DEDUCT | Database of Endocrine Disrupting chemicals and their Toxicity profiles

Clofibrate

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:21	Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2	Unclassified	WPHA/WNT Endorsed	Zebrafish, Medaka, Gallus gallus	0.2	KE:317	Altered, Cardiovascular development/function
AOP:27	Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)	Gastrointestinal system disease	Under Development	Humans	0.12	KE:1115	Increase, Reactive oxygen species
AOP:39	Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response	Respiratory system disease	Under Development	Human, Mouse	0.2	KE:272	Activation/Proliferation, T-cells
AOP:40	Covalent Protein binding leading to Skin Sensitisation	Integumentary system disease	WPHA/WNT Endorsed	Mouse, Human	0.2	KE:272	Activation/Proliferation, T-cells
AOP: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:60	NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-		0.08	KE:474	Down Regulation, HMGCS2
AOP:64	Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility	Reproductive system disease	-	Rattus norvegicus	0.14	KE:496	Increased apoptosis, decreased fetal/adult Leydig Cells
AOP:104	Altered ion channel activity leading impaired heart function	Unclassified	-		0.25	KE:699	Increased, cardiac arrthymia
AOP:105	Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)	Cancer; Urinary system disease	-	Rattus norvegicus	0.33	KE:709	Increase, Cytotoxicity (renal tubular cell)
AOP:105		Cancer; Urinary system disease	-	Rattus norvegicus	0.33	KE:710	Increase, Regenerative cell proliferation (tubular epithelial cells)
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:114	HPPD inhibition leading to corneal papillomas and carcinomas (in rat)	Cancer	-	Rattus norvegicus	0.17	KE:778	Increase, Regenerative cell proliferation (corneal cells)
AOP:115	Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)	Cancer	-	Mus musculus, Rattus norvegicus	0.2	KE:781	Increase, Regenerative cell proliferation (forestomach epithelial cells)
AOP:116	Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)	Cancer; Urinary system disease	-	Rattus norvegicus	0.25	KE:710	Increase, Regenerative cell proliferation (tubular epithelial cells)
AOP: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:121	Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)	Cancer; Urinary system disease	-	Mus musculus, Rattus norvegicus	0.2	KE:795	Increase, Regenerative cell proliferation (urothelial cells)
AOP:136	Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors	Benign neoplasm; Respiratory system disease	Under Review		0.29	KE:868	Increase, Tissue Degeneration, Necrosis & Atrophy
AOP:136		Benign neoplasm; Respiratory system disease	Under Review		0.29	KE:870	Increase, Cell Proliferation
AOP:149	Peptide Oxidation Leading to Hypertension	Cardiovascular system disease	Under Development	Human, Mouse, Rat, Cow	0.2	KE:933	KE6 : Depletion, Nitric Oxide
AOP:149	Peptide Oxidation Leading to Hypertension	Cardiovascular system disease	Under Development	Human, Mouse, Rat, Cow	0.2	KE:937	KE7 : Impaired, Vasodilation
AOP:150	Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF	Unclassified	WPHA/WNT Endorsed	Chicken, Zebrafish, Mouse, Rattus norvegicus	0.14	KE:317	Altered, Cardiovascular development/function
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:207	NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans	Reproductive system disease	-	Caenorhabditis elegans	0.25	KE:1115	Increase, Reactive oxygen species
AOP:207		Reproductive system disease	-	Caenorhabditis elegans	0.25	KE:1262	Apoptosis
AOP:209	Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP	Gastrointestinal system disease	-		0.25	KE:1289	Perturbation of cholesterol
AOP:209		Gastrointestinal system disease	-		0.25	KE:1287	Glutathione synthesis
AOP:212	Histone deacetylase inhibition leading to testicular atrophy	Reproductive system disease	WPHA/WNT Endorsed	Rat, Human, Mouse	0.17	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:256	Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity	Urinary system disease	Under Development	Human, Rat, Mouse	0.2	KE:709	Increase, Cytotoxicity (renal tubular cell)
AOP:257	Receptor mediated endocytosis and lysosomal overload leading to kidney toxicity	Urinary system disease	Under Development	Human, Rat, Mouse, Dog, Monkey	0.2	KE:709	Increase, Cytotoxicity (renal tubular cell)
AOP:258	Renal protein alkylation leading to kidney toxicity	Urinary system disease	Under Development	Human, Rat, Mouse	0.2	KE:709	Increase, Cytotoxicity (renal tubular cell)
AOP:263	Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation	Unclassified	WPHA/WNT Endorsed	Zebrafish, Mouse, Rat, Lemna minor, Human, Caenorhabditis elegans	0.25	KE:1821	Decrease, Cell proliferation
AOP:267	Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion	Unclassified	Under Development		0.2	KE:1821	Decrease, Cell proliferation
AOP:272	Deposition of energy leading to lung cancer	Cancer	WPHA/WNT Endorsed	Human, Rat, Mouse	0.14	KE:870	Increase, Cell Proliferation
AOP:286	Mitochondrial complex III antagonism leading to growth inhibition (1)	Unclassified	-	Lemna minor, Daphnia magna, Danio rerio	0.25	KE:1821	Decrease, Cell proliferation
AOP:290	Mitochondrial ATP synthase antagonism leading to growth inhibition (1)	Unclassified	-	Daphnia magna	0.25	KE:1821	Decrease, Cell proliferation
AOP:293	Increased DNA damage leading to increased risk of breast cancer	Genetic disease; Thoracic disease; Cancer	Under Development	Rattus rattus, Mus musculus	0.11	KE:1182	Increase, Cell Proliferation (Epithelial Cells)
AOP:294	Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer	Genetic disease; Thoracic disease; Cancer	Under Development		0.11	KE:1182	Increase, Cell Proliferation (Epithelial Cells)
AOP:303	Frustrated phagocytosis-induced lung cancer	Cancer	Under Development	Mammals	0.29	KE:870	Increase, Cell Proliferation
AOP:303	Frustrated phagocytosis-induced lung cancer	Cancer	Under Development	Mammals	0.29	KE:1115	Increase, Reactive oxygen species
AOP:335	AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment	Cancer; Urinary system disease	-	Rat	0.2	KE:795	Increase, Regenerative cell proliferation (urothelial cells)
AOP:382	Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis	Musculoskeletal system disease; Respiratory system disease	Under Development		0.17	KE:1115	Increase, Reactive oxygen species
AOP:383	Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis	Gastrointestinal system disease	Under Development		0.17	KE:1115	Increase, Reactive oxygen species
AOP:384	Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease	Urinary system disease	-		0.17	KE:1115	Increase, Reactive oxygen species
AOP:409	Frustrated phagocytosis leads to malignant mesothelioma	Cancer	-		0.25	KE:870	Increase, Cell Proliferation
AOP:409	Frustrated phagocytosis leads to malignant mesothelioma	Cancer	-		0.25	KE:1115	Increase, Reactive oxygen species
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:416	Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathway	Cancer	-		0.17	KE:1115	Increase, Reactive oxygen species
AOP:418	Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathway	Respiratory system disease	-		0.2	KE:1115	Increase, Reactive oxygen species
AOP:419	Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathway	Respiratory system disease	-		0.25	KE:1262	Apoptosis
AOP:420	Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathway	Cancer	-		0.25	KE:870	Increase, Cell Proliferation
AOP:432	Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia	Hematopoietic system disease; Cancer	-	Homo sapiens, Mus musculus	0.09	KE:870	Increase, Cell Proliferation
AOP:437	Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity	Urinary system disease	Under Development		0.2	KE:709	Increase, Cytotoxicity (renal tubular cell)
AOP:439	Activation of the AhR leading to metastatic breast cancer	Thoracic disease; Cancer	Under Development	Humans, Mice	0.22	KE:1971	Increased, tumor growth
AOP:439	Activation of the AhR leading to metastatic breast cancer	Thoracic disease; Cancer	Under Development	Humans, Mice	0.22	KE:1262	Apoptosis
AOP:441	Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation	Congenital nervous system abnormality; Nervous system disease	-	Homo sapiens, Mus musculus musculus, Rattus norvegicus	0.14	KE:1262	Apoptosis
AOP: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:451	Interaction with lung resident cell membrane components leads to lung cancer	Cancer	-	Human	0.22	KE:870	Increase, Cell Proliferation
AOP:451		Cancer	-	Human	0.22	KE:1115	Increase, Reactive oxygen species
AOP:452	Adverse outcome pathway of PM-induced respiratory toxicity	Respiratory system disease	-		0.18	KE:2013	Airway remodeling
AOP:452	Adverse outcome pathway of PM-induced respiratory toxicity	Respiratory system disease	-		0.18	KE:1262	Apoptosis
AOP:456	Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity	Unclassified	Under Review	Zebrafish, Mouse, Human, Chicken	0.17	KE:317	Altered, Cardiovascular development/function
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:748	Increased, Estrogen receptor (ER) activity
AOP:478	Deposition of energy leading to occurrence of cataracts	Nervous system disease; Monogenic disease	Under Review	Human, Mouse, Rat, Rhesus monkeys, Rabbit, Guinea pig	0.1	KE:870	Increase, Cell Proliferation
AOP: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:493	ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity	Acquired metabolic disease	-	Mus musculus, Homo sapiens	0.1	KE:2125	Increased fat mass
AOP:495	Androgen receptor activation leading to prostate cancer	Reproductive system disease; Cancer	-		0.22	KE:854	Alterations, Cellular proliferation / hyperplasia
AOP:495	Androgen receptor activation leading to prostate cancer	Reproductive system disease; Cancer	-		0.22	KE:1183	Decreased, Apoptosis (Epithelial Cells)
AOP:500	Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis	Developmental disorder of mental health	-	Rattus norvegicus, Mus musculus, Homo sapiens	0.29	KE:1115	Increase, Reactive oxygen species
AOP:500		Developmental disorder of mental health	-	Rattus norvegicus, Mus musculus, Homo sapiens	0.29	KE:1262	Apoptosis
AOP:510	Demethylation of PPAR promotor leading to vascular disrupting effects	Cardiovascular system disease	-	Human, Mouse, Zebrafish	0.1	KE:2165	Activation of PPAR
AOP:525	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory	Developmental disorder of mental health	-		0.08	KE:2115	Altered, cholesterol metabolism
AOP:535	Binding and activation of GPER leading to learning and memory impairments	Developmental disorder of mental health	-	Mouse, Human	0.11	KE:1262	Apoptosis
AOP:539	Decreased Sodium/Potassium ATPase activity leads to Heart failure	Cardiovascular system disease	-	Fish	0.14	KE:2261	Decreased, blood plasma volume
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: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:16	Acetylcholinesterase inhibition leading to acute mortality	Unclassified	Under Development		0.14	KE:360	Decrease, Population growth rate
AOP:23	Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)	Unclassified	WPHA/WNT Endorsed	Pimephales promelas	0.1	KE:360	Decrease, Population growth rate
AOP:25	Aromatase inhibition leading to reproductive dysfunction	Unclassified	WPHA/WNT Endorsed	Fathead minnow, Medaka, Zebrafish	0.12	KE:360	Decrease, Population growth rate
AOP:30	Estrogen receptor antagonism leading to reproductive dysfunction	Unclassified	Under Review	Zebra danio, Fathead minnow, Medaka	0.17	KE:360	Decrease, Population growth rate
AOP:34	LXR activation leading to hepatic steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-		0.08	KE:345	N/A, Liver Steatosis
AOP:63	Cyclooxygenase inhibition leading to reproductive dysfunction	Reproductive system disease	-	Goldfish, Human, Mouse, Rat	0.2	KE:360	Decrease, Population growth rate
AOP:97	5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline	Unclassified	-	Mytilus galloprovincialis, Tritonea diomedea, Lymnaea stagnalis, Melibe leonine, Helix lucorum, Lampsilis fasciola	0.1	KE:360	Decrease, Population growth rate
AOP:100	Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior	Reproductive system disease	-	Goldfish	0.14	KE:360	Decrease, Population growth rate
AOP:101	Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release	Reproductive system disease	-	Goldfish	0.14	KE:360	Decrease, Population growth rate
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:360	Decrease, Population growth rate
AOP:103	Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint	Reproductive system disease	-	Goldfish, Human, Rat, Mouse	0.1	KE:360	Decrease, Population growth rate
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:716	Increase, cell proliferation (hepatocytes)
AOP:107		Cancer; Gastrointestinal system disease	Under Review	Rattus norvegicus, Mus musculus	0.4	KE:719	Increase, hepatocellular adenomas and carcinomas
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:726	Increased, Induction of pyruvate dehydrogenase (PDH)
AOP:108		Cancer; Gastrointestinal system disease	-	Mus musculus, Rattus norvegicus	0.33	KE:719	Increase, hepatocellular adenomas and carcinomas
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:122	Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation	Unclassified	-	Pimephales promelas	0.1	KE:360	Decrease, Population growth rate
AOP:123	Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription	Unclassified	-	Pimephales promelas	0.09	KE:360	Decrease, Population growth rate
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:139	Alkylation of DNA leading to cancer 1	Cancer	-	Homo sapiens, Mus musculus	0.25	KE:885	Increase, Cancer
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:360	Decrease, Population growth rate
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:360	Decrease, Population growth rate
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:360	Decrease, Population growth rate
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:360	Decrease, Population growth rate
AOP:159	Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	Zebrafish, Fathead minnow	0.12	KE:360	Decrease, Population growth rate
AOP:203	5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline	Reproductive system disease	-		0.12	KE:360	Decrease, Population growth rate
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:216	Deposition of energy leading to population decline via DNA strand breaks and follicular atresia	Unclassified	-	Daphnia magna	0.17	KE:360	Decrease, Population growth rate
AOP:218	Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity	Unclassified	-	Japanese quail, Cynops pyrrhogaster	0.17	KE:360	Decrease, Population growth rate
AOP:219	Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior	Unclassified	-	Japanese quail, Cynops pyrrhogaster	0.17	KE:360	Decrease, Population growth rate
AOP:220	Cyp2E1 Activation Leading to Liver Cancer	Cancer; Gastrointestinal system disease	WPHA/WNT Endorsed	Rodents, Homo sapiens	0.4	KE:1395	Liver Cancer
AOP:220	Cyp2E1 Activation Leading to Liver Cancer	Cancer; Gastrointestinal system disease	WPHA/WNT Endorsed	Rodents, Homo sapiens	0.4	KE:1393	Hepatocytotoxicity
AOP:238	Deposition of energy leading to population decline via DNA strand breaks and oocyte apoptosis	Unclassified	-	Mice, Daphnia magna	0.17	KE:360	Decrease, Population growth rate
AOP:289	Inhibition of 5α-reductase leading to impaired fecundity in female fish	Unclassified	Under Development	Fish	0.17	KE:360	Decrease, Population growth rate
AOP:292	Inhibition of tyrosinase leads to decreased population in fish	Unclassified	Under Development	Fish	0.17	KE:360	Decrease, Population growth rate
AOP:297	Inhibition of retinaldehyde dehydrogenase leads to population decline	Unclassified	Under Development	Fish	0.17	KE:360	Decrease, Population growth rate
AOP:299	Deposition of energy leading to population decline via DNA oxidation and follicular atresia	Unclassified	-		0.29	KE:360	Decrease, Population growth rate
AOP:299		Unclassified	-		0.29	KE:1115	Increase, Reactive oxygen species
AOP:310	Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR	Unclassified	-	Zebrafish	0.08	KE:360	Decrease, Population growth rate
AOP:311	Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis	Unclassified	-	Daphnia magna, Fish	0.29	KE:360	Decrease, Population growth rate
AOP:311		Unclassified	-	Daphnia magna, Fish	0.29	KE:1115	Increase, Reactive oxygen species
AOP:312	Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement	Unclassified	-		0.17	KE:360	Decrease, Population growth rate
AOP:334	Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration	Unclassified	-	Teleost fish	0.17	KE:360	Decrease, Population growth rate
AOP:336	DNA methyltransferase inhibition leading to population decline (1)	Unclassified	-	Daphnia magna	0.14	KE:360	Decrease, Population growth rate
AOP:337	DNA methyltransferase inhibition leading to population decline (2)	Unclassified	-	Daphnia magna	0.12	KE:360	Decrease, Population growth rate
AOP:338	DNA methyltransferase inhibition leading to population decline (3)	Unclassified	-		0.14	KE:360	Decrease, Population growth rate
AOP:339	DNA methyltransferase inhibition leading to population decline (4)	Unclassified	-		0.12	KE:360	Decrease, Population growth rate
AOP:340	DNA methyltransferase inhibition leading to transgenerational effects (1)	Physical disorder	-		0.12	KE:360	Decrease, Population growth rate
AOP:341	DNA methyltransferase inhibition leading to transgenerational effects (2)	Physical disorder	-	Daphnia magna	0.11	KE:360	Decrease, Population growth rate
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:360	Decrease, Population growth rate
AOP:348	Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory	Unclassified	Under Development	Fish	0.6	KE:360	Decrease, Population growth rate
						KE:1756	Decreased, plasma 11-ketotestosterone level
						KE:1758	Impaired, Spermatogenesis
AOP:349	Inhibition of 11β-hydroxylase leading to decresed population trajectory	Unclassified	Under Development	Fish	0.25	KE:360	Decrease, Population growth rate
AOP:349		Unclassified	Under Development	Fish	0.25	KE:1756	Decreased, plasma 11-ketotestosterone level
AOP:363	Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure	Unclassified	Under Review	Zebrafish	0.12	KE:360	Decrease, Population growth rate
AOP:364	Thyroperoxidase inhibition leading to altered visual function via decreased eye size	Unclassified	Under Development		0.12	KE:360	Decrease, Population growth rate
AOP:365	Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning	Unclassified	Under Development		0.12	KE:360	Decrease, Population growth rate
AOP:376	Androgen receptor agonism leading to male-biased sex ratio	Unclassified	WPHA/WNT Endorsed	Zebrafish, Medaka, Fathead minnow, Channel catfish, Oreochromis niloticus, Chinook salmon	0.25	KE:360	Decrease, Population growth rate
AOP:386	Deposition of ionizing energy leading to population decline via inhibition of photosynthesis	Reproductive system disease	-	Lemna minor, Chlamydomonas reinhardtii	0.25	KE:360	Decrease, Population growth rate
AOP:386		Reproductive system disease	-	Lemna minor, Chlamydomonas reinhardtii	0.25	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:360	Decrease, Population growth rate
AOP:387		Reproductive system disease	-	Lemna minor	0.25	KE:1115	Increase, Reactive oxygen species
AOP:388	Deposition of ionising energy leading to population decline via programmed cell death	Reproductive system disease	-	Lemna minor	0.2	KE:360	Decrease, Population growth rate
AOP:389	Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis	Reproductive system disease	-	Lemna minor	0.14	KE:360	Decrease, Population growth rate
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:360	Decrease, Population growth rate
AOP:410	GSK3beta inactivation leading to increased mortality via defects in developing inner ear	Unclassified	-	Zebrafish	0.1	KE:360	Decrease, Population growth rate
AOP:444	Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability	Unclassified	-		0.11	KE:360	Decrease, Population growth rate
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:497	ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome	Inherited metabolic disorder; Disease of metabolism	-		0.25	KE:2145	Metabolic syndrome
AOP:497		Inherited metabolic disorder; Disease of metabolism	-		0.25	KE:1115	Increase, Reactive oxygen species
AOP:504	SULT1E1 inhibition leading to uterine adenocarcinoma via increased estrogen availability at target organ level	Unclassified	-	Mammals	0.33	KE:1065	Activation, estrogen receptor alpha
AOP:521	Essential element imbalance leads to reproductive failure via oxidative stress	Unclassified	-	Murinae gen. sp.	0.43	KE:1115	Increase, Reactive oxygen species
						KE:1758	Impaired, Spermatogenesis
						KE:2147	Decreased, Viable Offspring
AOP:534	Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress	Cancer	-	Vertebrates	0.33	KE:885	Increase, Cancer
AOP:534		Cancer	-	Vertebrates	0.33	KE:1115	Increase, Reactive oxygen species
AOP:536	Estrogen receptor agonism leading to reduced survival and population growth due to renal failure	Unclassified	-		0.17	KE:360	Decrease, Population growth rate
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: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: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:561	Aromatase induction leading to estrogen receptor alpha activation via increased estradiol	Unclassified	-	Vertebrates	0.2	KE:1065	Activation, estrogen receptor alpha
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	0.09	KE:360	Decrease, Population growth rate
AOP:567	Binding of plastoquinone B leading to decrease, population growth rate via decrease, photosystem II efficiency	Unclassified	-		0.17	KE:360	Decrease, Population growth rate

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:18	PPARα activation in utero leading to impaired fertility in males	Reproductive system disease	Under Review	Human, Rat, Mouse	0.12	KE:227	Activation, PPARα
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:167	Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.	Reproductive system disease; Cancer	-	Mouse, Homo sapiens	0.43	KE:1067	Proliferation/Clonal Expansion, aberrant basal cells
						KE:1065	Activation, estrogen receptor alpha
						KE:1064	prepubertal increase, Estrogen receptor (ER) activity
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	0.17	KE:1115	Increase, Reactive oxygen species
AOP:314	Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE)	Immune system disease; Musculoskeletal system disease	Under Development	Homo sapiens	0.2	KE:1710	Binding to estrogen receptor (ER)-α in immune cells
AOP:324	Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and cell death	Unclassified	-	Fish	0.25	KE:1115	Increase, Reactive oxygen species
AOP:325	Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and cell death	Unclassified	-	Fish	0.25	KE:1115	Increase, Reactive oxygen species
AOP:326	Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell death	Unclassified	-	Fish	0.25	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	0.2	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: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	0.33	KE:1821	Decrease, Cell proliferation
AOP:331		Unclassified	-		0.33	KE:1115	Increase, Reactive oxygen species
AOP:332	Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferation	Unclassified	-		0.4	KE:1821	Decrease, Cell proliferation
AOP:332		Unclassified	-		0.4	KE:1115	Increase, Reactive oxygen species
AOP:333	Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylation	Unclassified	-		0.4	KE:1821	Decrease, Cell proliferation
AOP:333		Unclassified	-		0.4	KE:1115	Increase, Reactive oxygen species
AOP:392	Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation	Unclassified	Under Development	Humans	0.2	KE:1867	Bradykinin system, hyperactivated
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:445	Estrogen Receptor Alpha Agonism leads to Impaired Reproduction	Reproductive system disease	-		0.12	KE:1065	Activation, estrogen receptor alpha
AOP:446	PM-related Adverse outcome pathway frameworks on various systems	Respiratory system disease	-		0.1	KE:1115	Increase, Reactive oxygen species
AOP:446		Respiratory system disease	-		0.1	KE:1262	Apoptosis
AOP:448	ROS, inflammation, and activation of nAChR lead to increased incidence of cardiovascular morbidity and mortality	Cardiovascular system disease	-		0.06	KE: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	-		0.15	KE:1115	Increase, Reactive oxygen species
AOP:453		Gastrointestinal system disease	-		0.15	KE:1995	Abnormal lipid metabolism
AOP:469	Reactive oxygen speicies overproduction leading to increased digestive morbidity and mortality in generation population	Gastrointestinal system disease	-		0.15	KE:1115	Increase, Reactive oxygen species
AOP:469		Gastrointestinal system disease	-		0.15	KE:1995	Abnormal lipid metabolism
AOP:472	DNA adduct formation leading to kidney failure	Urinary system disease	-		0.33	KE:1097	Occurrence, renal proximal tubular necrosis
						KE:1816	Mitochondrial dysfunction EMPTY
						KE:1115	Increase, Reactive oxygen species
AOP:488	Increased reactive oxygen species production leading to decreased cognitive function	Cognitive disorder	-	Human	0.14	KE:1115	Increase, Reactive oxygen species
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:1065	Activation, estrogen receptor alpha
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:541	Excessive ROS generation leading to increased incidence of vascular calcification by VSMC phenotype switching	Cardiovascular system disease	-		0.15	KE:1816	Mitochondrial dysfunction EMPTY
AOP:541		Cardiovascular system disease	-		0.15	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:37	PPARα activation leading to hepatocellular adenomas and carcinomas in rodents	Cancer; Gastrointestinal system disease	Under Development	Mouse, Rat	1.0	KE:1171	Increase, Clonal Expansion of Altered Hepatic Foci
						KE:227	Activation, PPARα
						KE:1170	Increase, Phenotypic enzyme activity
						KE:716	Increase, cell proliferation (hepatocytes)
						KE:719	Increase, hepatocellular adenomas and carcinomas
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:323	PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone	Unclassified	-	Teleost fish	1.0	KE:227	Activation, PPARα
						KE:360	Decrease, Population growth rate
						KE:807	Decreased, cholesterol
						KE:1756	Decreased, plasma 11-ketotestosterone level
						KE:1758	Impaired, Spermatogenesis
						KE:2147	Decreased, Viable Offspring
AOP:463	The AOP framwork on silica nanopariticles induced hepatoxicity	Gastrointestinal system disease	-		0.27	KE:2034	liver dysfunction
						KE:1115	Increase, Reactive oxygen species
						KE:1262	Apoptosis
AOP:505	Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway	Cancer	-	Human, Mouse, Rat	0.4	KE:885	Increase, Cancer
AOP:505		Cancer	-	Human, Mouse, Rat	0.4	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:540	Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production	Unclassified	-		0.33	KE:360	Decrease, Population growth rate
						KE:1115	Increase, Reactive oxygen species
						KE:1262	Apoptosis

DISCLAIMER

We have built a comprehensive resource which compiles potential endocrine disrupting chemicals (EDCs) based on the observed adverse effects or endocrine-mediated endpoints in published experiments on humans or rodents to support basic research. We are not responsible for any errors or omissions in the published research articles or supporting literature on potential EDCs compiled in this resource. Users are advised to exercise their own judgement on the weight of evidence for potential EDCs compiled in this resource. Importantly, our sole goal to build this resource on potential EDCs is to enable future basic research towards better understanding of the systems-level perturbations upon chemical exposure rather than influencing regulatory advice on chemical use.