DEDUCT | Database of Endocrine Disrupting chemicals and their Toxicity profiles

Tetrachlorodibenzodioxin

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:4	Ecdysone receptor agonism leading to incomplete ecdysis associated mortality	Unclassified	-	Insects, Crustaceans	0.2	KE:1265	Increase, Fushi tarazu factor-1 gene expression
AOP:4		Unclassified	-	Insects, Crustaceans	0.2	KE:1264	Increase, Nuclear receptor E75b gene expression
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	0.22	KE:756	Hippocampal gene expression, Altered
AOP:8		Nervous system disease	Under Development	Rat	0.22	KE:281	Thyroxine (T4) in serum, Decreased
AOP:23	Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)	Unclassified	WPHA/WNT Endorsed	Pimephales promelas	0.4	KE:274	Reduction, Testosterone synthesis by ovarian theca cells
						KE:285	Reduction, Vitellogenin synthesis in liver
						KE:219	Reduction, Plasma 17beta-estradiol concentrations
						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	0.38	KE:285	Reduction, Vitellogenin synthesis in liver
						KE:219	Reduction, Plasma 17beta-estradiol concentrations
						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	0.38	KE:149	Increase, Inflammation
						KE:288	Activation of specific nuclear receptors, Transcriptional change
						KE:1115	Increase, Reactive oxygen species
AOP:36	Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-		0.12	KE:140	Decreased, HSD17B10 expression
AOP:37	PPARα activation leading to hepatocellular adenomas and carcinomas in rodents	Cancer; Gastrointestinal system disease	Under Development	Mouse, Rat	0.2	KE:716	Increase, cell proliferation (hepatocytes)
AOP:39	Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response	Respiratory system disease	Under Development	Human, Mouse	0.2	KE:272	Activation/Proliferation, T-cells
AOP: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:58	NR1I3 (CAR) suppression leading to hepatic steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-	Human, Mouse, Rat	0.25	KE:454	Increased, Triglyceride formation
						KE:54	Up Regulation, CD36
						KE:463	Up Regulation, FAS
						KE:462	Up Regulation, SCD-1
AOP:60	NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-		0.42	KE:472	Down Regulation, CPT1A
						KE:454	Increased, Triglyceride formation
						KE:474	Down Regulation, HMGCS2
						KE:462	Up Regulation, SCD-1
						KE:54	Up Regulation, CD36
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:77	Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1	Unclassified	-	Honey bee	0.14	KE:341	Impairment, Learning and memory
AOP:78	Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1	Unclassified	-	Honey bee	0.12	KE:341	Impairment, Learning and memory
AOP:87	Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure	Unclassified	-	Honey bee	0.12	KE:341	Impairment, Learning and memory
AOP:88	Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within caste	Unclassified	-	Honey bee	0.14	KE:341	Impairment, Learning and memory
AOP:89	Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure	Unclassified	-	Honey bee	0.12	KE:341	Impairment, Learning and memory
AOP:90	Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2	Unclassified	-	Honey bee	0.12	KE:341	Impairment, Learning and memory
AOP: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: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:108	Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)	Cancer; Gastrointestinal system disease	-	Mus musculus, Rattus norvegicus	0.33	KE:768	Increase, Cytotoxicity
AOP:108		Cancer; Gastrointestinal system disease	-	Mus musculus, Rattus norvegicus	0.33	KE:769	Increase, Oxidative metabolism
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	0.43	KE:1023	Increased, Thyroid-stimulating hormone (TSH)
						KE:281	Thyroxine (T4) in serum, Decreased
						KE:739	Increase, Hypertrophy and proliferation (follicular cell)
AOP:114	HPPD inhibition leading to corneal papillomas and carcinomas (in rat)	Cancer	-	Rattus norvegicus	0.33	KE:778	Increase, Regenerative cell proliferation (corneal cells)
AOP:114		Cancer	-	Rattus norvegicus	0.33	KE:777	Increase, Inflammation (corneal cells)
AOP:115	Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)	Cancer	-	Mus musculus, Rattus norvegicus	0.4	KE:149	Increase, Inflammation
AOP:115		Cancer	-	Mus musculus, Rattus norvegicus	0.4	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: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:281	Thyroxine (T4) in serum, Decreased
						KE:739	Increase, Hypertrophy and proliferation (follicular cell)
AOP:120	Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)	Cancer; Reproductive system disease	-	Rattus norvegicus, Mus musculus	0.4	KE:791	Increased, Leutinizing hormone (LH)
AOP:120		Cancer; Reproductive system disease	-	Rattus norvegicus, Mus musculus	0.4	KE:1690	Decrease, circulating testosterone levels
AOP:121	Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)	Cancer; Urinary system disease	-	Mus musculus, Rattus norvegicus	0.2	KE:795	Increase, Regenerative cell proliferation (urothelial cells)
AOP:122	Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation	Unclassified	-	Pimephales promelas	0.4	KE:799	Increased, HIF-1 heterodimer
						KE:285	Reduction, Vitellogenin synthesis in liver
						KE:219	Reduction, Plasma 17beta-estradiol concentrations
						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	0.45	KE:802	Increased, HIF-1 alpha transcription
						KE:285	Reduction, Vitellogenin synthesis in liver
						KE:799	Increased, HIF-1 heterodimer
						KE:219	Reduction, Plasma 17beta-estradiol concentrations
						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:128	Kidney dysfunction by decreased thyroid hormone	Urinary system disease	Under Development	Sprague-Dawley, Homo sapiens	0.18	KE:821	Decreased, Sodium reabsorption
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:136	Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors	Benign neoplasm; Respiratory system disease	Under Review		0.43	KE:868	Increase, Tissue Degeneration, Necrosis & Atrophy
						KE:768	Increase, Cytotoxicity
						KE:870	Increase, Cell Proliferation
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	0.25	KE:1003	Decreased, Triiodothyronine (T3)
AOP:159		Unclassified	WPHA/WNT Endorsed	Zebrafish, Fathead minnow	0.25	KE:281	Thyroxine (T4) in serum, Decreased
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	0.29	KE:1067	Proliferation/Clonal Expansion, aberrant basal cells
AOP:167		Reproductive system disease; Cancer	-	Mouse, Homo sapiens	0.29	KE:1066	Promotion, SIX-1 postive basal-type progenitor cells
AOP:173	Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis	Musculoskeletal system disease; Respiratory system disease	WPHA/WNT Endorsed	Human, Mouse, Rat	0.12	KE:1497	Increased, recruitment of inflammatory cells
AOP:175	Thyroperoxidase inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.25	KE:281	Thyroxine (T4) in serum, Decreased
AOP:176	Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.2	KE:281	Thyroxine (T4) in serum, Decreased
AOP:188	Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.2	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	0.25	KE:1829	Altered, Thyroid hormone-dependent gene expression
AOP:192	Pendrin inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.25	KE:281	Thyroxine (T4) in serum, Decreased
AOP:193	Dual oxidase (DUOX) inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.25	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	0.25	KE:626	Increased, serotonin (5-HT)
AOP:195		Unclassified	-		0.25	KE:1163	Increased, Reproductive Success
AOP:201	Juvenile hormone receptor agonism leading to male offspring induction associated population decline	Unclassified	-	Daphnia magna, Daphnia pulex	0.17	KE:1206	Induction, Doublesex1 gene
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:1115	Increase, Reactive oxygen species
AOP:207		Reproductive system disease	-	Caenorhabditis elegans	0.25	KE:1262	Apoptosis
AOP:213	Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)	Gastrointestinal system disease; Inherited metabolic disorder	-	Vertebrates	0.17	KE:1115	Increase, Reactive oxygen species
AOP:218	Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity	Unclassified	-	Japanese quail, Cynops pyrrhogaster	0.17	KE:1141	Decreased, Reproductive Success
AOP:219	Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior	Unclassified	-	Japanese quail, Cynops pyrrhogaster	0.33	KE:1390	Sexual behavior, decreased
AOP:219		Unclassified	-	Japanese quail, Cynops pyrrhogaster	0.33	KE:1141	Decreased, Reproductive Success
AOP:260	CYP2E1 activation and formation of protein adducts leading to neurodegeneration	Nervous system disease	-	Human	0.29	KE:1392	Oxidative Stress
AOP:260		Nervous system disease	-	Human	0.29	KE:1513	General Apoptosis
AOP:271	Inhibition of thyroid peroxidase leading to impaired fertility in fish	Unclassified	Under Development	Fish	0.2	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:275	Histone deacetylase inhibition leads to neural tube defects	Neural tube defect	-		0.4	KE:1560	Altered differentiation
AOP:275	Histone deacetylase inhibition leads to neural tube defects	Neural tube defect	-		0.4	KE:1239	Altered, Gene Expression
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	0.12	KE:1690	Decrease, circulating testosterone levels
AOP:289	Inhibition of 5α-reductase leading to impaired fecundity in female fish	Unclassified	Under Development	Fish	0.17	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:299	Deposition of energy leading to population decline via DNA oxidation and follicular atresia	Unclassified	-		0.14	KE:1115	Increase, Reactive oxygen species
AOP:305	5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring	Unclassified	Under Development	Rat, Human, Mouse	0.2	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:306	Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring	Unclassified	Under Development	Rat, Human, Mouse	0.25	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:309	Luteinizing hormone receptor antagonism leading to reproductive dysfunction	Unclassified	-	Fish	0.43	KE:1693	Reduction, Plasma progesterone concentration
						KE:1692	Reduction, Progesterone synthesis
						KE:1695	Impaired ovulation
AOP:311	Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis	Unclassified	-	Daphnia magna, Fish	0.14	KE:1115	Increase, Reactive oxygen species
AOP:320	Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality	Unclassified	Under Development	Homo sapiens	0.11	KE:1750	Increased inflammatory immune responses
AOP:321	Reduced environmental pH leading to thinner shells in Mytilus edulis	Unclassified	-		0.36	KE:592	Reduced, survival
						KE:10042	Abnormal development
						KE:10039	Higher antioxidant enzyme activities and lipid peroxidation
						KE:10038	Deregulation of acid base status
AOP:334	Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration	Unclassified	-	Teleost fish	0.33	KE:2245	Altered Cell Differentiation Signaling
AOP:334		Unclassified	-	Teleost fish	0.33	KE:2089	Altered Bone Cell Homeostasis
AOP:335	AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment	Cancer; Urinary system disease	-	Rat	0.2	KE:795	Increase, Regenerative cell proliferation (urothelial cells)
AOP:337	DNA methyltransferase inhibition leading to population decline (2)	Unclassified	-	Daphnia magna	0.12	KE:1776	Increase, Ovarian somatic cell apoptosis
AOP:339	DNA methyltransferase inhibition leading to population decline (4)	Unclassified	-		0.12	KE:1776	Increase, Ovarian somatic cell apoptosis
AOP:341	DNA methyltransferase inhibition leading to transgenerational effects (2)	Physical disorder	-	Daphnia magna	0.11	KE:1783	Increase, Ovarian somatic cell apoptosis (F3)
AOP:344	Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspring	Unclassified	Under Development		0.25	KE:286	Altered, Transcription of genes by the androgen receptor
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	0.4	KE:1789	Reduction, 17beta-estradiol synthesis by the undifferentiated gonad
AOP:346		Unclassified	WPHA/WNT Endorsed		0.4	KE:1790	Increased, Differentiation to Testis
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	0.38	KE:1818	Immune cell activation
						KE:1817	Apoptotic cell death
						KE:1633	Increase in inflammation
AOP:363	Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure	Unclassified	Under Review	Zebrafish	0.25	KE:1003	Decreased, Triiodothyronine (T3)
AOP:363		Unclassified	Under Review	Zebrafish	0.25	KE:281	Thyroxine (T4) in serum, Decreased
AOP:364	Thyroperoxidase inhibition leading to altered visual function via decreased eye size	Unclassified	Under Development		0.25	KE:1003	Decreased, Triiodothyronine (T3)
AOP:364		Unclassified	Under Development		0.25	KE:281	Thyroxine (T4) in serum, Decreased
AOP:365	Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning	Unclassified	Under Development		0.25	KE:1003	Decreased, Triiodothyronine (T3)
AOP:365		Unclassified	Under Development		0.25	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:372	Androgen receptor antagonism leading to testicular cancer	Endocrine system disease; Reproductive system disease; Cancer	-		0.2	KE:286	Altered, Transcription of genes by the androgen receptor
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:1790	Increased, Differentiation to Testis
AOP:379	Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation	Cardiovascular system disease	Under Development	Homo sapiens	0.29	KE:1845	Coagulation
AOP:379		Cardiovascular system disease	Under Development	Homo sapiens	0.29	KE:1869	Diminished protective oxidative stress response
AOP:382	Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis	Musculoskeletal system disease; Respiratory system disease	Under Development		0.17	KE:1115	Increase, Reactive oxygen species
AOP:383	Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis	Gastrointestinal system disease	Under Development		0.17	KE:1115	Increase, Reactive oxygen species
AOP:386	Deposition of ionizing energy leading to population decline via inhibition of photosynthesis	Reproductive system disease	-	Lemna minor, Chlamydomonas reinhardtii	0.12	KE:1115	Increase, Reactive oxygen species
AOP:387	Deposition of ionising energy leading to population decline via mitochondrial dysfunction	Reproductive system disease	-	Lemna minor	0.12	KE:1115	Increase, Reactive oxygen species
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: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	-		0.38	KE:870	Increase, Cell Proliferation
						KE:1115	Increase, Reactive oxygen species
						KE:1497	Increased, recruitment of inflammatory cells
AOP:410	GSK3beta inactivation leading to increased mortality via defects in developing inner ear	Unclassified	-	Zebrafish	0.1	KE:1825	Increase, Cell death
AOP:413	Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure	Unclassified	-	Fish, Mice	0.33	KE:1607	Increase, Necrosis
AOP:413		Unclassified	-	Fish, Mice	0.33	KE:1115	Increase, Reactive oxygen species
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: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:445	Estrogen Receptor Alpha Agonism leads to Impaired Reproduction	Reproductive system disease	-		0.12	KE:1989	Impaired, Oocyte maturation and ovulation
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:460	Antagonism of Smoothened receptor leading to orofacial clefting	Unclassified	Under Development	Mouse	0.33	KE:1821	Decrease, Cell proliferation
						KE:2040	Decrease, GLI1/2 target gene expression
						KE:1262	Apoptosis
AOP:465	Alcohol dehydrogenase leading to reproductive dysfunction	Unclassified	-		0.12	KE:2050	Increase, developmental abnormalities
AOP:467	Knickkopf leading to mortality	Unclassified	-		0.11	KE:2050	Increase, developmental abnormalities
AOP: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:2084	Increase, Cardiac remodelling
AOP:479		Cardiovascular system disease; Thoracic disease	Under Development		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	0.57	KE:1392	Oxidative Stress
						KE:1825	Increase, Cell death
						KE:2245	Altered Cell Differentiation Signaling
						KE:2089	Altered Bone Cell Homeostasis
AOP:495	Androgen receptor activation leading to prostate cancer	Reproductive system disease; Cancer	-		0.33	KE:854	Alterations, Cellular proliferation / hyperplasia
						KE:286	Altered, Transcription of genes by the androgen receptor
						KE:1183	Decreased, Apoptosis (Epithelial Cells)
AOP:496	Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）	Unclassified	-	Zebrafish	0.3	KE:286	Altered, Transcription of genes by the androgen receptor
						KE:219	Reduction, Plasma 17beta-estradiol concentrations
						KE:1690	Decrease, circulating testosterone levels
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: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	-		0.29	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	0.1	KE:1392	Oxidative Stress
AOP:517	Pregnane X Receptor (PXR) activation leads to liver steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-	Vertebrates	0.2	KE:54	Up Regulation, CD36
AOP:524	Gluten-driven immune activation leading to celiac disease in genetically predisposed individuals	Immune system disease; Gastrointestinal system disease	-	Human	0.11	KE:2255	Innate immune response, activation
AOP:529	Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-	Vertebrates, Mouse, Rat, Zebrafish	0.12	KE:2224	Dysregulation of transcriptional expression within PPAR signaling network
AOP:536	Estrogen receptor agonism leading to reduced survival and population growth due to renal failure	Unclassified	-		0.17	KE:307	Increase, Vitellogenin synthesis in liver
AOP:537	Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liver	Unclassified	-		0.2	KE:307	Increase, Vitellogenin synthesis in liver
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:561	Aromatase induction leading to estrogen receptor alpha activation via increased estradiol	Unclassified	-	Vertebrates	0.6	KE:2294	Plasma estradiol, increased
						KE:1076	Increased, circulating estrogen levels
						KE:2251	Estradiol availability, increased
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: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: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:12	Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging	Nervous system disease; Developmental disorder of mental health	WPHA/WNT Endorsed	Monkey, Rat, Human, Mouse, Zebrafish	0.25	KE:381	Reduced levels of BDNF
AOP:12			WPHA/WNT Endorsed	Monkey, Rat, Human, Mouse, Zebrafish	0.25	KE:341	Impairment, Learning and memory
AOP:13	Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities	Developmental disorder of mental health	WPHA/WNT Endorsed	Human, Mouse, Monkey sp., Rat	0.2	KE:381	Reduced levels of BDNF
AOP:13		Developmental disorder of mental health	WPHA/WNT Endorsed	Human, Mouse, Monkey sp., Rat	0.2	KE:341	Impairment, Learning and memory
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	0.2	KE:1392	Oxidative Stress
AOP:17		Developmental disorder of mental health	WPHA/WNT Endorsed	Rat, Mouse, Human	0.2	KE:341	Impairment, Learning and memory
AOP:18	PPARα activation in utero leading to impaired fertility in males	Reproductive system disease	Under Review	Human, Rat, Mouse	0.5	KE:289	Decrease, Translocator protein (TSPO)
						KE:413	Reduction, Testosterone synthesis in Leydig cells
						KE:1690	Decrease, circulating testosterone levels
						KE:406	decreased, Fertility
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:337	N/A, Impairment of reproductive capacity
AOP:28	Cyclooxygenase inhibition leading reproductive failure	Reproductive system disease	-		0.17	KE:253	N/A, Reproductive failure
AOP:34	LXR activation leading to hepatic steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-		0.23	KE:54	Up Regulation, CD36
						KE:345	N/A, Liver Steatosis
						KE:258	Activation, SCD-1
AOP:42	Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	WPHA/WNT Endorsed	Human, Rat, Mouse	0.38	KE:756	Hippocampal gene expression, Altered
						KE:402	Cognitive function, decreased
						KE:281	Thyroxine (T4) in serum, Decreased
AOP:43	Disruption of VEGFR Signaling Leading to Developmental Defects	Unclassified	WPHA/WNT Endorsed	Mouse, Zebrafish, Rats, Human	0.2	KE:1001	Increased, Developmental Defects
AOP:48	Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.	Developmental disorder of mental health	WPHA/WNT Endorsed	Human, Mouse, Rat	0.11	KE:341	Impairment, Learning and memory
AOP:54	Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment	Developmental disorder of mental health	WPHA/WNT Endorsed	Homo sapiens, Rattus sp.	0.3	KE:381	Reduced levels of BDNF
						KE:281	Thyroxine (T4) in serum, Decreased
						KE:341	Impairment, Learning and memory
AOP:63	Cyclooxygenase inhibition leading to reproductive dysfunction	Reproductive system disease	-	Goldfish, Human, Mouse, Rat	0.4	KE:675	Reduced, Reproductive Success
AOP:63		Reproductive system disease	-	Goldfish, Human, Mouse, Rat	0.4	KE:488	Decrease, Ovulation
AOP:64	Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility	Reproductive system disease	-	Rattus norvegicus	0.71	KE:413	Reduction, Testosterone synthesis in Leydig cells
						KE:1690	Decrease, circulating testosterone levels
						KE:406	decreased, Fertility
						KE:520	Decreased sperm quantity or quality in the adult, Decreased fertility
						KE:496	Increased apoptosis, decreased fetal/adult Leydig Cells
AOP:91	Sodium channel inhibition leading to reduced survival	Unclassified	-	Medaka, Gammarus pulex, Hydra	0.17	KE:592	Reduced, survival
AOP:95	Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survival	Unclassified	-		0.17	KE:592	Reduced, survival
AOP:99	Histamine (H2) receptor antagonism leading to reduced survival	Unclassified	-	Zebrafish	0.29	KE:636	Decreased, survival
AOP:99		Unclassified	-	Zebrafish	0.29	KE:341	Impairment, Learning and memory
AOP:100	Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior	Reproductive system disease	-	Goldfish	0.29	KE:675	Reduced, Reproductive Success
AOP:100		Reproductive system disease	-	Goldfish	0.29	KE:672	Reduced, Prostaglandin F2alpha synthesis, ovary
AOP:101	Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release	Reproductive system disease	-	Goldfish	0.29	KE:675	Reduced, Reproductive Success
AOP:101		Reproductive system disease	-	Goldfish	0.29	KE:681	Decreased, Prostaglandin F2alpha synthesis, ovary
AOP:102	Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition	Reproductive system disease	-	Goldfish, Human, Rat, Mouse	0.2	KE:690	Reduced, Luteinizing hormone (LH), plasma
AOP:102		Reproductive system disease	-	Goldfish, Human, Rat, Mouse	0.2	KE:675	Reduced, Reproductive Success
AOP:103	Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint	Reproductive system disease	-	Goldfish, Human, Rat, Mouse	0.2	KE:690	Reduced, Luteinizing hormone (LH), plasma
AOP:103		Reproductive system disease	-	Goldfish, Human, Rat, Mouse	0.2	KE:675	Reduced, Reproductive Success
AOP:124	HMG-CoA reductase inhibition leading to decreased fertility	Reproductive system disease	-	Rattus rattus	0.5	KE:807	Decreased, cholesterol
						KE:1690	Decrease, circulating testosterone levels
						KE:330	Decrease, Fertility
AOP:134	Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Rat, Homo sapiens	0.33	KE:756	Hippocampal gene expression, Altered
						KE:402	Cognitive function, decreased
						KE:281	Thyroxine (T4) in serum, Decreased
AOP:139	Alkylation of DNA leading to cancer 1	Cancer	-	Homo sapiens, Mus musculus	0.25	KE:885	Increase, Cancer
AOP:148	EGFR Activation Leading to Decreased Lung Function	Respiratory system disease	Under Development	Human, Mouse, Rat	0.5	KE:1250	Decrease, Lung function
AOP:148	EGFR Activation Leading to Decreased Lung Function	Respiratory system disease	Under Development	Human, Mouse, Rat	0.5	KE:962	Increase, Mucin production
AOP:149	Peptide Oxidation Leading to Hypertension	Cardiovascular system disease	Under Development	Human, Mouse, Rat, Cow	0.2	KE:952	Hypertension
AOP:149	Peptide Oxidation Leading to Hypertension	Cardiovascular system disease	Under Development	Human, Mouse, Rat, Cow	0.2	KE:937	KE7 : Impaired, Vasodilation
AOP:196	Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation	Respiratory system disease	-		0.11	KE:1226	Increased Respiratory irritability and Chronic Cough,
AOP:203	5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline	Reproductive system disease	-		0.25	KE:626	Increased, serotonin (5-HT)
AOP:203		Reproductive system disease	-		0.25	KE:1141	Decreased, Reproductive Success
AOP:204	5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase	Unclassified	-		0.25	KE:626	Increased, serotonin (5-HT)
AOP:204		Unclassified	-		0.25	KE:1163	Increased, Reproductive Success
AOP:205	AOP from chemical insult to cell death	Unclassified	-	Vertebrates	0.33	KE:1263	Necrosis
AOP:205	AOP from chemical insult to cell death	Unclassified	-	Vertebrates	0.33	KE:1262	Apoptosis
AOP:212	Histone deacetylase inhibition leading to testicular atrophy	Reproductive system disease	WPHA/WNT Endorsed	Rat, Human, Mouse	0.33	KE:1506	Testicular atrophy
AOP:212		Reproductive system disease	WPHA/WNT Endorsed	Rat, Human, Mouse	0.33	KE:1262	Apoptosis
AOP:220	Cyp2E1 Activation Leading to Liver Cancer	Cancer; Gastrointestinal system disease	WPHA/WNT Endorsed	Rodents, Homo sapiens	0.8	KE:1395	Liver Cancer
						KE:1393	Hepatocytotoxicity
						KE:1392	Oxidative Stress
						KE:1394	Induction, persistent proliferation/sustained proliferation
AOP:237	Substance interaction with lung resident cell membrane components leading to atherosclerosis	Cardiovascular system disease	Under Development	Human, Mouse	0.2	KE:1443	Atherosclerosis
AOP:242	Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity	Unclassified	-	Fish	0.12	KE:636	Decreased, survival
AOP:245	Reduction in photophosphorylation leading to growth inhibition in aquatic plants	Unclassified	-	Lemna minor, Lemna gibba	0.09	KE:1521	Decrease, Growth
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:1535	Heart failure
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:272	Deposition of energy leading to lung cancer	Cancer	WPHA/WNT Endorsed	Human, Rat, Mouse	0.29	KE:870	Increase, Cell Proliferation
AOP:272	Deposition of energy leading to lung cancer	Cancer	WPHA/WNT Endorsed	Human, Rat, Mouse	0.29	KE:1556	Increase, lung cancer
AOP:274	Histone deacetylase inhibition leads to impeded craniofacial development	Musculoskeletal system disease	-		0.25	KE:1559	Facial cartilage structures are reduced in size and morphologically distorted
AOP:278	IKK complex inhibition leading to liver injury	Unclassified	-		0.12	KE:1549	Liver Injury
AOP:286	Mitochondrial complex III antagonism leading to growth inhibition (1)	Unclassified	-	Lemna minor, Daphnia magna, Danio rerio	0.5	KE:1821	Decrease, Cell proliferation
AOP:286		Unclassified	-	Lemna minor, Daphnia magna, Danio rerio	0.5	KE:1521	Decrease, Growth
AOP:287	Mitochondrial complex III antagonism leading to growth inhibition (2)	Unclassified	-	Lemna minor, Daphnia magna, Danio rerio	0.5	KE:1825	Increase, Cell death
AOP:287		Unclassified	-	Lemna minor, Daphnia magna, Danio rerio	0.5	KE:1521	Decrease, Growth
AOP:290	Mitochondrial ATP synthase antagonism leading to growth inhibition (1)	Unclassified	-	Daphnia magna	0.5	KE:1821	Decrease, Cell proliferation
AOP:290		Unclassified	-	Daphnia magna	0.5	KE:1521	Decrease, Growth
AOP:291	Mitochondrial ATP synthase antagonism leading to growth inhibition (2)	Unclassified	-	Daphnia magna	0.5	KE:1825	Increase, Cell death
AOP:291		Unclassified	-	Daphnia magna	0.5	KE:1521	Decrease, Growth
AOP:293	Increased DNA damage leading to increased risk of breast cancer	Genetic disease; Thoracic disease; Cancer	Under Development	Rattus rattus, Mus musculus	0.22	KE:1193	N/A, Breast Cancer
AOP:293		Genetic disease; Thoracic disease; Cancer	Under Development	Rattus rattus, Mus musculus	0.22	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		0.22	KE:1193	N/A, Breast Cancer
AOP:294		Genetic disease; Thoracic disease; Cancer	Under Development		0.22	KE:1182	Increase, Cell Proliferation (Epithelial Cells)
AOP:300	Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	Under Development	Human, Mouse	0.4	KE:402	Cognitive function, decreased
AOP:300		Cognitive disorder	Under Development	Human, Mouse	0.4	KE:756	Hippocampal gene expression, Altered
AOP:302	Lung surfactant function inhibition leading to decreased lung function	Respiratory system disease	Under Development	Human, Mouse, Rat	0.2	KE:1250	Decrease, Lung function
AOP:303	Frustrated phagocytosis-induced lung cancer	Cancer	Under Development	Mammals	0.57	KE:1497	Increased, recruitment of inflammatory cells
						KE:870	Increase, Cell Proliferation
						KE:1115	Increase, Reactive oxygen species
						KE:1670	Lung cancer
AOP:304	TBX1 inhibition leading to congenital cardiac conotruncal anomalies	Cardiovascular system disease	-		0.17	KE:1685	Anomalies, Congenital cardiac conotruncal
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:323	PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone	Unclassified	-	Teleost fish	0.5	KE:807	Decreased, cholesterol
						KE:1758	Impaired, Spermatogenesis
						KE:2147	Decreased, Viable Offspring
AOP:345	Androgen receptor (AR) antagonism leading to decreased fertility in females	Endocrine system disease; Reproductive system disease; Reproductive system disease	Under Development	Mammals	0.33	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:345			Under Development	Mammals	0.33	KE:406	decreased, Fertility
AOP:384	Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease	Urinary system disease	-		0.33	KE:1603	Chronic kidney disease
AOP:384		Urinary system disease	-		0.33	KE:1115	Increase, Reactive oxygen species
AOP:394	SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)	Endocrine system disease	Under Development		0.14	KE:1873	impaired olfactory function (anosmia)
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	0.17	KE:406	decreased, Fertility
AOP:405	Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function	Cognitive disorder	-	Rattus norvegicus, Mus musculus, Homo sapiens	0.2	KE:402	Cognitive function, decreased
AOP:406	SARS-CoV-2 infection leading to hyperinflammation	Unclassified	-		0.33	KE:1869	Diminished protective oxidative stress response
AOP:406	SARS-CoV-2 infection leading to hyperinflammation	Unclassified	-		0.33	KE:1868	Hyperinflammation
AOP:431	Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)	Inherited metabolic disorder	-	Human	0.4	KE:1953	Gestational diabetes mellitus
AOP:431		Inherited metabolic disorder	-	Human	0.4	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	0.27	KE:1955	Acute Myeloid Leukemia
						KE:870	Increase, Cell Proliferation
						KE:403	Suppression, Immune system
AOP:442	Binding to voltage gate sodium channels during development leads to cognitive impairment	Cognitive disorder	Under Review	Rattus norvegicus, Mouse, Humans	0.14	KE:402	Cognitive function, decreased
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	0.3	KE:1982	metastatic breast cancer
						KE:112	Antagonism, Estrogen receptor
						KE:1554	Increase Chromosomal Aberrations
AOP:451	Interaction with lung resident cell membrane components leads to lung cancer	Cancer	-	Human	0.44	KE:1497	Increased, recruitment of inflammatory cells
						KE:870	Increase, Cell Proliferation
						KE:1115	Increase, Reactive oxygen species
						KE:1670	Lung cancer
AOP:452	Adverse outcome pathway of PM-induced respiratory toxicity	Respiratory system disease	-		0.36	KE:1392	Oxidative Stress
						KE:2008	Chronic obstructive pulmonary disease
						KE:2013	Airway remodeling
						KE:1262	Apoptosis
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:2119	Insulin resistance, increased
						KE:2120	Superoxide generation, increased
						KE:281	Thyroxine (T4) in serum, Decreased
AOP:468	Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)	Unclassified	-		0.38	KE:1868	Hyperinflammation
						KE:1825	Increase, Cell death
						KE:1497	Increased, recruitment of inflammatory cells
AOP:474	Succinate dehydrogenase inactivation leads to cancer by promoting EMT	Cancer	Under Development	Human and other cells in culture	0.2	KE:885	Increase, Cancer
AOP:475	Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons	Developmental disorder of mental health	Under Development	Mouse, Rat, Human, Caenorhabditis elegans	0.12	KE:341	Impairment, Learning and memory
AOP:483	Deposition of Energy Leading to Learning and Memory Impairment	Developmental disorder of mental health	Under Review	Mouse, Rat, Rabbit, Dog, Pigs, Cow, Human	0.38	KE:1392	Oxidative Stress
						KE:2244	Altered Stress Response Signaling
						KE:341	Impairment, Learning and memory
AOP:485	Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognition	Cognitive disorder	-	Human	0.14	KE:402	Cognitive function, decreased
AOP:486	Binding to the extracellular protein laminin leading to decreased cognitive function	Cognitive disorder	-	Human	0.14	KE:402	Cognitive function, decreased
AOP:490	Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms	Developmental disorder of mental health	-		0.18	KE:2121	decreased, Intellectual Quotient
AOP:490		Developmental disorder of mental health	-		0.18	KE:341	Impairment, Learning and memory
AOP:492	Glutathione conjugation leading to reproductive dysfunction via oxidative stress	Reproductive system disease	-	Mammals, Fish	0.4	KE:1115	Increase, Reactive oxygen species
AOP:492		Reproductive system disease	-	Mammals, Fish	0.4	KE:406	decreased, Fertility
AOP:498	Increased LCN2/iron complex leading to neurological disorders	Nervous system disease	-	Homo sapiens	0.5	KE:2150	Neurological disorder
AOP:498		Nervous system disease	-	Homo sapiens	0.5	KE:191	Neuronal dysfunction
AOP:499	Activation of MEK-ERK1/2 leads to deficits in learning and cognition via disrupted neurotransmitter release	Developmental disorder of mental health	-	Rattus norvegicus, Mus musculus, Homo sapiens	0.25	KE:341	Impairment, Learning and memory
AOP:500	Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis	Developmental disorder of mental health	-	Rattus norvegicus, Mus musculus, Homo sapiens	0.43	KE:1115	Increase, Reactive oxygen species
						KE:1262	Apoptosis
						KE:341	Impairment, Learning and memory
AOP:501	Excessive iron accumulation leading to neurological disorders	Nervous system disease	-	Homo sapiens	0.5	KE:1392	Oxidative Stress
AOP:501		Nervous system disease	-	Homo sapiens	0.5	KE:2150	Neurological disorder
AOP:503	Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulation	Reproductive system disease; Cancer	Under Review	Human, Mouse	0.17	KE:2154	Uterine adenocarcinoma (endometrioid adenocarcinoma Type I)
AOP:520	Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory	Developmental disorder of mental health	-	Mouse, Rat, Human	0.4	KE:2204	Altered brain morphology
AOP:520		Developmental disorder of mental health	-	Mouse, Rat, Human	0.4	KE:341	Impairment, Learning and memory
AOP:521	Essential element imbalance leads to reproductive failure via oxidative stress	Unclassified	-	Murinae gen. sp.	0.71	KE:2206	Increased, histomorphological alteration of testis
						KE:1115	Increase, Reactive oxygen species
						KE:1392	Oxidative Stress
						KE:1758	Impaired, Spermatogenesis
						KE:2147	Decreased, Viable Offspring
AOP:533	Retinoic acid receptor antagonism during neurodevelopment leading to impaired learning and memory	Developmental disorder of mental health	-		0.33	KE:1239	Altered, Gene Expression
AOP:533		Developmental disorder of mental health	-		0.33	KE:341	Impairment, Learning and memory
AOP:534	Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress	Cancer	-	Vertebrates	0.67	KE:1392	Oxidative Stress
						KE:885	Increase, Cancer
						KE:1115	Increase, Reactive oxygen species
						KE:1446	Decrease, Coupling of oxidative phosphorylation
AOP:535	Binding and activation of GPER leading to learning and memory impairments	Developmental disorder of mental health	-	Mouse, Human	0.44	KE:1392	Oxidative Stress
						KE:2233	Decreased, ERαβ heterodimers
						KE:1262	Apoptosis
						KE:341	Impairment, Learning and memory
AOP:539	Decreased Sodium/Potassium ATPase activity leads to Heart failure	Cardiovascular system disease	-	Fish	0.29	KE:2261	Decreased, blood plasma volume
AOP:539		Cardiovascular system disease	-	Fish	0.29	KE:1535	Heart failure
AOP:546	Succinate dehydrogenase inactivation leads to cancer through hypoxic-like mechanisms	Cancer	-	Human and other cells in culture	0.2	KE:885	Increase, Cancer
AOP:550	Increased LMNA gene mutation leading to heart failure	Cardiovascular system disease	-	Human, Mouse, Rat	0.4	KE:2066	Altered Signaling Pathways
AOP:550	Increased LMNA gene mutation leading to heart failure	Cardiovascular system disease	-	Human, Mouse, Rat	0.4	KE:1535	Heart failure
AOP:552	Inhibiton of L-Type Calcium Channels leading to heart failure via QT interval prolongation and Torsades de Pointes (TdP)	Cardiovascular system disease	-	Human, Rat, Mouse	0.17	KE:1535	Heart failure
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:1535	Heart failure
AOP:555	Inhibition, Ether-a-go-go (ERG) Voltage-Gated Potassium Channel leading to heart failure	Cardiovascular system disease	-	Human and other cells in culture, Dogs, Rat, Guinea pig, Rabbits, Zebrafish	0.2	KE:1535	Heart failure
AOP:556	Decreased Na/K ATPase activity leading to heart failure	Cardiovascular system disease	-		0.17	KE:1535	Heart failure
AOP:558	Phosphodiesterase inhibition leading to heart failure	Cardiovascular system disease	-	Human and other cells in culture, Rodents, Dog, Pig, Zebrafish	0.17	KE:1535	Heart failure
AOP:569	Decreased DNA methylation of FAM50B/PTCHD3 leading to IQ loss of children via PI3K-Akt pathway	Developmental disorder of mental health	-		0.33	KE:1115	Increase, Reactive oxygen species
AOP:569		Developmental disorder of mental health	-		0.33	KE:2121	decreased, Intellectual Quotient

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

AOP Identifier	AOP Title	AO Classification	OECD Status	Taxonomic applicability	Coverage Score ⓘ The fraction of KEs within the AOP, that are mapped to the chemical-associated toxicological endpoints.	KE Identifier	KE Name
AOP:30	Estrogen receptor antagonism leading to reproductive dysfunction	Unclassified	Under Review	Zebra danio, Fathead minnow, Medaka	0.33	KE:112	Antagonism, Estrogen receptor
AOP:30		Unclassified	Under Review	Zebra danio, Fathead minnow, Medaka	0.33	KE:285	Reduction, Vitellogenin synthesis in liver
AOP:62	AKT2 activation leading to hepatic steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-		0.25	KE:486	systemic inflammation leading to hepatic steatosis
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	0.4	KE:645	Decreased Cholesterol, Decreased Testosterone Production by Adult Leydig Cells
AOP:69		Reproductive system disease	-	Rattus norvegicus, Homo sapiens	0.4	KE:642	Decreased Cholesterol, Decreased De Novo Biosynthesis of Choleseterol
AOP:118	Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)	Cancer; Gastrointestinal system disease	-	Mus musculus, Rattus norvegicus	0.5	KE:786	Increase, Cytotoxicity (hepatocytes)
AOP:118		Cancer; Gastrointestinal system disease	-	Mus musculus, Rattus norvegicus	0.5	KE:787	Increase, Regenerative cell proliferation (hepatocytes)
AOP: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:151	AhR activation leading to preeclampsia	Cardiovascular system disease	Under Development	Homo sapiens, Mus musculus	0.43	KE:18	Activation, AhR
						KE:1892	increase, placental insufficiency
						KE:948	reduced production, VEGF
AOP:209	Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP	Gastrointestinal system disease	-		0.12	KE:1284	Up Regulation, SREBF2
AOP:282	Adverse outcome pathway on photochemical toxicity initiated by light exposure	Unclassified	Under Review	Human	0.25	KE:1115	Increase, Reactive oxygen species
AOP:298	Increase in reactive oxygen species (ROS) leading to human treatment-resistant gastric cancer via chronic ROS	Cancer; Gastrointestinal system disease	Under Review	Homo sapiens	0.33	KE:1753	Chronic reactive oxygen species
AOP:298		Cancer; Gastrointestinal system disease	Under Review	Homo sapiens	0.33	KE:1115	Increase, Reactive oxygen species
AOP:310	Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR	Unclassified	-	Zebrafish	0.33	KE:18	Activation, AhR
						KE:285	Reduction, Vitellogenin synthesis in liver
						KE:219	Reduction, Plasma 17beta-estradiol concentrations
						KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:327	Excessive reactive oxygen species production leading to mortality (1)	Unclassified	-	Daphnia magna	0.4	KE:1115	Increase, Reactive oxygen species
AOP:327		Unclassified	-	Daphnia magna	0.4	KE:1769	Increase, Body fluid overload
AOP:328	Excessive reactive oxygen species production leading to mortality (2)	Unclassified	-	Daphnia magna	0.2	KE:1115	Increase, Reactive oxygen species
AOP:329	Excessive reactive oxygen species production leading to mortality (3)	Unclassified	-	Daphnia magna, Paracyclopina nana	0.2	KE:1115	Increase, Reactive oxygen species
AOP:330	Excessive reactive oxygen species production leading to mortality (4)	Unclassified	-	Daphnia magna	0.4	KE:1365	Increase, Apoptosis
AOP:330		Unclassified	-	Daphnia magna	0.4	KE:1115	Increase, Reactive oxygen species
AOP:414	Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathway	Musculoskeletal system disease; Respiratory system disease	-		0.4	KE:18	Activation, AhR
AOP:414		Musculoskeletal system disease; Respiratory system disease	-		0.4	KE:1920	Altered gene expression, TGF-β dependent fibrosis pathway
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: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:1115	Increase, Reactive oxygen species
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	0.33	KE:1052	Hyperplasia, ovarian epithelium
						KE:1076	Increased, circulating estrogen levels
						KE:1046	Suppression, Estrogen receptor (ER) activity
AOP:446	PM-related Adverse outcome pathway frameworks on various systems	Respiratory system disease	-		0.45	KE:1115	Increase, Reactive oxygen species
						KE:165	Activation, Long term AHR receptor driven direct and indirect gene expression changes
						KE:1392	Oxidative Stress
						KE:1250	Decrease, Lung function
						KE:18	Activation, AhR
						KE:1239	Altered, Gene Expression
						KE:1497	Increased, recruitment of inflammatory cells
						KE:149	Increase, Inflammation
						KE:1262	Apoptosis
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:1917	Altered gene expression, NRF2 dependent antioxidant pathway
						KE:1365	Increase, Apoptosis
						KE:1633	Increase in inflammation
AOP:448	ROS, inflammation, and activation of nAChR lead to increased incidence of cardiovascular morbidity and mortality	Cardiovascular system disease	-		0.29	KE:2002	Ventricular remodeling
						KE:1115	Increase, Reactive oxygen species
						KE:1392	Oxidative Stress
						KE:2001	Cardiac hypertrophy
						KE:1443	Atherosclerosis
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	-		0.23	KE:1392	Oxidative Stress
						KE:1115	Increase, Reactive oxygen species
						KE:1995	Abnormal lipid metabolism
AOP:464	Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits	Nervous system disease	-		0.16	KE:1392	Oxidative Stress
						KE:1825	Increase, Cell death
						KE:2039	Inhibition GABAA receptor
AOP:469	Reactive oxygen speicies overproduction leading to increased digestive morbidity and mortality in generation population	Gastrointestinal system disease	-		0.23	KE:1392	Oxidative Stress
						KE:1115	Increase, Reactive oxygen species
						KE:1995	Abnormal lipid metabolism
AOP:472	DNA adduct formation leading to kidney failure	Urinary system disease	-		0.44	KE:1392	Oxidative Stress
						KE:1825	Increase, Cell death
						KE:1115	Increase, Reactive oxygen species
						KE:149	Increase, Inflammation
AOP:491	Decrease, GLI1/2 target gene expression leads to orofacial clefting	Unclassified	Under Development	Mouse	0.5	KE:1821	Decrease, Cell proliferation
						KE:2040	Decrease, GLI1/2 target gene expression
						KE:1262	Apoptosis
AOP:494	AhR activation leading to liver fibrosis	Gastrointestinal system disease	-	Mus musculus, Homo sapiens	0.17	KE:18	Activation, AhR
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:1115	Increase, Reactive oxygen species
AOP:540	Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production	Unclassified	-		0.56	KE:1115	Increase, Reactive oxygen species
						KE:1392	Oxidative Stress
						KE:285	Reduction, Vitellogenin synthesis in liver
						KE:1262	Apoptosis
						KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
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:1115	Increase, Reactive oxygen species
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	0.33	KE:18	Activation, AhR
AOP:563		Reproductive system disease; Endocrine system disease	-	Rat, Mouse, Zebra fish, Human	0.33	KE:1262	Apoptosis

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:21	Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2	Unclassified	WPHA/WNT Endorsed	Zebrafish, Medaka, Gallus gallus	0.8	KE:18	Activation, AhR
						KE:317	Altered, Cardiovascular development/function
						KE:1269	Increase, COX-2 expression
						KE:947	Increase, Early Life Stage Mortality
AOP:41	Sustained AhR Activation leading to Rodent Liver Tumours	Cancer; Gastrointestinal system disease	Under Review	Rattus sp. ABTC 42503, Mus sp. 2000082	1.0	KE:165	Activation, Long term AHR receptor driven direct and indirect gene expression changes
						KE:139	N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects
						KE:854	Alterations, Cellular proliferation / hyperplasia
						KE:856	Formation, Hepatocellular and Bile duct tumors
						KE:853	Changes/Inhibition, Cellular Homeostasis and Apoptosis
AOP:112	Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)	Reproductive system disease; Cancer	-	Rattus norvegicus	0.5	KE:746	Increase, Dopaminergic activity
						KE:749	Decreased, Progesterone from corpus luteum
						KE:773	Increase, Endometrial adenocarcinomas
AOP:150	Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF	Unclassified	WPHA/WNT Endorsed	Chicken, Zebrafish, Mouse, Rattus norvegicus	0.57	KE:18	Activation, AhR
						KE:317	Altered, Cardiovascular development/function
						KE:948	reduced production, VEGF
						KE:947	Increase, Early Life Stage Mortality
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	0.75	KE:1821	Decrease, Cell proliferation
						KE:1521	Decrease, Growth
						KE:1446	Decrease, Coupling of oxidative phosphorylation
AOP:264	Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell death	Unclassified	Under Development		0.5	KE:1521	Decrease, Growth
AOP:264		Unclassified	Under Development		0.5	KE:1446	Decrease, Coupling of oxidative phosphorylation
AOP:265	Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calcium	Unclassified	Under Development		0.5	KE:1521	Decrease, Growth
AOP:265		Unclassified	Under Development		0.5	KE:1446	Decrease, Coupling of oxidative phosphorylation
AOP:266	Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity	Unclassified	Under Development		0.33	KE:1521	Decrease, Growth
AOP:266		Unclassified	Under Development		0.33	KE:1446	Decrease, Coupling of oxidative phosphorylation
AOP:267	Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion	Unclassified	Under Development		0.8	KE:1821	Decrease, Cell proliferation
						KE:1521	Decrease, Growth
						KE:1446	Decrease, Coupling of oxidative phosphorylation
						KE:2071	Decrease, Glucose pool
AOP:268	Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swelling	Unclassified	Under Development		0.5	KE:1521	Decrease, Growth
AOP:268		Unclassified	Under Development		0.5	KE:1446	Decrease, Coupling of oxidative phosphorylation
AOP:324	Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and cell death	Unclassified	-	Fish	0.5	KE:1521	Decrease, Growth
AOP:324		Unclassified	-	Fish	0.5	KE:1115	Increase, Reactive oxygen species
AOP:325	Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and cell death	Unclassified	-	Fish	0.5	KE:1521	Decrease, Growth
AOP:325		Unclassified	-	Fish	0.5	KE:1115	Increase, Reactive oxygen species
AOP:326	Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell death	Unclassified	-	Fish	0.5	KE:1521	Decrease, Growth
AOP:326		Unclassified	-	Fish	0.5	KE:1115	Increase, Reactive oxygen species
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	0.5	KE:1821	Decrease, Cell proliferation
						KE:1521	Decrease, Growth
						KE:1115	Increase, Reactive oxygen species
AOP:332	Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferation	Unclassified	-		0.6	KE:1821	Decrease, Cell proliferation
						KE:1521	Decrease, Growth
						KE:1115	Increase, Reactive oxygen species
AOP:333	Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylation	Unclassified	-		0.8	KE:1821	Decrease, Cell proliferation
						KE:1521	Decrease, Growth
						KE:1115	Increase, Reactive oxygen species
						KE:1446	Decrease, Coupling of oxidative phosphorylation
AOP:392	Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation	Unclassified	Under Development	Humans	0.6	KE:1497	Increased, recruitment of inflammatory cells
						KE:1868	Hyperinflammation
						KE:1867	Bradykinin system, hyperactivated
AOP:411	Oxidative stress Leading to Decreased Lung Function	Respiratory system disease	-	Homo sapiens	0.5	KE:1392	Oxidative Stress
AOP:411	Oxidative stress Leading to Decreased Lung Function	Respiratory system disease	-	Homo sapiens	0.5	KE:1250	Decrease, Lung function
AOP:416	Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathway	Cancer	-		0.5	KE:18	Activation, AhR
						KE:1115	Increase, Reactive oxygen species
						KE:1670	Lung cancer
AOP:417	Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathway	Cancer	-		0.6	KE:18	Activation, AhR
						KE:17	Altered gene expression, AHR nuclear translocator (ARNT)-dependent pathway
						KE:1670	Lung cancer
AOP:418	Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathway	Respiratory system disease	-		1.0	KE:1825	Increase, Cell death
						KE:1115	Increase, Reactive oxygen species
						KE:1250	Decrease, Lung function
						KE:18	Activation, AhR
						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	-		0.75	KE:18	Activation, AhR
						KE:1250	Decrease, Lung function
						KE:1262	Apoptosis
AOP:420	Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathway	Cancer	-		1.0	KE:18	Activation, AhR
						KE:1917	Altered gene expression, NRF2 dependent antioxidant pathway
						KE:870	Increase, Cell Proliferation
						KE:1670	Lung cancer
AOP:423	Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway	Unclassified	-		0.33	KE:1817	Apoptotic cell death
AOP:423		Unclassified	-		0.33	KE:1115	Increase, Reactive oxygen species
AOP:424	Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction	Respiratory system disease	-	Human	0.33	KE:1392	Oxidative Stress
AOP:424		Respiratory system disease	-	Human	0.33	KE:1250	Decrease, Lung function
AOP:425	Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1	Respiratory system disease	-	Human	0.33	KE:1392	Oxidative Stress
AOP:425		Respiratory system disease	-	Human	0.33	KE:1250	Decrease, Lung function
AOP:439	Activation of the AhR leading to metastatic breast cancer	Thoracic disease; Cancer	Under Development	Humans, Mice	0.67	KE:18	Activation, AhR
						KE:1971	Increased, tumor growth
						KE:1982	metastatic breast cancer
						KE:149	Increase, Inflammation
						KE:1241	Increased, Motility
						KE:1262	Apoptosis
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	0.83	KE:947	Increase, Early Life Stage Mortality
						KE:18	Activation, AhR
						KE:2020	Decrease, sox9 expression
						KE:1559	Facial cartilage structures are reduced in size and morphologically distorted
						KE:2021	Increase, slincR expression
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	0.83	KE:317	Altered, Cardiovascular development/function
						KE:947	Increase, Early Life Stage Mortality
						KE:18	Activation, AhR
						KE:2020	Decrease, sox9 expression
						KE:2021	Increase, slincR expression
AOP:458	AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Rat, Mouse, Monkey, Human	0.5	KE:18	Activation, AhR
						KE:756	Hippocampal gene expression, Altered
						KE:402	Cognitive function, decreased
						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	0.67	KE:402	Cognitive function, decreased
						KE:281	Thyroxine (T4) in serum, Decreased
						KE:850	Induction, CYP1A2/CYP1A5
						KE:1392	Oxidative Stress
						KE:18	Activation, AhR
						KE:756	Hippocampal gene expression, Altered
AOP:463	The AOP framwork on silica nanopariticles induced hepatoxicity	Gastrointestinal system disease	-		0.45	KE:1115	Increase, Reactive oxygen species
						KE:1392	Oxidative Stress
						KE:2034	liver dysfunction
						KE:149	Increase, Inflammation
						KE:1262	Apoptosis
AOP:488	Increased reactive oxygen species production leading to decreased cognitive function	Cognitive disorder	-	Human	0.57	KE:1392	Oxidative Stress
						KE:1869	Diminished protective oxidative stress response
						KE:1115	Increase, Reactive oxygen species
						KE:402	Cognitive function, decreased
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	0.6	KE:2126	Estrogen receptor alpha inactivation
						KE:1633	Increase in inflammation
						KE:2125	Increased fat mass
						KE:1497	Increased, recruitment of inflammatory cells
						KE:2119	Insulin resistance, increased
						KE:2129	Metabolically unhealthy Obesity
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	-		0.75	KE:2126	Estrogen receptor alpha inactivation
						KE:1115	Increase, Reactive oxygen species
						KE:1392	Oxidative Stress
						KE:2144	Impaired insulin signaling
						KE:2145	Metabolic syndrome
						KE:2119	Insulin resistance, increased
AOP:505	Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway	Cancer	-	Human, Mouse, Rat	1.0	KE:1513	General Apoptosis
						KE:1115	Increase, Reactive oxygen species
						KE:1392	Oxidative Stress
						KE:885	Increase, Cancer
						KE:149	Increase, Inflammation
AOP:513	Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway	Cancer	-	Human, Mouse, Rat	0.8	KE:1513	General Apoptosis
						KE:885	Increase, Cancer
						KE:1115	Increase, Reactive oxygen species
						KE:1060	Alteration, lipid metabolism
AOP:525	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory	Developmental disorder of mental health	-		0.23	KE:2216	Binding of antagonist to thyroid hormone receptor
						KE:2115	Altered, cholesterol metabolism
						KE:341	Impairment, Learning and memory

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.