DEDUCT | Database of Endocrine Disrupting chemicals and their Toxicity profiles

Carbonyl cyanide (m-chlorophenyl)hydrazone

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: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:139	N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects
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:122	Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation	Unclassified	-	Pimephales promelas	0.1	KE:800	Decreased, Aromatase (Cyp19a1) mRNA
AOP:123	Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription	Unclassified	-	Pimephales promelas	0.09	KE:800	Decreased, Aromatase (Cyp19a1) mRNA
AOP:190	Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.17	KE:1829	Altered, Thyroid hormone-dependent gene expression
AOP:191	Type III iodotyrosine deiodinase (DIO3) inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.5	KE:1154	Increased, Triiodothyronine (T3) in tissues
AOP:191		Unclassified	-	African clawed frog	0.5	KE:1829	Altered, Thyroid hormone-dependent gene expression
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:232	NFE2/Nrf2 repression to steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-		0.12	KE:1419	Reduced, FXR activity
AOP:286	Mitochondrial complex III antagonism leading to growth inhibition (1)	Unclassified	-	Lemna minor, Daphnia magna, Danio rerio	0.25	KE:1821	Decrease, Cell proliferation
AOP:287	Mitochondrial complex III antagonism leading to growth inhibition (2)	Unclassified	-	Lemna minor, Daphnia magna, Danio rerio	0.25	KE:1825	Increase, Cell death
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:290	Mitochondrial ATP synthase antagonism leading to growth inhibition (1)	Unclassified	-	Daphnia magna	0.25	KE:1821	Decrease, Cell proliferation
AOP:291	Mitochondrial ATP synthase antagonism leading to growth inhibition (2)	Unclassified	-	Daphnia magna	0.25	KE:1825	Increase, Cell death
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:322	Alkylation of DNA leading to reduced sperm count	Reproductive system disease	-		0.2	KE:1365	Increase, Apoptosis
AOP:330	Excessive reactive oxygen species production leading to mortality (4)	Unclassified	-	Daphnia magna	0.2	KE:1365	Increase, Apoptosis
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:1821	Decrease, Cell proliferation
AOP:332	Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferation	Unclassified	-		0.2	KE:1821	Decrease, Cell proliferation
AOP:333	Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylation	Unclassified	-		0.4	KE:1821	Decrease, Cell proliferation
AOP:333		Unclassified	-		0.4	KE:1446	Decrease, Coupling of oxidative phosphorylation
AOP:362	Immune mediated hepatitis	Gastrointestinal system disease; Immune system disease	-	Homo sapiens, Rat	0.12	KE:1817	Apoptotic cell death
AOP:368	Cytochrome oxidase inhibition leading to increased nasal lesions	Unclassified	-	Rodents, Human	0.33	KE:1825	Increase, Cell death
AOP:388	Deposition of ionising energy leading to population decline via programmed cell death	Reproductive system disease	-	Lemna minor	0.2	KE:1864	Increase, Programmed cell death
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:1881	Decreased, all-trans retinoic acid (atRA) concentration
AOP:399	Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)	Unclassified	-	Zebrafish	0.12	KE:1821	Decrease, Cell proliferation
AOP:410	GSK3beta inactivation leading to increased mortality via defects in developing inner ear	Unclassified	-	Zebrafish	0.1	KE:1825	Increase, Cell death
AOP:418	Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathway	Respiratory system disease	-		0.2	KE:1825	Increase, Cell death
AOP:419	Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathway	Respiratory system disease	-		0.5	KE:1923	Altered gene expression, P53 dependent apoptosis pathway
AOP:419		Respiratory system disease	-		0.5	KE:1262	Apoptosis
AOP:436	Inhibition of RALDH2 causes reduced all-trans retinoic acid levels, leading to transposition of the great arteries	Cardiovascular system disease	-	Chicken, Mouse, Vertebrates	0.2	KE:1881	Decreased, all-trans retinoic acid (atRA) concentration
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	0.29	KE:1974	Activation of Tumor Protein 53
AOP:441			-	Homo sapiens, Mus musculus musculus, Rattus norvegicus	0.29	KE:1262	Apoptosis
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	0.1	KE:112	Antagonism, Estrogen receptor
AOP:444	Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability	Unclassified	-		0.11	KE:1365	Increase, Apoptosis
AOP:446	PM-related Adverse outcome pathway frameworks on various systems	Respiratory system disease	-		0.05	KE:1262	Apoptosis
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:1365	Increase, 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	0.33	KE:1821	Decrease, Cell proliferation
						KE:2043	Decrease, Sonic Hedgehog second messenger production
						KE:1262	Apoptosis
AOP:463	The AOP framwork on silica nanopariticles induced hepatoxicity	Gastrointestinal system disease	-		0.09	KE:1262	Apoptosis
AOP:464	Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits	Nervous system disease	-		0.05	KE:1825	Increase, Cell death
AOP:468	Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)	Unclassified	-		0.12	KE:1825	Increase, Cell death
AOP:472	DNA adduct formation leading to kidney failure	Urinary system disease	-		0.11	KE:1825	Increase, Cell death
AOP:482	Deposition of energy leading to occurrence of bone loss	Musculoskeletal system disease	Under Review	Human, Mouse, Rat, Rhesus monkeys	0.14	KE:1825	Increase, Cell death
AOP:491	Decrease, GLI1/2 target gene expression leads to orofacial clefting	Unclassified	Under Development	Mouse	0.5	KE:1821	Decrease, Cell proliferation
						KE:2043	Decrease, Sonic Hedgehog second messenger production
						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	0.14	KE:1262	Apoptosis
AOP:509	Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction	Cardiovascular system disease	-		0.14	KE:1365	Increase, Apoptosis
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:525	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory	Developmental disorder of mental health	-		0.08	KE:1656	Antagonism, Thyroid Receptor
AOP:534	Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress	Cancer	-	Vertebrates	0.17	KE:1446	Decrease, Coupling of oxidative phosphorylation
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
AOP:573	Inhibition, cytochrome oxidase leads to Increased, pulmonary edema	Respiratory system disease	-	Rodents, Humans	0.33	KE:1825	Increase, Cell death
AOP:574	Inhibition, cytochrome oxidase leads to Loss of olfactory function	Unclassified	-	Rodents, Humans	0.33	KE:1825	Increase, Cell death

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:205	AOP from chemical insult to cell death	Unclassified	-	Vertebrates	0.17	KE:1262	Apoptosis
AOP:423	Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway	Unclassified	-		0.17	KE:1817	Apoptotic cell death

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: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:408	reduction in ovarian granulosa cells, Aromatase (Cyp19a1)
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:25	Aromatase inhibition leading to reproductive dysfunction	Unclassified	WPHA/WNT Endorsed	Fathead minnow, Medaka, Zebrafish	0.12	KE:36	Inhibition, Aromatase
AOP:30	Estrogen receptor antagonism leading to reproductive dysfunction	Unclassified	Under Review	Zebra danio, Fathead minnow, Medaka	0.17	KE:112	Antagonism, Estrogen receptor
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:118	Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)	Cancer; Gastrointestinal system disease	-	Mus musculus, Rattus norvegicus	0.25	KE:786	Increase, Cytotoxicity (hepatocytes)
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:263	Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation	Unclassified	WPHA/WNT Endorsed	Zebrafish, Mouse, Rat, Lemna minor, Human, Caenorhabditis elegans	0.5	KE:1821	Decrease, Cell proliferation
AOP:263		Unclassified	WPHA/WNT Endorsed		0.5	KE:1446	Decrease, Coupling of oxidative phosphorylation
AOP:264	Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell death	Unclassified	Under Development		0.25	KE:1446	Decrease, Coupling of oxidative phosphorylation
AOP:265	Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calcium	Unclassified	Under Development		0.25	KE:1446	Decrease, Coupling of oxidative phosphorylation
AOP:266	Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity	Unclassified	Under Development		0.17	KE:1446	Decrease, Coupling of oxidative phosphorylation
AOP:267	Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion	Unclassified	Under Development		0.4	KE:1821	Decrease, Cell proliferation
AOP:267		Unclassified	Under Development		0.4	KE:1446	Decrease, Coupling of oxidative phosphorylation
AOP:268	Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swelling	Unclassified	Under Development		0.25	KE:1446	Decrease, Coupling of oxidative phosphorylation
AOP:300	Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	Under Development	Human, Mouse	0.2	KE:1656	Antagonism, Thyroid Receptor
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: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: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:36	Inhibition, Aromatase
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: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: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:1046	Suppression, Estrogen receptor (ER) activity
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:485	Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognition	Cognitive disorder	-	Human	0.14	KE:1656	Antagonism, Thyroid Receptor
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:2126	Estrogen receptor alpha inactivation
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	-		0.12	KE:2126	Estrogen receptor alpha inactivation
AOP:549	Aromatase inhibition leads to reproductive toxicity (including growth and developmental toxicity) in adult female zebrafish	Unclassified	-		0.12	KE:36	Inhibition, Aromatase

No associated AOPs with Level of Relevance 5

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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.