DEDUCT | Database of Endocrine Disrupting chemicals and their Toxicity profiles

Methimazole

Associated AOPs with Level of Relevance - 1 AOPs with at least 1 KE associated with chemical, where the KE(s) are neither MIE nor AO

AOP Identifier	AOP Title	AO Classification	OECD Status	Taxonomic applicability	Coverage Score ⓘ The fraction of KEs within the AOP, that are mapped to the chemical-associated toxicological endpoints.	KE Identifier	KE Name
AOP:7	Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female	Reproductive system disease; Endocrine system disease; Reproductive system disease	Under Review	Rat, Mouse, Human	0.2	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:8	Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Nervous system disease	Under Development	Rat	0.56	KE:281	Thyroxine (T4) in serum, Decreased
						KE:280	Thyroxine (T4) in neuronal tissue, Decreased
						KE:757	Hippocampal anatomy, Altered
						KE:758	Hippocampal Physiology, Altered
						KE:756	Hippocampal gene expression, Altered
AOP:37	PPARα activation leading to hepatocellular adenomas and carcinomas in rodents	Cancer; Gastrointestinal system disease	Under Development	Mouse, Rat	0.2	KE:716	Increase, cell proliferation (hepatocytes)
AOP:39	Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response	Respiratory system disease	Under Development	Human, Mouse	0.2	KE:272	Activation/Proliferation, T-cells
AOP:41	Sustained AhR Activation leading to Rodent Liver Tumours	Cancer; Gastrointestinal system disease	Under Review	Rattus sp. ABTC 42503, Mus sp. 2000082	0.6	KE:854	Alterations, Cellular proliferation / hyperplasia
						KE:853	Changes/Inhibition, Cellular Homeostasis and Apoptosis
						KE:139	N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects
AOP:58	NR1I3 (CAR) suppression leading to hepatic steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-	Human, Mouse, Rat	0.06	KE:454	Increased, Triglyceride formation
AOP:60	NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-		0.08	KE:454	Increased, Triglyceride formation
AOP:64	Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility	Reproductive system disease	-	Rattus norvegicus	0.14	KE:496	Increased apoptosis, decreased fetal/adult Leydig Cells
AOP:77	Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1	Unclassified	-	Honey bee	0.14	KE:341	Impairment, Learning and memory
AOP:78	Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1	Unclassified	-	Honey bee	0.12	KE:341	Impairment, Learning and memory
AOP:87	Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure	Unclassified	-	Honey bee	0.12	KE:341	Impairment, Learning and memory
AOP:88	Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within caste	Unclassified	-	Honey bee	0.14	KE:341	Impairment, Learning and memory
AOP:89	Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure	Unclassified	-	Honey bee	0.12	KE:341	Impairment, Learning and memory
AOP:90	Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2	Unclassified	-	Honey bee	0.12	KE:341	Impairment, Learning and memory
AOP:99	Histamine (H2) receptor antagonism leading to reduced survival	Unclassified	-	Zebrafish	0.14	KE:341	Impairment, Learning and memory
AOP:105	Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)	Cancer; Urinary system disease	-	Rattus norvegicus	0.17	KE:710	Increase, Regenerative cell proliferation (tubular epithelial cells)
AOP:107	Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat	Cancer; Gastrointestinal system disease	Under Review	Rattus norvegicus, Mus musculus	0.4	KE:1214	Altered gene expression specific to CAR activation, Hepatocytes
AOP:107		Cancer; Gastrointestinal system disease	Under Review	Rattus norvegicus, Mus musculus	0.4	KE:716	Increase, cell proliferation (hepatocytes)
AOP:109	Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)	Cancer; Respiratory system disease	-	Mus musculus	0.2	KE:734	Increase, Regenerative cell proliferation (terminal bronchiolar epithelial cells)
AOP:110	Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse)	Cancer; Endocrine system disease	-	Rattus norvegicus, Mus musculus	0.57	KE:1023	Increased, Thyroid-stimulating hormone (TSH)
						KE:277	Thyroid hormone synthesis, Decreased
						KE:281	Thyroxine (T4) in serum, Decreased
						KE:739	Increase, Hypertrophy and proliferation (follicular cell)
AOP:114	HPPD inhibition leading to corneal papillomas and carcinomas (in rat)	Cancer	-	Rattus norvegicus	0.17	KE:778	Increase, Regenerative cell proliferation (corneal cells)
AOP:115	Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)	Cancer	-	Mus musculus, Rattus norvegicus	0.2	KE:781	Increase, Regenerative cell proliferation (forestomach epithelial cells)
AOP:116	Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)	Cancer; Urinary system disease	-	Rattus norvegicus	0.25	KE:710	Increase, Regenerative cell proliferation (tubular epithelial cells)
AOP:117	Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)	Cancer; Gastrointestinal system disease	Under Development	Mus musculus, Rattus norvegicus	0.25	KE:716	Increase, cell proliferation (hepatocytes)
AOP:136	Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors	Benign neoplasm; Respiratory system disease	Under Review		0.14	KE:870	Increase, Cell Proliferation
AOP:164	Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouse	Cancer; Reproductive system disease	-	CD-1 mouse, SD rat	0.17	KE:1042	Proliferation/Clonal Expansion, smooth muscle
AOP:167	Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.	Reproductive system disease; Cancer	-	Mouse, Homo sapiens	0.14	KE:1067	Proliferation/Clonal Expansion, aberrant basal cells
AOP:207	NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans	Reproductive system disease	-	Caenorhabditis elegans	0.12	KE:1262	Apoptosis
AOP:209	Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP	Gastrointestinal system disease	-		0.12	KE:1287	Glutathione synthesis
AOP:242	Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity	Unclassified	-	Fish	0.12	KE:1005	Reduced, Swimming performance
AOP:263	Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation	Unclassified	WPHA/WNT Endorsed	Zebrafish, Mouse, Rat, Lemna minor, Human, Caenorhabditis elegans	0.25	KE:1821	Decrease, Cell proliferation
AOP:267	Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion	Unclassified	Under Development		0.4	KE:1821	Decrease, Cell proliferation
AOP:267		Unclassified	Under Development		0.4	KE:2071	Decrease, Glucose pool
AOP:272	Deposition of energy leading to lung cancer	Cancer	WPHA/WNT Endorsed	Human, Rat, Mouse	0.14	KE:870	Increase, Cell Proliferation
AOP:286	Mitochondrial complex III antagonism leading to growth inhibition (1)	Unclassified	-	Lemna minor, Daphnia magna, Danio rerio	0.25	KE:1821	Decrease, Cell proliferation
AOP:288	Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)	Endocrine system disease	-	Human, Rat	0.12	KE:1614	Decrease, androgen receptor activation
AOP:290	Mitochondrial ATP synthase antagonism leading to growth inhibition (1)	Unclassified	-	Daphnia magna	0.25	KE:1821	Decrease, Cell proliferation
AOP:293	Increased DNA damage leading to increased risk of breast cancer	Genetic disease; Thoracic disease; Cancer	Under Development	Rattus rattus, Mus musculus	0.11	KE:1182	Increase, Cell Proliferation (Epithelial Cells)
AOP:294	Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer	Genetic disease; Thoracic disease; Cancer	Under Development		0.11	KE:1182	Increase, Cell Proliferation (Epithelial Cells)
AOP:303	Frustrated phagocytosis-induced lung cancer	Cancer	Under Development	Mammals	0.14	KE:870	Increase, Cell Proliferation
AOP:305	5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring	Unclassified	Under Development	Rat, Human, Mouse	0.4	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:305		Unclassified	Under Development	Rat, Human, Mouse	0.4	KE:1614	Decrease, androgen receptor activation
AOP:321	Reduced environmental pH leading to thinner shells in Mytilus edulis	Unclassified	-		0.09	KE:10042	Abnormal development
AOP:331	Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and reduced cell proliferation	Unclassified	-	Daphnia magna, Daphnia middendorffiana, Daphnia pulex, Daphnia pulicaria, Daphnia parvula	0.17	KE:1821	Decrease, Cell proliferation
AOP:332	Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferation	Unclassified	-		0.2	KE:1821	Decrease, Cell proliferation
AOP:333	Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylation	Unclassified	-		0.2	KE:1821	Decrease, Cell proliferation
AOP:335	AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment	Cancer; Urinary system disease	-	Rat	0.2	KE:795	Increase, Regenerative cell proliferation (urothelial cells)
AOP:347	Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis	Musculoskeletal system disease; Respiratory system disease	-		0.11	KE:1793	Activator protein 1 activation
AOP:379	Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation	Cardiovascular system disease	Under Development	Homo sapiens	0.14	KE:1869	Diminished protective oxidative stress response
AOP:406	SARS-CoV-2 infection leading to hyperinflammation	Unclassified	-		0.17	KE:1869	Diminished protective oxidative stress response
AOP:409	Frustrated phagocytosis leads to malignant mesothelioma	Cancer	-		0.12	KE:870	Increase, Cell Proliferation
AOP:419	Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathway	Respiratory system disease	-		0.25	KE:1262	Apoptosis
AOP:420	Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathway	Cancer	-		0.25	KE:870	Increase, Cell Proliferation
AOP:432	Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia	Hematopoietic system disease; Cancer	-	Homo sapiens, Mus musculus	0.09	KE:870	Increase, Cell Proliferation
AOP:439	Activation of the AhR leading to metastatic breast cancer	Thoracic disease; Cancer	Under Development	Humans, Mice	0.22	KE:1971	Increased, tumor growth
AOP:439	Activation of the AhR leading to metastatic breast cancer	Thoracic disease; Cancer	Under Development	Humans, Mice	0.22	KE:1262	Apoptosis
AOP:441	Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation	Congenital nervous system abnormality; Nervous system disease	-	Homo sapiens, Mus musculus musculus, Rattus norvegicus	0.14	KE:1262	Apoptosis
AOP:446	PM-related Adverse outcome pathway frameworks on various systems	Respiratory system disease	-		0.05	KE:1262	Apoptosis
AOP:451	Interaction with lung resident cell membrane components leads to lung cancer	Cancer	-	Human	0.11	KE:870	Increase, Cell Proliferation
AOP:452	Adverse outcome pathway of PM-induced respiratory toxicity	Respiratory system disease	-		0.18	KE:2013	Airway remodeling
AOP:452	Adverse outcome pathway of PM-induced respiratory toxicity	Respiratory system disease	-		0.18	KE:1262	Apoptosis
AOP:457	Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine	Inherited metabolic disorder	-	Human	0.33	KE:277	Thyroid hormone synthesis, Decreased
AOP:457		Inherited metabolic disorder	-	Human	0.33	KE:281	Thyroxine (T4) in serum, Decreased
AOP:460	Antagonism of Smoothened receptor leading to orofacial clefting	Unclassified	Under Development	Mouse	0.22	KE:1821	Decrease, Cell proliferation
AOP:460		Unclassified	Under Development	Mouse	0.22	KE:1262	Apoptosis
AOP:465	Alcohol dehydrogenase leading to reproductive dysfunction	Unclassified	-		0.12	KE:2050	Increase, developmental abnormalities
AOP:467	Knickkopf leading to mortality	Unclassified	-		0.11	KE:2050	Increase, developmental abnormalities
AOP:478	Deposition of energy leading to occurrence of cataracts	Nervous system disease; Monogenic disease	Under Review	Human, Mouse, Rat, Rhesus monkeys, Rabbit, Guinea pig	0.1	KE:870	Increase, Cell Proliferation
AOP:491	Decrease, GLI1/2 target gene expression leads to orofacial clefting	Unclassified	Under Development	Mouse	0.33	KE:1821	Decrease, Cell proliferation
AOP:491		Unclassified	Under Development	Mouse	0.33	KE:1262	Apoptosis
AOP:495	Androgen receptor activation leading to prostate cancer	Reproductive system disease; Cancer	-		0.33	KE:854	Alterations, Cellular proliferation / hyperplasia
						KE:286	Altered, Transcription of genes by the androgen receptor
						KE:1183	Decreased, Apoptosis (Epithelial Cells)
AOP:496	Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）	Unclassified	-	Zebrafish	0.4	KE:221	Reduction, Plasma vitellogenin concentrations
						KE:286	Altered, Transcription of genes by the androgen receptor
						KE:219	Reduction, Plasma 17beta-estradiol concentrations
						KE:78	Reduction, Cumulative fecundity and spawning
AOP:521	Essential element imbalance leads to reproductive failure via oxidative stress	Unclassified	-	Murinae gen. sp.	0.14	KE:2206	Increased, histomorphological alteration of testis
AOP:539	Decreased Sodium/Potassium ATPase activity leads to Heart failure	Cardiovascular system disease	-	Fish	0.14	KE:2261	Decreased, blood plasma volume
AOP:563	Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosis	Reproductive system disease; Endocrine system disease	-	Rat, Mouse, Zebra fish, Human	0.17	KE:1262	Apoptosis

Associated AOPs with Level of Relevance - 2 AOPs with at least 1 AO associated with chemical, and no associated MIE

AOP Identifier	AOP Title	AO Classification	OECD Status	Taxonomic applicability	Coverage Score ⓘ The fraction of KEs within the AOP, that are mapped to the chemical-associated toxicological endpoints.	KE Identifier	KE Name
AOP:6	Antagonist binding to PPARα leading to body-weight loss	Symptom	WPHA/WNT Endorsed	Mus musculus, Homo sapiens, Pimephales promelas, Colinus virginianus, Rattus norvegicus	0.12	KE:864	Decreased, Body Weight
AOP:12	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	Nervous system disease; Developmental disorder of mental health	WPHA/WNT Endorsed	Monkey, Rat, Human, Mouse, Zebrafish	0.12	KE:341	Impairment, Learning and memory
AOP:13	Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities	Developmental disorder of mental health	WPHA/WNT Endorsed	Human, Mouse, Monkey sp., Rat	0.1	KE:341	Impairment, Learning and memory
AOP:16	Acetylcholinesterase inhibition leading to acute mortality	Unclassified	Under Development		0.29	KE:360	Decrease, Population growth rate
AOP:16	Acetylcholinesterase inhibition leading to acute mortality	Unclassified	Under Development		0.29	KE:351	Increased Mortality
AOP:17	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	Developmental disorder of mental health	WPHA/WNT Endorsed	Rat, Mouse, Human	0.1	KE:341	Impairment, Learning and memory
AOP:23	Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)	Unclassified	WPHA/WNT Endorsed	Pimephales promelas	0.4	KE:221	Reduction, Plasma vitellogenin concentrations
						KE:360	Decrease, Population growth rate
						KE:219	Reduction, Plasma 17beta-estradiol concentrations
						KE:78	Reduction, Cumulative fecundity and spawning
AOP:25	Aromatase inhibition leading to reproductive dysfunction	Unclassified	WPHA/WNT Endorsed	Fathead minnow, Medaka, Zebrafish	0.5	KE:221	Reduction, Plasma vitellogenin concentrations
						KE:360	Decrease, Population growth rate
						KE:219	Reduction, Plasma 17beta-estradiol concentrations
						KE:78	Reduction, Cumulative fecundity and spawning
AOP:27	Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)	Gastrointestinal system disease	Under Development	Humans	0.12	KE:357	Cholestasis, Pathology
AOP:30	Estrogen receptor antagonism leading to reproductive dysfunction	Unclassified	Under Review	Zebra danio, Fathead minnow, Medaka	0.5	KE:221	Reduction, Plasma vitellogenin concentrations
						KE:360	Decrease, Population growth rate
						KE:78	Reduction, Cumulative fecundity and spawning
AOP:40	Covalent Protein binding leading to Skin Sensitisation	Integumentary system disease	WPHA/WNT Endorsed	Mouse, Human	0.4	KE:827	sensitisation, skin
AOP:40	Covalent Protein binding leading to Skin Sensitisation	Integumentary system disease	WPHA/WNT Endorsed	Mouse, Human	0.4	KE:272	Activation/Proliferation, T-cells
AOP:48	Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.	Developmental disorder of mental health	WPHA/WNT Endorsed	Human, Mouse, Rat	0.11	KE:341	Impairment, Learning and memory
AOP:54	Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment	Developmental disorder of mental health	WPHA/WNT Endorsed	Homo sapiens, Rattus sp.	0.4	KE:280	Thyroxine (T4) in neuronal tissue, Decreased
						KE:277	Thyroid hormone synthesis, Decreased
						KE:281	Thyroxine (T4) in serum, Decreased
						KE:341	Impairment, Learning and memory
AOP:63	Cyclooxygenase inhibition leading to reproductive dysfunction	Reproductive system disease	-	Goldfish, Human, Mouse, Rat	0.2	KE:360	Decrease, Population growth rate
AOP:96	Axonal sodium channel modulation leading to acute mortality	Unclassified	-	Insects, Fish	0.17	KE:351	Increased Mortality
AOP:97	5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline	Unclassified	-	Mytilus galloprovincialis, Tritonea diomedea, Lymnaea stagnalis, Melibe leonine, Helix lucorum, Lampsilis fasciola	0.1	KE:360	Decrease, Population growth rate
AOP:100	Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior	Reproductive system disease	-	Goldfish	0.14	KE:360	Decrease, Population growth rate
AOP:101	Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release	Reproductive system disease	-	Goldfish	0.14	KE:360	Decrease, Population growth rate
AOP:102	Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition	Reproductive system disease	-	Goldfish, Human, Rat, Mouse	0.1	KE:360	Decrease, Population growth rate
AOP:103	Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint	Reproductive system disease	-	Goldfish, Human, Rat, Mouse	0.1	KE:360	Decrease, Population growth rate
AOP:104	Altered ion channel activity leading impaired heart function	Unclassified	-		0.25	KE:351	Increased Mortality
AOP:113	Glutamate-gated chloride channel activation leading to acute mortality	Unclassified	-	Bombus impatiens, Chaetanaphothrips orchidii, Radopholus similis, Daphnia magna, Orius insidiosus, Hymenoptera, Helicoverpa zea, Lepidoptera, Liriomyza trifolii, Orius isidiosus, Acyrthosiphon kondoi	0.17	KE:351	Increased Mortality
AOP:122	Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation	Unclassified	-	Pimephales promelas	0.4	KE:221	Reduction, Plasma vitellogenin concentrations
						KE:360	Decrease, Population growth rate
						KE:219	Reduction, Plasma 17beta-estradiol concentrations
						KE:78	Reduction, Cumulative fecundity and spawning
AOP:123	Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription	Unclassified	-	Pimephales promelas	0.36	KE:221	Reduction, Plasma vitellogenin concentrations
						KE:360	Decrease, Population growth rate
						KE:219	Reduction, Plasma 17beta-estradiol concentrations
						KE:78	Reduction, Cumulative fecundity and spawning
AOP:134	Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Rat, Homo sapiens	0.78	KE:277	Thyroid hormone synthesis, Decreased
						KE:281	Thyroxine (T4) in serum, Decreased
						KE:402	Cognitive function, decreased
						KE:280	Thyroxine (T4) in neuronal tissue, Decreased
						KE:757	Hippocampal anatomy, Altered
						KE:758	Hippocampal Physiology, Altered
						KE:756	Hippocampal gene expression, Altered
AOP:139	Alkylation of DNA leading to cancer 1	Cancer	-	Homo sapiens, Mus musculus	0.25	KE:885	Increase, Cancer
AOP:155	Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	Fathead minnow, Zebrafish	0.67	KE:1005	Reduced, Swimming performance
						KE:360	Decrease, Population growth rate
						KE:1003	Decreased, Triiodothyronine (T3)
						KE:351	Increased Mortality
AOP:156	Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	Zebrafish, Fathead minnow	0.83	KE:351	Increased Mortality
						KE:360	Decrease, Population growth rate
						KE:1003	Decreased, Triiodothyronine (T3)
						KE:1007	Reduced, Anterior swim bladder inflation
						KE:1005	Reduced, Swimming performance
AOP:157	Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	Zebrafish, Fathead minnow	0.67	KE:1005	Reduced, Swimming performance
						KE:360	Decrease, Population growth rate
						KE:1003	Decreased, Triiodothyronine (T3)
						KE:351	Increased Mortality
AOP:158	Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	Zebrafish, Fathead minnow	0.83	KE:351	Increased Mortality
						KE:360	Decrease, Population growth rate
						KE:1003	Decreased, Triiodothyronine (T3)
						KE:1007	Reduced, Anterior swim bladder inflation
						KE:1005	Reduced, Swimming performance
AOP:160	Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality	Unclassified	-	Daphnia magna	0.14	KE:351	Increased Mortality
AOP:161	Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality	Unclassified	-	Nematode, Daphnia magna	0.14	KE:351	Increased Mortality
AOP:176	Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.6	KE:1101	Altered, Amphibian metamorphosis
						KE:277	Thyroid hormone synthesis, Decreased
						KE:281	Thyroxine (T4) in serum, Decreased
AOP:188	Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.6	KE:1101	Altered, Amphibian metamorphosis
						KE:277	Thyroid hormone synthesis, Decreased
						KE:281	Thyroxine (T4) in serum, Decreased
AOP:189	Type I iodothyronine deiodinase (DIO1) inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.75	KE:1116	Decreased, Triiodothyronine (T3) in tissues
						KE:1101	Altered, Amphibian metamorphosis
						KE:1003	Decreased, Triiodothyronine (T3)
AOP:190	Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.5	KE:1116	Decreased, Triiodothyronine (T3) in tissues
						KE:1101	Altered, Amphibian metamorphosis
						KE:1023	Increased, Thyroid-stimulating hormone (TSH)
AOP:191	Type III iodotyrosine deiodinase (DIO3) inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.5	KE:1101	Altered, Amphibian metamorphosis
AOP:191		Unclassified	-	African clawed frog	0.5	KE:1154	Increased, Triiodothyronine (T3) in tissues
AOP:192	Pendrin inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.75	KE:1101	Altered, Amphibian metamorphosis
						KE:277	Thyroid hormone synthesis, Decreased
						KE:281	Thyroxine (T4) in serum, Decreased
AOP:193	Dual oxidase (DUOX) inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.75	KE:1101	Altered, Amphibian metamorphosis
						KE:277	Thyroid hormone synthesis, Decreased
						KE:281	Thyroxine (T4) in serum, Decreased
AOP:194	Hepatic nuclear receptor activation leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.33	KE:1101	Altered, Amphibian metamorphosis
AOP:194		Unclassified	-	African clawed frog	0.33	KE:281	Thyroxine (T4) in serum, Decreased
AOP:203	5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline	Reproductive system disease	-		0.12	KE:360	Decrease, Population growth rate
AOP:205	AOP from chemical insult to cell death	Unclassified	-	Vertebrates	0.33	KE:1263	Necrosis
AOP:205	AOP from chemical insult to cell death	Unclassified	-	Vertebrates	0.33	KE:1262	Apoptosis
AOP:212	Histone deacetylase inhibition leading to testicular atrophy	Reproductive system disease	WPHA/WNT Endorsed	Rat, Human, Mouse	0.33	KE:1506	Testicular atrophy
AOP:212		Reproductive system disease	WPHA/WNT Endorsed	Rat, Human, Mouse	0.33	KE:1262	Apoptosis
AOP:216	Deposition of energy leading to population decline via DNA strand breaks and follicular atresia	Unclassified	-	Daphnia magna	0.33	KE:360	Decrease, Population growth rate
AOP:216		Unclassified	-	Daphnia magna	0.33	KE:78	Reduction, Cumulative fecundity and spawning
AOP:218	Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity	Unclassified	-	Japanese quail, Cynops pyrrhogaster	0.17	KE:360	Decrease, Population growth rate
AOP:219	Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior	Unclassified	-	Japanese quail, Cynops pyrrhogaster	0.17	KE:360	Decrease, Population growth rate
AOP:220	Cyp2E1 Activation Leading to Liver Cancer	Cancer; Gastrointestinal system disease	WPHA/WNT Endorsed	Rodents, Homo sapiens	0.6	KE:1395	Liver Cancer
						KE:1393	Hepatocytotoxicity
						KE:1394	Induction, persistent proliferation/sustained proliferation
AOP:238	Deposition of energy leading to population decline via DNA strand breaks and oocyte apoptosis	Unclassified	-	Mice, Daphnia magna	0.33	KE:360	Decrease, Population growth rate
AOP:238		Unclassified	-	Mice, Daphnia magna	0.33	KE:78	Reduction, Cumulative fecundity and spawning
AOP:269	Elevated ATP demand for detoxification and repair mechanisms leading to impaired growth and development	Unclassified	-		0.17	KE:10013	Impaired growth and development
AOP:274	Histone deacetylase inhibition leads to impeded craniofacial development	Musculoskeletal system disease	-		0.25	KE:1559	Facial cartilage structures are reduced in size and morphologically distorted
AOP:278	IKK complex inhibition leading to liver injury	Unclassified	-		0.12	KE:1549	Liver Injury
AOP:289	Inhibition of 5α-reductase leading to impaired fecundity in female fish	Unclassified	Under Development	Fish	0.67	KE:221	Reduction, Plasma vitellogenin concentrations
						KE:360	Decrease, Population growth rate
						KE:219	Reduction, Plasma 17beta-estradiol concentrations
						KE:78	Reduction, Cumulative fecundity and spawning
AOP:292	Inhibition of tyrosinase leads to decreased population in fish	Unclassified	Under Development	Fish	0.17	KE:360	Decrease, Population growth rate
AOP:297	Inhibition of retinaldehyde dehydrogenase leads to population decline	Unclassified	Under Development	Fish	0.33	KE:360	Decrease, Population growth rate
AOP:297		Unclassified	Under Development	Fish	0.33	KE:1643	Altered, Visual function
AOP:299	Deposition of energy leading to population decline via DNA oxidation and follicular atresia	Unclassified	-		0.29	KE:360	Decrease, Population growth rate
AOP:299		Unclassified	-		0.29	KE:78	Reduction, Cumulative fecundity and spawning
AOP:300	Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	Under Development	Human, Mouse	0.8	KE:757	Hippocampal anatomy, Altered
						KE:758	Hippocampal Physiology, Altered
						KE:402	Cognitive function, decreased
						KE:756	Hippocampal gene expression, Altered
AOP:310	Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR	Unclassified	-	Zebrafish	0.33	KE:221	Reduction, Plasma vitellogenin concentrations
						KE:360	Decrease, Population growth rate
						KE:219	Reduction, Plasma 17beta-estradiol concentrations
						KE:78	Reduction, Cumulative fecundity and spawning
AOP:311	Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis	Unclassified	-	Daphnia magna, Fish	0.29	KE:360	Decrease, Population growth rate
AOP:311		Unclassified	-	Daphnia magna, Fish	0.29	KE:78	Reduction, Cumulative fecundity and spawning
AOP:312	Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement	Unclassified	-		0.33	KE:360	Decrease, Population growth rate
AOP:312		Unclassified	-		0.33	KE:351	Increased Mortality
AOP:313	Stimulation of TLR7/8 in dendric cells leading to Psoriatic skin disease	Immune system disease; Integumentary system disease; Musculoskeletal system disease	Under Development	Homo sapiens, Mus musculus	0.2	KE:1709	Psoriatic skin disease
AOP:320	Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality	Unclassified	Under Development	Homo sapiens	0.11	KE:351	Increased Mortality
AOP:323	PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone	Unclassified	-	Teleost fish	0.17	KE:360	Decrease, Population growth rate
AOP:334	Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration	Unclassified	-	Teleost fish	0.33	KE:360	Decrease, Population growth rate
AOP:334		Unclassified	-	Teleost fish	0.33	KE:1005	Reduced, Swimming performance
AOP:336	DNA methyltransferase inhibition leading to population decline (1)	Unclassified	-	Daphnia magna	0.14	KE:360	Decrease, Population growth rate
AOP:337	DNA methyltransferase inhibition leading to population decline (2)	Unclassified	-	Daphnia magna	0.12	KE:360	Decrease, Population growth rate
AOP:338	DNA methyltransferase inhibition leading to population decline (3)	Unclassified	-		0.14	KE:360	Decrease, Population growth rate
AOP:339	DNA methyltransferase inhibition leading to population decline (4)	Unclassified	-		0.12	KE:360	Decrease, Population growth rate
AOP:340	DNA methyltransferase inhibition leading to transgenerational effects (1)	Physical disorder	-		0.12	KE:360	Decrease, Population growth rate
AOP:341	DNA methyltransferase inhibition leading to transgenerational effects (2)	Physical disorder	-	Daphnia magna	0.11	KE:360	Decrease, Population growth rate
AOP:346	Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation	Unclassified	WPHA/WNT Endorsed	Zebrafish, Oreochromis niloticus, Chinook salmon, Fathead minnow, European sea bass	0.2	KE:360	Decrease, Population growth rate
AOP:348	Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory	Unclassified	Under Development	Fish	0.2	KE:360	Decrease, Population growth rate
AOP:349	Inhibition of 11β-hydroxylase leading to decresed population trajectory	Unclassified	Under Development	Fish	0.12	KE:360	Decrease, Population growth rate
AOP:362	Immune mediated hepatitis	Gastrointestinal system disease; Immune system disease	-	Homo sapiens, Rat	0.12	KE:1820	Immune mediated hepatitis
AOP:366	Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis	Unclassified	-		0.29	KE:1101	Altered, Amphibian metamorphosis
AOP:366		Unclassified	-		0.29	KE:281	Thyroxine (T4) in serum, Decreased
AOP:367	Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis	Unclassified	-		0.29	KE:1101	Altered, Amphibian metamorphosis
AOP:367		Unclassified	-		0.29	KE:281	Thyroxine (T4) in serum, Decreased
AOP:376	Androgen receptor agonism leading to male-biased sex ratio	Unclassified	WPHA/WNT Endorsed	Zebrafish, Medaka, Fathead minnow, Channel catfish, Oreochromis niloticus, Chinook salmon	0.25	KE:360	Decrease, Population growth rate
AOP:384	Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease	Urinary system disease	-		0.17	KE:1603	Chronic kidney disease
AOP:386	Deposition of ionizing energy leading to population decline via inhibition of photosynthesis	Reproductive system disease	-	Lemna minor, Chlamydomonas reinhardtii	0.12	KE:360	Decrease, Population growth rate
AOP:387	Deposition of ionising energy leading to population decline via mitochondrial dysfunction	Reproductive system disease	-	Lemna minor	0.12	KE:360	Decrease, Population growth rate
AOP:388	Deposition of ionising energy leading to population decline via programmed cell death	Reproductive system disease	-	Lemna minor	0.2	KE:360	Decrease, Population growth rate
AOP:389	Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis	Reproductive system disease	-	Lemna minor	0.14	KE:360	Decrease, Population growth rate
AOP:399	Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)	Unclassified	-	Zebrafish	0.5	KE:1821	Decrease, Cell proliferation
						KE:360	Decrease, Population growth rate
						KE:1643	Altered, Visual function
						KE:351	Increased Mortality
AOP:405	Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function	Cognitive disorder	-	Rattus norvegicus, Mus musculus, Homo sapiens	0.2	KE:402	Cognitive function, decreased
AOP:410	GSK3beta inactivation leading to increased mortality via defects in developing inner ear	Unclassified	-	Zebrafish	0.2	KE:360	Decrease, Population growth rate
AOP:410		Unclassified	-	Zebrafish	0.2	KE:351	Increased Mortality
AOP:413	Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure	Unclassified	-	Fish, Mice	0.5	KE:1607	Increase, Necrosis
						KE:759	Increased, Kidney Failure
						KE:351	Increased Mortality
AOP:430	Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferation	Viral infectious disease	Under Development	Mink, Ferret, Cat, Dog, Syrian golden hamster, Rhesus macaque, Lowland gorilla, Crab eating macaque, African green monkeys, Humans, Hippopotamus amphibius, Bank vole, Lynx canadensis, Puma concolor, Panthera tigris jacksoni, Panthera uncia, Prionailurus viverrinus, Crocuta crocuta, Arctictis binturong, Odocoileus virginianus, American mink, Nasua nasua, Panthera leo, Sus scrofa, European rabbit, Castor fiber, Aonyx cinereus, Vulpes vulpes, Nyctereutes procyonoides, Tupaia belangeri, Bos taurus, Odocoileus hemionus, Peromyscus maniculatus bairdii, Cynopterus brachyotis, Common marmoset, Baboon	0.2	KE:1939	Viral infection and host-to-host transmission, proliferated
AOP:442	Binding to voltage gate sodium channels during development leads to cognitive impairment	Cognitive disorder	Under Review	Rattus norvegicus, Mouse, Humans	0.43	KE:757	Hippocampal anatomy, Altered
						KE:758	Hippocampal Physiology, Altered
						KE:402	Cognitive function, decreased
AOP:444	Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability	Unclassified	-		0.11	KE:360	Decrease, Population growth rate
AOP:447	Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways	Urinary system disease	-		0.08	KE:759	Increased, Kidney Failure
AOP:450	Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality	Nervous system disease	-	Rattus norvegicus, Mus musculus, Homo sapiens	0.14	KE:351	Increased Mortality
AOP:455	Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development	Musculoskeletal system disease	Under Review	Zebrafish, Mouse, Human, Sebastiscus marmoratus, Salmo salar, Chicken	0.17	KE:1559	Facial cartilage structures are reduced in size and morphologically distorted
AOP:458	AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Rat, Mouse, Monkey, Human	0.62	KE:402	Cognitive function, decreased
						KE:281	Thyroxine (T4) in serum, Decreased
						KE:280	Thyroxine (T4) in neuronal tissue, Decreased
						KE:758	Hippocampal Physiology, Altered
						KE:756	Hippocampal gene expression, Altered
AOP:459	AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Human, Mouse, Rat	0.67	KE:402	Cognitive function, decreased
						KE:277	Thyroid hormone synthesis, Decreased
						KE:281	Thyroxine (T4) in serum, Decreased
						KE:280	Thyroxine (T4) in neuronal tissue, Decreased
						KE:758	Hippocampal Physiology, Altered
						KE:756	Hippocampal gene expression, Altered
AOP:463	The AOP framwork on silica nanopariticles induced hepatoxicity	Gastrointestinal system disease	-		0.18	KE:2034	liver dysfunction
AOP:463		Gastrointestinal system disease	-		0.18	KE:1262	Apoptosis
AOP:472	DNA adduct formation leading to kidney failure	Urinary system disease	-		0.11	KE:759	Increased, Kidney Failure
AOP:474	Succinate dehydrogenase inactivation leads to cancer by promoting EMT	Cancer	Under Development	Human and other cells in culture	0.2	KE:885	Increase, Cancer
AOP:475	Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons	Developmental disorder of mental health	Under Development	Mouse, Rat, Human, Caenorhabditis elegans	0.12	KE:341	Impairment, Learning and memory
AOP:483	Deposition of Energy Leading to Learning and Memory Impairment	Developmental disorder of mental health	Under Review	Mouse, Rat, Rabbit, Dog, Pigs, Cow, Human	0.12	KE:341	Impairment, Learning and memory
AOP:485	Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognition	Cognitive disorder	-	Human	0.14	KE:402	Cognitive function, decreased
AOP:486	Binding to the extracellular protein laminin leading to decreased cognitive function	Cognitive disorder	-	Human	0.14	KE:402	Cognitive function, decreased
AOP:488	Increased reactive oxygen species production leading to decreased cognitive function	Cognitive disorder	-	Human	0.29	KE:1869	Diminished protective oxidative stress response
AOP:488		Cognitive disorder	-	Human	0.29	KE:402	Cognitive function, decreased
AOP:490	Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms	Developmental disorder of mental health	-		0.27	KE:758	Hippocampal Physiology, Altered
						KE:2121	decreased, Intellectual Quotient
						KE:341	Impairment, Learning and memory
AOP:498	Increased LCN2/iron complex leading to neurological disorders	Nervous system disease	-	Homo sapiens	0.25	KE:2150	Neurological disorder
AOP:499	Activation of MEK-ERK1/2 leads to deficits in learning and cognition via disrupted neurotransmitter release	Developmental disorder of mental health	-	Rattus norvegicus, Mus musculus, Homo sapiens	0.25	KE:341	Impairment, Learning and memory
AOP:500	Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis	Developmental disorder of mental health	-	Rattus norvegicus, Mus musculus, Homo sapiens	0.29	KE:1262	Apoptosis
AOP:500		Developmental disorder of mental health	-	Rattus norvegicus, Mus musculus, Homo sapiens	0.29	KE:341	Impairment, Learning and memory
AOP:501	Excessive iron accumulation leading to neurological disorders	Nervous system disease	-	Homo sapiens	0.25	KE:2150	Neurological disorder
AOP:505	Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway	Cancer	-	Human, Mouse, Rat	0.2	KE:885	Increase, Cancer
AOP:513	Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway	Cancer	-	Human, Mouse, Rat	0.2	KE:885	Increase, Cancer
AOP:520	Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory	Developmental disorder of mental health	-	Mouse, Rat, Human	0.4	KE:2204	Altered brain morphology
AOP:520		Developmental disorder of mental health	-	Mouse, Rat, Human	0.4	KE:341	Impairment, Learning and memory
AOP:525	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory	Developmental disorder of mental health	-		0.08	KE:341	Impairment, Learning and memory
AOP:533	Retinoic acid receptor antagonism during neurodevelopment leading to impaired learning and memory	Developmental disorder of mental health	-		0.17	KE:341	Impairment, Learning and memory
AOP:534	Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress	Cancer	-	Vertebrates	0.17	KE:885	Increase, Cancer
AOP:535	Binding and activation of GPER leading to learning and memory impairments	Developmental disorder of mental health	-	Mouse, Human	0.22	KE:1262	Apoptosis
AOP:535		Developmental disorder of mental health	-	Mouse, Human	0.22	KE:341	Impairment, Learning and memory
AOP:536	Estrogen receptor agonism leading to reduced survival and population growth due to renal failure	Unclassified	-		0.33	KE:360	Decrease, Population growth rate
AOP:536		Unclassified	-		0.33	KE:351	Increased Mortality
AOP:537	Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liver	Unclassified	-		0.2	KE:78	Reduction, Cumulative fecundity and spawning
AOP:540	Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production	Unclassified	-		0.44	KE:221	Reduction, Plasma vitellogenin concentrations
						KE:360	Decrease, Population growth rate
						KE:1262	Apoptosis
						KE:78	Reduction, Cumulative fecundity and spawning
AOP:546	Succinate dehydrogenase inactivation leads to cancer through hypoxic-like mechanisms	Cancer	-	Human and other cells in culture	0.2	KE:885	Increase, Cancer
AOP:549	Aromatase inhibition leads to reproductive toxicity (including growth and developmental toxicity) in adult female zebrafish	Unclassified	-		0.38	KE:221	Reduction, Plasma vitellogenin concentrations
						KE:219	Reduction, Plasma 17beta-estradiol concentrations
						KE:78	Reduction, Cumulative fecundity and spawning
AOP:564	DBDPE-induced inhibition of mitochondrial complex Ⅰ leading to population decline via neurotoxicity and metabotoxicity.	Unclassified	-	Zebrafish	0.27	KE:360	Decrease, Population growth rate
						KE:2301	Abnormal, Behavior
						KE:351	Increased Mortality
AOP:567	Binding of plastoquinone B leading to decrease, population growth rate via decrease, photosystem II efficiency	Unclassified	-		0.17	KE:360	Decrease, Population growth rate
AOP:569	Decreased DNA methylation of FAM50B/PTCHD3 leading to IQ loss of children via PI3K-Akt pathway	Developmental disorder of mental health	-		0.17	KE:2121	decreased, Intellectual Quotient

Associated AOPs with Level of Relevance - 3 AOPs with at least 1 MIE associated with chemical, and no associated AO

AOP Identifier	AOP Title	AO Classification	OECD Status	Taxonomic applicability	Coverage Score ⓘ The fraction of KEs within the AOP, that are mapped to the chemical-associated toxicological endpoints.	KE Identifier	KE Name
AOP:19	Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)	Reproductive system disease	-		0.4	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:19		Reproductive system disease	-		0.4	KE:26	Antagonism, Androgen receptor
AOP:111	Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)	Cancer; Reproductive system disease	-	Rattus norvegicus	0.2	KE:1614	Decrease, androgen receptor activation
AOP:118	Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)	Cancer; Gastrointestinal system disease	-	Mus musculus, Rattus norvegicus	0.5	KE:786	Increase, Cytotoxicity (hepatocytes)
AOP:118		Cancer; Gastrointestinal system disease	-	Mus musculus, Rattus norvegicus	0.5	KE:787	Increase, Regenerative cell proliferation (hepatocytes)
AOP:119	Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)	Cancer; Endocrine system disease	-	Rattus norvegicus, Mus musculus	0.71	KE:277	Thyroid hormone synthesis, Decreased
						KE:281	Thyroxine (T4) in serum, Decreased
						KE:1023	Increased, Thyroid-stimulating hormone (TSH)
						KE:279	Thyroperoxidase, Inhibition
						KE:739	Increase, Hypertrophy and proliferation (follicular cell)
AOP:121	Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)	Cancer; Urinary system disease	-	Mus musculus, Rattus norvegicus	0.4	KE:795	Increase, Regenerative cell proliferation (urothelial cells)
AOP:121		Cancer; Urinary system disease	-	Mus musculus, Rattus norvegicus	0.4	KE:793	Increase, Urinary bladder calculi
AOP:128	Kidney dysfunction by decreased thyroid hormone	Urinary system disease	Under Development	Sprague-Dawley, Homo sapiens	0.27	KE:277	Thyroid hormone synthesis, Decreased
						KE:281	Thyroxine (T4) in serum, Decreased
						KE:825	Decreased, Renal ability to dilute urine
AOP:232	NFE2/Nrf2 repression to steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-		0.12	KE:1417	NFE2/Nrf2 repression
AOP:298	Increase in reactive oxygen species (ROS) leading to human treatment-resistant gastric cancer via chronic ROS	Cancer; Gastrointestinal system disease	Under Review	Homo sapiens	0.17	KE:1753	Chronic reactive oxygen species
AOP:306	Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring	Unclassified	Under Development	Rat, Human, Mouse	0.75	KE:286	Altered, Transcription of genes by the androgen receptor
						KE:1614	Decrease, androgen receptor activation
						KE:26	Antagonism, Androgen receptor
AOP:344	Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspring	Unclassified	Under Development		0.75	KE:286	Altered, Transcription of genes by the androgen receptor
						KE:1614	Decrease, androgen receptor activation
						KE:26	Antagonism, Androgen receptor
AOP:345	Androgen receptor (AR) antagonism leading to decreased fertility in females	Endocrine system disease; Reproductive system disease; Reproductive system disease	Under Development	Mammals	0.5	KE:286	Altered, Transcription of genes by the androgen receptor
						KE:1614	Decrease, androgen receptor activation
						KE:26	Antagonism, Androgen receptor
AOP:372	Androgen receptor antagonism leading to testicular cancer	Endocrine system disease; Reproductive system disease; Cancer	-		0.6	KE:286	Altered, Transcription of genes by the androgen receptor
						KE:1614	Decrease, androgen receptor activation
						KE:26	Antagonism, Androgen receptor
AOP:477	Androgen receptor (AR) antagonism leading to hypospadias in male (mammalian) offspring	Physical disorder	-		0.67	KE:1614	Decrease, androgen receptor activation
AOP:477		Physical disorder	-		0.67	KE:26	Antagonism, Androgen receptor
AOP:507	Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway	Cardiovascular system disease	-	Mouse, Zebrafish, Human	0.17	KE:1417	NFE2/Nrf2 repression
AOP:508	Nrf2 inhibition leading to vascular disrupting effects through activating HIF1α, Semaphorin 6A, and Dll4-Notch pathway	Cardiovascular system disease	-	Mouse, Zebrafish, Human	0.14	KE:1417	NFE2/Nrf2 repression
AOP:509	Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction	Cardiovascular system disease	-		0.14	KE:1417	NFE2/Nrf2 repression

Associated AOPs with Level of Relevance - 5 AOPs with at least 1 MIE and AO associated with chemical, and there exists a directed path between that MIE and AO

AOP Identifier	AOP Title	AO Classification	OECD Status	Taxonomic applicability	Coverage Score ⓘ The fraction of KEs within the AOP, that are mapped to the chemical-associated toxicological endpoints.	KE Identifier	KE Name
AOP:42	Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	WPHA/WNT Endorsed	Human, Rat, Mouse	1.0	KE:277	Thyroid hormone synthesis, Decreased
						KE:281	Thyroxine (T4) in serum, Decreased
						KE:402	Cognitive function, decreased
						KE:280	Thyroxine (T4) in neuronal tissue, Decreased
						KE:279	Thyroperoxidase, Inhibition
						KE:757	Hippocampal anatomy, Altered
						KE:758	Hippocampal Physiology, Altered
						KE:756	Hippocampal gene expression, Altered
AOP:159	Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	Zebrafish, Fathead minnow	1.0	KE:277	Thyroid hormone synthesis, Decreased
						KE:281	Thyroxine (T4) in serum, Decreased
						KE:351	Increased Mortality
						KE:360	Decrease, Population growth rate
						KE:1003	Decreased, Triiodothyronine (T3)
						KE:279	Thyroperoxidase, Inhibition
						KE:1007	Reduced, Anterior swim bladder inflation
						KE:1005	Reduced, Swimming performance
AOP:175	Thyroperoxidase inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	1.0	KE:279	Thyroperoxidase, Inhibition
						KE:1101	Altered, Amphibian metamorphosis
						KE:277	Thyroid hormone synthesis, Decreased
						KE:281	Thyroxine (T4) in serum, Decreased
AOP:271	Inhibition of thyroid peroxidase leading to impaired fertility in fish	Unclassified	Under Development	Fish	1.0	KE:277	Thyroid hormone synthesis, Decreased
						KE:78	Reduction, Cumulative fecundity and spawning
						KE:279	Thyroperoxidase, Inhibition
						KE:221	Reduction, Plasma vitellogenin concentrations
						KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:363	Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure	Unclassified	Under Review	Zebrafish	1.0	KE:1877	Altered, retinal layer structure
						KE:277	Thyroid hormone synthesis, Decreased
						KE:281	Thyroxine (T4) in serum, Decreased
						KE:351	Increased Mortality
						KE:360	Decrease, Population growth rate
						KE:1003	Decreased, Triiodothyronine (T3)
						KE:279	Thyroperoxidase, Inhibition
						KE:1643	Altered, Visual function
AOP:364	Thyroperoxidase inhibition leading to altered visual function via decreased eye size	Unclassified	Under Development		0.88	KE:277	Thyroid hormone synthesis, Decreased
						KE:351	Increased Mortality
						KE:281	Thyroxine (T4) in serum, Decreased
						KE:360	Decrease, Population growth rate
						KE:1003	Decreased, Triiodothyronine (T3)
						KE:279	Thyroperoxidase, Inhibition
						KE:1643	Altered, Visual function
AOP:365	Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning	Unclassified	Under Development		0.88	KE:277	Thyroid hormone synthesis, Decreased
						KE:351	Increased Mortality
						KE:281	Thyroxine (T4) in serum, Decreased
						KE:360	Decrease, Population growth rate
						KE:1003	Decreased, Triiodothyronine (T3)
						KE:279	Thyroperoxidase, Inhibition
						KE:1643	Altered, Visual function

DISCLAIMER

We have built a comprehensive resource which compiles potential endocrine disrupting chemicals (EDCs) based on the observed adverse effects or endocrine-mediated endpoints in published experiments on humans or rodents to support basic research. We are not responsible for any errors or omissions in the published research articles or supporting literature on potential EDCs compiled in this resource. Users are advised to exercise their own judgement on the weight of evidence for potential EDCs compiled in this resource. Importantly, our sole goal to build this resource on potential EDCs is to enable future basic research towards better understanding of the systems-level perturbations upon chemical exposure rather than influencing regulatory advice on chemical use.