DEDUCT | Database of Endocrine Disrupting chemicals and their Toxicity profiles

Budesonide

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: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:41	Sustained AhR Activation leading to Rodent Liver Tumours	Cancer; Gastrointestinal system disease	Under Review	Rattus sp. ABTC 42503, Mus sp. 2000082	0.4	KE:853	Changes/Inhibition, Cellular Homeostasis and Apoptosis
AOP:41	Sustained AhR Activation leading to Rodent Liver Tumours	Cancer; Gastrointestinal system disease	Under Review	Rattus sp. ABTC 42503, Mus sp. 2000082	0.4	KE:139	N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects
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: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	0.12	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:220	Cyp2E1 Activation Leading to Liver Cancer	Cancer; Gastrointestinal system disease	WPHA/WNT Endorsed	Rodents, Homo sapiens	0.2	KE:1393	Hepatocytotoxicity
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: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: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: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:414	Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathway	Musculoskeletal system disease; Respiratory system disease	-		0.2	KE:1920	Altered gene expression, TGF-β dependent fibrosis pathway
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	0.22	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: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	0.11	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	0.14	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	0.22	KE:2043	Decrease, Sonic Hedgehog second messenger production
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:491	Decrease, GLI1/2 target gene expression leads to orofacial clefting	Unclassified	Under Development	Mouse	0.33	KE:2043	Decrease, Sonic Hedgehog second messenger production
AOP:491		Unclassified	Under Development	Mouse	0.33	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: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	0.11	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: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:37	PPARα activation leading to hepatocellular adenomas and carcinomas in rodents	Cancer; Gastrointestinal system disease	Under Development	Mouse, Rat	0.4	KE:716	Increase, cell proliferation (hepatocytes)
AOP:37		Cancer; Gastrointestinal system disease	Under Development	Mouse, Rat	0.4	KE:719	Increase, hepatocellular adenomas and carcinomas
AOP:40	Covalent Protein binding leading to Skin Sensitisation	Integumentary system disease	WPHA/WNT Endorsed	Mouse, Human	0.2	KE:827	sensitisation, skin
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	0.17	KE:719	Increase, hepatocellular adenomas and carcinomas
AOP:139	Alkylation of DNA leading to cancer 1	Cancer	-	Homo sapiens, Mus musculus	0.25	KE:885	Increase, Cancer
AOP:205	AOP from chemical insult to cell death	Unclassified	-	Vertebrates	0.17	KE:1262	Apoptosis
AOP:463	The AOP framwork on silica nanopariticles induced hepatoxicity	Gastrointestinal system disease	-		0.18	KE:2034	liver dysfunction
AOP:463		Gastrointestinal system disease	-		0.18	KE:1262	Apoptosis
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: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

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: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:23	Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)	Unclassified	WPHA/WNT Endorsed	Pimephales promelas	0.1	KE:25	Agonism, Androgen receptor
AOP:64	Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility	Reproductive system disease	-	Rattus norvegicus	0.29	KE:494	Glucocorticoid Receptor Agonist, Activation
AOP:64		Reproductive system disease	-	Rattus norvegicus	0.29	KE:496	Increased apoptosis, decreased fetal/adult Leydig Cells
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: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: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:318	Glucocorticoid Receptor activation leading to hepatic steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-		0.2	KE:122	Activation, Glucocorticoid Receptor
AOP:334	Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration	Unclassified	-	Teleost fish	0.17	KE:122	Activation, Glucocorticoid Receptor
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: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:25	Agonism, Androgen receptor
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: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:495	Androgen receptor activation leading to prostate cancer	Reproductive system disease; Cancer	-		0.33	KE:286	Altered, Transcription of genes by the androgen receptor
						KE:25	Agonism, Androgen receptor
						KE:1183	Decreased, Apoptosis (Epithelial Cells)
AOP:496	Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）	Unclassified	-	Zebrafish	0.2	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:496		Unclassified	-	Zebrafish	0.2	KE:25	Agonism, Androgen receptor
AOP:525	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory	Developmental disorder of mental health	-		0.15	KE:2217	Binding of antagonist to glucocorticoid hormone receptor
AOP:525		Developmental disorder of mental health	-		0.15	KE:2220	Antagonism, Glucocorticoid hormone 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

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:117	Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)	Cancer; Gastrointestinal system disease	Under Development	Mus musculus, Rattus norvegicus	0.75	KE:716	Increase, cell proliferation (hepatocytes)
						KE:25	Agonism, Androgen receptor
						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	0.5	KE:719	Increase, hepatocellular adenomas and carcinomas
AOP:118		Cancer; Gastrointestinal system disease	-	Mus musculus, Rattus norvegicus	0.5	KE:786	Increase, Cytotoxicity (hepatocytes)

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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.