DEDUCT | Database of Endocrine Disrupting chemicals and their Toxicity profiles

Diuron

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:34	LXR activation leading to hepatic steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-		0.15	KE:177	Mitochondrial dysfunction
AOP:34	LXR activation leading to hepatic steatosis		-		0.15	KE:116	Activation, FAS
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:40	Covalent Protein binding leading to Skin Sensitisation	Integumentary system disease	WPHA/WNT Endorsed	Mouse, Human	0.2	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: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.	0.1	KE:277	Thyroid hormone synthesis, Decreased
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: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	0.29	KE:277	Thyroid hormone synthesis, Decreased
AOP:110		Cancer; Endocrine system disease	-	Rattus norvegicus, Mus musculus	0.29	KE:739	Increase, Hypertrophy and proliferation (follicular cell)
AOP:112	Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)	Reproductive system disease; Cancer	-	Rattus norvegicus	0.17	KE:111	Agonism, Estrogen receptor
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:118	Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)	Cancer; Gastrointestinal system disease	-	Mus musculus, Rattus norvegicus	0.25	KE:787	Increase, Regenerative cell proliferation (hepatocytes)
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:796	Increase, Hyperplasia (urothelial)
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	0.11	KE:277	Thyroid hormone synthesis, 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: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:176	Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.2	KE:277	Thyroid hormone synthesis, Decreased
AOP:188	Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.2	KE:277	Thyroid hormone synthesis, Decreased
AOP:192	Pendrin inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:193	Dual oxidase (DUOX) inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:207	NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans	Reproductive system disease	-	Caenorhabditis elegans	0.12	KE:177	Mitochondrial dysfunction
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: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		0.2	KE:1821	Decrease, Cell proliferation
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: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:362	Immune mediated hepatitis	Gastrointestinal system disease; Immune system disease	-	Homo sapiens, Rat	0.12	KE:177	Mitochondrial dysfunction
AOP:399	Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)	Unclassified	-	Zebrafish	0.12	KE:1821	Decrease, Cell proliferation
AOP:409	Frustrated phagocytosis leads to malignant mesothelioma	Cancer	-		0.12	KE:870	Increase, Cell Proliferation
AOP:413	Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure	Unclassified	-	Fish, Mice	0.17	KE:1607	Increase, Necrosis
AOP:423	Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway	Unclassified	-		0.17	KE:177	Mitochondrial dysfunction
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		0.2	KE:177	Mitochondrial dysfunction
AOP:438	reactive oxygen species generation leading to increased cardiovascular morbidity and mortality	Cardiovascular system disease	-		0.08	KE:177	Mitochondrial dysfunction
AOP:440	Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia	Benign neoplasm; Endocrine system disease; Reproductive system disease; Reproductive system disease; Cancer; Endocrine system disease	Under Development	Human, Rat, Mice	0.11	KE:1973	Increased, estrogens
AOP:446	PM-related Adverse outcome pathway frameworks on various systems	Respiratory system disease	-		0.1	KE:18	Activation, AhR
AOP:446		Respiratory system disease	-		0.1	KE:165	Activation, Long term AHR receptor driven direct and indirect gene expression changes
AOP:451	Interaction with lung resident cell membrane components leads to lung cancer	Cancer	-	Human	0.11	KE:870	Increase, Cell Proliferation
AOP:457	Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine	Inherited metabolic disorder	-	Human	0.17	KE:277	Thyroid hormone synthesis, Decreased
AOP:460	Antagonism of Smoothened receptor leading to orofacial clefting	Unclassified	Under Development	Mouse	0.11	KE:1821	Decrease, Cell proliferation
AOP:463	The AOP framwork on silica nanopariticles induced hepatoxicity	Gastrointestinal system disease	-		0.09	KE:177	Mitochondrial dysfunction
AOP:464	Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits	Nervous system disease	-		0.05	KE:177	Mitochondrial dysfunction
AOP:465	Alcohol dehydrogenase leading to reproductive dysfunction	Unclassified	-		0.12	KE:748	Increased, Estrogen receptor (ER) activity
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: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: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:491	Decrease, GLI1/2 target gene expression leads to orofacial clefting	Unclassified	Under Development	Mouse	0.17	KE:1821	Decrease, Cell proliferation
AOP:495	Androgen receptor activation leading to prostate cancer	Reproductive system disease; Cancer	-		0.22	KE:854	Alterations, Cellular proliferation / hyperplasia
AOP:495	Androgen receptor activation leading to prostate cancer	Reproductive system disease; Cancer	-		0.22	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:496	Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）	Unclassified	-	Zebrafish	0.1	KE:286	Altered, Transcription of genes by the androgen receptor
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	-		0.12	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	0.14	KE:177	Mitochondrial dysfunction
AOP:510	Demethylation of PPAR promotor leading to vascular disrupting effects	Cardiovascular system disease	-	Human, Mouse, Zebrafish	0.1	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	0.06	KE:177	Mitochondrial dysfunction
AOP:530	Endocytotic lysosomal uptake leads to intestinal barrier disruption	Gastrointestinal system disease	-		0.2	KE:177	Mitochondrial dysfunction

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:139	Alkylation of DNA leading to cancer 1	Cancer	-	Homo sapiens, Mus musculus	0.25	KE:885	Increase, Cancer
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:177	Mitochondrial dysfunction
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: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:534	Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress	Cancer	-	Vertebrates	0.17	KE:885	Increase, Cancer
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

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: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:239	Activation, Pregnane-X receptor, NR1l2
AOP:18	PPARα activation in utero leading to impaired fertility in males	Reproductive system disease	Under Review	Human, Rat, Mouse	0.25	KE:227	Activation, PPARα
AOP:18		Reproductive system disease	Under Review	Human, Rat, Mouse	0.25	KE:289	Decrease, Translocator protein (TSPO)
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:21	Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2	Unclassified	WPHA/WNT Endorsed	Zebrafish, Medaka, Gallus gallus	0.2	KE:18	Activation, AhR
AOP:27	Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)	Gastrointestinal system disease	Under Development	Humans	0.25	KE:41	Inhibition, Bile Salt Export Pump (ABCB11)
AOP:27		Gastrointestinal system disease	Under Development	Humans	0.25	KE:288	Activation of specific nuclear receptors, Transcriptional change
AOP:37	PPARα activation leading to hepatocellular adenomas and carcinomas in rodents	Cancer; Gastrointestinal system disease	Under Development	Mouse, Rat	0.4	KE:716	Increase, cell proliferation (hepatocytes)
AOP:37		Cancer; Gastrointestinal system disease	Under Development	Mouse, Rat	0.4	KE:227	Activation, PPARα
AOP:41	Sustained AhR Activation leading to Rodent Liver Tumours	Cancer; Gastrointestinal system disease	Under Review	Rattus sp. ABTC 42503, Mus sp. 2000082	0.4	KE:854	Alterations, Cellular proliferation / hyperplasia
AOP:41	Sustained AhR Activation leading to Rodent Liver Tumours	Cancer; Gastrointestinal system disease	Under Review	Rattus sp. ABTC 42503, Mus sp. 2000082	0.4	KE:165	Activation, Long term AHR receptor driven direct and indirect gene expression changes
AOP:42	Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	WPHA/WNT Endorsed	Human, Rat, Mouse	0.25	KE:279	Thyroperoxidase, Inhibition
AOP:42		Cognitive disorder	WPHA/WNT Endorsed	Human, Rat, Mouse	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:60	NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-		0.08	KE:245	Activation, PXR/SXR
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: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:279	Thyroperoxidase, Inhibition
						KE:277	Thyroid hormone synthesis, Decreased
						KE:739	Increase, Hypertrophy and proliferation (follicular cell)
AOP:128	Kidney dysfunction by decreased thyroid hormone	Urinary system disease	Under Development	Sprague-Dawley, Homo sapiens	0.09	KE:277	Thyroid hormone synthesis, Decreased
AOP:131	Aryl hydrocarbon receptor activation leading to uroporphyria	Inherited metabolic disorder	WPHA/WNT Endorsed	Mouse, Rat, Human, Japanese quail, Chicken, Herring gull, Common Starling	0.33	KE:18	Activation, AhR
AOP:131		Inherited metabolic disorder	WPHA/WNT Endorsed		0.33	KE:850	Induction, CYP1A2/CYP1A5
AOP:150	Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF	Unclassified	WPHA/WNT Endorsed	Chicken, Zebrafish, Mouse, Rattus norvegicus	0.14	KE:18	Activation, AhR
AOP:151	AhR activation leading to preeclampsia	Cardiovascular system disease	Under Development	Homo sapiens, Mus musculus	0.14	KE:18	Activation, AhR
AOP:159	Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	Zebrafish, Fathead minnow	0.25	KE:279	Thyroperoxidase, Inhibition
AOP:159		Unclassified	WPHA/WNT Endorsed	Zebrafish, Fathead minnow	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:175	Thyroperoxidase inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.5	KE:279	Thyroperoxidase, Inhibition
AOP:175		Unclassified	-	African clawed frog	0.5	KE:277	Thyroid hormone synthesis, Decreased
AOP:209	Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP	Gastrointestinal system disease	-		0.12	KE:1286	Down Regulation, GSS and GSTs gene
AOP:232	NFE2/Nrf2 repression to steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-		0.12	KE:1417	NFE2/Nrf2 repression
AOP:269	Elevated ATP demand for detoxification and repair mechanisms leading to impaired growth and development	Unclassified	-		0.17	KE:10008	Increased transcription for detoxification and repair mechanism
AOP:270	Elevated ATP demand for detoxification and repair mechanisms leading to impaired locomotor activity	Unclassified	-		0.12	KE:10008	Increased transcription for detoxification and repair mechanism
AOP:271	Inhibition of thyroid peroxidase leading to impaired fertility in fish	Unclassified	Under Development	Fish	0.4	KE:279	Thyroperoxidase, Inhibition
AOP:271		Unclassified	Under Development	Fish	0.4	KE:277	Thyroid hormone synthesis, Decreased
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:310	Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR	Unclassified	-	Zebrafish	0.08	KE:18	Activation, AhR
AOP:323	PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone	Unclassified	-	Teleost fish	0.17	KE:227	Activation, PPARα
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:363	Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure	Unclassified	Under Review	Zebrafish	0.25	KE:279	Thyroperoxidase, Inhibition
AOP:363		Unclassified	Under Review	Zebrafish	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:364	Thyroperoxidase inhibition leading to altered visual function via decreased eye size	Unclassified	Under Development		0.25	KE:279	Thyroperoxidase, Inhibition
AOP:364		Unclassified	Under Development		0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:365	Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning	Unclassified	Under Development		0.25	KE:279	Thyroperoxidase, Inhibition
AOP:365		Unclassified	Under Development		0.25	KE:277	Thyroid hormone synthesis, Decreased
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: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:18	Activation, AhR
AOP:415	Aryl hydrocarbon receptor activation leading to lung fibrosis through IL-6 toxicity pathway	Musculoskeletal system disease; Respiratory system disease	-		0.2	KE:18	Activation, AhR
AOP:416	Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathway	Cancer	-		0.17	KE:18	Activation, AhR
AOP:417	Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathway	Cancer	-		0.4	KE:18	Activation, AhR
AOP:417		Cancer	-		0.4	KE:17	Altered gene expression, AHR nuclear translocator (ARNT)-dependent pathway
AOP:418	Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathway	Respiratory system disease	-		0.4	KE:18	Activation, AhR
AOP:418		Respiratory system disease	-		0.4	KE:17	Altered gene expression, AHR nuclear translocator (ARNT)-dependent pathway
AOP:419	Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathway	Respiratory system disease	-		0.25	KE:18	Activation, AhR
AOP:420	Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathway	Cancer	-		0.5	KE:18	Activation, AhR
AOP:420		Cancer	-		0.5	KE:870	Increase, Cell Proliferation
AOP:439	Activation of the AhR leading to metastatic breast cancer	Thoracic disease; Cancer	Under Development	Humans, Mice	0.11	KE:18	Activation, AhR
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:177	Mitochondrial dysfunction
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:18	Activation, AhR
AOP:456	Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity	Unclassified	Under Review	Zebrafish, Mouse, Human, Chicken	0.17	KE:18	Activation, AhR
AOP:458	AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Rat, Mouse, Monkey, Human	0.12	KE:18	Activation, AhR
AOP:459	AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Human, Mouse, Rat	0.33	KE:18	Activation, AhR
						KE:277	Thyroid hormone synthesis, Decreased
						KE:850	Induction, CYP1A2/CYP1A5
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:494	AhR activation leading to liver fibrosis	Gastrointestinal system disease	-	Mus musculus, Homo sapiens	0.17	KE:18	Activation, AhR
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	-		0.29	KE:1417	NFE2/Nrf2 repression
AOP:509		Cardiovascular system disease	-		0.29	KE:177	Mitochondrial dysfunction
AOP:517	Pregnane X Receptor (PXR) activation leads to liver steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-	Vertebrates	0.2	KE:239	Activation, Pregnane-X receptor, NR1l2
AOP:525	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory	Developmental disorder of mental health	-		0.08	KE:2216	Binding of antagonist to thyroid hormone receptor
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:545	Activation, Pregnane-X receptor, NR1l2 leads to increased plasma low-density lipoprotein (LDL) cholesterol via increased cholesterol synthesis	Unclassified	-	Mammals	0.2	KE:239	Activation, Pregnane-X receptor, NR1l2
AOP:548	Activation, Pregnane-X receptor, NR1l2 leads to increased plasma low-density lipoprotein (LDL) cholesterol via increased PCSK9 protein expression	Unclassified	-	Mammals	0.2	KE:239	Activation, Pregnane-X receptor, NR1l2
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:18	Activation, AhR

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:335	AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment	Cancer; Urinary system disease	-	Rat	1.0	KE:1763	Urothelial Tumor
						KE:177	Mitochondrial dysfunction
						KE:796	Increase, Hyperplasia (urothelial)
						KE:1762	Urothelial cell injury/death
						KE:795	Increase, Regenerative cell proliferation (urothelial cells)

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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.