DEDUCT | Database of Endocrine Disrupting chemicals and their Toxicity profiles

Tributylchlorostannane

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: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	0.11	KE:281	Thyroxine (T4) in serum, Decreased
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:1392	Oxidative Stress
AOP:25	Aromatase inhibition leading to reproductive dysfunction	Unclassified	WPHA/WNT Endorsed	Fathead minnow, Medaka, Zebrafish	0.25	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:25	Aromatase inhibition leading to reproductive dysfunction	Unclassified	WPHA/WNT Endorsed	Fathead minnow, Medaka, Zebrafish	0.25	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:27	Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)	Gastrointestinal system disease	Under Development	Humans	0.25	KE:149	Increase, Inflammation
AOP:27		Gastrointestinal system disease	Under Development	Humans	0.25	KE:288	Activation of specific nuclear receptors, Transcriptional change
AOP:34	LXR activation leading to hepatic steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-		0.08	KE:116	Activation, FAS
AOP:42	Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	WPHA/WNT Endorsed	Human, Rat, Mouse	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:42		Cognitive disorder	WPHA/WNT Endorsed	Human, Rat, Mouse	0.25	KE:281	Thyroxine (T4) in serum, Decreased
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.	0.2	KE:277	Thyroid hormone synthesis, Decreased
AOP:54		Developmental disorder of mental health	WPHA/WNT Endorsed	Homo sapiens, Rattus sp.	0.2	KE:281	Thyroxine (T4) in serum, Decreased
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:73	Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundity	Unclassified	-		0.15	KE:10059	Decreased LH surge for 24 hours
AOP:73		Unclassified	-		0.15	KE:531	Decreased, LH Surge
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:626	Increased, serotonin (5-HT)
AOP:98	5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to decreased shelter seeking and increased predation	Unclassified	-	Pimephales promelas, Echinogammarus marinus	0.2	KE:626	Increased, serotonin (5-HT)
AOP:99	Histamine (H2) receptor antagonism leading to reduced survival	Unclassified	-	Zebrafish	0.14	KE:635	Decreased, locomotion
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:690	Reduced, Luteinizing hormone (LH), plasma
AOP:103	Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint	Reproductive system disease	-	Goldfish, Human, Rat, Mouse	0.1	KE:690	Reduced, Luteinizing hormone (LH), plasma
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	0.2	KE:1214	Altered gene expression specific to CAR activation, Hepatocytes
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	0.43	KE:1023	Increased, Thyroid-stimulating hormone (TSH)
						KE:277	Thyroid hormone synthesis, Decreased
						KE:281	Thyroxine (T4) in serum, Decreased
AOP:115	Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)	Cancer	-	Mus musculus, Rattus norvegicus	0.2	KE:149	Increase, Inflammation
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	0.43	KE:1023	Increased, Thyroid-stimulating hormone (TSH)
						KE:277	Thyroid hormone synthesis, Decreased
						KE:281	Thyroxine (T4) in serum, Decreased
AOP:122	Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation	Unclassified	-	Pimephales promelas	0.2	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:122		Unclassified	-	Pimephales promelas	0.2	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:123	Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription	Unclassified	-	Pimephales promelas	0.18	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:123		Unclassified	-	Pimephales promelas	0.18	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:126	Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation	Unclassified	-		0.15	KE:10059	Decreased LH surge for 24 hours
AOP:126		Unclassified	-		0.15	KE:531	Decreased, LH Surge
AOP:134	Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Rat, Homo sapiens	0.22	KE:277	Thyroid hormone synthesis, Decreased
AOP:134		Cognitive disorder	-	Rat, Homo sapiens	0.22	KE:281	Thyroxine (T4) in serum, Decreased
AOP:155	Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	Fathead minnow, Zebrafish	0.17	KE:1003	Decreased, Triiodothyronine (T3)
AOP:156	Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	Zebrafish, Fathead minnow	0.17	KE:1003	Decreased, Triiodothyronine (T3)
AOP:157	Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	Zebrafish, Fathead minnow	0.17	KE:1003	Decreased, Triiodothyronine (T3)
AOP:158	Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	Zebrafish, Fathead minnow	0.17	KE:1003	Decreased, Triiodothyronine (T3)
AOP:159	Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	Zebrafish, Fathead minnow	0.38	KE:1003	Decreased, Triiodothyronine (T3)
						KE:277	Thyroid hormone synthesis, Decreased
						KE:281	Thyroxine (T4) in serum, Decreased
AOP:175	Thyroperoxidase inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.5	KE:277	Thyroid hormone synthesis, Decreased
AOP:175		Unclassified	-	African clawed frog	0.5	KE:281	Thyroxine (T4) in serum, Decreased
AOP:176	Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.4	KE:277	Thyroid hormone synthesis, Decreased
AOP:176		Unclassified	-	African clawed frog	0.4	KE:281	Thyroxine (T4) in serum, Decreased
AOP:188	Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.4	KE:277	Thyroid hormone synthesis, Decreased
AOP:188		Unclassified	-	African clawed frog	0.4	KE:281	Thyroxine (T4) in serum, Decreased
AOP:189	Type I iodothyronine deiodinase (DIO1) inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.5	KE:1116	Decreased, Triiodothyronine (T3) in tissues
AOP:189		Unclassified	-	African clawed frog	0.5	KE:1003	Decreased, Triiodothyronine (T3)
AOP:190	Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.67	KE:1116	Decreased, Triiodothyronine (T3) in tissues
						KE:1829	Altered, Thyroid hormone-dependent gene expression
						KE:1828	Increased, Thyroxine (T4) in serum
						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:1154	Increased, Triiodothyronine (T3) in tissues
AOP:191		Unclassified	-	African clawed frog	0.5	KE:1829	Altered, Thyroid hormone-dependent gene expression
AOP:192	Pendrin inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.5	KE:277	Thyroid hormone synthesis, Decreased
AOP:192		Unclassified	-	African clawed frog	0.5	KE:281	Thyroxine (T4) in serum, Decreased
AOP:193	Dual oxidase (DUOX) inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.5	KE:277	Thyroid hormone synthesis, Decreased
AOP:193		Unclassified	-	African clawed frog	0.5	KE:281	Thyroxine (T4) in serum, Decreased
AOP:194	Hepatic nuclear receptor activation leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.17	KE:281	Thyroxine (T4) in serum, Decreased
AOP:195	5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase	Unclassified	-	Argopecten irradians, Mercenaria mercenaria, Arctica islandica, Spisula solidissima, Anodonta cygnea, Dreissena polymorpha	0.12	KE:626	Increased, serotonin (5-HT)
AOP:203	5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline	Reproductive system disease	-		0.12	KE:626	Increased, serotonin (5-HT)
AOP:204	5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase	Unclassified	-		0.12	KE:626	Increased, serotonin (5-HT)
AOP:207	NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans	Reproductive system disease	-	Caenorhabditis elegans	0.25	KE:1281	Increased, DNA Damage-Repair
AOP:207		Reproductive system disease	-	Caenorhabditis elegans	0.25	KE:1262	Apoptosis
AOP:218	Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity	Unclassified	-	Japanese quail, Cynops pyrrhogaster	0.17	KE:1389	Locomotor activity, decreased
AOP:220	Cyp2E1 Activation Leading to Liver Cancer	Cancer; Gastrointestinal system disease	WPHA/WNT Endorsed	Rodents, Homo sapiens	0.2	KE:1392	Oxidative Stress
AOP:232	NFE2/Nrf2 repression to steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-		0.25	KE:1422	Reduced, PPARalpha
AOP:232	NFE2/Nrf2 repression to steatosis		-		0.25	KE:1419	Reduced, FXR activity
AOP:260	CYP2E1 activation and formation of protein adducts leading to neurodegeneration	Nervous system disease	-	Human	0.14	KE:1392	Oxidative Stress
AOP:261	L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility	Cardiovascular system disease	Under Development	Vertebrates	0.12	KE:1536	Disruption, Intracellular calcium mobilization
AOP:271	Inhibition of thyroid peroxidase leading to impaired fertility in fish	Unclassified	Under Development	Fish	0.4	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:271		Unclassified	Under Development	Fish	0.4	KE:277	Thyroid hormone synthesis, Decreased
AOP:278	IKK complex inhibition leading to liver injury	Unclassified	-		0.25	KE:202	Inhibition, Nuclear factor kappa B (NF-kB)
AOP:278	IKK complex inhibition leading to liver injury	Unclassified	-		0.25	KE:1579	Increase, proinflammatory mediators (TNFalpha)
AOP:280	α-diketone-induced bronchiolitis obliterans	Musculoskeletal system disease; Respiratory system disease	-		0.14	KE:149	Increase, Inflammation
AOP:287	Mitochondrial complex III antagonism leading to growth inhibition (2)	Unclassified	-	Lemna minor, Daphnia magna, Danio rerio	0.25	KE:1825	Increase, Cell death
AOP:291	Mitochondrial ATP synthase antagonism leading to growth inhibition (2)	Unclassified	-	Daphnia magna	0.25	KE:1825	Increase, Cell death
AOP:310	Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR	Unclassified	-	Zebrafish	0.17	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:310		Unclassified	-	Zebrafish	0.17	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:321	Reduced environmental pH leading to thinner shells in Mytilus edulis	Unclassified	-		0.09	KE:10042	Abnormal development
AOP:330	Excessive reactive oxygen species production leading to mortality (4)	Unclassified	-	Daphnia magna	0.2	KE:1365	Increase, Apoptosis
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:1789	Reduction, 17beta-estradiol synthesis by the undifferentiated gonad
AOP:348	Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory	Unclassified	Under Development	Fish	0.4	KE:1758	Impaired, Spermatogenesis
AOP:348		Unclassified	Under Development	Fish	0.4	KE:406	decreased, Fertility
AOP:349	Inhibition of 11β-hydroxylase leading to decresed population trajectory	Unclassified	Under Development	Fish	0.25	KE:1798	Decreased spermatogenesis
AOP:349		Unclassified	Under Development	Fish	0.25	KE:406	decreased, Fertility
AOP:362	Immune mediated hepatitis	Gastrointestinal system disease; Immune system disease	-	Homo sapiens, Rat	0.25	KE:1817	Apoptotic cell death
AOP:362	Immune mediated hepatitis	Gastrointestinal system disease; Immune system disease	-	Homo sapiens, Rat	0.25	KE:1633	Increase in inflammation
AOP:363	Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure	Unclassified	Under Review	Zebrafish	0.38	KE:1003	Decreased, Triiodothyronine (T3)
						KE:277	Thyroid hormone synthesis, Decreased
						KE:281	Thyroxine (T4) in serum, Decreased
AOP:364	Thyroperoxidase inhibition leading to altered visual function via decreased eye size	Unclassified	Under Development		0.38	KE:1003	Decreased, Triiodothyronine (T3)
						KE:277	Thyroid hormone synthesis, Decreased
						KE:281	Thyroxine (T4) in serum, Decreased
AOP:365	Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning	Unclassified	Under Development		0.38	KE:1003	Decreased, Triiodothyronine (T3)
						KE:277	Thyroid hormone synthesis, Decreased
						KE:281	Thyroxine (T4) in serum, Decreased
AOP:366	Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis	Unclassified	-		0.29	KE:959	Increased, Free serum thyroxine (T4)
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:959	Increased, Free serum thyroxine (T4)
AOP:367		Unclassified	-		0.29	KE:281	Thyroxine (T4) in serum, Decreased
AOP:368	Cytochrome oxidase inhibition leading to increased nasal lesions	Unclassified	-	Rodents, Human	0.33	KE:1825	Increase, Cell death
AOP:382	Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis	Musculoskeletal system disease; Respiratory system disease	Under Development		0.17	KE:1172	Increased activation, Nuclear factor kappa B (NF-kB)
AOP:388	Deposition of ionising energy leading to population decline via programmed cell death	Reproductive system disease	-	Lemna minor	0.2	KE:1864	Increase, Programmed cell death
AOP:410	GSK3beta inactivation leading to increased mortality via defects in developing inner ear	Unclassified	-	Zebrafish	0.1	KE:1825	Increase, Cell death
AOP:414	Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathway	Musculoskeletal system disease; Respiratory system disease	-		0.2	KE:1920	Altered gene expression, TGF-β dependent fibrosis pathway
AOP:416	Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathway	Cancer	-		0.17	KE:1933	Increased, Interleukin-6 production
AOP:418	Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathway	Respiratory system disease	-		0.2	KE:1825	Increase, Cell death
AOP:419	Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathway	Respiratory system disease	-		0.5	KE:1923	Altered gene expression, P53 dependent apoptosis pathway
AOP:419		Respiratory system disease	-		0.5	KE:1262	Apoptosis
AOP:436	Inhibition of RALDH2 causes reduced all-trans retinoic acid levels, leading to transposition of the great arteries	Cardiovascular system disease	-	Chicken, Mouse, Vertebrates	0.2	KE:1881	Decreased, all-trans retinoic acid (atRA) concentration
AOP:437	Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity	Urinary system disease	Under Development		0.2	KE:1392	Oxidative Stress
AOP:438	reactive oxygen species generation leading to increased cardiovascular morbidity and mortality	Cardiovascular system disease	-		0.08	KE:1392	Oxidative Stress
AOP:439	Activation of the AhR leading to metastatic breast cancer	Thoracic disease; Cancer	Under Development	Humans, Mice	0.22	KE:149	Increase, Inflammation
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	0.29	KE:1974	Activation of Tumor Protein 53
AOP:441			-	Homo sapiens, Mus musculus musculus, Rattus norvegicus	0.29	KE:1262	Apoptosis
AOP:443	DNA damage and mutations leading to Metastatic Breast Cancer	Thoracic disease; Cancer	Under Development	Human and other cells in culture, Human, Mice, Rat, Canine heartworm nematode, Yeast	0.1	KE:1172	Increased activation, Nuclear factor kappa B (NF-kB)
AOP:444	Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability	Unclassified	-		0.33	KE:1392	Oxidative Stress
						KE:1365	Increase, Apoptosis
						KE:1798	Decreased spermatogenesis
AOP:446	PM-related Adverse outcome pathway frameworks on various systems	Respiratory system disease	-		0.15	KE:1392	Oxidative Stress
						KE:149	Increase, Inflammation
						KE:1262	Apoptosis
AOP:448	ROS, inflammation, and activation of nAChR lead to increased incidence of cardiovascular morbidity and mortality	Cardiovascular system disease	-		0.06	KE:1392	Oxidative Stress
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:1392	Oxidative Stress
AOP:452	Adverse outcome pathway of PM-induced respiratory toxicity	Respiratory system disease	-		0.27	KE:1392	Oxidative Stress
						KE:2009	Activation of inflammation pathway
						KE:1262	Apoptosis
AOP:453	Reactive oxygen species and subsequent oxidative stress lead to increased incidence of digestive morbidity and mortality in the general population	Gastrointestinal system disease	-		0.15	KE:1392	Oxidative Stress
AOP:453		Gastrointestinal system disease	-		0.15	KE:1995	Abnormal lipid metabolism
AOP:458	AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Rat, Mouse, Monkey, Human	0.12	KE:281	Thyroxine (T4) in serum, Decreased
AOP:459	AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Human, Mouse, Rat	0.33	KE:1392	Oxidative Stress
						KE:277	Thyroid hormone synthesis, Decreased
						KE:281	Thyroxine (T4) in serum, Decreased
AOP:460	Antagonism of Smoothened receptor leading to orofacial clefting	Unclassified	Under Development	Mouse	0.22	KE:2043	Decrease, Sonic Hedgehog second messenger production
AOP:460		Unclassified	Under Development	Mouse	0.22	KE:1262	Apoptosis
AOP:463	The AOP framwork on silica nanopariticles induced hepatoxicity	Gastrointestinal system disease	-		0.27	KE:1392	Oxidative Stress
						KE:149	Increase, Inflammation
						KE:1262	Apoptosis
AOP:464	Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits	Nervous system disease	-		0.11	KE:1392	Oxidative Stress
AOP:464		Nervous system disease	-		0.11	KE:1825	Increase, Cell death
AOP:469	Reactive oxygen speicies overproduction leading to increased digestive morbidity and mortality in generation population	Gastrointestinal system disease	-		0.15	KE:1392	Oxidative Stress
AOP:469		Gastrointestinal system disease	-		0.15	KE:1995	Abnormal lipid metabolism
AOP:470	Deposition of energy leads to abnormal vascular remodeling	Cardiovascular system disease	Under Review	Human, Rat, Mouse, Rabbit	0.25	KE:1392	Oxidative Stress
AOP:470	Deposition of energy leads to abnormal vascular remodeling	Cardiovascular system disease	Under Review	Human, Rat, Mouse, Rabbit	0.25	KE:2244	Altered Stress Response Signaling
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:1392	Oxidative Stress
AOP:479	Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress	Cardiovascular system disease; Thoracic disease	Under Development		0.14	KE:1392	Oxidative Stress
AOP:482	Deposition of energy leading to occurrence of bone loss	Musculoskeletal system disease	Under Review	Human, Mouse, Rat, Rhesus monkeys	0.29	KE:1392	Oxidative Stress
AOP:482	Deposition of energy leading to occurrence of bone loss	Musculoskeletal system disease	Under Review	Human, Mouse, Rat, Rhesus monkeys	0.29	KE:1825	Increase, Cell death
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	0.25	KE:1392	Oxidative Stress
AOP:483		Developmental disorder of mental health	Under Review	Mouse, Rat, Rabbit, Dog, Pigs, Cow, Human	0.25	KE:2244	Altered Stress Response Signaling
AOP:488	Increased reactive oxygen species production leading to decreased cognitive function	Cognitive disorder	-	Human	0.14	KE:1392	Oxidative Stress
AOP:491	Decrease, GLI1/2 target gene expression leads to orofacial clefting	Unclassified	Under Development	Mouse	0.33	KE:2043	Decrease, Sonic Hedgehog second messenger production
AOP:491		Unclassified	Under Development	Mouse	0.33	KE:1262	Apoptosis
AOP:497	ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome	Inherited metabolic disorder; Disease of metabolism	-		0.25	KE:1392	Oxidative Stress
AOP:497		Inherited metabolic disorder; Disease of metabolism	-		0.25	KE:2144	Impaired insulin signaling
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	0.14	KE:1262	Apoptosis
AOP:501	Excessive iron accumulation leading to neurological disorders	Nervous system disease	-	Homo sapiens	0.25	KE:1392	Oxidative Stress
AOP:505	Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway	Cancer	-	Human, Mouse, Rat	0.4	KE:1392	Oxidative Stress
AOP:505		Cancer	-	Human, Mouse, Rat	0.4	KE:149	Increase, Inflammation
AOP:507	Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway	Cardiovascular system disease	-	Mouse, Zebrafish, Human	0.33	KE:1392	Oxidative Stress
AOP:507		Cardiovascular system disease	-	Mouse, Zebrafish, Human	0.33	KE:2009	Activation of inflammation pathway
AOP:509	Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction	Cardiovascular system disease	-		0.29	KE:1392	Oxidative Stress
AOP:509		Cardiovascular system disease	-		0.29	KE:1365	Increase, Apoptosis
AOP:510	Demethylation of PPAR promotor leading to vascular disrupting effects	Cardiovascular system disease	-	Human, Mouse, Zebrafish	0.2	KE:1392	Oxidative Stress
AOP:510		Cardiovascular system disease	-	Human, Mouse, Zebrafish	0.2	KE:2165	Activation of PPAR
AOP:511	The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects	Cardiovascular system disease	-	Human, Mouse, Zebrafish	0.12	KE:1392	Oxidative Stress
AOP:511		Cardiovascular system disease	-	Human, Mouse, Zebrafish	0.12	KE:2009	Activation of inflammation pathway
AOP:513	Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway	Cancer	-	Human, Mouse, Rat	0.4	KE:233	Decreased, PPAR-gamma activation
AOP:513		Cancer	-	Human, Mouse, Rat	0.4	KE:1060	Alteration, lipid metabolism
AOP:521	Essential element imbalance leads to reproductive failure via oxidative stress	Unclassified	-	Murinae gen. sp.	0.43	KE:1392	Oxidative Stress
						KE:2206	Increased, histomorphological alteration of testis
						KE:1758	Impaired, Spermatogenesis
AOP:535	Binding and activation of GPER leading to learning and memory impairments	Developmental disorder of mental health	-	Mouse, Human	0.33	KE:1392	Oxidative Stress
						KE:2233	Decreased, ERαβ heterodimers
						KE:1262	Apoptosis
AOP:540	Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production	Unclassified	-		0.33	KE:1392	Oxidative Stress
						KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
						KE:1262	Apoptosis
AOP:541	Excessive ROS generation leading to increased incidence of vascular calcification by VSMC phenotype switching	Cardiovascular system disease	-		0.15	KE:1392	Oxidative Stress
AOP:541		Cardiovascular system disease	-		0.15	KE:2009	Activation of inflammation pathway
AOP:544	Inhibition of neuropathy target esterase leading to delayed neuropathy via increased inflammation	Nervous system disease	-	Homo sapiens, Mus musculus	0.17	KE:149	Increase, Inflammation
AOP:549	Aromatase inhibition leads to reproductive toxicity (including growth and developmental toxicity) in adult female zebrafish	Unclassified	-		0.12	KE:219	Reduction, Plasma 17beta-estradiol concentrations
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
AOP:564	DBDPE-induced inhibition of mitochondrial complex Ⅰ leading to population decline via neurotoxicity and metabotoxicity.	Unclassified	-	Zebrafish	0.09	KE:2301	Abnormal, Behavior
AOP:568	Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) leads to Inhibition, Feeding	Unclassified	-	Fish	0.25	KE:1320	Increased, extracellular serotonin
AOP:573	Inhibition, cytochrome oxidase leads to Increased, pulmonary edema	Respiratory system disease	-	Rodents, Humans	0.33	KE:1825	Increase, Cell death
AOP:574	Inhibition, cytochrome oxidase leads to Loss of olfactory function	Unclassified	-	Rodents, Humans	0.33	KE:1825	Increase, Cell death

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: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	0.6	KE:219	Reduction, Plasma 17beta-estradiol concentrations
						KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
						KE:406	decreased, Fertility
AOP:69	Modulation of Adult Leydig Cell Function Subsequent to Decreased Cholesterol Synthesis or Transport in the Adult Leydig Cell	Reproductive system disease	-	Rattus norvegicus, Homo sapiens	0.2	KE:646	Decreased Cholesterol, Decreased sperm quantity and/or quality in the adult testis
AOP:124	HMG-CoA reductase inhibition leading to decreased fertility	Reproductive system disease	-	Rattus rattus	0.33	KE:1690	Decrease, circulating testosterone levels
AOP:124	HMG-CoA reductase inhibition leading to decreased fertility	Reproductive system disease	-	Rattus rattus	0.33	KE:330	Decrease, Fertility
AOP:205	AOP from chemical insult to cell death	Unclassified	-	Vertebrates	0.17	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: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:270	Elevated ATP demand for detoxification and repair mechanisms leading to impaired locomotor activity	Unclassified	-		0.12	KE:10016	Impaired locomotor activity
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	0.38	KE:1614	Decrease, androgen receptor activation
						KE:1690	Decrease, circulating testosterone levels
						KE:1616	Malformation, cryptorchidism - maldescended testis
AOP:322	Alkylation of DNA leading to reduced sperm count	Reproductive system disease	-		0.4	KE:1365	Increase, Apoptosis
AOP:322	Alkylation of DNA leading to reduced sperm count	Reproductive system disease	-		0.4	KE:1757	Reduce, Sperm count
AOP:398	Decreased ALDH1A (RALDH) activity leading to decreased fertility via disrupted meiotic initiation of fetal oogonia	Reproductive system disease	Under Development	Mouse, Rat, Human	0.33	KE:1881	Decreased, all-trans retinoic acid (atRA) concentration
AOP:398		Reproductive system disease	Under Development	Mouse, Rat, Human	0.33	KE:406	decreased, Fertility
AOP:406	SARS-CoV-2 infection leading to hyperinflammation	Unclassified	-		0.17	KE:1868	Hyperinflammation
AOP:423	Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway	Unclassified	-		0.17	KE:1817	Apoptotic cell death
AOP:468	Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)	Unclassified	-		0.25	KE:1825	Increase, Cell death
AOP:468		Unclassified	-		0.25	KE:1868	Hyperinflammation
AOP:492	Glutathione conjugation leading to reproductive dysfunction via oxidative stress	Reproductive system disease	-	Mammals, Fish	0.4	KE:130	Depletion, GSH
AOP:492		Reproductive system disease	-	Mammals, Fish	0.4	KE:406	decreased, Fertility
AOP:493	ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity	Acquired metabolic disease	-	Mus musculus, Homo sapiens	0.4	KE:2129	Metabolically unhealthy Obesity
						KE:1633	Increase in inflammation
						KE:2128	Increased adipocyte numbers
						KE:2127	Increased adipocyte size

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	-		0.2	KE:26	Antagonism, Androgen receptor
AOP:23	Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)	Unclassified	WPHA/WNT Endorsed	Pimephales promelas	0.3	KE:25	Agonism, Androgen receptor
						KE:219	Reduction, Plasma 17beta-estradiol concentrations
						KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:36	Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-		0.25	KE:231	Decreased, PPAR-alpha activation
AOP:36			-		0.25	KE:233	Decreased, PPAR-gamma activation
AOP:37	PPARα activation leading to hepatocellular adenomas and carcinomas in rodents	Cancer; Gastrointestinal system disease	Under Development	Mouse, Rat	0.2	KE:227	Activation, PPARα
AOP:58	NR1I3 (CAR) suppression leading to hepatic steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-	Human, Mouse, Rat	0.12	KE:468	Inhibition, PPAR alpha
AOP:58	NR1I3 (CAR) suppression leading to hepatic steatosis		-	Human, Mouse, Rat	0.12	KE:454	Increased, Triglyceride formation
AOP:91	Sodium channel inhibition leading to reduced survival	Unclassified	-	Medaka, Gammarus pulex, Hydra	0.17	KE:584	Inhibition, sodium channel
AOP:93	sodium channel inhibition leading to increased predation	Unclassified	-		0.25	KE:584	Inhibition, sodium channel
AOP:94	Sodium channel inhibition leading to congenital malformations	Unclassified	-	Human, Rat, Mouse	0.17	KE:584	Inhibition, sodium channel
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:112	Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)	Reproductive system disease; Cancer	-	Rattus norvegicus	0.33	KE:111	Agonism, Estrogen receptor
AOP:112		Reproductive system disease; Cancer	-	Rattus norvegicus	0.33	KE:746	Increase, Dopaminergic activity
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:25	Agonism, Androgen receptor
AOP:120	Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)	Cancer; Reproductive system disease	-	Rattus norvegicus, Mus musculus	0.4	KE:1617	Inhibition, 5α-reductase
AOP:120		Cancer; Reproductive system disease	-	Rattus norvegicus, Mus musculus	0.4	KE:1690	Decrease, circulating testosterone levels
AOP:128	Kidney dysfunction by decreased thyroid hormone	Urinary system disease	Under Development	Sprague-Dawley, Homo sapiens	0.18	KE:277	Thyroid hormone synthesis, Decreased
AOP:128	Kidney dysfunction by decreased thyroid hormone	Urinary system disease	Under Development	Sprague-Dawley, Homo sapiens	0.18	KE:281	Thyroxine (T4) in serum, Decreased
AOP:206	Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis	Musculoskeletal system disease; Respiratory system disease	Under Development	Homo sapiens	0.33	KE:1270	Inactivation of PPARγ
AOP:206		Musculoskeletal system disease; Respiratory system disease	Under Development	Homo sapiens	0.33	KE:149	Increase, Inflammation
AOP:277	Impaired IL-1R1 signaling leading to Impaired T-Cell Dependent Antibody Response	Immune system disease	WPHA/WNT Endorsed	Homo sapiens, Mus musculus, Rattus norvegicus	0.5	KE:1700	Impaired IL-1R1 signaling in T cell
AOP:277		Immune system disease	WPHA/WNT Endorsed	Homo sapiens, Mus musculus, Rattus norvegicus	0.5	KE:202	Inhibition, Nuclear factor kappa B (NF-kB)
AOP:289	Inhibition of 5α-reductase leading to impaired fecundity in female fish	Unclassified	Under Development	Fish	0.33	KE:1617	Inhibition, 5α-reductase
AOP:289		Unclassified	Under Development	Fish	0.33	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:300	Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	Under Development	Human, Mouse	0.2	KE:1656	Antagonism, Thyroid Receptor
AOP:305	5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring	Unclassified	Under Development	Rat, Human, Mouse	0.4	KE:1614	Decrease, androgen receptor activation
AOP:305		Unclassified	Under Development	Rat, Human, Mouse	0.4	KE:1617	Inhibition, 5α-reductase
AOP:306	Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring	Unclassified	Under Development	Rat, Human, Mouse	0.5	KE:1614	Decrease, androgen receptor activation
AOP:306		Unclassified	Under Development	Rat, Human, Mouse	0.5	KE:26	Antagonism, Androgen receptor
AOP:318	Glucocorticoid Receptor activation leading to hepatic steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-		0.2	KE:122	Activation, Glucocorticoid Receptor
AOP:323	PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone	Unclassified	-	Teleost fish	0.33	KE:227	Activation, PPARα
AOP:323		Unclassified	-	Teleost fish	0.33	KE:1758	Impaired, Spermatogenesis
AOP:334	Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration	Unclassified	-	Teleost fish	0.17	KE:122	Activation, Glucocorticoid Receptor
AOP:344	Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspring	Unclassified	Under Development		0.5	KE:1614	Decrease, androgen receptor activation
AOP:344		Unclassified	Under Development		0.5	KE:26	Antagonism, Androgen receptor
AOP:347	Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis	Musculoskeletal system disease; Respiratory system disease	-		0.22	KE:1270	Inactivation of PPARγ
AOP:347		Musculoskeletal system disease; Respiratory system disease	-		0.22	KE:1793	Activator protein 1 activation
AOP:372	Androgen receptor antagonism leading to testicular cancer	Endocrine system disease; Reproductive system disease; Cancer	-		0.6	KE:1614	Decrease, androgen receptor activation
						KE:26	Antagonism, Androgen receptor
						KE:1616	Malformation, cryptorchidism - maldescended testis
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:25	Agonism, Androgen receptor
AOP:411	Oxidative stress Leading to Decreased Lung Function	Respiratory system disease	-	Homo sapiens	0.25	KE:1392	Oxidative Stress
AOP:424	Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction	Respiratory system disease	-	Human	0.17	KE:1392	Oxidative Stress
AOP:425	Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1	Respiratory system disease	-	Human	0.17	KE:1392	Oxidative Stress
AOP:431	Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)	Inherited metabolic disorder	-	Human	0.2	KE:1950	Increase, TNF
AOP:447	Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways	Urinary system disease	-		0.33	KE:1392	Oxidative Stress
						KE:1365	Increase, Apoptosis
						KE:202	Inhibition, Nuclear factor kappa B (NF-kB)
						KE:1633	Increase in inflammation
AOP:457	Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine	Inherited metabolic disorder	-	Human	0.67	KE:1392	Oxidative Stress
						KE:2118	Succinate dehydrogenase, inhibited
						KE:277	Thyroid hormone synthesis, Decreased
						KE:281	Thyroxine (T4) in serum, Decreased
AOP:472	DNA adduct formation leading to kidney failure	Urinary system disease	-		0.33	KE:1392	Oxidative Stress
						KE:1825	Increase, Cell death
						KE:149	Increase, Inflammation
AOP:474	Succinate dehydrogenase inactivation leads to cancer by promoting EMT	Cancer	Under Development	Human and other cells in culture	0.2	KE:2118	Succinate dehydrogenase, inhibited
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:485	Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognition	Cognitive disorder	-	Human	0.14	KE:1656	Antagonism, Thyroid Receptor
AOP:495	Androgen receptor activation leading to prostate cancer	Reproductive system disease; Cancer	-		0.11	KE:25	Agonism, Androgen receptor
AOP:496	Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）	Unclassified	-	Zebrafish	0.3	KE:25	Agonism, Androgen receptor
						KE:219	Reduction, Plasma 17beta-estradiol concentrations
						KE:1690	Decrease, circulating testosterone levels
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:2201	Agonism, Retinoic acid receptor
AOP:523	Retinoic acid receptor agonism during neurodevelopment leading to microcephaly	Congenital nervous system abnormality; Nervous system disease	-		0.2	KE:2201	Agonism, Retinoic acid receptor
AOP:525	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory	Developmental disorder of mental health	-		0.15	KE:2216	Binding of antagonist to thyroid hormone receptor
AOP:525		Developmental disorder of mental health	-		0.15	KE:1656	Antagonism, Thyroid Receptor
AOP:533	Retinoic acid receptor antagonism during neurodevelopment leading to impaired learning and memory	Developmental disorder of mental health	-		0.17	KE:2232	Antagonism, Retinoic acid receptors
AOP:534	Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress	Cancer	-	Vertebrates	0.33	KE:1392	Oxidative Stress
AOP:534		Cancer	-	Vertebrates	0.33	KE:2118	Succinate dehydrogenase, inhibited
AOP:536	Estrogen receptor agonism leading to reduced survival and population growth due to renal failure	Unclassified	-		0.17	KE:111	Agonism, Estrogen receptor
AOP:537	Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liver	Unclassified	-		0.2	KE:111	Agonism, Estrogen receptor
AOP:546	Succinate dehydrogenase inactivation leads to cancer through hypoxic-like mechanisms	Cancer	-	Human and other cells in culture	0.2	KE:2118	Succinate dehydrogenase, inhibited
AOP:553	Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure	Cardiovascular system disease	-	Human, Rodents, Dogs, Pigs, Insects, Fish	0.25	KE:584	Inhibition, sodium channel

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:6	Antagonist binding to PPARα leading to body-weight loss	Symptom	WPHA/WNT Endorsed	Mus musculus, Homo sapiens, Pimephales promelas, Colinus virginianus, Rattus norvegicus	0.25	KE:864	Decreased, Body Weight
AOP:6	Antagonist binding to PPARα leading to body-weight loss	Symptom	WPHA/WNT Endorsed		0.25	KE:998	Binding of antagonist, PPAR alpha
AOP:18	PPARα activation in utero leading to impaired fertility in males	Reproductive system disease	Under Review	Human, Rat, Mouse	0.38	KE:227	Activation, PPARα
						KE:1690	Decrease, circulating testosterone levels
						KE:406	decreased, Fertility
AOP:64	Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility	Reproductive system disease	-	Rattus norvegicus	0.57	KE:520	Decreased sperm quantity or quality in the adult, Decreased fertility
						KE:494	Glucocorticoid Receptor Agonist, Activation
						KE:1690	Decrease, circulating testosterone levels
						KE:406	decreased, Fertility
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:1614	Decrease, androgen receptor activation
						KE:26	Antagonism, Androgen receptor
						KE:406	decreased, Fertility
AOP:392	Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation	Unclassified	Under Development	Humans	0.4	KE:1866	Fibrinolysis, decreased
AOP:392		Unclassified	Under Development	Humans	0.4	KE:1868	Hyperinflammation
AOP:532	Retinoic acid receptor agonism during cerebellar development leading to impaired locomotor function	Unclassified	-		0.4	KE:2201	Agonism, Retinoic acid receptor
AOP:532		Unclassified	-		0.4	KE:2231	Locomotor function. Impaired

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.