DEDUCT | Database of Endocrine Disrupting chemicals and their Toxicity profiles

Uranium

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	0.14	KE:177	Mitochondrial dysfunction
AOP:7	Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female	Reproductive system disease; Endocrine system disease; Reproductive system disease	Under Review	Rat, Mouse, Human	0.4	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:7			Under Review	Rat, Mouse, Human	0.4	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP: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	0.1	KE:1392	Oxidative Stress
AOP:18	PPARα activation in utero leading to impaired fertility in males	Reproductive system disease	Under Review	Human, Rat, Mouse	0.12	KE:1690	Decrease, circulating testosterone levels
AOP:23	Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)	Unclassified	WPHA/WNT Endorsed	Pimephales promelas	0.2	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:23		Unclassified	WPHA/WNT Endorsed	Pimephales promelas	0.2	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:25	Aromatase inhibition leading to reproductive dysfunction	Unclassified	WPHA/WNT Endorsed	Fathead minnow, Medaka, Zebrafish	0.25	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:25	Aromatase inhibition leading to reproductive dysfunction	Unclassified	WPHA/WNT Endorsed	Fathead minnow, Medaka, Zebrafish	0.25	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP: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:34	LXR activation leading to hepatic steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-		0.08	KE:177	Mitochondrial dysfunction
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:177	Mitochondrial dysfunction
AOP:64	Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility	Reproductive system disease	-	Rattus norvegicus	0.29	KE:496	Increased apoptosis, decreased fetal/adult Leydig Cells
AOP:64		Reproductive system disease	-	Rattus norvegicus	0.29	KE:1690	Decrease, circulating testosterone levels
AOP:77	Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1	Unclassified	-	Honey bee	0.14	KE:177	Mitochondrial dysfunction
AOP:78	Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1	Unclassified	-	Honey bee	0.12	KE:177	Mitochondrial dysfunction
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	0.12	KE:177	Mitochondrial dysfunction
AOP:87	Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure	Unclassified	-	Honey bee	0.12	KE:177	Mitochondrial dysfunction
AOP:111	Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)	Cancer; Reproductive system disease	-	Rattus norvegicus	0.2	KE:754	Increased, Luteinizing hormone (LH)
AOP:120	Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)	Cancer; Reproductive system disease	-	Rattus norvegicus, Mus musculus	0.4	KE:791	Increased, Leutinizing hormone (LH)
AOP:120		Cancer; Reproductive system disease	-	Rattus norvegicus, Mus musculus	0.4	KE:1690	Decrease, circulating testosterone levels
AOP:122	Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation	Unclassified	-	Pimephales promelas	0.2	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:122		Unclassified	-	Pimephales promelas	0.2	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:123	Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription	Unclassified	-	Pimephales promelas	0.18	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:123		Unclassified	-	Pimephales promelas	0.18	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:124	HMG-CoA reductase inhibition leading to decreased fertility	Reproductive system disease	-	Rattus rattus	0.17	KE:1690	Decrease, circulating testosterone levels
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:144	Endocytic lysosomal uptake leading to liver fibrosis	Gastrointestinal system disease	Under Review	Human, Mouse, Rat	0.11	KE:177	Mitochondrial dysfunction
AOP:207	NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans	Reproductive system disease	-	Caenorhabditis elegans	0.38	KE:1115	Increase, Reactive oxygen species
						KE:177	Mitochondrial dysfunction
						KE:1262	Apoptosis
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:220	Cyp2E1 Activation Leading to Liver Cancer	Cancer; Gastrointestinal system disease	WPHA/WNT Endorsed	Rodents, Homo sapiens	0.2	KE:1392	Oxidative Stress
AOP:260	CYP2E1 activation and formation of protein adducts leading to neurodegeneration	Nervous system disease	-	Human	0.14	KE:1392	Oxidative Stress
AOP:271	Inhibition of thyroid peroxidase leading to impaired fertility in fish	Unclassified	Under Development	Fish	0.2	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP: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:1690	Decrease, circulating testosterone levels
AOP:289	Inhibition of 5α-reductase leading to impaired fecundity in female fish	Unclassified	Under Development	Fish	0.17	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:299	Deposition of energy leading to population decline via DNA oxidation and follicular atresia	Unclassified	-		0.14	KE:1115	Increase, Reactive oxygen species
AOP:303	Frustrated phagocytosis-induced lung cancer	Cancer	Under Development	Mammals	0.14	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	0.17	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:310		Unclassified	-	Zebrafish	0.17	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:311	Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis	Unclassified	-	Daphnia magna, Fish	0.14	KE:1115	Increase, Reactive oxygen species
AOP:322	Alkylation of DNA leading to reduced sperm count	Reproductive system disease	-		0.2	KE:1365	Increase, Apoptosis
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	0.38	KE:1815	Activation of ER stress
						KE:1633	Increase in inflammation
						KE:177	Mitochondrial dysfunction
AOP:382	Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis	Musculoskeletal system disease; Respiratory system disease	Under Development		0.17	KE:1115	Increase, Reactive oxygen species
AOP:383	Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis	Gastrointestinal system disease	Under Development		0.17	KE:1115	Increase, Reactive oxygen species
AOP:386	Deposition of ionizing energy leading to population decline via inhibition of photosynthesis	Reproductive system disease	-	Lemna minor, Chlamydomonas reinhardtii	0.12	KE:1115	Increase, Reactive oxygen species
AOP:387	Deposition of ionising energy leading to population decline via mitochondrial dysfunction	Reproductive system disease	-	Lemna minor	0.25	KE:1770	Decrease, Mitochondrial membrane potential
AOP:387		Reproductive system disease	-	Lemna minor	0.25	KE:1115	Increase, Reactive oxygen species
AOP:409	Frustrated phagocytosis leads to malignant mesothelioma	Cancer	-		0.12	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:1917	Altered gene expression, NRF2 dependent antioxidant pathway
AOP:439	Activation of the AhR leading to metastatic breast cancer	Thoracic disease; Cancer	Under Development	Humans, Mice	0.11	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:444	Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability	Unclassified	-		0.22	KE:1392	Oxidative Stress
AOP:444		Unclassified	-		0.22	KE:1365	Increase, Apoptosis
AOP:451	Interaction with lung resident cell membrane components leads to lung cancer	Cancer	-	Human	0.11	KE:1115	Increase, Reactive oxygen species
AOP:452	Adverse outcome pathway of PM-induced respiratory toxicity	Respiratory system disease	-		0.18	KE:1392	Oxidative Stress
AOP:452	Adverse outcome pathway of PM-induced respiratory toxicity	Respiratory system disease	-		0.18	KE:1262	Apoptosis
AOP:457	Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine	Inherited metabolic disorder	-	Human	0.17	KE:1392	Oxidative Stress
AOP:459	AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Human, Mouse, Rat	0.11	KE:1392	Oxidative Stress
AOP:460	Antagonism of Smoothened receptor leading to orofacial clefting	Unclassified	Under Development	Mouse	0.11	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:470	Deposition of energy leads to abnormal vascular remodeling	Cardiovascular system disease	Under Review	Human, Rat, Mouse, Rabbit	0.12	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	0.1	KE:1392	Oxidative Stress
AOP:483	Deposition of Energy Leading to Learning and Memory Impairment	Developmental disorder of mental health	Under Review	Mouse, Rat, Rabbit, Dog, Pigs, Cow, Human	0.12	KE:1392	Oxidative Stress
AOP:491	Decrease, GLI1/2 target gene expression leads to orofacial clefting	Unclassified	Under Development	Mouse	0.17	KE:1262	Apoptosis
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	0.1	KE:1633	Increase in inflammation
AOP:496	Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）	Unclassified	-	Zebrafish	0.2	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:496		Unclassified	-	Zebrafish	0.2	KE:1690	Decrease, circulating testosterone levels
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	-		0.38	KE:1392	Oxidative Stress
						KE:1115	Increase, Reactive oxygen species
						KE:177	Mitochondrial dysfunction
AOP:500	Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis	Developmental disorder of mental health	-	Rattus norvegicus, Mus musculus, Homo sapiens	0.43	KE:1115	Increase, Reactive oxygen species
						KE:177	Mitochondrial dysfunction
						KE:1262	Apoptosis
AOP:501	Excessive iron accumulation leading to neurological disorders	Nervous system disease	-	Homo sapiens	0.25	KE:1392	Oxidative Stress
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	-		0.43	KE:1392	Oxidative Stress
						KE:1365	Increase, Apoptosis
						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: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:530	Endocytotic lysosomal uptake leads to intestinal barrier disruption	Gastrointestinal system disease	-		0.2	KE:177	Mitochondrial dysfunction
AOP:534	Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress	Cancer	-	Vertebrates	0.33	KE:1392	Oxidative Stress
AOP:534		Cancer	-	Vertebrates	0.33	KE:1115	Increase, Reactive oxygen species
AOP:535	Binding and activation of GPER leading to learning and memory impairments	Developmental disorder of mental health	-	Mouse, Human	0.22	KE:1392	Oxidative Stress
AOP:535		Developmental disorder of mental health	-	Mouse, Human	0.22	KE:1262	Apoptosis
AOP:549	Aromatase inhibition leads to reproductive toxicity (including growth and developmental toxicity) in adult female zebrafish	Unclassified	-		0.12	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:563	Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosis	Reproductive system disease; Endocrine system disease	-	Rat, Mouse, Zebra fish, Human	0.17	KE:1262	Apoptosis
AOP: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:351	Increased Mortality
AOP:96	Axonal sodium channel modulation leading to acute mortality	Unclassified	-	Insects, Fish	0.17	KE:351	Increased Mortality
AOP:104	Altered ion channel activity leading impaired heart function	Unclassified	-		0.25	KE:351	Increased Mortality
AOP:113	Glutamate-gated chloride channel activation leading to acute mortality	Unclassified	-	Bombus impatiens, Chaetanaphothrips orchidii, Radopholus similis, Daphnia magna, Orius insidiosus, Hymenoptera, Helicoverpa zea, Lepidoptera, Liriomyza trifolii, Orius isidiosus, Acyrthosiphon kondoi	0.17	KE:351	Increased Mortality
AOP:128	Kidney dysfunction by decreased thyroid hormone	Urinary system disease	Under Development	Sprague-Dawley, Homo sapiens	0.18	KE:814	Occurrence, Kidney toxicity
AOP:128	Kidney dysfunction by decreased thyroid hormone	Urinary system disease	Under Development	Sprague-Dawley, Homo sapiens	0.18	KE:825	Decreased, Renal ability to dilute urine
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	0.12	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:205	AOP from chemical insult to cell death	Unclassified	-	Vertebrates	0.33	KE:177	Mitochondrial dysfunction
AOP:205	AOP from chemical insult to cell death	Unclassified	-	Vertebrates	0.33	KE:1262	Apoptosis
AOP:256	Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity	Urinary system disease	Under Development	Human, Rat, Mouse	0.4	KE:814	Occurrence, Kidney toxicity
AOP:256		Urinary system disease	Under Development	Human, Rat, Mouse	0.4	KE:177	Mitochondrial dysfunction
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:814	Occurrence, Kidney toxicity
AOP:258	Renal protein alkylation leading to kidney toxicity	Urinary system disease	Under Development	Human, Rat, Mouse	0.4	KE:814	Occurrence, Kidney toxicity
AOP:258	Renal protein alkylation leading to kidney toxicity	Urinary system disease	Under Development	Human, Rat, Mouse	0.4	KE:177	Mitochondrial dysfunction
AOP:312	Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement	Unclassified	-		0.17	KE:351	Increased Mortality
AOP:320	Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality	Unclassified	Under Development	Homo sapiens	0.22	KE:351	Increased Mortality
AOP:320		Unclassified	Under Development	Homo sapiens	0.22	KE:1750	Increased inflammatory immune responses
AOP:363	Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure	Unclassified	Under Review	Zebrafish	0.12	KE:351	Increased Mortality
AOP:364	Thyroperoxidase inhibition leading to altered visual function via decreased eye size	Unclassified	Under Development		0.12	KE:351	Increased Mortality
AOP:365	Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning	Unclassified	Under Development		0.12	KE:351	Increased Mortality
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	0.12	KE:351	Increased Mortality
AOP:410	GSK3beta inactivation leading to increased mortality via defects in developing inner ear	Unclassified	-	Zebrafish	0.1	KE:351	Increased Mortality
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	0.29	KE:1392	Oxidative Stress
AOP:450		Nervous system disease	-	Rattus norvegicus, Mus musculus, Homo sapiens	0.29	KE:351	Increased Mortality
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:2091	Occurrence, Bone Loss
AOP:536	Estrogen receptor agonism leading to reduced survival and population growth due to renal failure	Unclassified	-		0.17	KE:351	Increased Mortality
AOP:564	DBDPE-induced inhibition of mitochondrial complex Ⅰ leading to population decline via neurotoxicity and metabotoxicity.	Unclassified	-	Zebrafish	0.09	KE:351	Increased Mortality

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: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: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	0.5	KE:1115	Increase, Reactive oxygen species
AOP:325		Unclassified	-	Fish	0.5	KE:1445	Increase, Lipid peroxidation
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	0.2	KE:1115	Increase, Reactive oxygen species
AOP:328	Excessive reactive oxygen species production leading to mortality (2)	Unclassified	-	Daphnia magna	0.4	KE:1770	Decrease, Mitochondrial membrane potential
AOP:328		Unclassified	-	Daphnia magna	0.4	KE:1115	Increase, Reactive oxygen species
AOP:329	Excessive reactive oxygen species production leading to mortality (3)	Unclassified	-	Daphnia magna, Paracyclopina nana	0.4	KE: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	0.4	KE:1365	Increase, Apoptosis
AOP:330		Unclassified	-	Daphnia magna	0.4	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	0.17	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:1115	Increase, Reactive oxygen species
AOP:332		Unclassified	-		0.4	KE:1445	Increase, Lipid peroxidation
AOP:333	Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylation	Unclassified	-		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	0.2	KE:177	Mitochondrial dysfunction
AOP:411	Oxidative stress Leading to Decreased Lung Function	Respiratory system disease	-	Homo sapiens	0.25	KE:1392	Oxidative Stress
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:424	Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction	Respiratory system disease	-	Human	0.17	KE:1392	Oxidative Stress
AOP:425	Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1	Respiratory system disease	-	Human	0.17	KE:1392	Oxidative Stress
AOP:438	reactive oxygen species generation leading to increased cardiovascular morbidity and mortality	Cardiovascular system disease	-		0.25	KE:1392	Oxidative Stress
						KE:1115	Increase, Reactive oxygen species
						KE:177	Mitochondrial dysfunction
AOP:446	PM-related Adverse outcome pathway frameworks on various systems	Respiratory system disease	-		0.2	KE:1392	Oxidative Stress
						KE:1115	Increase, Reactive oxygen species
						KE:1445	Increase, Lipid peroxidation
						KE:1262	Apoptosis
AOP:448	ROS, inflammation, and activation of nAChR lead to increased incidence of cardiovascular morbidity and mortality	Cardiovascular system disease	-		0.12	KE:1392	Oxidative Stress
AOP:448		Cardiovascular system disease	-		0.12	KE:1115	Increase, Reactive oxygen species
AOP:453	Reactive oxygen species and subsequent oxidative stress lead to increased incidence of digestive morbidity and mortality in the general population	Gastrointestinal system disease	-		0.15	KE:1392	Oxidative Stress
AOP:453		Gastrointestinal system disease	-		0.15	KE:1115	Increase, Reactive oxygen species
AOP:463	The AOP framwork on silica nanopariticles induced hepatoxicity	Gastrointestinal system disease	-		0.36	KE:1392	Oxidative Stress
						KE:1115	Increase, Reactive oxygen species
						KE:177	Mitochondrial dysfunction
						KE:1262	Apoptosis
AOP:469	Reactive oxygen speicies overproduction leading to increased digestive morbidity and mortality in generation population	Gastrointestinal system disease	-		0.15	KE:1392	Oxidative Stress
AOP:469		Gastrointestinal system disease	-		0.15	KE:1115	Increase, Reactive oxygen species
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:177	Mitochondrial dysfunction
						KE:105	Inhibition, Mitochondrial Electron Transport Chain Complexes
AOP:480	Mitochondrial complexes inhibition leading to heart failure via decreased ATP production	Cardiovascular system disease; Thoracic disease	Under Development		0.4	KE:177	Mitochondrial dysfunction
AOP:480		Cardiovascular system disease; Thoracic disease	Under Development		0.4	KE:105	Inhibition, Mitochondrial Electron Transport Chain Complexes
AOP:488	Increased reactive oxygen species production leading to decreased cognitive function	Cognitive disorder	-	Human	0.29	KE:1392	Oxidative Stress
AOP:488		Cognitive disorder	-	Human	0.29	KE:1115	Increase, Reactive oxygen species
AOP:505	Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway	Cancer	-	Human, Mouse, Rat	0.4	KE:1392	Oxidative Stress
AOP:505		Cancer	-	Human, Mouse, Rat	0.4	KE:1115	Increase, Reactive oxygen species
AOP:511	The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects	Cardiovascular system disease	-	Human, Mouse, Zebrafish	0.19	KE:1392	Oxidative Stress
						KE:1115	Increase, Reactive oxygen species
						KE:177	Mitochondrial dysfunction
AOP:513	Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway	Cancer	-	Human, Mouse, Rat	0.2	KE:1115	Increase, Reactive oxygen species
AOP:540	Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production	Unclassified	-		0.44	KE:1392	Oxidative Stress
						KE:1115	Increase, Reactive oxygen species
						KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
						KE:1262	Apoptosis
AOP:541	Excessive ROS generation leading to increased incidence of vascular calcification by VSMC phenotype switching	Cardiovascular system disease	-		0.15	KE:1392	Oxidative Stress
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: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:437	Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity	Urinary system disease	Under Development		0.8	KE:1392	Oxidative Stress
						KE:814	Occurrence, Kidney toxicity
						KE:177	Mitochondrial dysfunction
						KE:105	Inhibition, Mitochondrial Electron Transport Chain Complexes
AOP:447	Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways	Urinary system disease	-		1.0	KE:1097	Occurrence, renal proximal tubular necrosis
						KE:1815	Activation of ER stress
						KE:202	Inhibition, Nuclear factor kappa B (NF-kB)
						KE:177	Mitochondrial dysfunction
						KE:105	Inhibition, Mitochondrial Electron Transport Chain Complexes
						KE:1392	Oxidative Stress
						KE:814	Occurrence, Kidney toxicity
						KE:759	Increased, Kidney Failure
						KE:1365	Increase, Apoptosis
						KE:1633	Increase in inflammation
						KE:1770	Decrease, Mitochondrial membrane potential
						KE:1917	Altered gene expression, NRF2 dependent antioxidant pathway
AOP:472	DNA adduct formation leading to kidney failure	Urinary system disease	-		0.44	KE:1392	Oxidative Stress
						KE:759	Increased, Kidney Failure
						KE:1097	Occurrence, renal proximal tubular necrosis
						KE:1115	Increase, Reactive oxygen species

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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.