DEDUCT | Database of Endocrine Disrupting chemicals and their Toxicity profiles

Sodium arsenite

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:3	Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits	Nervous system disease	WPHA/WNT Endorsed	Human, Rat	0.14	KE:177	Mitochondrial dysfunction
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	0.4	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:7			Under Review	Rat, Mouse, Human	0.4	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
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:18	PPARα activation in utero leading to impaired fertility in males	Reproductive system disease	Under Review	Human, Rat, Mouse	0.12	KE:1690	Decrease, circulating testosterone levels
AOP:23	Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)	Unclassified	WPHA/WNT Endorsed	Pimephales promelas	0.2	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:23		Unclassified	WPHA/WNT Endorsed	Pimephales promelas	0.2	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
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	0.12	KE:149	Increase, Inflammation
AOP:34	LXR activation leading to hepatic steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-		0.08	KE:177	Mitochondrial dysfunction
AOP:41	Sustained AhR Activation leading to Rodent Liver Tumours	Cancer; Gastrointestinal system disease	Under Review	Rattus sp. ABTC 42503, Mus sp. 2000082	0.2	KE:854	Alterations, Cellular proliferation / hyperplasia
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: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:177	Mitochondrial dysfunction
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:64	Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility	Reproductive system disease	-	Rattus norvegicus	0.29	KE:520	Decreased sperm quantity or quality in the adult, Decreased fertility
AOP:64		Reproductive system disease	-	Rattus norvegicus	0.29	KE:1690	Decrease, circulating testosterone levels
AOP:77	Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1	Unclassified	-	Honey bee	0.14	KE:177	Mitochondrial dysfunction
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:177	Mitochondrial dysfunction
AOP:79	Nicotinic acetylcholine receptor activation contributes to impaired hive thermoregulation and leads to colony loss/failure	Unclassified	-		0.2	KE:177	Mitochondrial dysfunction
AOP:80	Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure	Unclassified	-	Honey bee	0.12	KE:177	Mitochondrial dysfunction
AOP:87	Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure	Unclassified	-	Honey bee	0.12	KE:177	Mitochondrial dysfunction
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:120	Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)	Cancer; Reproductive system disease	-	Rattus norvegicus, Mus musculus	0.2	KE:1690	Decrease, circulating testosterone levels
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:124	HMG-CoA reductase inhibition leading to decreased fertility	Reproductive system disease	-	Rattus rattus	0.17	KE:1690	Decrease, circulating testosterone levels
AOP:130	Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity	Gastrointestinal system disease	Under Development	Sprague-Dawley, Homo sapiens	0.09	KE:177	Mitochondrial dysfunction
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: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:144	Endocytic lysosomal uptake leading to liver fibrosis	Gastrointestinal system disease	Under Review	Human, Mouse, Rat	0.11	KE:177	Mitochondrial dysfunction
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	0.33	KE:1116	Decreased, Triiodothyronine (T3) in tissues
AOP:190		Unclassified	-	African clawed frog	0.33	KE:1023	Increased, Thyroid-stimulating hormone (TSH)
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:206	Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis	Musculoskeletal system disease; Respiratory system disease	Under Development	Homo sapiens	0.17	KE:149	Increase, Inflammation
AOP:207	NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans	Reproductive system disease	-	Caenorhabditis elegans	0.25	KE:177	Mitochondrial dysfunction
AOP:207		Reproductive system disease	-	Caenorhabditis elegans	0.25	KE:1262	Apoptosis
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:256	Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity	Urinary system disease	Under Development	Human, Rat, Mouse	0.2	KE:177	Mitochondrial dysfunction
AOP:258	Renal protein alkylation leading to kidney toxicity	Urinary system disease	Under Development	Human, Rat, Mouse	0.2	KE:177	Mitochondrial dysfunction
AOP:260	CYP2E1 activation and formation of protein adducts leading to neurodegeneration	Nervous system disease	-	Human	0.14	KE:1392	Oxidative Stress
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:272	Deposition of energy leading to lung cancer	Cancer	WPHA/WNT Endorsed	Human, Rat, Mouse	0.14	KE:870	Increase, Cell Proliferation
AOP:280	α-diketone-induced bronchiolitis obliterans	Musculoskeletal system disease; Respiratory system disease	-		0.14	KE:149	Increase, Inflammation
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	0.25	KE:1613	Decrease, dihydrotestosterone (DHT) level
AOP:288		Endocrine system disease	-	Human, Rat	0.25	KE:1690	Decrease, circulating testosterone levels
AOP:289	Inhibition of 5α-reductase leading to impaired fecundity in female fish	Unclassified	Under Development	Fish	0.33	KE:1613	Decrease, dihydrotestosterone (DHT) level
AOP:289		Unclassified	Under Development	Fish	0.33	KE:219	Reduction, Plasma 17beta-estradiol concentrations
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	0.2	KE:1613	Decrease, dihydrotestosterone (DHT) level
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	-		0.18	KE:10039	Higher antioxidant enzyme activities and lipid peroxidation
AOP:321		Unclassified	-		0.18	KE:10042	Abnormal development
AOP:323	PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone	Unclassified	-	Teleost fish	0.17	KE:1758	Impaired, Spermatogenesis
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	0.2	KE:1758	Impaired, Spermatogenesis
AOP:349	Inhibition of 11β-hydroxylase leading to decresed population trajectory	Unclassified	Under Development	Fish	0.12	KE:1798	Decreased spermatogenesis
AOP:362	Immune mediated hepatitis	Gastrointestinal system disease; Immune system disease	-	Homo sapiens, Rat	0.25	KE:1633	Increase in inflammation
AOP:362	Immune mediated hepatitis	Gastrointestinal system disease; Immune system disease	-	Homo sapiens, Rat	0.25	KE:177	Mitochondrial dysfunction
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	-		0.14	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	-		0.14	KE:281	Thyroxine (T4) in serum, Decreased
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:423	Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway	Unclassified	-		0.17	KE:177	Mitochondrial dysfunction
AOP:431	Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)	Inherited metabolic disorder	-	Human	0.2	KE:1952	Abnormal, Glucose homeostasis
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:437	Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity	Urinary system disease	Under Development		0.4	KE:1392	Oxidative Stress
AOP:437		Urinary system disease	Under Development		0.4	KE:177	Mitochondrial dysfunction
AOP:438	reactive oxygen species generation leading to increased cardiovascular morbidity and mortality	Cardiovascular system disease	-		0.17	KE:1392	Oxidative Stress
AOP:438		Cardiovascular system disease	-		0.17	KE:177	Mitochondrial dysfunction
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	0.14	KE:1262	Apoptosis
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: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:1392	Oxidative Stress
AOP:452	Adverse outcome pathway of PM-induced respiratory toxicity	Respiratory system disease	-		0.18	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	-		0.08	KE:1392	Oxidative Stress
AOP:457	Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine	Inherited metabolic disorder	-	Human	0.5	KE:1392	Oxidative Stress
						KE:277	Thyroid hormone synthesis, Decreased
						KE:281	Thyroxine (T4) in serum, Decreased
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	0.11	KE:1262	Apoptosis
AOP:463	The AOP framwork on silica nanopariticles induced hepatoxicity	Gastrointestinal system disease	-		0.36	KE:1392	Oxidative Stress
						KE:149	Increase, Inflammation
						KE:177	Mitochondrial dysfunction
						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:177	Mitochondrial dysfunction
AOP:469	Reactive oxygen speicies overproduction leading to increased digestive morbidity and mortality in generation population	Gastrointestinal system disease	-		0.08	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: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	0.2	KE:1392	Oxidative Stress
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	0.2	KE:870	Increase, Cell Proliferation
AOP:479	Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress	Cardiovascular system disease; Thoracic disease	Under Development		0.29	KE:1392	Oxidative Stress
AOP:479		Cardiovascular system disease; Thoracic disease	Under Development		0.29	KE:177	Mitochondrial dysfunction
AOP:480	Mitochondrial complexes inhibition leading to heart failure via decreased ATP production	Cardiovascular system disease; Thoracic disease	Under Development		0.2	KE:177	Mitochondrial dysfunction
AOP:482	Deposition of energy leading to occurrence of bone loss	Musculoskeletal system disease	Under Review	Human, Mouse, Rat, Rhesus monkeys	0.14	KE:1392	Oxidative Stress
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	0.17	KE:1262	Apoptosis
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	0.1	KE:1633	Increase in inflammation
AOP:495	Androgen receptor activation leading to prostate cancer	Reproductive system disease; Cancer	-		0.11	KE:854	Alterations, Cellular proliferation / hyperplasia
AOP:496	Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）	Unclassified	-	Zebrafish	0.2	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:496		Unclassified	-	Zebrafish	0.2	KE:1690	Decrease, circulating testosterone levels
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:177	Mitochondrial dysfunction
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:177	Mitochondrial dysfunction
AOP:500		Developmental disorder of mental health	-	Rattus norvegicus, Mus musculus, Homo sapiens	0.29	KE:1262	Apoptosis
AOP:501	Excessive iron accumulation leading to neurological disorders	Nervous system disease	-	Homo sapiens	0.25	KE:1392	Oxidative Stress
AOP:504	SULT1E1 inhibition leading to uterine adenocarcinoma via increased estrogen availability at target organ level	Unclassified	-	Mammals	0.33	KE:2251	Estradiol availability, increased
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	0.17	KE:1392	Oxidative Stress
AOP:509	Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction	Cardiovascular system disease	-		0.43	KE:1392	Oxidative Stress
						KE:1365	Increase, Apoptosis
						KE:177	Mitochondrial dysfunction
AOP:510	Demethylation of PPAR promotor leading to vascular disrupting effects	Cardiovascular system disease	-	Human, Mouse, Zebrafish	0.1	KE:1392	Oxidative Stress
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:177	Mitochondrial dysfunction
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:530	Endocytotic lysosomal uptake leads to intestinal barrier disruption	Gastrointestinal system disease	-		0.2	KE:177	Mitochondrial dysfunction
AOP:534	Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress	Cancer	-	Vertebrates	0.17	KE:1392	Oxidative Stress
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:1816	Mitochondrial dysfunction EMPTY
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:550	Increased LMNA gene mutation leading to heart failure	Cardiovascular system disease	-	Human, Mouse, Rat	0.2	KE:2066	Altered Signaling Pathways
AOP:561	Aromatase induction leading to estrogen receptor alpha activation via increased estradiol	Unclassified	-	Vertebrates	0.4	KE:2294	Plasma estradiol, increased
AOP:561		Unclassified	-	Vertebrates	0.4	KE:2251	Estradiol availability, increased
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:205	AOP from chemical insult to cell death	Unclassified	-	Vertebrates	0.33	KE:177	Mitochondrial dysfunction
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: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: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:392	Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation	Unclassified	Under Development	Humans	0.2	KE:1868	Hyperinflammation
AOP:406	SARS-CoV-2 infection leading to hyperinflammation	Unclassified	-		0.17	KE:1868	Hyperinflammation
AOP:468	Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)	Unclassified	-		0.12	KE:1868	Hyperinflammation

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: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:335	AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment	Cancer; Urinary system disease	-	Rat	0.2	KE:177	Mitochondrial dysfunction
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: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:177	Mitochondrial dysfunction
						KE:1633	Increase in inflammation
AOP:472	DNA adduct formation leading to kidney failure	Urinary system disease	-		0.33	KE:1392	Oxidative Stress
						KE:1816	Mitochondrial dysfunction EMPTY
						KE:149	Increase, Inflammation

No associated AOPs with Level of Relevance 5

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.