DEDUCT | Database of Endocrine Disrupting chemicals and their Toxicity profiles

Etomidate

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: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:207	NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans	Reproductive system disease	-	Caenorhabditis elegans	0.12	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:419	Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathway	Respiratory system disease	-		0.25	KE:1262	Apoptosis
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:446	PM-related Adverse outcome pathway frameworks on various systems	Respiratory system disease	-		0.05	KE:1262	Apoptosis
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:491	Decrease, GLI1/2 target gene expression leads to orofacial clefting	Unclassified	Under Development	Mouse	0.17	KE:1262	Apoptosis
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	0.14	KE:1262	Apoptosis
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:563	Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosis	Reproductive system disease; Endocrine system disease	-	Rat, Mouse, Zebra fish, Human	0.17	KE:1262	Apoptosis

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

AOP Identifier	AOP Title	AO Classification	OECD Status	Taxonomic applicability	Coverage Score ⓘ The fraction of KEs within the AOP, that are mapped to the chemical-associated toxicological endpoints.	KE Identifier	KE Name
AOP: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	0.2	KE:406	decreased, Fertility
AOP:16	Acetylcholinesterase inhibition leading to acute mortality	Unclassified	Under Development		0.14	KE:360	Decrease, Population growth rate
AOP:18	PPARα activation in utero leading to impaired fertility in males	Reproductive system disease	Under Review	Human, Rat, Mouse	0.12	KE:406	decreased, Fertility
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:63	Cyclooxygenase inhibition leading to reproductive dysfunction	Reproductive system disease	-	Goldfish, Human, Mouse, Rat	0.2	KE:360	Decrease, Population growth rate
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:406	decreased, Fertility
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: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: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	0.17	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: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	-		0.14	KE:360	Decrease, Population growth rate
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	0.14	KE:360	Decrease, Population growth rate
AOP:312	Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement	Unclassified	-		0.17	KE:360	Decrease, Population growth rate
AOP:323	PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone	Unclassified	-	Teleost fish	0.33	KE:360	Decrease, Population growth rate
AOP:323		Unclassified	-	Teleost fish	0.33	KE:1756	Decreased, plasma 11-ketotestosterone level
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:345	Androgen receptor (AR) antagonism leading to decreased fertility in females	Endocrine system disease; Reproductive system disease; Reproductive system disease	Under Development	Mammals	0.17	KE:406	decreased, Fertility
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:406	decreased, Fertility
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	0.12	KE:360	Decrease, Population growth rate
AOP:387	Deposition of ionising energy leading to population decline via mitochondrial dysfunction	Reproductive system disease	-	Lemna minor	0.12	KE:360	Decrease, Population growth rate
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:398	Decreased ALDH1A (RALDH) activity leading to decreased fertility via disrupted meiotic initiation of fetal oogonia	Reproductive system disease	Under Development	Mouse, Rat, Human	0.17	KE:406	decreased, Fertility
AOP:399	Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)	Unclassified	-	Zebrafish	0.12	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	-		0.22	KE:1798	Decreased spermatogenesis
AOP:444		Unclassified	-		0.22	KE:360	Decrease, Population growth rate
AOP:492	Glutathione conjugation leading to reproductive dysfunction via oxidative stress	Reproductive system disease	-	Mammals, Fish	0.2	KE:406	decreased, Fertility
AOP:498	Increased LCN2/iron complex leading to neurological disorders	Nervous system disease	-	Homo sapiens	0.25	KE:2150	Neurological disorder
AOP:501	Excessive iron accumulation leading to neurological disorders	Nervous system disease	-	Homo sapiens	0.25	KE:2150	Neurological disorder
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:540	Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production	Unclassified	-		0.22	KE:360	Decrease, Population growth rate
AOP:540		Unclassified	-		0.22	KE:1262	Apoptosis
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: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: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: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

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:349	Inhibition of 11β-hydroxylase leading to decresed population trajectory	Unclassified	Under Development	Fish	1.0	KE:1796	11β-hydroxylase inhibition
						KE:1798	Decreased spermatogenesis
						KE:360	Decrease, Population growth rate
						KE:1835	Cortisol and 11β-(OH) testosterone decreased
						KE:1756	Decreased, plasma 11-ketotestosterone level
						KE:406	decreased, Fertility
						KE:1836	Decreased plasma Cortisol level
						KE:1837	decreased oocyte maturation

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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.