DEDUCT | Database of Endocrine Disrupting chemicals and their Toxicity profiles

1H-Pyrrole-1-carboxamide, 3-ethyl-2,5-dihydro-4-methyl-N-2-4-(trans-4-methylcyclohexyl)aminocarbonylaminosulfonylphenylethyl-2-oxo-

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: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: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: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: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: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: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:305	5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring	Unclassified	Under Development	Rat, Human, Mouse	0.2	KE:1614	Decrease, androgen receptor activation
AOP:306	Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring	Unclassified	Under Development	Rat, Human, Mouse	0.25	KE:1614	Decrease, androgen receptor activation
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:344	Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspring	Unclassified	Under Development		0.25	KE:1614	Decrease, androgen receptor activation
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:1614	Decrease, androgen receptor activation
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:349	Inhibition of 11β-hydroxylase leading to decresed population trajectory	Unclassified	Under Development	Fish	0.25	KE:1835	Cortisol and 11β-(OH) testosterone decreased
AOP:349		Unclassified	Under Development	Fish	0.25	KE:1836	Decreased plasma Cortisol level
AOP:372	Androgen receptor antagonism leading to testicular cancer	Endocrine system disease; Reproductive system disease; Cancer	-		0.2	KE:1614	Decrease, androgen receptor activation
AOP:477	Androgen receptor (AR) antagonism leading to hypospadias in male (mammalian) offspring	Physical disorder	-		0.33	KE:1614	Decrease, androgen receptor activation
AOP:496	Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）	Unclassified	-	Zebrafish	0.1	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:513	Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway	Cancer	-	Human, Mouse, Rat	0.2	KE:233	Decreased, PPAR-gamma activation
AOP:540	Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production	Unclassified	-		0.11	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
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

No associated AOPs with Level of Relevance 2

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:36	Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-		0.12	KE:233	Decreased, PPAR-gamma activation
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:206	Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis	Musculoskeletal system disease; Respiratory system disease	Under Development	Homo sapiens	0.17	KE:1270	Inactivation of PPARγ
AOP:347	Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis	Musculoskeletal system disease; Respiratory system disease	-		0.11	KE:1270	Inactivation of PPARγ
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

No associated AOPs with Level of Relevance 5

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.