DEDUCT | Database of Endocrine Disrupting chemicals and their Toxicity profiles

Benzophenone-3

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: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:27	Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)	Gastrointestinal system disease	Under Development	Humans	0.12	KE:288	Activation of specific nuclear receptors, Transcriptional change
AOP:48	Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.	Developmental disorder of mental health	WPHA/WNT Endorsed	Human, Mouse, Rat	0.11	KE:352	N/A, Neurodegeneration
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:80	Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure	Unclassified	-	Honey bee	0.12	KE:664	Overwhelmed, Mitochondrial DNA repair mechanisms
AOP: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	0.2	KE:1214	Altered gene expression specific to CAR activation, 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	0.17	KE:768	Increase, Cytotoxicity
AOP:112	Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)	Reproductive system disease; Cancer	-	Rattus norvegicus	0.17	KE:111	Agonism, Estrogen receptor
AOP:136	Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors	Benign neoplasm; Respiratory system disease	Under Review		0.14	KE:768	Increase, Cytotoxicity
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:1271	Activation of TGF-β signaling
AOP:207	NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans	Reproductive system disease	-	Caenorhabditis elegans	0.25	KE:1281	Increased, DNA Damage-Repair
AOP:207		Reproductive system disease	-	Caenorhabditis elegans	0.25	KE:1262	Apoptosis
AOP:218	Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity	Unclassified	-	Japanese quail, Cynops pyrrhogaster	0.17	KE:1141	Decreased, Reproductive Success
AOP:219	Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior	Unclassified	-	Japanese quail, Cynops pyrrhogaster	0.17	KE:1141	Decreased, Reproductive Success
AOP:272	Deposition of energy leading to lung cancer	Cancer	WPHA/WNT Endorsed	Human, Rat, Mouse	0.14	KE:155	Inadequate DNA repair
AOP:277	Impaired IL-1R1 signaling leading to Impaired T-Cell Dependent Antibody Response	Immune system disease	WPHA/WNT Endorsed	Homo sapiens, Mus musculus, Rattus norvegicus	0.25	KE:202	Inhibition, Nuclear factor kappa B (NF-kB)
AOP:278	IKK complex inhibition leading to liver injury	Unclassified	-		0.12	KE:202	Inhibition, Nuclear factor kappa B (NF-kB)
AOP:288	Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)	Endocrine system disease	-	Human, Rat	0.12	KE:1614	Decrease, androgen receptor activation
AOP:296	Oxidative DNA damage leading to chromosomal aberrations and mutations	Genetic disease; Chromosomal disease	WPHA/WNT Endorsed	Human, Mice, Rat, Fish	0.2	KE:155	Inadequate DNA repair
AOP:305	5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring	Unclassified	Under Development	Rat, Human, Mouse	0.4	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:305		Unclassified	Under Development	Rat, Human, Mouse	0.4	KE:1614	Decrease, androgen receptor activation
AOP:321	Reduced environmental pH leading to thinner shells in Mytilus edulis	Unclassified	-		0.09	KE:10042	Abnormal development
AOP:322	Alkylation of DNA leading to reduced sperm count	Reproductive system disease	-		0.2	KE:155	Inadequate DNA repair
AOP:347	Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis	Musculoskeletal system disease; Respiratory system disease	-		0.22	KE:1795	Latent Transforming growth Factor beta expression
AOP:347		Musculoskeletal system disease; Respiratory system disease	-		0.22	KE:1283	Activation, TGF-beta pathway
AOP:374	Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on brain cells (neuronal and non-neuronal) leads to neuroinflammation resulting in encephalitis	Nervous system disease	Under Development	Human	0.25	KE:352	N/A, Neurodegeneration
AOP:388	Deposition of ionising energy leading to population decline via programmed cell death	Reproductive system disease	-	Lemna minor	0.2	KE:1194	Increase, DNA damage
AOP:397	Bulky DNA adducts leading to mutations	Genetic disease	Under Development		0.33	KE:155	Inadequate DNA repair
AOP:423	Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway	Unclassified	-		0.17	KE:1194	Increase, DNA damage
AOP:432	Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia	Hematopoietic system disease; Cancer	-	Homo sapiens, Mus musculus	0.18	KE:1194	Increase, DNA damage
AOP:432		Hematopoietic system disease; Cancer	-	Homo sapiens, Mus musculus	0.18	KE:155	Inadequate DNA repair
AOP:435	Deposition of ionising energy leads to population decline via pollen abnormal	Reproductive system disease	-		0.17	KE:1194	Increase, DNA damage
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	0.22	KE:1052	Hyperplasia, ovarian epithelium
AOP:440			Under Development	Human, Rat, Mice	0.22	KE:1973	Increased, estrogens
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	0.29	KE:1194	Increase, DNA damage
AOP:441			-	Homo sapiens, Mus musculus musculus, Rattus norvegicus	0.29	KE:1262	Apoptosis
AOP:446	PM-related Adverse outcome pathway frameworks on various systems	Respiratory system disease	-		0.2	KE:18	Activation, AhR
						KE:1194	Increase, DNA damage
						KE:165	Activation, Long term AHR receptor driven direct and indirect gene expression changes
						KE:1262	Apoptosis
AOP:449	Ceramide synthase inhibition leading to neural tube defects	Neural tube defect	-		0.14	KE:1502	Histone deacetylase inhibition
AOP:450	Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality	Nervous system disease	-	Rattus norvegicus, Mus musculus, Homo sapiens	0.14	KE:352	N/A, Neurodegeneration
AOP:452	Adverse outcome pathway of PM-induced respiratory toxicity	Respiratory system disease	-		0.09	KE:1262	Apoptosis
AOP:460	Antagonism of Smoothened receptor leading to orofacial clefting	Unclassified	Under Development	Mouse	0.11	KE:1262	Apoptosis
AOP:463	The AOP framwork on silica nanopariticles induced hepatoxicity	Gastrointestinal system disease	-		0.09	KE:1262	Apoptosis
AOP:465	Alcohol dehydrogenase leading to reproductive dysfunction	Unclassified	-		0.25	KE:748	Increased, Estrogen receptor (ER) activity
AOP:465	Alcohol dehydrogenase leading to reproductive dysfunction	Unclassified	-		0.25	KE:2050	Increase, developmental abnormalities
AOP:467	Knickkopf leading to mortality	Unclassified	-		0.11	KE:2050	Increase, developmental abnormalities
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:155	Inadequate DNA repair
AOP:491	Decrease, GLI1/2 target gene expression leads to orofacial clefting	Unclassified	Under Development	Mouse	0.17	KE:1262	Apoptosis
AOP:495	Androgen receptor activation leading to prostate cancer	Reproductive system disease; Cancer	-		0.11	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:496	Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）	Unclassified	-	Zebrafish	0.1	KE:286	Altered, Transcription of genes by the androgen receptor
AOP: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:352	N/A, Neurodegeneration
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:511	The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects	Cardiovascular system disease	-	Human, Mouse, Zebrafish	0.06	KE:2171	Activated BMP/TGF-beta pathway
AOP:535	Binding and activation of GPER leading to learning and memory impairments	Developmental disorder of mental health	-	Mouse, Human	0.22	KE:2233	Decreased, ERαβ heterodimers
AOP:535		Developmental disorder of mental health	-	Mouse, Human	0.22	KE:1262	Apoptosis
AOP:540	Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production	Unclassified	-		0.11	KE:1262	Apoptosis
AOP:550	Increased LMNA gene mutation leading to heart failure	Cardiovascular system disease	-	Human, Mouse, Rat	0.2	KE:2066	Altered Signaling Pathways

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	0.12	KE:352	N/A, Neurodegeneration
AOP:63	Cyclooxygenase inhibition leading to reproductive dysfunction	Reproductive system disease	-	Goldfish, Human, Mouse, Rat	0.2	KE:675	Reduced, Reproductive Success
AOP:100	Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior	Reproductive system disease	-	Goldfish	0.14	KE:675	Reduced, Reproductive Success
AOP:101	Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release	Reproductive system disease	-	Goldfish	0.14	KE:675	Reduced, Reproductive Success
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:675	Reduced, Reproductive Success
AOP:103	Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint	Reproductive system disease	-	Goldfish, Human, Rat, Mouse	0.1	KE:675	Reduced, Reproductive Success
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:203	5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline	Reproductive system disease	-		0.12	KE:1141	Decreased, Reproductive Success
AOP:205	AOP from chemical insult to cell death	Unclassified	-	Vertebrates	0.17	KE:1262	Apoptosis
AOP:260	CYP2E1 activation and formation of protein adducts leading to neurodegeneration	Nervous system disease	-	Human	0.14	KE:1514	Neurodegeneration
AOP:281	Acetylcholinesterase Inhibition Leading to Neurodegeneration	Nervous system disease	-		0.1	KE:352	N/A, Neurodegeneration
AOP:294	Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer	Genetic disease; Thoracic disease; Cancer	Under Development		0.22	KE:1194	Increase, DNA damage
AOP:294		Genetic disease; Thoracic disease; Cancer	Under Development		0.22	KE:1193	N/A, Breast Cancer
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:1982	metastatic breast cancer
AOP:443		Thoracic disease; Cancer	Under Development		0.2	KE:155	Inadequate DNA repair
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:504	SULT1E1 inhibition leading to uterine adenocarcinoma via increased estrogen availability at target organ level	Unclassified	-	Mammals	0.67	KE:1065	Activation, estrogen receptor alpha
AOP:504		Unclassified	-	Mammals	0.67	KE:2251	Estradiol availability, increased
AOP:505	Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway	Cancer	-	Human, Mouse, Rat	0.2	KE:885	Increase, Cancer
AOP:513	Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway	Cancer	-	Human, Mouse, Rat	0.2	KE:885	Increase, Cancer
AOP:534	Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress	Cancer	-	Vertebrates	0.17	KE:885	Increase, Cancer
AOP:546	Succinate dehydrogenase inactivation leads to cancer through hypoxic-like mechanisms	Cancer	-	Human and other cells in culture	0.2	KE:885	Increase, Cancer
AOP:561	Aromatase induction leading to estrogen receptor alpha activation via increased estradiol	Unclassified	-	Vertebrates	0.6	KE:2294	Plasma estradiol, increased
						KE:1065	Activation, estrogen receptor alpha
						KE:2251	Estradiol availability, increased

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

AOP Identifier	AOP Title	AO Classification	OECD Status	Taxonomic applicability	Coverage Score ⓘ The fraction of KEs within the AOP, that are mapped to the chemical-associated toxicological endpoints.	KE Identifier	KE Name
AOP:8	Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Nervous system disease	Under Development	Rat	0.11	KE:239	Activation, Pregnane-X receptor, NR1l2
AOP:18	PPARα activation in utero leading to impaired fertility in males	Reproductive system disease	Under Review	Human, Rat, Mouse	0.12	KE:227	Activation, PPARα
AOP:19	Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)	Reproductive system disease	-		0.4	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:19		Reproductive system disease	-		0.4	KE:26	Antagonism, Androgen receptor
AOP:21	Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2	Unclassified	WPHA/WNT Endorsed	Zebrafish, Medaka, Gallus gallus	0.2	KE:18	Activation, AhR
AOP:37	PPARα activation leading to hepatocellular adenomas and carcinomas in rodents	Cancer; Gastrointestinal system disease	Under Development	Mouse, Rat	0.2	KE:227	Activation, PPARα
AOP:41	Sustained AhR Activation leading to Rodent Liver Tumours	Cancer; Gastrointestinal system disease	Under Review	Rattus sp. ABTC 42503, Mus sp. 2000082	0.2	KE:165	Activation, Long term AHR receptor driven direct and indirect gene expression changes
AOP:111	Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)	Cancer; Reproductive system disease	-	Rattus norvegicus	0.2	KE:1614	Decrease, androgen receptor activation
AOP: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:18	Activation, AhR
AOP:150	Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF	Unclassified	WPHA/WNT Endorsed	Chicken, Zebrafish, Mouse, Rattus norvegicus	0.14	KE:18	Activation, AhR
AOP:151	AhR activation leading to preeclampsia	Cardiovascular system disease	Under Development	Homo sapiens, Mus musculus	0.14	KE:18	Activation, AhR
AOP:167	Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.	Reproductive system disease; Cancer	-	Mouse, Homo sapiens	0.29	KE:1065	Activation, estrogen receptor alpha
AOP:167		Reproductive system disease; Cancer	-	Mouse, Homo sapiens	0.29	KE:1064	prepubertal increase, Estrogen receptor (ER) activity
AOP:212	Histone deacetylase inhibition leading to testicular atrophy	Reproductive system disease	WPHA/WNT Endorsed	Rat, Human, Mouse	0.33	KE:1502	Histone deacetylase inhibition
AOP:212		Reproductive system disease	WPHA/WNT Endorsed	Rat, Human, Mouse	0.33	KE:1262	Apoptosis
AOP:232	NFE2/Nrf2 repression to steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-		0.12	KE:1417	NFE2/Nrf2 repression
AOP:241	Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis	Musculoskeletal system disease; Respiratory system disease	-		0.33	KE:1468	Activation, Latent Transforming Growth Factor Beta 1
AOP:241		Musculoskeletal system disease; Respiratory system disease	-		0.33	KE:1469	Activation, Transforming Growth Factor beta pathway
AOP:270	Elevated ATP demand for detoxification and repair mechanisms leading to impaired locomotor activity	Unclassified	-		0.12	KE:10008	Increased transcription for detoxification and repair mechanism
AOP:274	Histone deacetylase inhibition leads to impeded craniofacial development	Musculoskeletal system disease	-		0.25	KE:1502	Histone deacetylase inhibition
AOP:275	Histone deacetylase inhibition leads to neural tube defects	Neural tube defect	-		0.2	KE:1502	Histone deacetylase inhibition
AOP:306	Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring	Unclassified	Under Development	Rat, Human, Mouse	0.75	KE:286	Altered, Transcription of genes by the androgen receptor
						KE:1614	Decrease, androgen receptor activation
						KE:26	Antagonism, Androgen receptor
AOP:310	Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR	Unclassified	-	Zebrafish	0.08	KE:18	Activation, AhR
AOP: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:323	PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone	Unclassified	-	Teleost fish	0.17	KE:227	Activation, PPARα
AOP:344	Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspring	Unclassified	Under Development		0.75	KE:286	Altered, Transcription of genes by the androgen receptor
						KE:1614	Decrease, androgen receptor activation
						KE:26	Antagonism, Androgen receptor
AOP:345	Androgen receptor (AR) antagonism leading to decreased fertility in females	Endocrine system disease; Reproductive system disease; Reproductive system disease	Under Development	Mammals	0.5	KE:286	Altered, Transcription of genes by the androgen receptor
						KE:1614	Decrease, androgen receptor activation
						KE:26	Antagonism, Androgen receptor
AOP:372	Androgen receptor antagonism leading to testicular cancer	Endocrine system disease; Reproductive system disease; Cancer	-		0.6	KE:286	Altered, Transcription of genes by the androgen receptor
						KE:1614	Decrease, androgen receptor activation
						KE:26	Antagonism, Androgen receptor
AOP:414	Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathway	Musculoskeletal system disease; Respiratory system disease	-		0.4	KE:18	Activation, AhR
AOP:414		Musculoskeletal system disease; Respiratory system disease	-		0.4	KE:1920	Altered gene expression, TGF-β dependent fibrosis pathway
AOP:415	Aryl hydrocarbon receptor activation leading to lung fibrosis through IL-6 toxicity pathway	Musculoskeletal system disease; Respiratory system disease	-		0.2	KE:18	Activation, AhR
AOP:416	Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathway	Cancer	-		0.17	KE:18	Activation, AhR
AOP:417	Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathway	Cancer	-		0.4	KE:18	Activation, AhR
AOP:417		Cancer	-		0.4	KE:17	Altered gene expression, AHR nuclear translocator (ARNT)-dependent pathway
AOP:418	Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathway	Respiratory system disease	-		0.4	KE:18	Activation, AhR
AOP:418		Respiratory system disease	-		0.4	KE:17	Altered gene expression, AHR nuclear translocator (ARNT)-dependent pathway
AOP:419	Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathway	Respiratory system disease	-		0.5	KE:18	Activation, AhR
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	-		0.25	KE:18	Activation, AhR
AOP:444	Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability	Unclassified	-		0.11	KE:1194	Increase, DNA damage
AOP:445	Estrogen Receptor Alpha Agonism leads to Impaired Reproduction	Reproductive system disease	-		0.25	KE:1065	Activation, estrogen receptor alpha
AOP:445		Reproductive system disease	-		0.25	KE:1987	Decreased, Androgen and Progestin
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:202	Inhibition, Nuclear factor kappa B (NF-kB)
AOP:455	Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development	Musculoskeletal system disease	Under Review	Zebrafish, Mouse, Human, Sebastiscus marmoratus, Salmo salar, Chicken	0.17	KE:18	Activation, AhR
AOP:456	Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity	Unclassified	Under Review	Zebrafish, Mouse, Human, Chicken	0.17	KE:18	Activation, AhR
AOP:458	AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Rat, Mouse, Monkey, Human	0.12	KE:18	Activation, AhR
AOP:459	AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Human, Mouse, Rat	0.11	KE:18	Activation, AhR
AOP:472	DNA adduct formation leading to kidney failure	Urinary system disease	-		0.11	KE:1194	Increase, DNA damage
AOP:477	Androgen receptor (AR) antagonism leading to hypospadias in male (mammalian) offspring	Physical disorder	-		0.67	KE:1614	Decrease, androgen receptor activation
AOP:477		Physical disorder	-		0.67	KE:26	Antagonism, Androgen receptor
AOP:494	AhR activation leading to liver fibrosis	Gastrointestinal system disease	-	Mus musculus, Homo sapiens	0.17	KE:18	Activation, AhR
AOP: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:507	Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway	Cardiovascular system disease	-	Mouse, Zebrafish, Human	0.17	KE:1417	NFE2/Nrf2 repression
AOP:508	Nrf2 inhibition leading to vascular disrupting effects through activating HIF1α, Semaphorin 6A, and Dll4-Notch pathway	Cardiovascular system disease	-	Mouse, Zebrafish, Human	0.14	KE:1417	NFE2/Nrf2 repression
AOP:509	Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction	Cardiovascular system disease	-		0.14	KE:1417	NFE2/Nrf2 repression
AOP:517	Pregnane X Receptor (PXR) activation leads to liver steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-	Vertebrates	0.2	KE:239	Activation, Pregnane-X receptor, NR1l2
AOP:520	Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory	Developmental disorder of mental health	-	Mouse, Rat, Human	0.2	KE:2201	Agonism, Retinoic acid receptor
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:532	Retinoic acid receptor agonism during cerebellar development leading to impaired locomotor function	Unclassified	-		0.2	KE:2201	Agonism, Retinoic acid receptor
AOP:536	Estrogen receptor agonism leading to reduced survival and population growth due to renal failure	Unclassified	-		0.17	KE:111	Agonism, Estrogen receptor
AOP:537	Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liver	Unclassified	-		0.2	KE:111	Agonism, Estrogen receptor
AOP:545	Activation, Pregnane-X receptor, NR1l2 leads to increased plasma low-density lipoprotein (LDL) cholesterol via increased cholesterol synthesis	Unclassified	-	Mammals	0.2	KE:239	Activation, Pregnane-X receptor, NR1l2
AOP:548	Activation, Pregnane-X receptor, NR1l2 leads to increased plasma low-density lipoprotein (LDL) cholesterol via increased PCSK9 protein expression	Unclassified	-	Mammals	0.2	KE:239	Activation, Pregnane-X receptor, NR1l2
AOP:563	Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosis	Reproductive system disease; Endocrine system disease	-	Rat, Mouse, Zebra fish, Human	0.33	KE:18	Activation, AhR
AOP:563		Reproductive system disease; Endocrine system disease	-	Rat, Mouse, Zebra fish, Human	0.33	KE:1262	Apoptosis

Associated AOPs with Level of Relevance - 5 AOPs with at least 1 MIE and AO associated with chemical, and there exists a directed path between that MIE and AO

AOP Identifier	AOP Title	AO Classification	OECD Status	Taxonomic applicability	Coverage Score ⓘ The fraction of KEs within the AOP, that are mapped to the chemical-associated toxicological endpoints.	KE Identifier	KE Name
AOP:269	Elevated ATP demand for detoxification and repair mechanisms leading to impaired growth and development	Unclassified	-		0.33	KE:10008	Increased transcription for detoxification and repair mechanism
AOP:269		Unclassified	-		0.33	KE:10013	Impaired growth and development
AOP:293	Increased DNA damage leading to increased risk of breast cancer	Genetic disease; Thoracic disease; Cancer	Under Development	Rattus rattus, Mus musculus	0.22	KE:1194	Increase, DNA damage
AOP:293		Genetic disease; Thoracic disease; Cancer	Under Development	Rattus rattus, Mus musculus	0.22	KE:1193	N/A, Breast Cancer
AOP:439	Activation of the AhR leading to metastatic breast cancer	Thoracic disease; Cancer	Under Development	Humans, Mice	0.44	KE:18	Activation, AhR
						KE:1971	Increased, tumor growth
						KE:1982	metastatic breast cancer
						KE:1262	Apoptosis

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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.