DEDUCT | Database of Endocrine Disrupting chemicals and their Toxicity profiles

Valproic acid

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	0.1	KE:993	Decrease, Abdominal muscle contraction
AOP:7	Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female	Reproductive system disease; Endocrine system disease; Reproductive system disease	Under Review	Rat, Mouse, Human	0.4	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:7			Under Review	Rat, Mouse, Human	0.4	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:8	Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Nervous system disease	Under Development	Rat	0.11	KE:756	Hippocampal gene expression, Altered
AOP:15	Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutations	Genetic disease	WPHA/WNT Endorsed	Mus musculus, Drosophila melanogaster, Oryzias latipes, Syrian golden hamster	0.25	KE:155	Inadequate DNA repair
AOP:16	Acetylcholinesterase inhibition leading to acute mortality	Unclassified	Under Development		0.14	KE:1703	Dysregulation of heart rate and vascular tone
AOP:18	PPARα activation in utero leading to impaired fertility in males	Reproductive system disease	Under Review	Human, Rat, Mouse	0.12	KE:1690	Decrease, circulating testosterone levels
AOP:19	Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)	Reproductive system disease	-		0.2	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:23	Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)	Unclassified	WPHA/WNT Endorsed	Pimephales promelas	0.2	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:23		Unclassified	WPHA/WNT Endorsed	Pimephales promelas	0.2	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:25	Aromatase inhibition leading to reproductive dysfunction	Unclassified	WPHA/WNT Endorsed	Fathead minnow, Medaka, Zebrafish	0.25	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:25	Aromatase inhibition leading to reproductive dysfunction	Unclassified	WPHA/WNT Endorsed	Fathead minnow, Medaka, Zebrafish	0.25	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP: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:38	Protein Alkylation leading to Liver Fibrosis	Gastrointestinal system disease	WPHA/WNT Endorsed	Human, Rat	0.14	KE:1493	Increased Pro-inflammatory mediators
AOP:39	Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response	Respiratory system disease	Under Development	Human, Mouse	0.4	KE:272	Activation/Proliferation, T-cells
AOP:39		Respiratory system disease	Under Development	Human, Mouse	0.4	KE:1496	Increased, secretion of proinflammatory mediators
AOP:41	Sustained AhR Activation leading to Rodent Liver Tumours	Cancer; Gastrointestinal system disease	Under Review	Rattus sp. ABTC 42503, Mus sp. 2000082	0.6	KE:854	Alterations, Cellular proliferation / hyperplasia
						KE:853	Changes/Inhibition, Cellular Homeostasis and Apoptosis
						KE:139	N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects
AOP:58	NR1I3 (CAR) suppression leading to hepatic steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-	Human, Mouse, Rat	0.06	KE:454	Increased, Triglyceride formation
AOP:60	NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-		0.08	KE:454	Increased, Triglyceride formation
AOP:64	Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility	Reproductive system disease	-	Rattus norvegicus	0.29	KE:496	Increased apoptosis, decreased fetal/adult Leydig Cells
AOP:64		Reproductive system disease	-	Rattus norvegicus	0.29	KE:1690	Decrease, circulating testosterone levels
AOP:77	Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1	Unclassified	-	Honey bee	0.14	KE: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:80	Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure	Unclassified	-	Honey bee	0.12	KE:664	Overwhelmed, Mitochondrial DNA repair mechanisms
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:96	Axonal sodium channel modulation leading to acute mortality	Unclassified	-	Insects, Fish	0.33	KE:602	Increased, Ataxia, paralysis, or hyperactivity
AOP:96	Axonal sodium channel modulation leading to acute mortality	Unclassified	-	Insects, Fish	0.33	KE:601	Overactivation, muscle contraction
AOP:105	Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)	Cancer; Urinary system disease	-	Rattus norvegicus	0.33	KE:767	Increase, Hyperplasia (renal tubular cells)
AOP:105		Cancer; Urinary system disease	-	Rattus norvegicus	0.33	KE:710	Increase, Regenerative cell proliferation (tubular epithelial cells)
AOP:106	Chemical binding to tubulin in oocytes leading to aneuploid offspring	Chromosomal disease	Under Review	Mus musculus, Homo sapiens, Hamster	0.17	KE:721	Disorganization, Meiotic Spindle
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	0.14	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:749	Decreased, Progesterone from corpus luteum
AOP:113	Glutamate-gated chloride channel activation leading to acute mortality	Unclassified	-	Bombus impatiens, Chaetanaphothrips orchidii, Radopholus similis, Daphnia magna, Orius insidiosus, Hymenoptera, Helicoverpa zea, Lepidoptera, Liriomyza trifolii, Orius isidiosus, Acyrthosiphon kondoi	0.17	KE:764	N/A, Ataxia, paralysis, or hyperactivity
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	0.14	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	0.2	KE:1690	Decrease, circulating testosterone levels
AOP:122	Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation	Unclassified	-	Pimephales promelas	0.2	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:122		Unclassified	-	Pimephales promelas	0.2	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:123	Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription	Unclassified	-	Pimephales promelas	0.18	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:123		Unclassified	-	Pimephales promelas	0.18	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:124	HMG-CoA reductase inhibition leading to decreased fertility	Reproductive system disease	-	Rattus rattus	0.33	KE:807	Decreased, cholesterol
AOP:124	HMG-CoA reductase inhibition leading to decreased fertility	Reproductive system disease	-	Rattus rattus	0.33	KE:1690	Decrease, circulating testosterone levels
AOP:128	Kidney dysfunction by decreased thyroid hormone	Urinary system disease	Under Development	Sprague-Dawley, Homo sapiens	0.09	KE:825	Decreased, Renal ability to dilute urine
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:144	Endocytic lysosomal uptake leading to liver fibrosis	Gastrointestinal system disease	Under Review	Human, Mouse, Rat	0.11	KE:1493	Increased Pro-inflammatory mediators
AOP:149	Peptide Oxidation Leading to Hypertension	Cardiovascular system disease	Under Development	Human, Mouse, Rat, Cow	0.1	KE:933	KE6 : Depletion, Nitric Oxide
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	0.33	KE:1043	Hypertrophy/hyperplasia, smooth muscle
AOP:164		Cancer; Reproductive system disease	-	CD-1 mouse, SD rat	0.33	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: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	0.25	KE:1497	Increased, recruitment of inflammatory cells
AOP:173		Musculoskeletal system disease; Respiratory system disease	WPHA/WNT Endorsed	Human, Mouse, Rat	0.25	KE:1496	Increased, secretion of proinflammatory mediators
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	0.38	KE:1115	Increase, Reactive oxygen species
						KE:1281	Increased, DNA Damage-Repair
						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:219	Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior	Unclassified	-	Japanese quail, Cynops pyrrhogaster	0.17	KE:1390	Sexual behavior, decreased
AOP:227	NSAID induced PTGS1 inactivation to gastric ulcer	Gastrointestinal system disease	-		0.14	KE:1403	Reduced, platelet aggregation
AOP:237	Substance interaction with lung resident cell membrane components leading to atherosclerosis	Cardiovascular system disease	Under Development	Human, Mouse	0.2	KE:1496	Increased, secretion of proinflammatory mediators
AOP:258	Renal protein alkylation leading to kidney toxicity	Urinary system disease	Under Development	Human, Rat, Mouse	0.2	KE:40	Decrease, Mitochondrial ATP production
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:272	Deposition of energy leading to lung cancer	Cancer	WPHA/WNT Endorsed	Human, Rat, Mouse	0.29	KE:155	Inadequate DNA repair
AOP:272	Deposition of energy leading to lung cancer	Cancer	WPHA/WNT Endorsed	Human, Rat, Mouse	0.29	KE:870	Increase, Cell Proliferation
AOP:276	Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndrome	Urinary system disease	-		0.17	KE:887	Inhibition, NADH-ubiquinone oxidoreductase (complex I)
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: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:1493	Increased Pro-inflammatory mediators
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:1493	Increased Pro-inflammatory mediators
AOP:294		Genetic disease; Thoracic disease; Cancer	Under Development		0.22	KE:1182	Increase, Cell Proliferation (Epithelial Cells)
AOP:296	Oxidative DNA damage leading to chromosomal aberrations and mutations	Genetic disease; Chromosomal disease	WPHA/WNT Endorsed	Human, Mice, Rat, Fish	0.2	KE:155	Inadequate DNA repair
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:303	Frustrated phagocytosis-induced lung cancer	Cancer	Under Development	Mammals	0.43	KE:870	Increase, Cell Proliferation
						KE:1115	Increase, Reactive oxygen species
						KE:1497	Increased, recruitment of inflammatory cells
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	0.29	KE:1693	Reduction, Plasma progesterone concentration
AOP:309		Unclassified	-	Fish	0.29	KE:1692	Reduction, Progesterone synthesis
AOP:310	Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR	Unclassified	-	Zebrafish	0.17	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:310		Unclassified	-	Zebrafish	0.17	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP: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:1496	Increased, secretion of proinflammatory mediators
AOP:321	Reduced environmental pH leading to thinner shells in Mytilus edulis	Unclassified	-		0.18	KE:592	Reduced, survival
AOP:321		Unclassified	-		0.18	KE:10042	Abnormal development
AOP:322	Alkylation of DNA leading to reduced sperm count	Reproductive system disease	-		0.2	KE:155	Inadequate DNA repair
AOP:323	PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone	Unclassified	-	Teleost fish	0.17	KE:807	Decreased, cholesterol
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: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:345	Androgen receptor (AR) antagonism leading to decreased fertility in females	Endocrine system disease; Reproductive system disease; Reproductive system disease	Under Development	Mammals	0.17	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	0.2	KE:1789	Reduction, 17beta-estradiol synthesis by the undifferentiated gonad
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:374	Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on brain cells (neuronal and non-neuronal) leads to neuroinflammation resulting in encephalitis	Nervous system disease	Under Development	Human	0.25	KE:352	N/A, Neurodegeneration
AOP:382	Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis	Musculoskeletal system disease; Respiratory system disease	Under Development		0.33	KE:1115	Increase, Reactive oxygen species
AOP:382		Musculoskeletal system disease; Respiratory system disease	Under Development		0.33	KE:1496	Increased, secretion of proinflammatory mediators
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	0.25	KE:1115	Increase, Reactive oxygen species
AOP:387		Reproductive system disease	-	Lemna minor	0.25	KE:40	Decrease, Mitochondrial ATP production
AOP:397	Bulky DNA adducts leading to mutations	Genetic disease	Under Development		0.33	KE:155	Inadequate DNA repair
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	-		0.5	KE:1497	Increased, recruitment of inflammatory cells
						KE:870	Increase, Cell Proliferation
						KE:1115	Increase, Reactive oxygen species
						KE:1496	Increased, secretion of proinflammatory mediators
AOP:410	GSK3beta inactivation leading to increased mortality via defects in developing inner ear	Unclassified	-	Zebrafish	0.1	KE:1008	Reduced, Hearing
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:414	Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathway	Musculoskeletal system disease; Respiratory system disease	-		0.2	KE:1920	Altered gene expression, TGF-β dependent fibrosis pathway
AOP:416	Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathway	Cancer	-		0.17	KE:1115	Increase, Reactive oxygen species
AOP:420	Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathway	Cancer	-		0.25	KE:870	Increase, Cell Proliferation
AOP:432	Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia	Hematopoietic system disease; Cancer	-	Homo sapiens, Mus musculus	0.27	KE:1493	Increased Pro-inflammatory mediators
						KE:155	Inadequate DNA repair
						KE:870	Increase, Cell Proliferation
AOP:436	Inhibition of RALDH2 causes reduced all-trans retinoic acid levels, leading to transposition of the great arteries	Cardiovascular system disease	-	Chicken, Mouse, Vertebrates	0.2	KE:1557	Neural crest cell migration, reduced
AOP:439	Activation of the AhR leading to metastatic breast cancer	Thoracic disease; Cancer	Under Development	Humans, Mice	0.44	KE:1971	Increased, tumor growth
						KE:149	Increase, Inflammation
						KE:1241	Increased, Motility
						KE:1262	Apoptosis
AOP:441	Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation	Congenital nervous system abnormality; Nervous system disease	-	Homo sapiens, Mus musculus musculus, Rattus norvegicus	0.14	KE:1262	Apoptosis
AOP:443	DNA damage and mutations leading to Metastatic Breast Cancer	Thoracic disease; Cancer	Under Development	Human and other cells in culture, Human, Mice, Rat, Canine heartworm nematode, Yeast	0.1	KE:155	Inadequate DNA repair
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:1097	Occurrence, renal proximal tubular necrosis
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:352	N/A, Neurodegeneration
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:1496	Increased, secretion of proinflammatory mediators
AOP:452	Adverse outcome pathway of PM-induced respiratory toxicity	Respiratory system disease	-		0.09	KE:1262	Apoptosis
AOP:460	Antagonism of Smoothened receptor leading to orofacial clefting	Unclassified	Under Development	Mouse	0.22	KE:1821	Decrease, Cell proliferation
AOP:460		Unclassified	Under Development	Mouse	0.22	KE:1262	Apoptosis
AOP:465	Alcohol dehydrogenase leading to reproductive dysfunction	Unclassified	-		0.12	KE:2050	Increase, developmental abnormalities
AOP:467	Knickkopf leading to mortality	Unclassified	-		0.11	KE:2050	Increase, developmental abnormalities
AOP:470	Deposition of energy leads to abnormal vascular remodeling	Cardiovascular system disease	Under Review	Human, Rat, Mouse, Rabbit	0.12	KE:1493	Increased Pro-inflammatory mediators
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:155	Inadequate DNA repair
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:480	Mitochondrial complexes inhibition leading to heart failure via decreased ATP production	Cardiovascular system disease; Thoracic disease	Under Development		0.2	KE:40	Decrease, Mitochondrial ATP production
AOP:482	Deposition of energy leading to occurrence of bone loss	Musculoskeletal system disease	Under Review	Human, Mouse, Rat, Rhesus monkeys	0.29	KE:2245	Altered Cell Differentiation Signaling
AOP:482	Deposition of energy leading to occurrence of bone loss	Musculoskeletal system disease	Under Review	Human, Mouse, Rat, Rhesus monkeys	0.29	KE:2089	Altered Bone Cell Homeostasis
AOP:491	Decrease, GLI1/2 target gene expression leads to orofacial clefting	Unclassified	Under Development	Mouse	0.33	KE:1821	Decrease, Cell proliferation
AOP:491		Unclassified	Under Development	Mouse	0.33	KE:1262	Apoptosis
AOP:492	Glutathione conjugation leading to reproductive dysfunction via oxidative stress	Reproductive system disease	-	Mammals, Fish	0.2	KE:1115	Increase, Reactive oxygen species
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:521	Essential element imbalance leads to reproductive failure via oxidative stress	Unclassified	-	Murinae gen. sp.	0.14	KE:1115	Increase, Reactive oxygen species
AOP:539	Decreased Sodium/Potassium ATPase activity leads to Heart failure	Cardiovascular system disease	-	Fish	0.29	KE:2237	Decreased, Plasma sodium concentrations
AOP:539		Cardiovascular system disease	-	Fish	0.29	KE:2261	Decreased, blood plasma volume
AOP:544	Inhibition of neuropathy target esterase leading to delayed neuropathy via increased inflammation	Nervous system disease	-	Homo sapiens, Mus musculus	0.17	KE:149	Increase, Inflammation
AOP:549	Aromatase inhibition leads to reproductive toxicity (including growth and developmental toxicity) in adult female zebrafish	Unclassified	-		0.12	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:563	Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosis	Reproductive system disease; Endocrine system disease	-	Rat, Mouse, Zebra fish, Human	0.17	KE:1262	Apoptosis
AOP:564	DBDPE-induced inhibition of mitochondrial complex Ⅰ leading to population decline via neurotoxicity and metabotoxicity.	Unclassified	-	Zebrafish	0.18	KE:2301	Abnormal, Behavior
AOP:564		Unclassified	-	Zebrafish	0.18	KE:40	Decrease, Mitochondrial ATP production
AOP:569	Decreased DNA methylation of FAM50B/PTCHD3 leading to IQ loss of children via PI3K-Akt pathway	Developmental disorder of mental health	-		0.17	KE:1115	Increase, Reactive oxygen species

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:3	Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits	Nervous system disease	WPHA/WNT Endorsed	Human, Rat	0.29	KE:896	Parkinsonian motor deficits
AOP:3		Nervous system disease	WPHA/WNT Endorsed	Human, Rat	0.29	KE:887	Inhibition, NADH-ubiquinone oxidoreductase (complex I)
AOP:6	Antagonist binding to PPARα leading to body-weight loss	Symptom	WPHA/WNT Endorsed	Mus musculus, Homo sapiens, Pimephales promelas, Colinus virginianus, Rattus norvegicus	0.12	KE:864	Decreased, Body Weight
AOP:12	Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging	Nervous system disease; Developmental disorder of mental health	WPHA/WNT Endorsed	Monkey, Rat, Human, Mouse, Zebrafish	0.25	KE:352	N/A, Neurodegeneration
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	0.1	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:1493	Increased Pro-inflammatory mediators
AOP:17		Developmental disorder of mental health	WPHA/WNT Endorsed	Rat, Mouse, Human	0.2	KE:341	Impairment, Learning and memory
AOP:21	Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2	Unclassified	WPHA/WNT Endorsed	Zebrafish, Medaka, Gallus gallus	0.4	KE:317	Altered, Cardiovascular development/function
AOP:21		Unclassified	WPHA/WNT Endorsed	Zebrafish, Medaka, Gallus gallus	0.4	KE:947	Increase, Early Life Stage Mortality
AOP:34	LXR activation leading to hepatic steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-		0.08	KE:345	N/A, Liver Steatosis
AOP:40	Covalent Protein binding leading to Skin Sensitisation	Integumentary system disease	WPHA/WNT Endorsed	Mouse, Human	0.6	KE:827	sensitisation, skin
						KE:272	Activation/Proliferation, T-cells
						KE:826	Activation, Keratinocytes
AOP:42	Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	WPHA/WNT Endorsed	Human, Rat, Mouse	0.25	KE:402	Cognitive function, decreased
AOP:42		Cognitive disorder	WPHA/WNT Endorsed	Human, Rat, Mouse	0.25	KE:756	Hippocampal gene expression, Altered
AOP:43	Disruption of VEGFR Signaling Leading to Developmental Defects	Unclassified	WPHA/WNT Endorsed	Mouse, Zebrafish, Rats, Human	0.4	KE:1001	Increased, Developmental Defects
AOP:43		Unclassified	WPHA/WNT Endorsed	Mouse, Zebrafish, Rats, Human	0.4	KE:28	Reduction, Angiogenesis
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	0.22	KE:352	N/A, Neurodegeneration
AOP:48		Developmental disorder of mental health	WPHA/WNT Endorsed	Human, Mouse, Rat	0.22	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.	0.1	KE:341	Impairment, Learning and memory
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:134	Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Rat, Homo sapiens	0.22	KE:402	Cognitive function, decreased
AOP:134		Cognitive disorder	-	Rat, Homo sapiens	0.22	KE:756	Hippocampal gene expression, Altered
AOP:139	Alkylation of DNA leading to cancer 1	Cancer	-	Homo sapiens, Mus musculus	0.5	KE:885	Increase, Cancer
AOP:139	Alkylation of DNA leading to cancer 1	Cancer	-	Homo sapiens, Mus musculus	0.5	KE:155	Inadequate DNA repair
AOP:148	EGFR Activation Leading to Decreased Lung Function	Respiratory system disease	Under Development	Human, Mouse, Rat	0.25	KE:1250	Decrease, Lung function
AOP:150	Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF	Unclassified	WPHA/WNT Endorsed	Chicken, Zebrafish, Mouse, Rattus norvegicus	0.29	KE:317	Altered, Cardiovascular development/function
AOP:150		Unclassified	WPHA/WNT Endorsed	Chicken, Zebrafish, Mouse, Rattus norvegicus	0.29	KE:947	Increase, Early Life Stage Mortality
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: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:220	Cyp2E1 Activation Leading to Liver Cancer	Cancer; Gastrointestinal system disease	WPHA/WNT Endorsed	Rodents, Homo sapiens	0.6	KE:1395	Liver Cancer
						KE:1393	Hepatocytotoxicity
						KE:1394	Induction, persistent proliferation/sustained proliferation
AOP: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	0.18	KE:1521	Decrease, Growth
AOP:245		Unclassified	-	Lemna minor, Lemna gibba	0.18	KE:40	Decrease, Mitochondrial ATP production
AOP:260	CYP2E1 activation and formation of protein adducts leading to neurodegeneration	Nervous system disease	-	Human	0.14	KE:1514	Neurodegeneration
AOP:269	Elevated ATP demand for detoxification and repair mechanisms leading to impaired growth and development	Unclassified	-		0.17	KE:10013	Impaired growth and development
AOP:270	Elevated ATP demand for detoxification and repair mechanisms leading to impaired locomotor activity	Unclassified	-		0.12	KE:10016	Impaired locomotor activity
AOP:278	IKK complex inhibition leading to liver injury	Unclassified	-		0.12	KE:1549	Liver Injury
AOP:281	Acetylcholinesterase Inhibition Leading to Neurodegeneration	Nervous system disease	-		0.1	KE:352	N/A, Neurodegeneration
AOP:286	Mitochondrial complex III antagonism leading to growth inhibition (1)	Unclassified	-	Lemna minor, Daphnia magna, Danio rerio	0.75	KE:1821	Decrease, Cell proliferation
						KE:1521	Decrease, Growth
						KE:1771	Decrease, Adenosine triphosphate pool
AOP:287	Mitochondrial complex III antagonism leading to growth inhibition (2)	Unclassified	-	Lemna minor, Daphnia magna, Danio rerio	0.5	KE:1771	Decrease, Adenosine triphosphate pool
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	0.75	KE:1821	Decrease, Cell proliferation
						KE:1521	Decrease, Growth
						KE:1771	Decrease, Adenosine triphosphate pool
AOP:291	Mitochondrial ATP synthase antagonism leading to growth inhibition (2)	Unclassified	-	Daphnia magna	0.5	KE:1771	Decrease, Adenosine triphosphate pool
AOP:291		Unclassified	-	Daphnia magna	0.5	KE:1521	Decrease, Growth
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:304	TBX1 inhibition leading to congenital cardiac conotruncal anomalies	Cardiovascular system disease	-		0.17	KE:1685	Anomalies, Congenital cardiac conotruncal
AOP:313	Stimulation of TLR7/8 in dendric cells leading to Psoriatic skin disease	Immune system disease; Integumentary system disease; Musculoskeletal system disease	Under Development	Homo sapiens, Mus musculus	0.2	KE:1709	Psoriatic skin disease
AOP:362	Immune mediated hepatitis	Gastrointestinal system disease; Immune system disease	-	Homo sapiens, Rat	0.12	KE:1820	Immune mediated hepatitis
AOP:379	Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation	Cardiovascular system disease	Under Development	Homo sapiens	0.43	KE:1846	Thrombosis and Disseminated Intravascular Coagulation
						KE:1845	Coagulation
						KE:1869	Diminished protective oxidative stress response
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:392	Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation	Unclassified	Under Development	Humans	0.6	KE:1868	Hyperinflammation
						KE:1497	Increased, recruitment of inflammatory cells
						KE:1496	Increased, secretion of proinflammatory mediators
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:411	Oxidative stress Leading to Decreased Lung Function	Respiratory system disease	-	Homo sapiens	0.25	KE:1250	Decrease, Lung function
AOP:418	Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathway	Respiratory system disease	-		0.4	KE:1250	Decrease, Lung function
AOP:418		Respiratory system disease	-		0.4	KE:1115	Increase, Reactive oxygen species
AOP:419	Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathway	Respiratory system disease	-		0.5	KE:1250	Decrease, Lung function
AOP:419		Respiratory system disease	-		0.5	KE:1262	Apoptosis
AOP:424	Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction	Respiratory system disease	-	Human	0.17	KE:1250	Decrease, Lung function
AOP:425	Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1	Respiratory system disease	-	Human	0.17	KE:1250	Decrease, Lung function
AOP:430	Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferation	Viral infectious disease	Under Development	Mink, Ferret, Cat, Dog, Syrian golden hamster, Rhesus macaque, Lowland gorilla, Crab eating macaque, African green monkeys, Humans, Hippopotamus amphibius, Bank vole, Lynx canadensis, Puma concolor, Panthera tigris jacksoni, Panthera uncia, Prionailurus viverrinus, Crocuta crocuta, Arctictis binturong, Odocoileus virginianus, American mink, Nasua nasua, Panthera leo, Sus scrofa, European rabbit, Castor fiber, Aonyx cinereus, Vulpes vulpes, Nyctereutes procyonoides, Tupaia belangeri, Bos taurus, Odocoileus hemionus, Peromyscus maniculatus bairdii, Cynopterus brachyotis, Common marmoset, Baboon	0.2	KE:1939	Viral infection and host-to-host transmission, proliferated
AOP: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: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:449	Ceramide synthase inhibition leading to neural tube defects	Neural tube defect	-		0.29	KE:1561	Neural tube defects
AOP:449	Ceramide synthase inhibition leading to neural tube defects	Neural tube defect	-		0.29	KE:1502	Histone deacetylase inhibition
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	0.33	KE:947	Increase, Early Life Stage Mortality
AOP:455		Musculoskeletal system disease	Under Review		0.33	KE:1559	Facial cartilage structures are reduced in size and morphologically distorted
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	0.33	KE:317	Altered, Cardiovascular development/function
AOP:456		Unclassified	Under Review	Zebrafish, Mouse, Human, Chicken	0.33	KE:947	Increase, Early Life Stage Mortality
AOP:457	Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine	Inherited metabolic disorder	-	Human	0.17	KE:2119	Insulin resistance, increased
AOP:458	AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Rat, Mouse, Monkey, Human	0.25	KE:402	Cognitive function, decreased
AOP:458		Cognitive disorder	-	Rat, Mouse, Monkey, Human	0.25	KE:756	Hippocampal gene expression, Altered
AOP:459	AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Human, Mouse, Rat	0.22	KE:402	Cognitive function, decreased
AOP:459		Cognitive disorder	-	Human, Mouse, Rat	0.22	KE:756	Hippocampal gene expression, Altered
AOP:464	Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits	Nervous system disease	-		0.05	KE:896	Parkinsonian motor deficits
AOP:468	Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)	Unclassified	-		0.38	KE:1868	Hyperinflammation
						KE:1497	Increased, recruitment of inflammatory cells
						KE:1496	Increased, secretion of proinflammatory mediators
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	0.25	KE:2242	Abnormality, dendritic spine morphology
AOP:475		Developmental disorder of mental health	Under Development	Mouse, Rat, Human, Caenorhabditis elegans	0.25	KE:341	Impairment, Learning and memory
AOP:483	Deposition of Energy Leading to Learning and Memory Impairment	Developmental disorder of mental health	Under Review	Mouse, Rat, Rabbit, Dog, Pigs, Cow, Human	0.12	KE:341	Impairment, Learning and memory
AOP:485	Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognition	Cognitive disorder	-	Human	0.14	KE:402	Cognitive function, decreased
AOP:486	Binding to the extracellular protein laminin leading to decreased cognitive function	Cognitive disorder	-	Human	0.14	KE:402	Cognitive function, decreased
AOP:490	Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms	Developmental disorder of mental health	-		0.09	KE:341	Impairment, Learning and memory
AOP:493	ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity	Acquired metabolic disease	-	Mus musculus, Homo sapiens	0.4	KE:2119	Insulin resistance, increased
						KE:2125	Increased fat mass
						KE:1497	Increased, recruitment of inflammatory cells
						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	-		0.5	KE:2144	Impaired insulin signaling
						KE:2119	Insulin resistance, increased
						KE:1115	Increase, Reactive oxygen species
						KE:2145	Metabolic syndrome
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	0.57	KE:1262	Apoptosis
						KE:1115	Increase, Reactive oxygen species
						KE:352	N/A, Neurodegeneration
						KE:341	Impairment, Learning and memory
AOP:501	Excessive iron accumulation leading to neurological disorders	Nervous system disease	-	Homo sapiens	0.25	KE:2150	Neurological disorder
AOP: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:525	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory	Developmental disorder of mental health	-		0.08	KE:341	Impairment, Learning and memory
AOP:532	Retinoic acid receptor agonism during cerebellar development leading to impaired locomotor function	Unclassified	-		0.4	KE:2230	Cerebellar hypoplasia
AOP:532		Unclassified	-		0.4	KE:2231	Locomotor function. Impaired
AOP:533	Retinoic acid receptor antagonism during neurodevelopment leading to impaired learning and memory	Developmental disorder of mental health	-		0.17	KE:341	Impairment, Learning and memory
AOP:534	Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress	Cancer	-	Vertebrates	0.5	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	0.22	KE:1262	Apoptosis
AOP:535		Developmental disorder of mental health	-	Mouse, Human	0.22	KE:341	Impairment, Learning and memory
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:572	Imidacloprid-Induced BMP4 inhibition Leading to Neural Tube Closure Defects	Neural tube defect	-		0.2	KE:1561	Neural tube defects

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: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	0.2	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:121	Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)	Cancer; Urinary system disease	-	Mus musculus, Rattus norvegicus	0.4	KE:795	Increase, Regenerative cell proliferation (urothelial cells)
AOP:121		Cancer; Urinary system disease	-	Mus musculus, Rattus norvegicus	0.4	KE:793	Increase, Urinary bladder calculi
AOP:209	Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP	Gastrointestinal system disease	-		0.25	KE:1286	Down Regulation, GSS and GSTs gene
AOP:209		Gastrointestinal system disease	-		0.25	KE:1287	Glutathione synthesis
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: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	0.4	KE:1771	Decrease, Adenosine triphosphate pool
AOP:328		Unclassified	-	Daphnia magna	0.4	KE:1115	Increase, Reactive oxygen species
AOP:329	Excessive reactive oxygen species production leading to mortality (3)	Unclassified	-	Daphnia magna, Paracyclopina nana	0.4	KE:1771	Decrease, Adenosine triphosphate pool
AOP:329		Unclassified	-	Daphnia magna, Paracyclopina nana	0.4	KE:1115	Increase, Reactive oxygen species
AOP:330	Excessive reactive oxygen species production leading to mortality (4)	Unclassified	-	Daphnia magna	0.2	KE:1115	Increase, Reactive oxygen species
AOP:423	Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway	Unclassified	-		0.17	KE:1115	Increase, Reactive oxygen species
AOP:438	reactive oxygen species generation leading to increased cardiovascular morbidity and mortality	Cardiovascular system disease	-		0.17	KE:1115	Increase, Reactive oxygen species
AOP:438		Cardiovascular system disease	-		0.17	KE:1919	Increased, Cardiac Dysregulation
AOP:446	PM-related Adverse outcome pathway frameworks on various systems	Respiratory system disease	-		0.35	KE:1115	Increase, Reactive oxygen species
						KE:1250	Decrease, Lung function
						KE:1496	Increased, secretion of proinflammatory mediators
						KE:1198	Activation, Macrophages
						KE:149	Increase, Inflammation
						KE:1497	Increased, recruitment of inflammatory cells
						KE:1262	Apoptosis
AOP:448	ROS, inflammation, and activation of nAChR lead to increased incidence of cardiovascular morbidity and mortality	Cardiovascular system disease	-		0.12	KE:1198	Activation, Macrophages
AOP:448		Cardiovascular system disease	-		0.12	KE:1115	Increase, Reactive oxygen species
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:1198	Activation, Macrophages
						KE:1115	Increase, Reactive oxygen species
						KE:1995	Abnormal lipid metabolism
AOP:469	Reactive oxygen speicies overproduction leading to increased digestive morbidity and mortality in generation population	Gastrointestinal system disease	-		0.23	KE:1198	Activation, Macrophages
						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:1097	Occurrence, renal proximal tubular necrosis
						KE:1816	Mitochondrial dysfunction EMPTY
						KE:149	Increase, Inflammation
						KE:1115	Increase, Reactive oxygen species
AOP:511	The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects	Cardiovascular system disease	-	Human, Mouse, Zebrafish	0.06	KE:1115	Increase, Reactive oxygen species
AOP:540	Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production	Unclassified	-		0.33	KE:1115	Increase, Reactive oxygen species
						KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
						KE:1262	Apoptosis
AOP:541	Excessive ROS generation leading to increased incidence of vascular calcification by VSMC phenotype switching	Cardiovascular system disease	-		0.31	KE:1493	Increased Pro-inflammatory mediators
						KE:1198	Activation, Macrophages
						KE:1816	Mitochondrial dysfunction EMPTY
						KE:1115	Increase, Reactive oxygen species

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:27	Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)	Gastrointestinal system disease	Under Development	Humans	0.5	KE:357	Cholestasis, Pathology
						KE:41	Inhibition, Bile Salt Export Pump (ABCB11)
						KE:149	Increase, Inflammation
						KE:1115	Increase, Reactive oxygen species
AOP:212	Histone deacetylase inhibition leading to testicular atrophy	Reproductive system disease	WPHA/WNT Endorsed	Rat, Human, Mouse	0.5	KE:1506	Testicular atrophy
						KE:1502	Histone deacetylase inhibition
						KE:1262	Apoptosis
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	1.0	KE:1771	Decrease, Adenosine triphosphate pool
						KE:1446	Decrease, Coupling of oxidative phosphorylation
						KE:1521	Decrease, Growth
						KE:1821	Decrease, Cell proliferation
AOP:264	Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell death	Unclassified	Under Development		0.75	KE:1771	Decrease, Adenosine triphosphate pool
						KE:1521	Decrease, Growth
						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		0.5	KE:1771	Decrease, Adenosine triphosphate pool
						KE:1521	Decrease, Growth
						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:274	Histone deacetylase inhibition leads to impeded craniofacial development	Musculoskeletal system disease	-		1.0	KE:1502	Histone deacetylase inhibition
						KE:1557	Neural crest cell migration, reduced
						KE:1559	Facial cartilage structures are reduced in size and morphologically distorted
						KE:1558	Collagen production, reduced
AOP:275	Histone deacetylase inhibition leads to neural tube defects	Neural tube defect	-		0.4	KE:1561	Neural tube defects
AOP:275	Histone deacetylase inhibition leads to neural tube defects	Neural tube defect	-		0.4	KE:1502	Histone deacetylase inhibition
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	-		1.0	KE:1821	Decrease, Cell proliferation
						KE:1115	Increase, Reactive oxygen species
						KE:1446	Decrease, Coupling of oxidative phosphorylation
						KE:1771	Decrease, Adenosine triphosphate pool
						KE:1521	Decrease, Growth
AOP:463	The AOP framwork on silica nanopariticles induced hepatoxicity	Gastrointestinal system disease	-		0.36	KE:2034	liver dysfunction
						KE:149	Increase, Inflammation
						KE:1115	Increase, Reactive oxygen species
						KE:1262	Apoptosis
AOP:488	Increased reactive oxygen species production leading to decreased cognitive function	Cognitive disorder	-	Human	0.43	KE:1869	Diminished protective oxidative stress response
						KE:1115	Increase, Reactive oxygen species
						KE:402	Cognitive function, decreased
AOP:505	Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway	Cancer	-	Human, Mouse, Rat	0.6	KE:885	Increase, Cancer
						KE:149	Increase, Inflammation
						KE:1115	Increase, Reactive oxygen species
AOP:513	Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway	Cancer	-	Human, Mouse, Rat	0.6	KE:885	Increase, Cancer
						KE:1115	Increase, Reactive oxygen species
						KE:1060	Alteration, lipid metabolism

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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.