DEDUCT | Database of Endocrine Disrupting chemicals and their Toxicity profiles

Arsenic

Associated AOPs with Level of Relevance - 1 AOPs with at least 1 KE associated with chemical, where the KE(s) are neither MIE nor AO

AOP Identifier	AOP Title	AO Classification	OECD Status	Taxonomic applicability	Coverage Score ⓘ The fraction of KEs within the AOP, that are mapped to the chemical-associated toxicological endpoints.	KE Identifier	KE Name
AOP:3	Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits	Nervous system disease	WPHA/WNT Endorsed	Human, Rat	0.43	KE:188	Neuroinflammation
						KE:887	Inhibition, NADH-ubiquinone oxidoreductase (complex I)
						KE:177	Mitochondrial dysfunction
AOP:4	Ecdysone receptor agonism leading to incomplete ecdysis associated mortality	Unclassified	-	Insects, Crustaceans	0.3	KE:993	Decrease, Abdominal muscle contraction
						KE:1265	Increase, Fushi tarazu factor-1 gene expression
						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:757	Hippocampal anatomy, Altered
AOP:8		Nervous system disease	Under Development	Rat	0.22	KE:756	Hippocampal gene expression, Altered
AOP:10	Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain	Nervous system disease	WPHA/WNT Endorsed	Human, Mouse, Rat, Bobwhite quail, Zebrafish	0.17	KE:616	Occurrence, A paroxysmal depolarizing shift
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: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:266	Decrease, Steroidogenic acute regulatory protein (STAR)
						KE:413	Reduction, Testosterone synthesis in Leydig cells
						KE:447	Reduction, Cholesterol transport in mitochondria
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:1269	Increase, COX-2 expression
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:30	Estrogen receptor antagonism leading to reproductive dysfunction	Unclassified	Under Review	Zebra danio, Fathead minnow, Medaka	0.17	KE:285	Reduction, Vitellogenin synthesis in liver
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: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: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	0.31	KE:454	Increased, Triglyceride formation
						KE:463	Up Regulation, FAS
						KE:462	Up Regulation, SCD-1
						KE:54	Up Regulation, CD36
						KE:458	Increased, De Novo FA synthesis
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: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:413	Reduction, Testosterone synthesis in Leydig cells
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	0.29	KE:177	Mitochondrial dysfunction
AOP:77		Unclassified	-	Honey bee	0.29	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	0.25	KE:177	Mitochondrial dysfunction
AOP:78		Unclassified	-	Honey bee	0.25	KE:341	Impairment, Learning and memory
AOP:79	Nicotinic acetylcholine receptor activation contributes to impaired hive thermoregulation and leads to colony loss/failure	Unclassified	-		0.2	KE:177	Mitochondrial dysfunction
AOP:80	Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure	Unclassified	-	Honey bee	0.25	KE:664	Overwhelmed, Mitochondrial DNA repair mechanisms
AOP:80		Unclassified	-	Honey bee	0.25	KE:177	Mitochondrial dysfunction
AOP:87	Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure	Unclassified	-	Honey bee	0.25	KE:177	Mitochondrial dysfunction
AOP:87		Unclassified	-	Honey bee	0.25	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:94	Sodium channel inhibition leading to congenital malformations	Unclassified	-	Human, Rat, Mouse	0.17	KE:445	Respiratory distress/arrest
AOP:102	Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition	Reproductive system disease	-	Goldfish, Human, Rat, Mouse	0.1	KE:690	Reduced, Luteinizing hormone (LH), plasma
AOP:103	Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint	Reproductive system disease	-	Goldfish, Human, Rat, Mouse	0.1	KE:690	Reduced, Luteinizing hormone (LH), plasma
AOP:109	Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)	Cancer; Respiratory system disease	-	Mus musculus	0.2	KE:734	Increase, Regenerative cell proliferation (terminal bronchiolar epithelial cells)
AOP:110	Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse)	Cancer; Endocrine system disease	-	Rattus norvegicus, Mus musculus	0.29	KE:277	Thyroid hormone synthesis, Decreased
AOP:110		Cancer; Endocrine system disease	-	Rattus norvegicus, Mus musculus	0.29	KE:739	Increase, Hypertrophy and proliferation (follicular cell)
AOP:112	Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)	Reproductive system disease; Cancer	-	Rattus norvegicus	0.33	KE:747	Decreased, Prolactin
AOP:112		Reproductive system disease; Cancer	-	Rattus norvegicus	0.33	KE:749	Decreased, Progesterone from corpus luteum
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:119	Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)	Cancer; Endocrine system disease	-	Rattus norvegicus, Mus musculus	0.29	KE:277	Thyroid hormone synthesis, Decreased
AOP:119		Cancer; Endocrine system disease	-	Rattus norvegicus, Mus musculus	0.29	KE:739	Increase, Hypertrophy and proliferation (follicular cell)
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:130	Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity	Gastrointestinal system disease	Under Development	Sprague-Dawley, Homo sapiens	0.09	KE:177	Mitochondrial dysfunction
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	0.17	KE:850	Induction, CYP1A2/CYP1A5
AOP:136	Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors	Benign neoplasm; Respiratory system disease	Under Review		0.29	KE:768	Increase, Cytotoxicity
AOP:136		Benign neoplasm; Respiratory system disease	Under Review		0.29	KE:870	Increase, Cell Proliferation
AOP:144	Endocytic lysosomal uptake leading to liver fibrosis	Gastrointestinal system disease	Under Review	Human, Mouse, Rat	0.33	KE:1493	Increased Pro-inflammatory mediators
						KE:68	Accumulation, Collagen
						KE:177	Mitochondrial dysfunction
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:948	reduced production, VEGF
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	0.29	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	0.25	KE:68	Accumulation, Collagen
AOP:173		Musculoskeletal system disease; Respiratory system disease	WPHA/WNT Endorsed	Human, Mouse, Rat	0.25	KE:1497	Increased, recruitment of inflammatory cells
AOP:175	Thyroperoxidase inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:176	Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.2	KE:277	Thyroid hormone synthesis, Decreased
AOP:188	Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.2	KE:277	Thyroid hormone synthesis, Decreased
AOP:190	Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.17	KE:1829	Altered, Thyroid hormone-dependent gene expression
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:277	Thyroid hormone synthesis, Decreased
AOP:193	Dual oxidase (DUOX) inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP: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	0.5	KE:1115	Increase, Reactive oxygen species
						KE:177	Mitochondrial dysfunction
						KE:1281	Increased, DNA Damage-Repair
						KE:1262	Apoptosis
AOP:212	Histone deacetylase inhibition leading to testicular atrophy	Reproductive system disease	WPHA/WNT Endorsed	Rat, Human, Mouse	0.5	KE:1505	Cell cycle, disrupted
						KE:1503	Histone acetylation, increase
						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:241	Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis	Musculoskeletal system disease; Respiratory system disease	-		0.17	KE:68	Accumulation, Collagen
AOP:256	Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity	Urinary system disease	Under Development	Human, Rat, Mouse	0.2	KE:177	Mitochondrial dysfunction
AOP:271	Inhibition of thyroid peroxidase leading to impaired fertility in fish	Unclassified	Under Development	Fish	0.4	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:271		Unclassified	Under Development	Fish	0.4	KE:277	Thyroid hormone synthesis, Decreased
AOP: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: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	0.29	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	0.25	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: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:315	Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody Response	Immune system disease	Under Development	Homo sapiens, Mus musculus	0.2	KE:1716	Blockade of STAT5 phosphorylation
AOP:318	Glucocorticoid Receptor activation leading to hepatic steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-		0.2	KE:291	Accumulation, Triglyceride
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: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	0.17	KE:2245	Altered Cell Differentiation Signaling
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:362	Immune mediated hepatitis	Gastrointestinal system disease; Immune system disease	-	Homo sapiens, Rat	0.12	KE:177	Mitochondrial dysfunction
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	0.5	KE:188	Neuroinflammation
AOP:374		Nervous system disease	Under Development	Human	0.5	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:68	Accumulation, Collagen
AOP:382		Musculoskeletal system disease; Respiratory system disease	Under Development		0.33	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	0.25	KE:1115	Increase, Reactive oxygen species
AOP:387		Reproductive system disease	-	Lemna minor	0.25	KE:40	Decrease, Mitochondrial ATP production
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:1847	Increased SARS-CoV-2 production
AOP:397	Bulky DNA adducts leading to mutations	Genetic disease	Under Development		0.33	KE:155	Inadequate DNA repair
AOP:428	Binding of S-protein to ACE2 in enterocytes induces ACE2 dysregulation leading to gut dysbiosis	Gastrointestinal system disease	Under Development		0.33	KE:1854	Dysregulation, ACE2 expression and activity
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:433	hERG channel blockade leading to sudden cardiac death	Cardiovascular system disease	-	Human	0.17	KE:1961	Prolongation of Action Potential Duration
AOP:437	Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity	Urinary system disease	Under Development		0.4	KE:1392	Oxidative Stress
AOP:437		Urinary system disease	Under Development		0.4	KE:177	Mitochondrial dysfunction
AOP: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:440	Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia	Benign neoplasm; Endocrine system disease; Reproductive system disease; Reproductive system disease; Cancer; Endocrine system disease	Under Development	Human, Rat, Mice	0.11	KE:1052	Hyperplasia, ovarian epithelium
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	0.2	KE:155	Inadequate DNA repair
AOP:443		Thoracic disease; Cancer	Under Development		0.2	KE:1554	Increase Chromosomal Aberrations
AOP:444	Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability	Unclassified	-		0.11	KE:1392	Oxidative Stress
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:2020	Decrease, sox9 expression
AOP:455		Musculoskeletal system disease	Under Review		0.33	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	0.5	KE:317	Altered, Cardiovascular development/function
						KE:2020	Decrease, sox9 expression
						KE:2021	Increase, slincR expression
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:464	Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits	Nervous system disease	-		0.11	KE:1392	Oxidative Stress
AOP:464		Nervous system disease	-		0.11	KE:177	Mitochondrial dysfunction
AOP: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:1493	Increased Pro-inflammatory mediators
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:478	Deposition of energy leading to occurrence of cataracts	Nervous system disease; Monogenic disease	Under Review	Human, Mouse, Rat, Rhesus monkeys, Rabbit, Guinea pig	0.5	KE:155	Inadequate DNA repair
						KE:1636	Increase, Chromosomal aberrations
						KE:1392	Oxidative Stress
						KE:870	Increase, Cell Proliferation
						KE:2081	Increased Modified Proteins
AOP:479	Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress	Cardiovascular system disease; Thoracic disease	Under Development		0.43	KE:1392	Oxidative Stress
						KE:1532	Decrease, Cardiac contractility
						KE:177	Mitochondrial dysfunction
AOP:480	Mitochondrial complexes inhibition leading to heart failure via decreased ATP production	Cardiovascular system disease; Thoracic disease	Under Development		0.6	KE:1532	Decrease, Cardiac contractility
						KE:177	Mitochondrial dysfunction
						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:1392	Oxidative Stress
AOP:482	Deposition of energy leading to occurrence of bone loss	Musculoskeletal system disease	Under Review	Human, Mouse, Rat, Rhesus monkeys	0.29	KE:2245	Altered Cell Differentiation Signaling
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:1445	Increase, Lipid peroxidation
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	0.5	KE:2127	Increased adipocyte size
						KE:1497	Increased, recruitment of inflammatory cells
						KE:2125	Increased fat mass
						KE:2119	Insulin resistance, increased
						KE:2128	Increased adipocyte numbers
AOP:496	Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）	Unclassified	-	Zebrafish	0.2	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:496		Unclassified	-	Zebrafish	0.2	KE:219	Reduction, Plasma 17beta-estradiol concentrations
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:2152	Epigenetic modification process
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:177	Mitochondrial dysfunction
AOP:510	Demethylation of PPAR promotor leading to vascular disrupting effects	Cardiovascular system disease	-	Human, Mouse, Zebrafish	0.1	KE:1392	Oxidative Stress
AOP:517	Pregnane X Receptor (PXR) activation leads to liver steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-	Vertebrates	0.4	KE:291	Accumulation, Triglyceride
AOP:517			-	Vertebrates	0.4	KE:54	Up Regulation, CD36
AOP:518	Liver X Receptor (LXR) activation leads to liver steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-	Vertebrates	0.4	KE:291	Accumulation, Triglyceride
AOP:518	Liver X Receptor (LXR) activation leads to liver steatosis		-	Vertebrates	0.4	KE:89	Synthesis, De Novo Fatty Acid (FA)
AOP:521	Essential element imbalance leads to reproductive failure via oxidative stress	Unclassified	-	Murinae gen. sp.	0.43	KE:1392	Oxidative Stress
						KE:1115	Increase, Reactive oxygen species
						KE:1445	Increase, Lipid peroxidation
AOP:524	Gluten-driven immune activation leading to celiac disease in genetically predisposed individuals	Immune system disease; Gastrointestinal system disease	-	Human	0.11	KE:1931	Intestinal barrier, disruption
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	0.25	KE:2224	Dysregulation of transcriptional expression within PPAR signaling network
AOP:529			-	Vertebrates, Mouse, Rat, Zebrafish	0.25	KE:291	Accumulation, Triglyceride
AOP:531	VEGFR inhibition leading to Keratinocyte differentiation-associate Hand-foot skin reaction	Unclassified	-		0.12	KE:11005	Hyperkeratosis
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	0.4	KE:2294	Plasma estradiol, increased
AOP:561		Unclassified	-	Vertebrates	0.4	KE:2251	Estradiol availability, increased
AOP:563	Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosis	Reproductive system disease; Endocrine system disease	-	Rat, Mouse, Zebra fish, Human	0.17	KE:1262	Apoptosis

Associated AOPs with Level of Relevance - 2 AOPs with at least 1 AO associated with chemical, and no associated MIE

AOP Identifier	AOP Title	AO Classification	OECD Status	Taxonomic applicability	Coverage Score ⓘ The fraction of KEs within the AOP, that are mapped to the chemical-associated toxicological endpoints.	KE Identifier	KE Name
AOP:6	Antagonist binding to PPARα leading to body-weight loss	Symptom	WPHA/WNT Endorsed	Mus musculus, Homo sapiens, Pimephales promelas, Colinus virginianus, Rattus norvegicus	0.12	KE:864	Decreased, Body Weight
AOP: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	0.5	KE:188	Neuroinflammation
						KE:381	Reduced levels of BDNF
						KE:352	N/A, Neurodegeneration
						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:16	Acetylcholinesterase inhibition leading to acute mortality	Unclassified	Under Development		0.29	KE:445	Respiratory distress/arrest
AOP:16	Acetylcholinesterase inhibition leading to acute mortality	Unclassified	Under Development		0.29	KE:351	Increased Mortality
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	0.4	KE:1493	Increased Pro-inflammatory mediators
						KE:188	Neuroinflammation
						KE:1392	Oxidative Stress
						KE:341	Impairment, Learning and memory
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	-		0.46	KE:177	Mitochondrial dysfunction
						KE:345	N/A, Liver Steatosis
						KE:291	Accumulation, Triglyceride
						KE:54	Up Regulation, CD36
						KE:89	Synthesis, De Novo Fatty Acid (FA)
						KE:258	Activation, SCD-1
AOP:37	PPARα activation leading to hepatocellular adenomas and carcinomas in rodents	Cancer; Gastrointestinal system disease	Under Development	Mouse, Rat	0.4	KE:716	Increase, cell proliferation (hepatocytes)
AOP:37		Cancer; Gastrointestinal system disease	Under Development	Mouse, Rat	0.4	KE:719	Increase, hepatocellular adenomas and carcinomas
AOP:40	Covalent Protein binding leading to Skin Sensitisation	Integumentary system disease	WPHA/WNT Endorsed	Mouse, Human	0.4	KE:827	sensitisation, skin
AOP:40	Covalent Protein binding leading to Skin Sensitisation	Integumentary system disease	WPHA/WNT Endorsed	Mouse, Human	0.4	KE:272	Activation/Proliferation, T-cells
AOP:42	Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	WPHA/WNT Endorsed	Human, Rat, Mouse	0.5	KE:757	Hippocampal anatomy, Altered
						KE:402	Cognitive function, decreased
						KE:756	Hippocampal gene expression, Altered
						KE:277	Thyroid hormone synthesis, 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	0.44	KE:188	Neuroinflammation
						KE:177	Mitochondrial dysfunction
						KE:352	N/A, Neurodegeneration
						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:277	Thyroid hormone synthesis, Decreased
						KE:381	Reduced levels of BDNF
						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:96	Axonal sodium channel modulation leading to acute mortality	Unclassified	-	Insects, Fish	0.5	KE:602	Increased, Ataxia, paralysis, or hyperactivity
						KE:599	prolonged, Depolarization of neuronal membrane
						KE:351	Increased Mortality
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:104	Altered ion channel activity leading impaired heart function	Unclassified	-		0.5	KE:699	Increased, cardiac arrthymia
AOP:104		Unclassified	-		0.5	KE:351	Increased Mortality
AOP:105	Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)	Cancer; Urinary system disease	-	Rattus norvegicus	0.33	KE:713	Increase, Adenomas/carcinomas (renal tubular)
AOP:105		Cancer; Urinary system disease	-	Rattus norvegicus	0.33	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	0.6	KE:1214	Altered gene expression specific to CAR activation, Hepatocytes
						KE:719	Increase, hepatocellular adenomas and carcinomas
						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	0.5	KE:768	Increase, Cytotoxicity
						KE:719	Increase, hepatocellular adenomas and carcinomas
						KE:769	Increase, Oxidative metabolism
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	0.33	KE:351	Increased Mortality
AOP:113		Unclassified	-		0.33	KE:764	N/A, Ataxia, paralysis, or hyperactivity
AOP:116	Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)	Cancer; Urinary system disease	-	Rattus norvegicus	0.5	KE:713	Increase, Adenomas/carcinomas (renal tubular)
AOP:116		Cancer; Urinary system disease	-	Rattus norvegicus	0.5	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	0.5	KE:716	Increase, cell proliferation (hepatocytes)
AOP:117		Cancer; Gastrointestinal system disease	Under Development	Mus musculus, Rattus norvegicus	0.5	KE:719	Increase, hepatocellular adenomas and carcinomas
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:330	Decrease, Fertility
AOP:134	Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Rat, Homo sapiens	0.44	KE:757	Hippocampal anatomy, Altered
						KE:402	Cognitive function, decreased
						KE:756	Hippocampal gene expression, Altered
						KE:277	Thyroid hormone synthesis, Decreased
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	0.5	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	0.4	KE:952	Hypertension
						KE:927	KE1 : S-Glutathionylation, eNOS
						KE:933	KE6 : Depletion, Nitric Oxide
						KE:937	KE7 : Impaired, Vasodilation
AOP:151	AhR activation leading to preeclampsia	Cardiovascular system disease	Under Development	Homo sapiens, Mus musculus	0.29	KE:1893	increase, Preeclampsia
AOP:151	AhR activation leading to preeclampsia	Cardiovascular system disease	Under Development	Homo sapiens, Mus musculus	0.29	KE:948	reduced production, VEGF
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:351	Increased Mortality
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:351	Increased Mortality
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:351	Increased Mortality
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:351	Increased Mortality
AOP:159	Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	Zebrafish, Fathead minnow	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:159		Unclassified	WPHA/WNT Endorsed	Zebrafish, Fathead minnow	0.25	KE:351	Increased Mortality
AOP:160	Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality	Unclassified	-	Daphnia magna	0.14	KE:351	Increased Mortality
AOP:161	Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality	Unclassified	-	Nematode, Daphnia magna	0.14	KE:351	Increased 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: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	0.18	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	0.29	KE:1392	Oxidative Stress
AOP:260		Nervous system disease	-	Human	0.29	KE:1514	Neurodegeneration
AOP:261	L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility	Cardiovascular system disease	Under Development	Vertebrates	0.25	KE:1532	Decrease, Cardiac contractility
AOP:261		Cardiovascular system disease	Under Development	Vertebrates	0.25	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:270	Elevated ATP demand for detoxification and repair mechanisms leading to impaired locomotor activity	Unclassified	-		0.12	KE:10016	Impaired locomotor activity
AOP:272	Deposition of energy leading to lung cancer	Cancer	WPHA/WNT Endorsed	Human, Rat, Mouse	0.57	KE:155	Inadequate DNA repair
						KE:870	Increase, Cell Proliferation
						KE:1636	Increase, Chromosomal aberrations
						KE:1556	Increase, lung cancer
AOP:275	Histone deacetylase inhibition leads to neural tube defects	Neural tube defect	-		0.6	KE:1239	Altered, Gene Expression
						KE:1561	Neural tube defects
						KE:1503	Histone acetylation, increase
AOP:279	Microtubule interacting drugs lead to peripheral neuropathy	Nervous system disease	-		0.25	KE:1583	Sensory axonal peripheral neuropathy
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	0.5	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	0.25	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	0.25	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	0.33	KE:1493	Increased Pro-inflammatory mediators
						KE:1193	N/A, Breast Cancer
						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		0.33	KE:1493	Increased Pro-inflammatory mediators
						KE:1193	N/A, Breast Cancer
						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	0.4	KE:155	Inadequate DNA repair
AOP:296		Genetic disease; Chromosomal disease	WPHA/WNT Endorsed	Human, Mice, Rat, Fish	0.4	KE:1636	Increase, Chromosomal aberrations
AOP:300	Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	Under Development	Human, Mouse	0.6	KE:757	Hippocampal anatomy, Altered
						KE:402	Cognitive function, decreased
						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:312	Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement	Unclassified	-		0.17	KE:351	Increased Mortality
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:320	Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality	Unclassified	Under Development	Homo sapiens	0.33	KE:1847	Increased SARS-CoV-2 production
						KE:351	Increased Mortality
						KE:1750	Increased inflammatory immune responses
AOP:322	Alkylation of DNA leading to reduced sperm count	Reproductive system disease	-		0.4	KE:155	Inadequate DNA repair
AOP:322	Alkylation of DNA leading to reduced sperm count	Reproductive system disease	-		0.4	KE:1757	Reduce, Sperm count
AOP:363	Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure	Unclassified	Under Review	Zebrafish	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:363		Unclassified	Under Review	Zebrafish	0.25	KE:351	Increased Mortality
AOP:364	Thyroperoxidase inhibition leading to altered visual function via decreased eye size	Unclassified	Under Development		0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:364		Unclassified	Under Development		0.25	KE:351	Increased Mortality
AOP:365	Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning	Unclassified	Under Development		0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:365		Unclassified	Under Development		0.25	KE:351	Increased Mortality
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:1847	Increased SARS-CoV-2 production
						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:399	Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)	Unclassified	-	Zebrafish	0.25	KE:1821	Decrease, Cell proliferation
AOP:399		Unclassified	-	Zebrafish	0.25	KE:351	Increased Mortality
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	-		0.67	KE:1847	Increased SARS-CoV-2 production
						KE:1869	Diminished protective oxidative stress response
						KE:1868	Hyperinflammation
						KE:1895	NLRP3 inflammasome activity, increased
AOP:410	GSK3beta inactivation leading to increased mortality via defects in developing inner ear	Unclassified	-	Zebrafish	0.1	KE:351	Increased Mortality
AOP:416	Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathway	Cancer	-		0.33	KE:1115	Increase, Reactive oxygen species
AOP:416		Cancer	-		0.33	KE:1670	Lung cancer
AOP:417	Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathway	Cancer	-		0.2	KE:1670	Lung cancer
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:420	Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathway	Cancer	-		0.5	KE:870	Increase, Cell Proliferation
AOP:420		Cancer	-		0.5	KE:1670	Lung cancer
AOP:422	Binding of SARS-CoV-2 to ACE2 in enterocytes leads to intestinal barrier disruption	Gastrointestinal system disease	Under Development		0.4	KE:1847	Increased SARS-CoV-2 production
AOP:422		Gastrointestinal system disease	Under Development		0.4	KE:1931	Intestinal barrier, disruption
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	0.4	KE:1847	Increased SARS-CoV-2 production
AOP:430		Viral infectious disease	Under Development		0.4	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	0.29	KE:757	Hippocampal anatomy, Altered
AOP:442		Cognitive disorder	Under Review	Rattus norvegicus, Mouse, Humans	0.29	KE:402	Cognitive function, decreased
AOP:449	Ceramide synthase inhibition leading to neural tube defects	Neural tube defect	-		0.14	KE:1561	Neural tube defects
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	0.57	KE:1392	Oxidative Stress
						KE:351	Increased Mortality
						KE:1583	Sensory axonal peripheral neuropathy
						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:1670	Lung cancer
AOP:452	Adverse outcome pathway of PM-induced respiratory toxicity	Respiratory system disease	-		0.27	KE:1392	Oxidative Stress
						KE:2008	Chronic obstructive pulmonary disease
						KE:1262	Apoptosis
AOP:457	Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine	Inherited metabolic disorder	-	Human	0.5	KE:1392	Oxidative Stress
						KE:2119	Insulin resistance, increased
						KE:277	Thyroid hormone synthesis, Decreased
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	0.56	KE:402	Cognitive function, decreased
						KE:277	Thyroid hormone synthesis, Decreased
						KE:850	Induction, CYP1A2/CYP1A5
						KE:1392	Oxidative Stress
						KE:756	Hippocampal gene expression, Altered
AOP:468	Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)	Unclassified	-		0.38	KE:1868	Hyperinflammation
						KE:1847	Increased SARS-CoV-2 production
						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	0.25	KE:1392	Oxidative Stress
AOP:483		Developmental disorder of mental health	Under Review	Mouse, Rat, Rabbit, Dog, Pigs, Cow, Human	0.25	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	-		0.27	KE:188	Neuroinflammation
						KE:2121	decreased, Intellectual Quotient
						KE:341	Impairment, Learning and memory
AOP:495	Androgen receptor activation leading to prostate cancer	Reproductive system disease; Cancer	-		0.44	KE:854	Alterations, Cellular proliferation / hyperplasia
						KE:286	Altered, Transcription of genes by the androgen receptor
						KE:2135	Prostate cancer
						KE:1183	Decreased, Apoptosis (Epithelial Cells)
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	-		0.62	KE:1115	Increase, Reactive oxygen species
						KE:177	Mitochondrial dysfunction
						KE:1392	Oxidative Stress
						KE:2145	Metabolic syndrome
						KE:2119	Insulin resistance, increased
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: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:525	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory	Developmental disorder of mental health	-		0.15	KE:2115	Altered, cholesterol metabolism
AOP:525		Developmental disorder of mental health	-		0.15	KE:341	Impairment, Learning and memory
AOP:530	Endocytotic lysosomal uptake leads to intestinal barrier disruption	Gastrointestinal system disease	-		0.4	KE:177	Mitochondrial dysfunction
AOP:530		Gastrointestinal system disease	-		0.4	KE:1931	Intestinal barrier, disruption
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	0.67	KE:1392	Oxidative Stress
						KE:2151	Disruption, neurotransmitter release
						KE:2233	Decreased, ERαβ heterodimers
						KE:341	Impairment, Learning and memory
						KE:188	Neuroinflammation
						KE:1262	Apoptosis
AOP:536	Estrogen receptor agonism leading to reduced survival and population growth due to renal failure	Unclassified	-		0.33	KE:307	Increase, Vitellogenin synthesis in liver
AOP:536		Unclassified	-		0.33	KE:351	Increased Mortality
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:551	Increased Muscarinic M2 Receptor leading to Arrhythmia	Symptom	-	Human, Mouse, Rat	0.2	KE:1106	Occurrence, cardiac arrhythmia
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	0.5	KE:1532	Decrease, Cardiac contractility
AOP:553		Cardiovascular system disease	-	Human, Rodents, Dogs, Pigs, Insects, Fish	0.5	KE:1535	Heart failure
AOP:554	β-adrenergic receptor agonists leading to arrhythmias.	Symptom	-	Human and other cells in culture, Rodents, Macaca mulatta, Zebrafish, Gallus gallus	0.25	KE:1106	Occurrence, cardiac arrhythmia
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	0.6	KE:1961	Prolongation of Action Potential Duration
						KE:2283	Increased the early premature depolarizations during repolarization
						KE:1535	Heart failure
AOP:556	Decreased Na/K ATPase activity leading to heart failure	Cardiovascular system disease	-		0.33	KE:1532	Decrease, Cardiac contractility
AOP:556	Decreased Na/K ATPase activity leading to heart failure	Cardiovascular system disease	-		0.33	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	0.33	KE:1532	Decrease, Cardiac contractility
AOP:558	Phosphodiesterase inhibition leading to heart failure	Cardiovascular system disease	-		0.33	KE:1535	Heart failure
AOP:559	Inhibition of acetylcholinesterase (AChE) leading to arrhythmias	Symptom	-	Human and other cells in culture, Rattus norvegicus, Dogs, Sus scrofa, Zebrafish, Insecta sp. BOLD:AAN5199	0.2	KE:1106	Occurrence, cardiac arrhythmia
AOP:560	Inhibition of Funny current (If) leading to Arrhythmias	Symptom	-	Human and other cells in culture, Rodents, Dogs, Zebrafish	0.25	KE:1106	Occurrence, cardiac arrhythmia
AOP:562	HCN Channel Inhibition leading to Arrhythmias	Symptom	-	Human and other cells in culture, Dogs, Zebrafish, Rodents, Pigs	0.2	KE:1106	Occurrence, cardiac arrhythmia
AOP:564	DBDPE-induced inhibition of mitochondrial complex Ⅰ leading to population decline via neurotoxicity and metabotoxicity.	Unclassified	-	Zebrafish	0.27	KE:2151	Disruption, neurotransmitter release
						KE:40	Decrease, Mitochondrial ATP production
						KE:351	Increased Mortality
AOP:569	Decreased DNA methylation of FAM50B/PTCHD3 leading to IQ loss of children via PI3K-Akt pathway	Developmental disorder of mental health	-		0.5	KE:1115	Increase, Reactive oxygen species
						KE:2121	decreased, Intellectual Quotient
						KE:2195	Increase, CNS Neural cell death
AOP:572	Imidacloprid-Induced BMP4 inhibition Leading to Neural Tube Closure Defects	Neural tube defect	-		0.2	KE:1561	Neural tube defects
AOP:573	Inhibition, cytochrome oxidase leads to Increased, pulmonary edema	Respiratory system disease	-	Rodents, Humans	0.33	KE:2316	Increased, pulmonary edema

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: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:408	reduction in ovarian granulosa cells, Aromatase (Cyp19a1)
						KE:219	Reduction, Plasma 17beta-estradiol concentrations
						KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:38	Protein Alkylation leading to Liver Fibrosis	Gastrointestinal system disease	WPHA/WNT Endorsed	Human, Rat	0.43	KE:244	Alkylation, Protein
						KE:1493	Increased Pro-inflammatory mediators
						KE:68	Accumulation, Collagen
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: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:128	Kidney dysfunction by decreased thyroid hormone	Urinary system disease	Under Development	Sprague-Dawley, Homo sapiens	0.18	KE:819	Decreased, Glomerular filtration
AOP:128	Kidney dysfunction by decreased thyroid hormone	Urinary system disease	Under Development	Sprague-Dawley, Homo sapiens	0.18	KE:277	Thyroid hormone synthesis, Decreased
AOP:209	Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP	Gastrointestinal system disease	-		0.38	KE:1286	Down Regulation, GSS and GSTs gene
						KE:1287	Glutathione synthesis
						KE:1284	Up Regulation, SREBF2
AOP:258	Renal protein alkylation leading to kidney toxicity	Urinary system disease	Under Development	Human, Rat, Mouse	0.6	KE:244	Alkylation, Protein
						KE:177	Mitochondrial dysfunction
						KE:40	Decrease, Mitochondrial ATP production
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	0.2	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:1115	Increase, Reactive oxygen species
AOP:329		Unclassified	-	Daphnia magna, Paracyclopina nana	0.4	KE:1445	Increase, Lipid peroxidation
AOP:330	Excessive reactive oxygen species production leading to mortality (4)	Unclassified	-	Daphnia magna	0.2	KE:1115	Increase, Reactive oxygen species
AOP:335	AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment	Cancer; Urinary system disease	-	Rat	0.4	KE:795	Increase, Regenerative cell proliferation (urothelial cells)
AOP:335		Cancer; Urinary system disease	-	Rat	0.4	KE:177	Mitochondrial dysfunction
AOP:409	Frustrated phagocytosis leads to malignant mesothelioma	Cancer	-		0.5	KE:870	Increase, Cell Proliferation
						KE:1115	Increase, Reactive oxygen species
						KE:1497	Increased, recruitment of inflammatory cells
						KE:1668	Frustrated phagocytosis
AOP:423	Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway	Unclassified	-		0.33	KE:1115	Increase, Reactive oxygen species
AOP:423		Unclassified	-		0.33	KE:177	Mitochondrial dysfunction
AOP:446	PM-related Adverse outcome pathway frameworks on various systems	Respiratory system disease	-		0.5	KE:1115	Increase, Reactive oxygen species
						KE:1445	Increase, Lipid peroxidation
						KE:1993	Increase, Pneumonia
						KE:1392	Oxidative Stress
						KE:1250	Decrease, Lung function
						KE:1198	Activation, Macrophages
						KE:1239	Altered, Gene Expression
						KE:1497	Increased, recruitment of inflammatory cells
						KE:149	Increase, Inflammation
						KE:1262	Apoptosis
AOP:453	Reactive oxygen species and subsequent oxidative stress lead to increased incidence of digestive morbidity and mortality in the general population	Gastrointestinal system disease	-		0.38	KE:1115	Increase, Reactive oxygen species
						KE:1931	Intestinal barrier, disruption
						KE:1392	Oxidative Stress
						KE:1995	Abnormal lipid metabolism
						KE:1198	Activation, Macrophages
AOP:469	Reactive oxygen speicies overproduction leading to increased digestive morbidity and mortality in generation population	Gastrointestinal system disease	-		0.38	KE:1115	Increase, Reactive oxygen species
						KE:1931	Intestinal barrier, disruption
						KE:1392	Oxidative Stress
						KE:1995	Abnormal lipid metabolism
						KE:1198	Activation, Macrophages
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:511	The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects	Cardiovascular system disease	-	Human, Mouse, Zebrafish	0.19	KE:1392	Oxidative Stress
						KE:1115	Increase, Reactive oxygen species
						KE:177	Mitochondrial dysfunction
AOP:523	Retinoic acid receptor agonism during neurodevelopment leading to microcephaly	Congenital nervous system abnormality; Nervous system disease	-		0.2	KE:2201	Agonism, Retinoic acid receptor
AOP: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	-		0.31	KE:1493	Increased Pro-inflammatory mediators
						KE:1198	Activation, Macrophages
						KE:1392	Oxidative Stress
						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:118	Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)	Cancer; Gastrointestinal system disease	-	Mus musculus, Rattus norvegicus	0.75	KE:719	Increase, hepatocellular adenomas and carcinomas
						KE:786	Increase, Cytotoxicity (hepatocytes)
						KE:787	Increase, Regenerative cell proliferation (hepatocytes)
AOP:205	AOP from chemical insult to cell death	Unclassified	-	Vertebrates	0.67	KE:1259	narcosis
						KE:1263	Necrosis
						KE:177	Mitochondrial dysfunction
						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	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		0.6	KE:1821	Decrease, Cell proliferation
						KE:1521	Decrease, Growth
						KE:1446	Decrease, Coupling of oxidative phosphorylation
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:303	Frustrated phagocytosis-induced lung cancer	Cancer	Under Development	Mammals	0.71	KE:1115	Increase, Reactive oxygen species
						KE:870	Increase, Cell Proliferation
						KE:1670	Lung cancer
						KE:1497	Increased, recruitment of inflammatory cells
						KE:1668	Frustrated phagocytosis
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	0.75	KE:1521	Decrease, Growth
						KE:1115	Increase, Reactive oxygen species
						KE:1445	Increase, Lipid peroxidation
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	0.67	KE:1821	Decrease, Cell proliferation
						KE:1505	Cell cycle, disrupted
						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	-		1.0	KE:1821	Decrease, Cell proliferation
						KE:1115	Increase, Reactive oxygen species
						KE:1445	Increase, Lipid peroxidation
						KE:1505	Cell cycle, disrupted
						KE:1521	Decrease, Growth
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:413	Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure	Unclassified	-	Fish, Mice	1.0	KE:1115	Increase, Reactive oxygen species
						KE:1445	Increase, Lipid peroxidation
						KE:351	Increased Mortality
						KE:759	Increased, Kidney Failure
						KE:1607	Increase, Necrosis
						KE:926	Oxidation, Glutathione (To be considered with MIE)
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:438	reactive oxygen species generation leading to increased cardiovascular morbidity and mortality	Cardiovascular system disease	-		0.5	KE:1929	Increased incidence of cardiovascular morbidity and mortality in the general population
						KE:1115	Increase, Reactive oxygen species
						KE:177	Mitochondrial dysfunction
						KE:1919	Increased, Cardiac Dysregulation
						KE:1392	Oxidative Stress
						KE:1924	Increased，Cardiac fibrosis
AOP:447	Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways	Urinary system disease	-		0.25	KE:1392	Oxidative Stress
						KE:759	Increased, Kidney Failure
						KE:177	Mitochondrial dysfunction
AOP:448	ROS, inflammation, and activation of nAChR lead to increased incidence of cardiovascular morbidity and mortality	Cardiovascular system disease	-		0.41	KE:1929	Increased incidence of cardiovascular morbidity and mortality in the general population
						KE:1115	Increase, Reactive oxygen species
						KE:1392	Oxidative Stress
						KE:2001	Cardiac hypertrophy
						KE:1198	Activation, Macrophages
						KE:1443	Atherosclerosis
						KE:1924	Increased，Cardiac fibrosis
AOP:463	The AOP framwork on silica nanopariticles induced hepatoxicity	Gastrointestinal system disease	-		0.55	KE:1115	Increase, Reactive oxygen species
						KE:177	Mitochondrial dysfunction
						KE:1392	Oxidative Stress
						KE:2034	liver dysfunction
						KE:149	Increase, Inflammation
						KE:1262	Apoptosis
AOP:472	DNA adduct formation leading to kidney failure	Urinary system disease	-		0.44	KE:1392	Oxidative Stress
						KE:759	Increased, Kidney Failure
						KE:149	Increase, Inflammation
						KE:1115	Increase, Reactive oxygen species
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: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	1.0	KE:1339	Increase, intracellular calcium
						KE:2151	Disruption, neurotransmitter release
						KE:2146	Activation of mitogen-activated protein kinase kinase, extracellular signal-regulated kinase 1/2
						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	1.0	KE:1115	Increase, Reactive oxygen species
						KE:177	Mitochondrial dysfunction
						KE:352	N/A, Neurodegeneration
						KE:341	Impairment, Learning and memory
						KE:1262	Apoptosis
						KE:1339	Increase, intracellular calcium
						KE:2146	Activation of mitogen-activated protein kinase kinase, extracellular signal-regulated kinase 1/2
AOP:505	Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway	Cancer	-	Human, Mouse, Rat	0.8	KE:1392	Oxidative Stress
						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
AOP:519	Cardiac ion channels blockade leading to increased incidence of cardiovascular morbidity and mortality	Cardiovascular system disease	-	Human and other cells in culture, Guinea pig, Rabbit	1.0	KE:1929	Increased incidence of cardiovascular morbidity and mortality in the general population
						KE:2282	Cardiac ion channels blockade
						KE:2283	Increased the early premature depolarizations during repolarization
						KE:1961	Prolongation of Action Potential Duration
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:2201	Agonism, Retinoic acid receptor
AOP:520		Developmental disorder of mental health	-	Mouse, Rat, Human	0.4	KE:341	Impairment, Learning and memory
AOP:532	Retinoic acid receptor agonism during cerebellar development leading to impaired locomotor function	Unclassified	-		0.4	KE:2201	Agonism, Retinoic acid receptor
AOP:532		Unclassified	-		0.4	KE:2231	Locomotor function. Impaired
AOP:550	Increased LMNA gene mutation leading to heart failure	Cardiovascular system disease	-	Human, Mouse, Rat	1.0	KE:1535	Heart failure
						KE:2278	Increased LMNA Mutation
						KE:2279	Structural changes in lamin A/C
						KE:1924	Increased，Cardiac fibrosis
						KE:2066	Altered Signaling Pathways

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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.