increased, LPO	impaired, Fertility	Apr 5, 2023	Sep 14, 2023	Glutathione conjugation leading to reproductive dysfunction via oxidative stress
3117	Increased, LPO	Increased, histomorphological alteration of testis	Jan 24, 2024	Apr 11, 2024	Essential element imbalance leads to reproductive failure via oxidative stress
1477	Increase, leukocyte adherence	Activate, leukocyte	Apr 17, 2017	Apr 17, 2017	Gastric ulcer formation
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
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
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
1390	Increase, insulin	Activation, insulin receptor	Apr 12, 2017	Apr 12, 2017
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
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)
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)
1722	Increase, Inflammation	Expression of Collagen	Mar 18, 2018	Mar 18, 2018
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
1839	Increase, Inflammation	Fibroproliferative airway lesions	Jan 30, 2019	Jan 30, 2019	α-diketone-induced bronchiolitis obliterans
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
2976	Increase, Inflammation	General Apoptosis	Jul 31, 2023	Oct 19, 2023	Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway
1002	Increase, Incomplete ecdysis	Increase, Mortality	Nov 29, 2016	Dec 3, 2016	Ecdysone receptor agonism leading to incomplete ecdysis associated mortality Doda decarboxylase leading to mortality
1190	Increase, Incomplete ecdysis	Increased Mortality	Nov 29, 2016	Dec 3, 2016
2750	Increase, Incomplete ecdysis	Increase, delay in oviposition	Aug 28, 2022	Aug 28, 2022	Doda decarboxylase leading to mortality
2751	Increase, Incomplete ecdysis	Decrease, hatching of egg	Aug 28, 2022	Aug 28, 2022	Doda decarboxylase leading to mortality
2759	Increase, Incomplete ecdysis	Increase, developmental abnormalities	Aug 28, 2022	Aug 28, 2022	Knickkopf leading to mortality
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
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
1581	Increase, hypertension	Respiratory irritability	Jun 23, 2017	Jun 23, 2017
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
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)
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)
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)
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)
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
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)
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
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
3212	Increase, Gonadotropins concentration in plasma	Decrease, testosterone levels	May 8, 2024	May 8, 2024	Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）
2858	Increase, goblet cell number	Increase, Mucin production	Mar 15, 2023	Mar 17, 2023	EGFR Activation Leading to Decreased Lung Function
2794	Increase, Glycolysis	Decrease, Glucose pool	Nov 1, 2022	Nov 1, 2022	Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion
2885	Increase, Glucuronidation of T4	Increased, Clearance of thyroxine from serum	Apr 12, 2023	Apr 12, 2023
2226	Increase, Global methylation	Increase, Apoptosis	Dec 4, 2020	Dec 4, 2020	Thermal stress leading to population decline (3)
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
1885	Increase, Gene expression	Decrease, Fecundity	Apr 22, 2019	Apr 22, 2019
1462	Increase, GABA	Activate, GABA-A receptor	Apr 14, 2017	Apr 14, 2017	Molecular events lead to epilepsy
1345	Increase, Ftz-f1 expression	Decrease, Circulating ETH	Feb 9, 2017	Feb 9, 2017	Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
3097	Increase, Formation of DNA photoproducts	Increase, DSB	Nov 16, 2023	Nov 16, 2023	Formation of DNA photoproducts leading to growth inhibition (1)
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
1417	Increase, Fatty acid β-oxidation	Decrease, cytosolic fatty acid	Apr 13, 2017	Apr 13, 2017
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
2330	Excitation of intracellular water	Increase in RONS	Apr 11, 2021	Apr 11, 2021
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
2778	Increase, Endothelial Dysfunction	Vascular remodeling	Sep 28, 2022	Sep 28, 2022
2784	Increase, Endothelial Dysfunction	Occurrence, Vascular Remodeling	Oct 17, 2022	Aug 26, 2024	Deposition of energy leads to vascular remodeling
116	Increase, EcR agonism	Induction, Chitin degradation and resorption	Nov 29, 2016	Dec 3, 2016
998	Increase, EcR agonism	Decrease, Circulating ETH	Nov 29, 2016	Dec 3, 2016
999	Increase, EcR agonism	Decreased, synthesis and secretion of molting fluid proteases	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
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
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
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
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
2074	Increase, DNA strand breaks	Increase, Apoptosis	Apr 6, 2020	Apr 6, 2020	Alkylation of DNA leading to reduced sperm count
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
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
2841	Increase, DNA strand breaks	Abnormal Neural Remodeling	Jan 25, 2023	Jul 29, 2024	Deposition of Energy Leading to Learning and Memory Impairment
2856	Increase, DNA strand breaks	Altered Signaling	Mar 10, 2023	Mar 21, 2023
3315	Increase, DNA strand breaks	Altered Stress Response Signaling	Jul 24, 2024	Aug 26, 2024	Deposition of energy leads to vascular remodeling Deposition of Energy Leading to Learning and Memory Impairment
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)
3305	Increase, DNMT inhibition	EMT	Jul 18, 2024	Jul 18, 2024	Succinate dehydrogenase inactivation leading to cancer
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
1884	Increase, DNA hypomethylation	Increase, Gene expression	Apr 22, 2019	Apr 22, 2019
1887	Increase, DNA hypomethylation	Decrease, Transgenerational DNA methylation	Apr 22, 2019	Apr 22, 2019
1635	Increase, DSB	MLL translocation	Aug 2, 2017	Aug 1, 2022	Inhibitor binding to topoisomerase II leading to infant leukaemia
3096	Increase, DSB	Increase, Apoptosis	Nov 16, 2023	Nov 16, 2023	Formation of DNA photoproducts leading to growth inhibition (1) Excessive reactive oxygen species production leading to mortality (4)
3099	Increase, DSB	Increase, Casp transcription	Nov 16, 2023	Nov 16, 2023	DNA methyltransferase inhibition leading to population decline (3)
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
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
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
1899	Increase, DNA Damage	Increase mutations	May 7, 2019	May 7, 2019
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
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
2382	Increase, DNA Damage	Increase, Oocyte apoptosis	May 12, 2021	May 12, 2021	Deposition of ionizing energy leads to population decline via impaired meiosis
2595	Increase, DNA Damage	Activation of TP53	Mar 9, 2022	Mar 9, 2022	Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation
2622	Increase, DNA Damage	Decreased spermatogenesis	Mar 28, 2022	Mar 28, 2022	Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
2790	Increase, DNA Damage	Cell cycle, disrupted	Oct 25, 2022	Oct 25, 2022	Deposition of ionizing energy leads to population decline via impaired meiosis
1626	Differentiation of fibroblasts	Expression of Collagen	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
2743	Increase, developmental abnormalities	Increase, Mortality	Aug 28, 2022	Aug 28, 2022	Alcohol dehydrogenase leading to reproductive dysfunction Knickkopf 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
2332	D1 protein deactivation	Decrease, Photosystem II efficiency	Apr 11, 2021	Apr 11, 2021
1736	Increase, D1 protein antagonism	Decrease, PSII activity	May 24, 2018	May 24, 2018
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)
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)
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
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)
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)	Increased, Reactive oxygen species	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
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)
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)
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
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)
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
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
2078	Increase, Cripto-1 expression	Inhibition, Activin signaling	Apr 21, 2020	Jul 7, 2020	Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
2082	Increase, Cripto-1 expression	Inhibition, Fin regeneration	Apr 21, 2020	Jul 10, 2020	Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
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
1450	Increase, cortisone	Activation, Glucocorticoid Receptor	Apr 14, 2017	Apr 14, 2017	Network of SSRIs (selective serotonin reuptake inhibitors)
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
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
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
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
1979	Increase, Chromosomal aberrations	Increase, Cell Proliferation	Aug 29, 2019	Mar 8, 2024	Deposition of energy leading to lung cancer Deposition of energy leading to occurrence of cataracts
1985	Increase, Chromosomal aberrations	Increase, lung cancer	Aug 29, 2019	Jan 10, 2023	Deposition of energy leading to lung cancer
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)
1239	Increase, cell proliferation (hepatocytes)	Increase, Clonal Expansion of Altered Hepatic Foci	Nov 29, 2016	Dec 3, 2016	PPARα activation leading to hepatocellular adenomas and carcinomas in rodents
2254	Increase, cell proliferation (hepatocytes)	Increase, hepatocellular adenomas and carcinomas	Dec 31, 2020	Dec 31, 2020	PPARα activation leading to hepatocellular adenomas and carcinomas in rodents
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
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
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
2708	Increase, Cell membrane depolarization	Increased, Intracellular Calcium overload	Jul 25, 2022	Jul 25, 2022
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
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
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.
924	Cell injury/death	Release, Cytokine	Nov 29, 2016	Nov 9, 2018
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
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
1776	Cell injury/death	Increased pro-inflammatory mediators	Nov 12, 2018	Nov 12, 2018	Endocytic lysosomal uptake leading to liver fibrosis
1830	Cell injury/death	Necrotic Tissue	Jan 7, 2019	Mar 7, 2019	IKK complex inhibition leading to liver injury Mitochondrial complex inhibition leading to liver injury
1831	Cell injury/death	Activation, Tissue resident cells (Kuppfer cells)	Jan 7, 2019	Jan 7, 2019	IKK complex inhibition leading to liver injury
1863	Cell injury/death	Neurodegeneration	Feb 19, 2019	Feb 19, 2019
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
2875	Cell injury/death	Hippocampal Physiology, Altered	Apr 5, 2023	Apr 5, 2023	Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
2890	Cell injury/death	Leukocyte recruitment/activation	Apr 13, 2023	Apr 13, 2023	AhR activation leading to liver fibrosis
3197	Cell injury/death	Disruption of the intestinal barrier	Apr 17, 2024	Apr 17, 2024	Endocytotic lysosomal uptake leads to intestinal barrier disruption
3198	Cell injury/death	Mitochondrial dysfunction	Apr 17, 2024	Apr 17, 2024
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
2215	Increase, Cell death	Decrease, Growth	Dec 4, 2020	Dec 4, 2020	Mitochondrial ATP synthase antagonism leading to growth inhibition (2)
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
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
2718	Increase, Cell death	Neuroinflammation	Jul 25, 2022	Jul 25, 2022
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	Aug 23, 2024	Deposition of energy leading to occurrence of bone loss
2863	Increase, Cell death	Hippocampal Physiology, Altered	Apr 3, 2023	Apr 3, 2023
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)
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)
2105	Increase, Casp transcription	Increase, Ovarian somatic cell apoptosis	Apr 30, 2020	Apr 30, 2020	DNA methyltransferase inhibition leading to population decline (2)
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
60	Increase, Ca++ (intracellular)	Disruption, Mitochondrial electron transport chain	Nov 29, 2016	Dec 3, 2016	Calcium-mediated neuronal ROS production and energy imbalance
2845	Bone Remodeling	Bone Loss	Jan 25, 2023	Aug 9, 2024	Deposition of energy leading to occurrence of bone loss
2741	Increase, Body volume of female adults	Increase, developmental abnormalities	Aug 28, 2022	Aug 28, 2022	Alcohol dehydrogenase leading to reproductive dysfunction
2092	Increase, Body fluid overload	Increase, Mortality	Apr 30, 2020	Apr 30, 2020	Excessive reactive oxygen species production leading to mortality (1)
2236	Increase, Biliary excretion TH glucuronide	T4 in serum, Decreased	Dec 9, 2020	Dec 9, 2020
1484	Increase, bicarbonate	Activate, mucosal defense	Apr 17, 2017	Apr 17, 2017	Gastric ulcer formation
1469	Increase, Apoptosis	Decrease, Oogenesis	Apr 15, 2017	Apr 15, 2017	Thermal stress leading to population decline (3) Thermal stress leading to population decline (2)
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	Formation of DNA photoproducts leading to growth inhibition (1) Excessive reactive oxygen species production leading to mortality (4)
2075	Increase, Apoptosis	Reduce, Sperm count	Apr 6, 2020	Apr 6, 2020	Alkylation of DNA leading to reduced sperm count
2185	Increase, Apoptosis	Increase, Tissue/organ damage	Nov 2, 2020	Nov 2, 2020
2461	Increase, Apoptosis	Increased, Kidney Failure	Aug 5, 2021	Aug 5, 2021
2602	Increase, Apoptosis	Microcephaly	Mar 17, 2022	Mar 17, 2022
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
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
2725	Increase, Apoptosis	Decrease, outgrowth	Jul 28, 2022	Jul 28, 2022
2948	Increase, Apoptosis	Inhibition of neurotransmitter release	Jun 20, 2023	Jun 20, 2023
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
1473	Increase, angiogenesis	Inhibit, gastric ulcer formation	Apr 17, 2017	Apr 17, 2017	Gastric ulcer formation
2578	Increase, angiogenesis	N/A, Breast Cancer	Feb 15, 2022	Feb 15, 2022
3137	Increase, angiogenesis	Metastasis, Breast Cancer	Mar 5, 2024	Mar 5, 2024	Activation of the AhR leading to metastatic breast cancer
3308	Increase, angiogenesis	Increase, Cancer	Jul 18, 2024	Jul 18, 2024	Succinate dehydrogenase inactivation leading to cancer
2910	Increase, Androgen receptor	Alterations, Cellular proliferation / hyperplasia	May 11, 2023	May 11, 2023	Androgen receptor activation leading to prostate cancer
1487	Increase, ammonium (NH4+)	Decrease, surfactant	Apr 17, 2017	Apr 17, 2017	Gastric ulcer formation Helicobacter pylori to gastric ulcer
2736	Increase, Alcohol dehydrogenase	Increased, Estrogen receptor (ER) activity	Aug 28, 2022	Aug 28, 2022	Alcohol dehydrogenase leading to reproductive dysfunction
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	Aug 6, 2024	Decreased Sodium/Potassium ATPase activity leads to Heart failure
2836	Abnormal Neural Remodeling	Impairment, Learning and memory	Jan 25, 2023	Jul 26, 2024	Deposition of Energy Leading to Learning and Memory Impairment
2749	Increase, pigmentation	Increase, Incomplete ecdysis	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
398	Increase proliferation, Leydig cell	Hyperplasia, Leydig cell	Nov 29, 2016	Dec 3, 2016	PPARα activation leading to impaired fertility in adult male rodents
2067	Increase plasma Ang II	Increase,collagen synthesis	Mar 17, 2020	Mar 17, 2020
2138	Increase plasma Ang II	Accumulation, Collagen	May 15, 2020	May 15, 2020
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
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
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)
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
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
2331	Increase in RONS	D1 protein deactivation	Apr 11, 2021	Apr 11, 2021
2337	Increase in RONS	Decrease, MMP	Apr 11, 2021	Apr 11, 2021
2617	Increase in RONS	Increased, Oxidative Stress	Mar 28, 2022	Mar 28, 2022
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
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
2199	Increase in inflammation	hepatitis	Nov 2, 2020	Nov 2, 2020	Immune mediated hepatitis
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
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
2729	Increase chromosomal aberrations	Increase,miRNA levels	Aug 14, 2022	Aug 27, 2023	DNA damage and mutations leading to Metastatic Breast Cancer
1797	Increase cell proliferation	Increase, lung cancer	Dec 19, 2018	Dec 19, 2018
1793	DNA repair	Increase mutations	Dec 19, 2018	Dec 19, 2018
1794	DNA repair	Increase chromosomal aberrations	Dec 19, 2018	Dec 19, 2018
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	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
2817	Inadequate DNA repair	Cataracts	Dec 18, 2022	Mar 11, 2024	Deposition of energy leading to occurrence of cataracts
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
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
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
1644	Impairment, Learning and memory	Decreased, locomotion	Aug 11, 2017	Aug 11, 2017	Histamine (H2) receptor antagonism leading to reduced survival
2872	Impairment, Learning and memory	decreased, IQ	Apr 4, 2023	Apr 4, 2023	Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
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
3173	Impaired, urethral tube closure	Hypospadias	Mar 20, 2024	Jul 16, 2024	Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Hypospadias, increased
665	impaired, Thoracic shivering	impaired, Hive thermoregulation	Nov 29, 2016	Dec 3, 2016
2164	Impaired, Spermatogenesis	Decrease, Fertility	Jul 13, 2020	Jul 13, 2020
2274	Impaired, Spermatogenesis	impaired, Fertility	Jan 29, 2021	Aug 15, 2022	Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory
2692	Impaired, Spermatogenesis	Viable offspring, decreased	Jul 18, 2022	Jul 18, 2022
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
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
2632	Impaired, Oocyte maturation and ovulation	Increased, Oocyte Atresia	Apr 5, 2022	Apr 5, 2022	Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
3079	impaired, Learning and memory	Parkinsonian motor deficits	Oct 17, 2023	Oct 17, 2023	Various neuronal effects induced by elavl3, sox10, and mbp
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
701	impaired, ion channels	Altered, Action Potential	Nov 29, 2016	Dec 3, 2016	Altered ion channel activity leading impaired heart function
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
2292	impaired, 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	impaired, 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
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
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
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
1976	Impaired oxygenation of the blood	Acute inhalation toxicity	Jul 3, 2019	Jul 3, 2019
1990	Impaired ovulation	Decrease of egg production and cummulative fecundity	Oct 3, 2019	Oct 3, 2019	Luteinizing hormone receptor antagonism leading to reproductive dysfunction
2515	Altered mechanotransduction properties of pericytes	Pericyte dysfunction	Oct 28, 2021	Oct 28, 2021
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
1938	Impaired inguinoscrotal phase	Malformation, cryptorchidism	Jun 3, 2019	Jul 18, 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
2000	Impaired IL-1R1 signaling	Suppression of T cell activation	Nov 17, 2019	Nov 17, 2019
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
1815	Impaired IL-1 signaling	Suppressed AP-1	Dec 25, 2018	Dec 25, 2018
1816	Impaired IL-1 signaling	Suppressed NF-kB	Dec 25, 2018	Dec 25, 2018
1825	Impaired IL-1 signaling	Suppressed MyD88	Jan 6, 2019	Mar 14, 2019
1920	Impaired IL-1 signaling	Inhibition, Nuclear factor kappa B (NF-kB)	May 23, 2019	Jun 25, 2019
2296	Impaired gustatory nerve	taste impairment	Mar 28, 2021	Mar 28, 2021	Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia
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
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
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
1820	Impaired antigen presentation	Impaired T cell activation	Dec 25, 2018	Dec 25, 2018
1923	Impaired Ab production	Impairment of TDAR	May 23, 2019	Jun 25, 2019
1278	Leukocyte infiltration	Respiratory irritability	Nov 29, 2016	Dec 3, 2016
1290	Leukocyte infiltration	Sensitization, Immune system	Nov 29, 2016	Dec 3, 2016
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
2196	Immune cell activation	IFNγ signaling	Nov 2, 2020	Nov 2, 2020	Immune mediated hepatitis
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
2197	IFNγ signaling	Increase in inflammation	Nov 2, 2020	Nov 2, 2020	Immune mediated hepatitis
3191	Hypomyelination	Altered, white brain matter	Apr 12, 2024	Apr 12, 2024	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
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
755	hyperpolarisation, neuron	N/A, Ataxia, paralysis, or hyperactivity	Nov 29, 2016	Dec 3, 2016	Glutamate-gated chloride channel activation leading to acute 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
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
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.
462	Hyperplasia, Leydig cell	impaired, Fertility	Nov 29, 2016	Dec 3, 2016	PPARα activation leading to impaired fertility in adult male rodents
158	Hyperplasia, Hyperplasia	Promotion, Hepatocelluar carcinoma	Nov 29, 2016	Dec 3, 2016	Uncharacterized liver damage leading to hepatocellular carcinoma
2762	Hyperinflammation	Increase, the risk of acute respiratory failure	Sep 1, 2022	Sep 1, 2022
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
3328	HLA-DQ2/8-gluten complexes, formation	Activation/Proliferation, T-cells	Aug 13, 2024	Aug 13, 2024	Gluten intake leading to celiac disease example test - under development
1709	Histone deacetylase inhibition	Histone acetylation, increase	Jan 21, 2018	Aug 5, 2021	Histone deacetylase inhibition leading to testicular atrophy Histone deacetylase inhibition leads to neural tube defects
1714	Histone deacetylase inhibition	p21 (CDKN1A) expression, increase	Jan 21, 2018	Jul 25, 2018
1715	Histone deacetylase inhibition	Cell cycle, disrupted	Jan 21, 2018	Jul 28, 2021	Histone deacetylase inhibition leading to testicular atrophy
1716	Histone deacetylase inhibition	Apoptosis	Jan 21, 2018	Jul 1, 2021	Histone deacetylase inhibition leading to testicular atrophy
1717	Histone deacetylase inhibition	Testicular atrophy	Jan 21, 2018	Jul 28, 2021	Histone deacetylase inhibition leading to testicular atrophy
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
2699	Histone deacetylase inhibition	Neural tube defects	Jul 19, 2022	Jul 19, 2022	Ceramide synthase inhibition leading to neural tube defects
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
1997	Histone acetylation, increase	Cell cycle, disrupted	Nov 11, 2019	Jul 1, 2021	Histone deacetylase inhibition leading to testicular atrophy
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
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
2864	Hippocampal Physiology, Altered	Impairment, Learning and memory	Apr 3, 2023	Apr 3, 2023	Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
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
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
2535	hERG channel biogenesis interference	Direct hERG channel blockage	Dec 13, 2021	Dec 13, 2021
2536	hERG channel biogenesis interference	Induction of hERG trafficking defects	Dec 13, 2021	Dec 13, 2021
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
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
1546	Helicobacter pylori infection	Increase, ammonium (NH4+)	Jun 2, 2017	Jun 2, 2017	Helicobacter pylori to gastric ulcer
2508	Heart failure	Upregulation of ACE2	Oct 28, 2021	Oct 28, 2021
2514	Heart failure	Altered mechanotransduction properties of pericytes	Oct 28, 2021	Oct 28, 2021
2825	Heart failure	Increase, Mortality	Jan 5, 2023	Jan 5, 2023
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
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
3142	Reduced granulosa cell proliferation	irregularities, ovarian cycle	Mar 7, 2024	Jun 23, 2024	Androgen receptor (AR) antagonism leading to decreased fertility in females
3329	Gluten-reactive T cell receptors, generation	Activation/Proliferation, T-cells	Aug 13, 2024	Aug 13, 2024	Gluten intake leading to celiac disease example test - under development
3330	Gluten-reactive and TG2-reactive B cell receptors, generation	Activation/Proliferation, T-cells	Aug 13, 2024	Aug 13, 2024	Gluten intake leading to celiac disease example test - under development
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
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
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
1691	Glutamate dyshomeostasis	Neuronal network function, Decreased	Nov 9, 2017	Nov 9, 2017
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
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
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
1289	Generation of novel epitopes , Antigen presentation	Sensitization, Immune system	Nov 29, 2016	Dec 3, 2016
1733	General Apoptosis	Neurodegeneration	Apr 4, 2018	Apr 5, 2018	CYP2E1 activation and formation of protein adducts leading to neurodegeneration
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
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	Increased, Reactive oxygen species	Jul 6, 2021	Jul 6, 2021	Frustrated phagocytosis leads to malignant mesothelioma
1925	Frizzled activation	GSK3beta inactivation	May 29, 2019	May 29, 2019
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
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
1062	Formation, The binding of FK506 with FKBP12	Inhibition, Calcineurin Activity	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)
860	Formation, Mallory body	Formation, Liver fibrosis	Nov 29, 2016	Dec 3, 2016	Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
1854	Protein photo-adducts	Inflammatory events	Feb 4, 2019	Feb 4, 2019
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
1853	DNA photo-adducts	Inflammatory events	Feb 4, 2019	Feb 4, 2019
1594	Foam cell formation	Atherosclerosis	Jun 29, 2017	Jun 29, 2017
1841	Fibroproliferative airway lesions	Bronchiolitis obliterans	Jan 30, 2019	Jan 30, 2019	α-diketone-induced bronchiolitis obliterans
2678	Fibroblast proliferation and differentiation	Airway remodeling	Jun 17, 2022	Jun 17, 2022	Adverse outcome pathway of PM-induced respiratory toxicity
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
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
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)
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
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
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
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
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
1357	Expression of Collagen	Collagen Deposition	Feb 15, 2017	Feb 15, 2017
1273	Sensory Airway Irritation	Cough, Dyspnea, Sneezing, Acute respiratory effect	Nov 29, 2016	Dec 3, 2016
2880	ERa inactivation	Increased adipocyte size	Apr 6, 2023	Apr 6, 2023	ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
2881	ERa inactivation	Increased adipocyte numbers	Apr 6, 2023	Apr 6, 2023	ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
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	Increased, Reactive oxygen species	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
1627	EMT	Expression of Collagen	Jul 26, 2017	Jul 26, 2017
1655	EMT	Accumulation, Collagen	Aug 16, 2017	Aug 16, 2017	Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis
1725	EMT	Lung fibrosis	Mar 18, 2018	Mar 18, 2018
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
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
2614	EMT	Metastasis, Breast Cancer	Mar 22, 2022	Sep 26, 2023	DNA damage and mutations leading to Metastatic Breast Cancer
3200	EMT	Resistant gastric cancer	Apr 23, 2024	Apr 23, 2024	Increases in cellular reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer
3204	EMT	Airway remodeling	May 1, 2024	May 1, 2024	Adverse outcome pathway of PM-induced respiratory toxicity
3306	EMT	Increase, Cancer	Jul 18, 2024	Jul 18, 2024	Succinate dehydrogenase inactivation leading to cancer
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
3170	Epididymal agenesis	Impaired, Spermatogenesis	Mar 20, 2024	Jul 16, 2024	Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Impaired, Spermatogenesis
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
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
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
2680	Emphysema	Chronic obstructive pulmonary disease	Jun 17, 2022	Jun 17, 2022	Adverse outcome pathway of PM-induced respiratory toxicity
1856	Eczematous eruption	Scaling, Lichenification	Feb 4, 2019	Feb 4, 2019
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
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
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
2006	Cardiovascular dysregulation	Respiratory distress/arrest	Nov 25, 2019	Dec 19, 2019	Acetylcholinesterase inhibition leading to acute mortality
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
2676	Dysfunctional autophagy	Emphysema	Jun 17, 2022	Jun 17, 2022	Adverse outcome pathway of PM-induced respiratory toxicity
2136	Downregulation of ACE2	Increase plasma Ang II	May 15, 2020	May 15, 2020
2137	Downregulation of ACE2	Increased AngII	May 15, 2020	May 15, 2020	Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia
2517	Downregulation of ACE2	Ang (1-7) levels reduced	Oct 28, 2021	Oct 28, 2021
446	Down Regulation, K-Cl co-transporter 2 (KCC2)	Delay, Developmental GABA shift	Nov 29, 2016	Dec 3, 2016
524	Down Regulation, HMGCS2	Decreased, Ketogenesis	Nov 29, 2016	Dec 3, 2016	NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
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
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
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
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
1834	Disturbance in microtubule dynamic instability	Impaired axonial transport	Jan 29, 2019	Jan 29, 2019	Microtubule interacting drugs lead to peripheral neuropathy
1842	Distribution of chemicals	Absorption of photon energy	Feb 4, 2019	Feb 4, 2019
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
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
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
188	Disruption, Mitochondrial electron transport chain	Decrease, Mitochondrial ATP production	Nov 29, 2016	Dec 3, 2016	Calcium-mediated neuronal ROS production and energy imbalance
189	Disruption, Mitochondrial electron transport chain	Increase, ROS production	Nov 29, 2016	Dec 3, 2016	Calcium-mediated neuronal ROS production and energy imbalance
715	Disruption, Microtubule dynamics	Disorganization, Meiotic Spindle	Nov 29, 2016	Dec 13, 2019	Chemical binding to tubulin in oocytes leading to aneuploid offspring
911	Disruption, Lysosome	Increase, ROS production	Nov 29, 2016	Dec 3, 2016
921	Disruption, Lysosome	Peptide Oxidation	Nov 29, 2016	Nov 29, 2016
993	Disruption, Lysosome	Mitochondrial dysfunction	Nov 29, 2016	Nov 12, 2018	Endocytic lysosomal uptake leading to liver fibrosis Endocytotic lysosomal uptake leads to intestinal barrier disruption
1679	Disruption, Lysosome	Increase, Cytotoxicity (renal tubular cell)	Oct 25, 2017	Oct 25, 2017	Receptor mediated endocytosis and lysosomal overload leading to kidney toxicity
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
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
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
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
3222	Disrupted PPAR isoform nuclear signaling	Decreased, Mitochondrial fatty acid beta-oxidation	May 14, 2024	May 14, 2024
2481	Oocyte meiosis, disrupted	Ovarian reserve, reduced	Sep 13, 2021	Nov 11, 2021	Inhibition of ALDH1A (RALDH) leading to impaired fertility via disrupted meiotic initiation of fetal oogonia of the ovary
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
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
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
737	Disorganization, Meiotic Spindle	Altered, Meiotic chromosome dynamics	Nov 29, 2016	Dec 13, 2019	Chemical binding to tubulin in oocytes leading to aneuploid offspring
3145	Direct mitochondrial inhibition	Mitochondrial dysfunction	Mar 13, 2024	Mar 13, 2024	AOP from chemical insult to cell death
2537	Direct hERG channel blockage	Inhibition of Ikr	Dec 13, 2021	Dec 13, 2021
2359	Diminished Protective Response to ROS	Coagulation	Apr 20, 2021	Jan 26, 2024	Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation
2413	Diminished Protective Response to ROS	inflammasome activity, increased	Jun 25, 2021	Jun 25, 2021	SARS-CoV-2 infection leading to hyperinflammation
973	dimerization, AHR/ARNT	reduced dimerization, ARNT/HIF1-alpha	Nov 29, 2016	Mar 23, 2018	Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF AhR activation leading to preeclampsia
1350	dimerization, AHR/ARNT	Increase, COX-2 expression	Feb 9, 2017	May 9, 2017	Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2
1996	dimerization, AHR/ARNT	Increase, DNMT expression	Oct 30, 2019	Oct 30, 2019	Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
2682	dimerization, AHR/ARNT	Decrease, sox9 expression	Jun 30, 2022	Jun 30, 2022
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
1356	Differentiation of Myofibroblast	Production of α-smooth muscle actin	Feb 15, 2017	Feb 15, 2017
659	Desensitization, Nicotinic acetylcholine receptor	Neuronal network function, Decreased	Nov 29, 2016	Dec 3, 2016	Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2
1309	Desensitization, Nicotinic acetylcholine receptor	Altered, Ca2+-calmodulin activated signal transduction	Nov 29, 2016	Dec 3, 2016	Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within caste
1798	Ionizing Energy	Increase mutations	Dec 19, 2018	Dec 19, 2018
1799	Ionizing Energy	Increase chromosomal aberrations	Dec 19, 2018	Dec 19, 2018
2379	Ionizing Energy	Increased, Reactive oxygen species	May 12, 2021	May 12, 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
2390	Ionizing Energy	Increased, Oxidative Stress	May 12, 2021	May 12, 2021
2392	Ionizing Energy	Altered, Meiotic chromosome dynamics	May 14, 2021	May 14, 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
2394	Ionizing Energy	impaired, Fertility	May 14, 2021	May 14, 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
2396	Ionizing Energy	Decreased, Population size	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
3240	Ionizing Energy	Oxidative Stress	May 31, 2024	May 31, 2024	Deposition of ionizing energy leads to population decline via impaired meiosis
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 vascular remodeling Deposition of Energy Leading to Learning and Memory Impairment
1981	Energy Deposition	Increase, Mutations	Aug 29, 2019	Mar 8, 2024	Deposition of energy leading to lung cancer Deposition of energy leading to occurrence of cataracts
1982	Energy Deposition	Increase, Chromosomal aberrations	Aug 29, 2019	Mar 8, 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
2548	Energy Deposition	Increased, Reactive oxygen species	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
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
2557	Energy Deposition	Increase, ROS production	Feb 4, 2022	Feb 4, 2022	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
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
2769	Energy Deposition	Oxidative Stress	Sep 28, 2022	Aug 26, 2024	Deposition of energy leads to 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
2779	Energy Deposition	Altered, Nitric Oxide Levels	Sep 28, 2022	Aug 26, 2024	Deposition of energy leads to vascular remodeling
2780	Energy Deposition	Increase, Endothelial Dysfunction	Sep 28, 2022	Aug 26, 2024	Deposition of energy leads to vascular remodeling
2785	Energy Deposition	Occurrence, Vascular Remodeling	Oct 17, 2022	Aug 26, 2024	Deposition of energy leads to vascular remodeling
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
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
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
3133	Depletion, mtDNA	Mitochondrial dysfunction	Feb 28, 2024	Feb 28, 2024	Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity
2878	Depletion, GSH	Increased, Reactive oxygen species	Apr 5, 2023	Sep 14, 2023	Glutathione conjugation leading to reproductive dysfunction via oxidative stress
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
1182	Delayed, Sexual maturity	Decreased, Reproductive Success	Nov 29, 2016	Dec 3, 2016
2739	Delay, Ovarian maturation	Increase, Body volume of female adults	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
447	Delay, Developmental GABA shift	Synaptogenesis, Decreased	Nov 29, 2016	Dec 3, 2016
907	Degeneration of dopaminergic neurons of the nigrostriatal pathway	Neuroinflammation	Nov 29, 2016	Oct 2, 2017	Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits
910	Degeneration of dopaminergic neurons of the nigrostriatal pathway	Parkinsonian motor deficits	Nov 29, 2016	Aug 25, 2017	Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits
3077	Degeneration of dopaminergic neurons of the nigrostriatal pathway	impaired, Learning and memory	Oct 17, 2023	Oct 17, 2023	Various neuronal effects induced by elavl3, sox10, and mbp
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
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
334	Decreased, VegfR2	Inhibition, VegfR2	Nov 29, 2016	Dec 3, 2016
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
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
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
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
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
2376	Decreased, Triiodothyronine (T3)	Decreased, Eye size	May 11, 2021	Jun 16, 2021	Thyroperoxidase inhibition leading to altered visual function via decreased eye size
2378	Decreased, Triiodothyronine (T3)	Altered, Photoreceptor patterning	May 11, 2021	Oct 17, 2021	Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning
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
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)
1009	Decreased, Synthesis of molting fluid proteases	Decrease, Digestion of old cuticle	Nov 29, 2016	Dec 3, 2016
1001	Decreased, synthesis and secretion of molting fluid proteases	Increase, Incomplete ecdysis	Nov 29, 2016	Dec 3, 2016
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
3168	Decreased, steroidogenic protein expression	Decrease, testosterone levels	Mar 20, 2024	Jul 16, 2024	Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Impaired, Spermatogenesis
3171	Decreased, steroidogenic protein expression	Decrease, DHT level	Mar 20, 2024	Jul 16, 2024	Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Hypospadias, increased
3288	Decreased, sodium uptake	Decreased, Sodium plasma concentrations	Jul 8, 2024	Aug 6, 2024	Decreased Sodium/Potassium ATPase activity leads to Heart failure
831	Decreased, Sodium reabsorption	Occurrence, Kidney toxicity	Nov 29, 2016	Dec 3, 2016	Kidney dysfunction by decreased thyroid hormone
3289	Decreased, Sodium plasma concentrations	Increase, Abnormal osmoregulation	Jul 8, 2024	Aug 6, 2024	Decreased Sodium/Potassium ATPase activity leads to Heart failure
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
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
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
1065	Decreased, serum T4/T3	Increased, Thyroid-stimulating hormone (TSH)	Nov 29, 2016	Dec 3, 2016
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
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
830	Decreased, Renal plasma flow	Occurrence, Kidney toxicity	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
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
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
733	Decreased, Prolactin	Increased, Estrogen receptor (ER) activity	Nov 29, 2016	Dec 3, 2016	Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)
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)
878	Decreased, PPARalpha transactivation of gene expression	Decreased, Peroxisomal Fatty Acid Beta Oxidation of Fatty Acids	Nov 29, 2016	Jun 2, 2017
879	Decreased, PPARalpha transactivation of gene expression	Decreased, Mitochondrial Fatty Acid Beta Oxidation	Nov 29, 2016	Jun 2, 2017
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
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
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
259	Decreased, PPAR-beta activation	Decreased, HSD17B10 expression	Nov 29, 2016	Dec 3, 2016	Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis
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
1491	Decreased, Population trajectory	Increased Mortality	Apr 18, 2017	Apr 18, 2017
881	Decreased, Peroxisomal Fatty Acid Beta Oxidation of Fatty Acids	Decreased, Mitochondrial Fatty Acid Beta Oxidation	Nov 29, 2016	Nov 29, 2016
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
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
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
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
212	Decreased, Nitric Oxide	Decreased, Long-term potentiation (LTP)	Nov 29, 2016	Dec 3, 2016	Calcium-mediated neuronal ROS production and energy imbalance
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
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
1538	Decreased, mucous	Reduced, mucosal defense	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
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
617	Decreased, Mitochondrial fatty acid beta-oxidation	Increased, Liver Steatosis	Nov 29, 2016	Dec 3, 2016
2931	Decreased, Mitochondrial fatty acid beta-oxidation	Mitochondrial dysfunction EMPTY	May 25, 2023	May 25, 2023
3159	Decreased, Mitochondrial fatty acid beta-oxidation	Mitochondrial dysfunction	Mar 13, 2024	Mar 13, 2024	ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
3209	Decreased, Mitochondrial fatty acid beta-oxidation	Disrupted Lipid Storage	May 8, 2024	May 28, 2024	Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
882	Decreased, Mitochondrial Fatty Acid Beta Oxidation	Decreased, Ketogenesis (production of ketone bodies)	Nov 29, 2016	Nov 29, 2016
2040	Decreased, Mitochondrial Fatty Acid Beta Oxidation	Increased, Liver Steatosis	Feb 22, 2020	Feb 22, 2020
2264	Decreased, Mitochondrial Fatty Acid Beta Oxidation	Accumulation, Triglyceride	Jan 15, 2021	Jan 15, 2021	Glucocorticoid Receptor activation leading to hepatic steatosis
805	Decreased, mevalonate	Decreased, cholesterol	Nov 29, 2016	Dec 3, 2016	HMG-CoA reductase inhibition leading to decreased fertility
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
389	Decreased, Lymphocytes	Increased, Disease susceptibility	Nov 29, 2016	Dec 3, 2016
390	Decreased, Lymphocytes	Suppression, Immune system	Nov 29, 2016	Dec 3, 2016	Glucocorticoid Receptor Activation Leading to Increased Disease Susceptibility
651	Decreased, locomotion	Increased, predation	Nov 29, 2016	Dec 3, 2016	Histamine (H2) receptor antagonism leading to reduced survival
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.
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
1660	Decreased, Ketogenesis	Accumulation, Fatty acid	Aug 31, 2017	Aug 31, 2017	NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
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
1554	Decreased, intracellular chloride	Activated, membrane depolarization	Jun 2, 2017	Jun 2, 2017	presynaptic neuron 2 repression to epilepsy
2867	decreased, IQ	increased, Economic Burden	Apr 4, 2023	Apr 4, 2023	Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
3174	Decreased, INSL3	Impaired inguinoscrotal phase	Mar 20, 2024	Jul 16, 2024	Decreased Insulin-like peptide 3 (INSL3) leads to Malformation, cryptorchidism - maldescended testis
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
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
2629	Decreased, Gonadotropins	Decreased , Androgen and Progestin	Apr 5, 2022	Apr 5, 2022	Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
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.
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
829	Decreased, Glomerular filtration	Occurrence, Kidney toxicity	Nov 29, 2016	Dec 3, 2016	Kidney dysfunction by decreased thyroid hormone
1188	Decreased, gametogenesis	Decreased, Reproductive Success	Nov 29, 2016	Dec 3, 2016
1245	Decreased, GABA release	Decreased, Chloride conductance	Nov 29, 2016	Dec 3, 2016
1552	Decreased, GABA	Reduced, GABA-A receptor activation	Jun 2, 2017	Jun 2, 2017	presynaptic neuron 2 repression to epilepsy
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
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)
1519	Decreased, extracellular serotonin	Decreased, synaptic release	May 30, 2017	May 30, 2017
3254	Decreased, ERαβ heterodimers	Apoptosis	Jun 19, 2024	Jun 19, 2024	Binding and activation of GPER leading to learning and memory impairments
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
537	Decreased, DHB4/HSD17B4	Inhibition, Mitochondrial fatty acid beta-oxidation	Nov 29, 2016	Dec 3, 2016	NFE2L2/FXR activation leading to hepatic steatosis
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, testosterone levels	Apr 25, 2024	Apr 25, 2024	HMG-CoA reductase inhibition leading to decreased fertility
3167	Decreased COUP-TFII in Leydig cells	Decreased, steroidogenic protein expression	Mar 20, 2024	Jul 16, 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
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
1101	Decreased, bile flow	Increased, cholestasis	Nov 29, 2016	Dec 3, 2016	PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
1540	Decreased, bicarbonate	Reduced, mucosal defense	Jun 2, 2017	Jun 2, 2017	NSAID induced PTGS1 inactivation to gastric ulcer
2870	decreased, Bcl-2	Cell injury/death	Apr 4, 2023	Apr 4, 2023	Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
2873	decreased, Bcl-2	Increase, Cell death	Apr 4, 2023	Apr 4, 2023
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
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
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
1542	Decreased, angiogenesis	Activated, gastric ulcer formation	Jun 2, 2017	Jun 2, 2017	NSAID induced PTGS2 inactivation to gastric ulcer
729	Decreased, Androgen receptor activity	Decreased, Testosterone binding to androgen receptor (hypothalamus)	Nov 29, 2016	Dec 3, 2016	Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)
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
2477	Decreased, atRA concentration	Oocyte meiosis, disrupted	Sep 10, 2021	Feb 27, 2022	Inhibition of ALDH1A (RALDH) leading to impaired fertility via disrupted meiotic initiation of fetal oogonia of the ovary
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
1530	Decreased, 5-HT3	Increased, seizure	Jun 1, 2017	Jun 1, 2017	Serotonin transporter activation to seizure
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
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
2161	Decreased spermatogenesis	impaired, Fertility	Jul 13, 2020	Jul 13, 2020	Inhibition of 11β-hydroxylase leading to decresed population trajectory Deposition of ionizing energy leads to population decline via impaired meiosis
2388	Decreased spermatogenesis	Decrease of egg production and cummulative fecundity	May 12, 2021	May 12, 2021	Deposition of ionizing energy leads to population decline via impaired meiosis
2620	Decreased spermatogenesis	Decrease, Fecundity	Mar 28, 2022	Mar 28, 2022	Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
2623	Decreased spermatogenesis	Decrease, Reproduction	Mar 28, 2022	Mar 28, 2022	Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
2624	Decreased spermatogenesis	Decrease, Population growth rate	Mar 28, 2022	Mar 28, 2022	Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
1650	Decreased sperm quantity or quality in the adult, Decreased fertility	impaired, Fertility	Aug 11, 2017	Aug 11, 2017	Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
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
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
1916	retinoic acid	plasma retionic acid	May 22, 2019	May 22, 2019	Inhibition of retinaldehyde dehydrogenase leads to population decline
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
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
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
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
1917	plasma retionic acid	Altered, Photoreceptor patterning	May 22, 2019	May 22, 2019	Inhibition of retinaldehyde dehydrogenase leads to population decline
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	impaired, Fertility	Mar 26, 2021	Mar 26, 2021	Inhibition of 11β-hydroxylase leading to decresed population trajectory
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
3287	Decreased Na/K ATPase activity	Decreased, sodium uptake	Jul 8, 2024	Aug 6, 2024	Decreased Sodium/Potassium ATPase activity leads to Heart failure
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
1814	Decreased IL-1 production	Impaired IL-1 signaling	Dec 25, 2018	Jun 25, 2019
1824	Decreased IL-1 production	Suppressed MyD88	Jan 6, 2019	Jan 6, 2019
2700	decrease folate	Neural tube defects	Jul 19, 2022	Jul 19, 2022	Ceramide synthase inhibition leading to neural tube defects
1614	decreased dopamine	decreased reward	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
2744	Decrease, Tyrosine	Decrease, dopa decarboxylase	Aug 28, 2022	Aug 28, 2022	Doda decarboxylase leading to mortality
2098	Decrease, TAG	Decrease, ATP pool	Apr 30, 2020	Apr 30, 2020	Excessive reactive oxygen species production leading to mortality (3)
399	Decrease, Translocator protein (TSPO)	Reduction, Testosterone synthesis in Leydig cells	Nov 29, 2016	Dec 3, 2016
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
1888	Decrease, Transgenerational DNA methylation	Increase, Gene expression	Apr 22, 2019	Apr 22, 2019
2129	decrease, transcription of genes by AR	AGD, decreased	May 11, 2020	May 11, 2020
2126	Decrease, 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, 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
3169	Decrease, testosterone levels	Epididymal agenesis	Mar 20, 2024	Jul 16, 2024	Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Impaired, Spermatogenesis
3202	Decrease, testosterone levels	malformed, Male reproductive tract	Apr 25, 2024	Apr 25, 2024	HMG-CoA reductase inhibition leading to decreased fertility
3205	Decrease, testosterone levels	Malformation, Male reproductive tract	May 1, 2024	May 1, 2024	PPARα activation in utero leading to impaired fertility in males
3206	Decrease, testosterone levels	Increase, Luteinizing hormone (LH)	May 1, 2024	May 1, 2024	PPARα activation leading to impaired fertility in adult male rodents
3213	Decrease, testosterone levels	Reduction, Plasma 17beta-estradiol concentrations	May 8, 2024	May 8, 2024	Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）
3214	Decrease, 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）
3225	Decrease, testosterone levels	Decreased sperm quantity or quality in the adult, Decreased fertility	May 24, 2024	May 24, 2024	Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
3227	Decrease, testosterone levels	Increased, Leutinizing hormone (LH)	May 24, 2024	May 24, 2024	Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)
1547	Decrease, surfactant	Reduced, mucosal defense	Jun 2, 2017	Jun 2, 2017	Helicobacter pylori to gastric ulcer
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
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
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
3060	Decrease, sox10	N/A, Neurodegeneration	Oct 17, 2023	Oct 17, 2023	Various neuronal effects induced by elavl3, sox10, and mbp
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
769	Decrease, Serum thyroid hormone (T4/T3)	Increase, Thyroid-stimulating hormone (TSH)	Nov 29, 2016	Dec 3, 2016
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
2756	Decrease, Prevent chitin degradation by chitinases	Weak, Procuticle protection	Aug 28, 2022	Aug 28, 2022	Knickkopf leading to mortality
2180	Decrease, ATPase activity	Increase, Abnormal osmoregulation	Nov 2, 2020	Nov 2, 2020
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
1737	Decrease, PSII activity	Decrease, Photosynthesis	May 24, 2018	May 24, 2018
1740	Decrease, PSII activity	Increase, ROS	May 24, 2018	May 24, 2018
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
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
1669	Decrease, OXPHOS	Decrease, Mitochondrial ATP production	Oct 10, 2017	Oct 10, 2017	Reduction in photophosphorylation leading to growth inhibition in aquatic plants Deposition of ionising energy leading to population decline via mitochondrial dysfunction
1810	Decrease, OXPHOS	Decreased Na/K ATPase activity	Dec 20, 2018	Dec 20, 2018	Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndrome
2095	Decrease, OXPHOS	Decrease, ATP pool	Apr 30, 2020	Apr 30, 2020	Excessive reactive oxygen species production leading to mortality (2)
2346	Decrease, OXPHOS	Decrease, ATP synthase activity	Apr 11, 2021	Apr 11, 2021
2713	Decrease, OXPHOS	Oxidative Stress	Jul 25, 2022	Jul 25, 2022
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
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)
1470	Decrease, Oogenesis	Decrease, Ovulation	Apr 15, 2017	Apr 15, 2017
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) Thermal stress leading to population decline (3) Thermal stress leading to population decline (1) Thermal stress leading to population decline (2)
2586	Decrease, Oogenesis	Decrease, Reproduction	Mar 1, 2022	Mar 1, 2022
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
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
2758	Decrease, New cuticle secretion	Increase, Incomplete ecdysis	Aug 28, 2022	Aug 28, 2022	Knickkopf leading to mortality
2094	Decrease, MMP	Decrease, OXPHOS	Apr 30, 2020	Apr 30, 2020	Excessive reactive oxygen species production leading to mortality (2) Deposition of ionising energy leading to population decline via mitochondrial dysfunction
2347	Decrease, MMP	Increase, Programmed cell death	Apr 11, 2021	Apr 11, 2021
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
1601	Decrease, Mitochondrial ATP production	Decrease, Oogenesis	Jun 29, 2017	Jun 29, 2017
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
1739	Decrease, Mitochondrial ATP production	Decrease, Growth	May 24, 2018	May 24, 2018
1750	Decrease, Mitochondrial ATP production	Increase, Apoptosis	Jun 12, 2018	Jun 12, 2018
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
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
3061	Decrease, mbp	N/A, Neurodegeneration	Oct 17, 2023	Oct 17, 2023	Various neuronal effects induced by elavl3, sox10, and mbp
1666	Decrease, Light harvest capacity	Decrease, Photosynthesis	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
2283	Decrease, Leaf development	Decrease, Growth	Feb 16, 2021	Feb 16, 2021	Reduction in photophosphorylation leading to growth inhibition in aquatic plants
2335	Decrease, Leaf development	Decrease, Reproduction	Apr 11, 2021	Apr 11, 2021	Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis
1671	Decrease, Leaf cell mitosis	Decrease, Leaf development	Oct 10, 2017	Oct 10, 2017	Reduction in photophosphorylation leading to growth inhibition in aquatic plants
2753	Decrease, knickkopf gene	Decrease, Chitin laminar organization	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
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
791	Decrease, Incorporation of active iodide into iodotyrosines	Decrease, Serum thyroid hormone (T4/T3)	Nov 29, 2016	Dec 3, 2016
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
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)
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
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
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)
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)
2795	Decrease, Glucose pool	Decrease, Cell proliferation	Nov 1, 2022	Nov 1, 2022	Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion
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)
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)
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
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
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
2805	Decrease, GLI1/2 target gene expression	Decrease, outgrowth	Nov 17, 2022	Nov 17, 2022
2882	Decrease, GLI1/2 target gene expression	Apoptosis	Apr 6, 2023	May 1, 2023	Antagonism of Smoothened receptor leading to orofacial clefting
1472	Decrease, Fertility	Decrease, Population growth rate	Apr 15, 2017	Apr 15, 2017
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)
135	Decrease, Fecundity	Decline, Population	Nov 29, 2016	Dec 3, 2016
1886	Decrease, Fecundity	Decrease, Population growth rate	Apr 22, 2019	Apr 22, 2019	DNA methyltransferase inhibition leading to population decline (1) DNA methyltransferase inhibition leading to population decline (2) DNA methyltransferase inhibition leading to population decline (3) Thermal stress leading to population decline (3) Thermal stress leading to population decline (1) Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability Thermal stress leading to population decline (2)
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
2208	Decrease, FAO	Decrease, ATP pool	Nov 25, 2020	Nov 25, 2020
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
1349	Decrease, Excitatory postsynaptic potential	Decrease, Abdominal muscle contraction	Feb 9, 2017	Feb 9, 2017	Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
3059	Decrease, elavl3	N/A, Neurodegeneration	Oct 17, 2023	Oct 17, 2023	Various neuronal effects induced by elavl3, sox10, and mbp
1348	Decrease, Ecdysis motoneuron bursts	Decrease, Excitatory postsynaptic potential	Feb 9, 2017	Feb 9, 2017	Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
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
2745	Decrease, dopa decarboxylase	Increase, Defects in tanning of new cuticle	Aug 28, 2022	Aug 28, 2022	Doda decarboxylase leading to mortality
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
3172	Decrease, DHT level	Impaired, urethral tube closure	Mar 20, 2024	Jul 16, 2024	Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Hypospadias, increased
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
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
1600	Decrease, Coupling of OXPHOS	Decrease, Mitochondrial ATP production	Jun 29, 2017	Jun 29, 2017
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
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
2219	Decrease, Coupling of OXPHOS	Increase, Oxygen consumption	Dec 4, 2020	Dec 4, 2020
2763	Decrease, Coupling of OXPHOS	Increase, Cytosolic Ca	Sep 13, 2022	Sep 13, 2022	Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calcium
2793	Decrease, Coupling of OXPHOS	Increase, Glycolysis	Nov 1, 2022	Nov 1, 2022	Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion
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
3234	Decrease, Coupling of OXPHOS	Increase, ROS production	May 28, 2024	May 28, 2024	Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress
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
1347	Decrease, Circulating CCAP	Decrease, Ecdysis motoneuron bursts	Feb 9, 2017	Feb 9, 2017	Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
1665	Decrease, Chlorophyll synthesis	Decrease, Light harvest capacity	Oct 10, 2017	Oct 10, 2017	Reduction in photophosphorylation leading to growth inhibition in aquatic plants
2755	Decrease, Chitin laminar organization	Weak, Procuticle protection	Aug 28, 2022	Aug 28, 2022	Knickkopf leading to mortality
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
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
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
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
2824	Decrease, Cardiac contractility	Heart failure	Jan 5, 2023	Jan 5, 2023
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
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
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
1664	Decrease, ATP production	Decrease, Chlorophyll synthesis	Oct 10, 2017	Oct 10, 2017	Reduction in photophosphorylation leading to growth inhibition in aquatic plants
2341	Decrease, ATP production	Decrease, Leaf development	Apr 11, 2021	Apr 11, 2021	Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis
2547	Decrease, ATP production	Decrease, Reproduction	Jan 21, 2022	Jan 21, 2022	Deposition of ionizing energy leading to population decline via inhibition of photosynthesis
43	Decrease, Aromatase (Cyp19a1)	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells	Nov 29, 2016	Dec 3, 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
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)
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
2128	Decrease, AR activation	decrease, transcription of genes by AR	May 11, 2020	Nov 2, 2020
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
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)
2120	Decrease, ATP pool	Increase, Oocyte apoptosis	May 8, 2020	May 8, 2020
2121	Decrease, ATP pool	Increase, Necrosis	May 8, 2020	May 8, 2020
2179	Decrease, ATP pool	Decrease, ATPase activity	Nov 2, 2020	Nov 2, 2020
2204	Decrease, ATP pool	Decrease, Cell proliferation	Nov 12, 2020	Dec 7, 2020	Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation Mitochondrial ATP synthase antagonism leading to growth inhibition (1) Mitochondrial complex III antagonism leading to growth inhibition (1)
2209	Decrease, ATP pool	Decrease, Oogenesis	Nov 25, 2020	Nov 25, 2020	Thermal stress leading to population decline (1)
2214	Decrease, ATP pool	Increase, Cell death	Dec 4, 2020	Dec 4, 2020	Mitochondrial ATP synthase antagonism leading to growth inhibition (2)
2216	Decrease, ATP pool	Increase, Fatty acid β-oxidation	Dec 4, 2020	Dec 4, 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
2267	Decrease, ACAD	Decreased, Mitochondrial Fatty Acid Beta Oxidation	Jan 15, 2021	Jan 15, 2021	Glucocorticoid Receptor activation leading to hepatic steatosis
1010	Decrease, Abdominal muscle contraction	Increase, Incomplete ecdysis	Nov 29, 2016	Dec 3, 2016	Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
2752	Decrease, 20-hydroxyecdysone	Decrease, knickkopf gene	Aug 28, 2022	Aug 28, 2022	Knickkopf leading to mortality
443	Thyroidal Iodide, Decreased	T4 in serum, Decreased	Nov 29, 2016	Nov 29, 2016
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
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
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
2411	Neuronal network function, Decreased	Cognitive function, decreased	Jun 24, 2021	Aug 27, 2021	Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function
2501	Neuronal network function, Decreased	Memory Loss	Oct 26, 2021	Oct 26, 2021	A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants
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
871	GABAergic interneurons, Decreased	Synaptogenesis, Decreased	Nov 29, 2016	Jan 19, 2018	Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
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
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
3147	Decompartmentalization	Mitochondrial dysfunction	Mar 13, 2024	Mar 13, 2024	AOP from chemical insult to cell death
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
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
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
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
2440	CFTR Function, Decreased	ASL Height, Decreased	Jul 19, 2021	Sep 7, 2021	Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction
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
1726	CYP2E1 Activation	Oxidative Stress in Brain	Apr 4, 2018	Apr 5, 2018
3309	CYP2E1 Activation	Oxidative Stress	Jul 23, 2024	Jul 23, 2024	CYP2E1 activation and formation of protein adducts leading to neurodegeneration
376	Covalent Binding, Protein	Response, Keratinocytes	Nov 29, 2016	Dec 3, 2016
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
833	Covalent Binding, Protein	Activation, Keratinocytes	Nov 29, 2016	Dec 3, 2016	Covalent Protein binding leading to Skin Sensitisation
2202	Covalent Binding, Protein	Activation, Inflammatory cytokines, chemokines, cytoprotective gene pathways	Nov 5, 2020	Feb 11, 2021
2649	Covalent Binding, Protein	Increased proinflammatory mediators	Apr 28, 2022	Sep 8, 2022	Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response
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
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
2277	Cortisol and 11β-(OH) testosterone decreased	Decreased, 11KT	Feb 9, 2021	Feb 9, 2021	Inhibition of 11β-hydroxylase leading to decresed population trajectory
2877	Conjugation, GSH	Depletion, GSH	Apr 5, 2023	Sep 14, 2023	Glutathione conjugation leading to reproductive dysfunction via oxidative stress
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
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
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
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
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)
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
1314	Chronic, Mucus hypersecretion	Decreased lung function	Nov 29, 2016	Aug 30, 2021
2069	Chronic ROS	Porcupine-induced Wnt secretion and Wnt signaling activation	Mar 23, 2020	May 13, 2021	Increases in cellular reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer
1613	chronic high fat diet	decreased dopamine	Jul 24, 2017	Jul 24, 2017	Epigenetic modification of PPARG leading to adipogenesis
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
1712	Cell cycle, disrupted	Apoptosis	Jan 21, 2018	Jul 28, 2021	Histone deacetylase inhibition leading to testicular atrophy
2791	Cell cycle, disrupted	Altered, Meiotic chromosome dynamics	Oct 25, 2022	Oct 25, 2022	Deposition of ionizing energy leads to population decline via impaired meiosis
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
2398	Bulky DNA adducts, increase	Inadequate DNA repair	May 17, 2021	May 17, 2021	Bulky DNA adducts leading to mutations
2399	Bulky DNA adducts, increase	Increase, Mutations	May 17, 2021	Sep 14, 2021	Bulky DNA adducts leading to mutations
2353	Bradykinin, activated	Increased proinflammatory mediators	Apr 20, 2021	Jan 14, 2022	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
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
1973	Blood extravasation into the lungs	Acute inhalation toxicity	Jul 3, 2019	Jul 3, 2019
1813	Blocking of IL-1R	Impaired IL-1 signaling	Dec 24, 2018	Jun 25, 2019
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
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
330	Binding, VEGF-A	Decreased, VegfR2	Nov 29, 2016	Dec 3, 2016
331	Binding, VEGF-A	Inhibition, VegfR2	Nov 29, 2016	Dec 3, 2016
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
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
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
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
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
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
287	Binding, SH-/selen-proteins	N/A, Interferences with SH-/selen-proteins	Nov 29, 2016	Dec 3, 2016
1253	Binding, Immunophilins	Inhibition, Calcineurin Activity	Nov 29, 2016	Oct 25, 2017
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
2534	Binding to hERG channel	Direct hERG channel blockage	Dec 13, 2021	Dec 13, 2021
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)
2056	Binding to ACE2	SARS-CoV-2 cell entry	Mar 2, 2020	Feb 7, 2023	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)
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
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
2299	Binding to ACE2	ACE2 enzymatic inhibition	Mar 28, 2021	Mar 28, 2021
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
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
2452	Binding to ACE2	Endothelial cell dysfunction	Aug 4, 2021	Aug 4, 2021
2522	Binding to ACE2	ADAM17 induction	Oct 28, 2021	Oct 28, 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
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
1833	Binding of MSAs to microtubules	Disturbance in microtubule dynamic instability	Jan 29, 2019	Jan 29, 2019	Microtubule interacting drugs lead to peripheral neuropathy
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
1946	Binding of inhibitor, mitochondrial complex V	Mitochondrial Complex V inhibition	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
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
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
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
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
360	Binding of agonist, NMDARs	Overactivation, NMDARs	Nov 29, 2016	Nov 29, 2016
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
2304	Binding of agonist, Angiotensin II receptor type 1 receptor (AT1R)	Increase, ROS production	Mar 30, 2021	Mar 30, 2021
2319	Binding of agonist, Angiotensin II receptor type 1 receptor (AT1R)	Increased, Reactive oxygen species	Apr 10, 2021	Apr 10, 2021	Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis Binding to ACE2 leading to lung fibrosis
3184	Binding of (ant)agonist to PPAR alpha	Binding of antagonist to thyroid hormone receptor	Apr 12, 2024	Apr 12, 2024
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
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
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
877	Binding as antagonist, Antagonist binding to PPARalpha ligand binding domain	Decreased, PPARalpha transactivation of gene expression	Nov 29, 2016	Nov 29, 2016
248	Bile accumulation, Pathological condition	Activation of specific nuclear receptors, Transcriptional change	Nov 29, 2016	Dec 3, 2016	Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
928	Bile accumulation, Pathological condition	Release, Cytokine	Nov 29, 2016	Dec 3, 2016	Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
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)
3199	beta-catenin activation	EMT	Apr 23, 2024	Apr 23, 2024	Increases in cellular reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer
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
2198	Apoptotic cell death	Increase in inflammation	Nov 2, 2020	Nov 2, 2020	Immune mediated hepatitis
1368	Apoptosis	Reproductive failure	Feb 15, 2017	Feb 15, 2017	NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
1713	Apoptosis	Testicular atrophy	Jan 21, 2018	Jan 21, 2018
1735	Apoptosis	Spermatocyte depletion	May 22, 2018	Jul 28, 2021	Histone deacetylase inhibition leading to testicular atrophy
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
2191	Apoptosis	Increase, Tissue/organ damage	Nov 2, 2020	Nov 2, 2020
2577	Apoptosis	tumor growth	Feb 15, 2022	Mar 5, 2024	Activation of the AhR leading to metastatic breast cancer
2675	Apoptosis	Emphysema	Jun 17, 2022	Jun 17, 2022	Adverse outcome pathway of PM-induced respiratory toxicity
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
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
3250	Apoptosis	Aberrant, synaptic formation and plasticity	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
3257	Apoptosis	Neuroinflammation	Jun 19, 2024	Jun 19, 2024	Binding and activation of GPER leading to learning and memory impairments
3327	Apoptosis	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells	Jul 26, 2024	Jul 26, 2024	Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production
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
1986	Antagonism,LH receptor	Reduction, Progesterone synthesis	Oct 3, 2019	Oct 3, 2019	Luteinizing hormone receptor antagonism leading to reproductive dysfunction
1947	TR Antagnoism	Hippocampal gene expression, Altered	Jun 8, 2019	Jun 8, 2019	Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
1948	TR Antagnoism	Cognitive function, decreased	Jun 8, 2019	Jun 8, 2019	Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
3186	TR Antagnoism	Reduced number of oligodendrocytes	Apr 12, 2024	Apr 12, 2024	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
3193	TR Antagnoism	Hypomyelination	Apr 12, 2024	Apr 12, 2024	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
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
1061	Antagonism, Histamine Receptor (H2)	Decrease, histaminergic neuron excitation	Nov 29, 2016	Dec 3, 2016	Histamine (H2) receptor antagonism leading to reduced survival
129	Antagonism, Estrogen receptor	Reduction, Vitellogenin synthesis in liver	Nov 29, 2016	Nov 30, 2016	Estrogen receptor antagonism leading to reproductive dysfunction
2613	Antagonism, Estrogen receptor	EMT	Mar 22, 2022	Aug 27, 2023	DNA damage and mutations leading to Metastatic Breast Cancer
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
2123	Antagonism, Androgen receptor	AGD, decreased	May 11, 2020	Aug 7, 2020
2130	Antagonism, Androgen receptor	Decrease, AR activation	May 11, 2020	Apr 5, 2024	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
2201	Antagonism, Androgen receptor	Altered, Transcription of genes by the AR	Nov 2, 2020	Feb 2, 2021
2519	Degradation of Ang-II reduced	Induced, Angiotensin (Ang) II accumulation	Oct 28, 2021	Oct 28, 2021
2518	Ang (1-7) levels reduced	Degradation of Ang-II reduced	Oct 28, 2021	Oct 28, 2021
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
2983	Angiogenesis disfunction	Increase, Vascular disrupting effects	Aug 19, 2023	Aug 19, 2023
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
1970	Alveolar collapse	Alveolar reopening	Jul 3, 2019	Jul 3, 2019