DEDUCT | Database of Endocrine Disrupting chemicals and their Toxicity profiles

Reserpine

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:4	Ecdysone receptor agonism leading to incomplete ecdysis associated mortality	Unclassified	-	Insects, Crustaceans	0.1	KE:993	Decrease, Abdominal muscle contraction
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:37	PPARα activation leading to hepatocellular adenomas and carcinomas in rodents	Cancer; Gastrointestinal system disease	Under Development	Mouse, Rat	0.2	KE:716	Increase, cell proliferation (hepatocytes)
AOP:38	Protein Alkylation leading to Liver Fibrosis	Gastrointestinal system disease	WPHA/WNT Endorsed	Human, Rat	0.14	KE:68	Accumulation, Collagen
AOP:39	Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response	Respiratory system disease	Under Development	Human, Mouse	0.2	KE:272	Activation/Proliferation, T-cells
AOP:40	Covalent Protein binding leading to Skin Sensitisation	Integumentary system disease	WPHA/WNT Endorsed	Mouse, Human	0.2	KE:272	Activation/Proliferation, T-cells
AOP:41	Sustained AhR Activation leading to Rodent Liver Tumours	Cancer; Gastrointestinal system disease	Under Review	Rattus sp. ABTC 42503, Mus sp. 2000082	0.6	KE:854	Alterations, Cellular proliferation / hyperplasia
						KE:853	Changes/Inhibition, Cellular Homeostasis and Apoptosis
						KE:139	N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects
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:352	N/A, Neurodegeneration
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:96	Axonal sodium channel modulation leading to acute mortality	Unclassified	-	Insects, Fish	0.17	KE:601	Overactivation, muscle contraction
AOP:105	Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)	Cancer; Urinary system disease	-	Rattus norvegicus	0.17	KE:710	Increase, Regenerative cell proliferation (tubular epithelial cells)
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:716	Increase, cell proliferation (hepatocytes)
AOP:109	Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)	Cancer; Respiratory system disease	-	Mus musculus	0.2	KE:734	Increase, Regenerative cell proliferation (terminal bronchiolar epithelial cells)
AOP:110	Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse)	Cancer; Endocrine system disease	-	Rattus norvegicus, Mus musculus	0.14	KE:739	Increase, Hypertrophy and proliferation (follicular cell)
AOP:114	HPPD inhibition leading to corneal papillomas and carcinomas (in rat)	Cancer	-	Rattus norvegicus	0.17	KE:778	Increase, Regenerative cell proliferation (corneal cells)
AOP:115	Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)	Cancer	-	Mus musculus, Rattus norvegicus	0.2	KE:781	Increase, Regenerative cell proliferation (forestomach epithelial cells)
AOP:116	Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)	Cancer; Urinary system disease	-	Rattus norvegicus	0.25	KE:710	Increase, Regenerative cell proliferation (tubular epithelial cells)
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	0.25	KE:716	Increase, cell proliferation (hepatocytes)
AOP:119	Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)	Cancer; Endocrine system disease	-	Rattus norvegicus, Mus musculus	0.14	KE:739	Increase, Hypertrophy and proliferation (follicular cell)
AOP:121	Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)	Cancer; Urinary system disease	-	Mus musculus, Rattus norvegicus	0.2	KE:795	Increase, Regenerative cell proliferation (urothelial cells)
AOP:122	Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation	Unclassified	-	Pimephales promelas	0.1	KE:799	Increased, HIF-1 heterodimer
AOP:136	Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors	Benign neoplasm; Respiratory system disease	Under Review		0.14	KE:870	Increase, Cell Proliferation
AOP:144	Endocytic lysosomal uptake leading to liver fibrosis	Gastrointestinal system disease	Under Review	Human, Mouse, Rat	0.11	KE:68	Accumulation, Collagen
AOP:164	Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouse	Cancer; Reproductive system disease	-	CD-1 mouse, SD rat	0.17	KE:1042	Proliferation/Clonal Expansion, smooth muscle
AOP:167	Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.	Reproductive system disease; Cancer	-	Mouse, Homo sapiens	0.14	KE:1067	Proliferation/Clonal Expansion, aberrant basal cells
AOP:173	Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis	Musculoskeletal system disease; Respiratory system disease	WPHA/WNT Endorsed	Human, Mouse, Rat	0.12	KE:68	Accumulation, Collagen
AOP:207	NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans	Reproductive system disease	-	Caenorhabditis elegans	0.25	KE:1280	Activation, HIF-1
AOP:207		Reproductive system disease	-	Caenorhabditis elegans	0.25	KE:1262	Apoptosis
AOP:209	Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP	Gastrointestinal system disease	-		0.12	KE:1289	Perturbation of cholesterol
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	0.4	KE:1393	Hepatocytotoxicity
AOP:220	Cyp2E1 Activation Leading to Liver Cancer	Cancer; Gastrointestinal system disease	WPHA/WNT Endorsed	Rodents, Homo sapiens	0.4	KE:1394	Induction, persistent proliferation/sustained proliferation
AOP:241	Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis	Musculoskeletal system disease; Respiratory system disease	-		0.17	KE:68	Accumulation, Collagen
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	0.25	KE:1821	Decrease, Cell proliferation
AOP:267	Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion	Unclassified	Under Development		0.2	KE:1821	Decrease, Cell proliferation
AOP:272	Deposition of energy leading to lung cancer	Cancer	WPHA/WNT Endorsed	Human, Rat, Mouse	0.14	KE:870	Increase, Cell Proliferation
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:290	Mitochondrial ATP synthase antagonism leading to growth inhibition (1)	Unclassified	-	Daphnia magna	0.25	KE:1821	Decrease, Cell proliferation
AOP:303	Frustrated phagocytosis-induced lung cancer	Cancer	Under Development	Mammals	0.14	KE:870	Increase, Cell Proliferation
AOP:321	Reduced environmental pH leading to thinner shells in Mytilus edulis	Unclassified	-		0.09	KE:592	Reduced, survival
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	-		0.2	KE:1821	Decrease, Cell proliferation
AOP:335	AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment	Cancer; Urinary system disease	-	Rat	0.2	KE:795	Increase, Regenerative cell proliferation (urothelial cells)
AOP:374	Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on brain cells (neuronal and non-neuronal) leads to neuroinflammation resulting in encephalitis	Nervous system disease	Under Development	Human	0.25	KE:352	N/A, Neurodegeneration
AOP:379	Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation	Cardiovascular system disease	Under Development	Homo sapiens	0.14	KE:1869	Diminished protective oxidative stress response
AOP:382	Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis	Musculoskeletal system disease; Respiratory system disease	Under Development		0.17	KE:68	Accumulation, Collagen
AOP:399	Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)	Unclassified	-	Zebrafish	0.12	KE:1821	Decrease, Cell proliferation
AOP:406	SARS-CoV-2 infection leading to hyperinflammation	Unclassified	-		0.17	KE:1869	Diminished protective oxidative stress response
AOP:409	Frustrated phagocytosis leads to malignant mesothelioma	Cancer	-		0.12	KE:870	Increase, Cell Proliferation
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:870	Increase, Cell Proliferation
AOP:432	Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia	Hematopoietic system disease; Cancer	-	Homo sapiens, Mus musculus	0.09	KE:870	Increase, Cell Proliferation
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:451	Interaction with lung resident cell membrane components leads to lung cancer	Cancer	-	Human	0.11	KE:870	Increase, Cell Proliferation
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:1821	Decrease, Cell proliferation
AOP:460		Unclassified	Under Development	Mouse	0.22	KE:1262	Apoptosis
AOP:463	The AOP framwork on silica nanopariticles induced hepatoxicity	Gastrointestinal system disease	-		0.09	KE:1262	Apoptosis
AOP:465	Alcohol dehydrogenase leading to reproductive dysfunction	Unclassified	-		0.12	KE:748	Increased, Estrogen receptor (ER) activity
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:870	Increase, Cell Proliferation
AOP:491	Decrease, GLI1/2 target gene expression leads to orofacial clefting	Unclassified	Under Development	Mouse	0.33	KE:1821	Decrease, Cell proliferation
AOP:491		Unclassified	Under Development	Mouse	0.33	KE:1262	Apoptosis
AOP:495	Androgen receptor activation leading to prostate cancer	Reproductive system disease; Cancer	-		0.22	KE:854	Alterations, Cellular proliferation / hyperplasia
AOP:495	Androgen receptor activation leading to prostate cancer	Reproductive system disease; Cancer	-		0.22	KE:1183	Decreased, Apoptosis (Epithelial Cells)
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	0.29	KE:352	N/A, Neurodegeneration
AOP:500		Developmental disorder of mental health	-	Rattus norvegicus, Mus musculus, Homo sapiens	0.29	KE:1262	Apoptosis
AOP:525	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory	Developmental disorder of mental health	-		0.08	KE:2115	Altered, cholesterol metabolism
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:539	Decreased Sodium/Potassium ATPase activity leads to Heart failure	Cardiovascular system disease	-	Fish	0.14	KE:2261	Decreased, blood plasma volume
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: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:2195	Increase, CNS Neural 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: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:896	Parkinsonian motor deficits
AOP:12	Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging	Nervous system disease; Developmental disorder of mental health	WPHA/WNT Endorsed	Monkey, Rat, Human, Mouse, Zebrafish	0.12	KE:352	N/A, Neurodegeneration
AOP:42	Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	WPHA/WNT Endorsed	Human, Rat, Mouse	0.12	KE:402	Cognitive function, decreased
AOP:95	Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survival	Unclassified	-		0.17	KE:592	Reduced, survival
AOP:99	Histamine (H2) receptor antagonism leading to reduced survival	Unclassified	-	Zebrafish	0.14	KE:636	Decreased, survival
AOP:134	Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Rat, Homo sapiens	0.11	KE:402	Cognitive function, decreased
AOP:139	Alkylation of DNA leading to cancer 1	Cancer	-	Homo sapiens, Mus musculus	0.25	KE:885	Increase, Cancer
AOP:149	Peptide Oxidation Leading to Hypertension	Cardiovascular system disease	Under Development	Human, Mouse, Rat, Cow	0.1	KE:952	Hypertension
AOP:205	AOP from chemical insult to cell death	Unclassified	-	Vertebrates	0.17	KE:1262	Apoptosis
AOP:242	Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity	Unclassified	-	Fish	0.12	KE:636	Decreased, survival
AOP:260	CYP2E1 activation and formation of protein adducts leading to neurodegeneration	Nervous system disease	-	Human	0.14	KE:1514	Neurodegeneration
AOP:293	Increased DNA damage leading to increased risk of breast cancer	Genetic disease; Thoracic disease; Cancer	Under Development	Rattus rattus, Mus musculus	0.22	KE:1193	N/A, Breast Cancer
AOP:293		Genetic disease; Thoracic disease; Cancer	Under Development	Rattus rattus, Mus musculus	0.22	KE:1182	Increase, Cell Proliferation (Epithelial Cells)
AOP:294	Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer	Genetic disease; Thoracic disease; Cancer	Under Development		0.22	KE:1193	N/A, Breast Cancer
AOP:294		Genetic disease; Thoracic disease; Cancer	Under Development		0.22	KE:1182	Increase, Cell Proliferation (Epithelial Cells)
AOP:300	Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	Under Development	Human, Mouse	0.2	KE:402	Cognitive function, decreased
AOP:442	Binding to voltage gate sodium channels during development leads to cognitive impairment	Cognitive disorder	Under Review	Rattus norvegicus, Mouse, Humans	0.14	KE:402	Cognitive function, decreased
AOP:458	AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Rat, Mouse, Monkey, Human	0.12	KE:402	Cognitive function, decreased
AOP:459	AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Human, Mouse, Rat	0.11	KE:402	Cognitive function, decreased
AOP:464	Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits	Nervous system disease	-		0.05	KE:896	Parkinsonian motor deficits
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:485	Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognition	Cognitive disorder	-	Human	0.14	KE:402	Cognitive function, decreased
AOP:486	Binding to the extracellular protein laminin leading to decreased cognitive function	Cognitive disorder	-	Human	0.14	KE:402	Cognitive function, decreased
AOP:488	Increased reactive oxygen species production leading to decreased cognitive function	Cognitive disorder	-	Human	0.29	KE:1869	Diminished protective oxidative stress response
AOP:488		Cognitive disorder	-	Human	0.29	KE:402	Cognitive function, decreased
AOP:498	Increased LCN2/iron complex leading to neurological disorders	Nervous system disease	-	Homo sapiens	0.5	KE:2150	Neurological disorder
AOP:498		Nervous system disease	-	Homo sapiens	0.5	KE:191	Neuronal dysfunction
AOP:501	Excessive iron accumulation leading to neurological disorders	Nervous system disease	-	Homo sapiens	0.25	KE:2150	Neurological disorder
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
AOP:551	Increased Muscarinic M2 Receptor leading to Arrhythmia	Symptom	-	Human, Mouse, Rat	0.2	KE:1106	Occurrence, cardiac arrhythmia
AOP:554	β-adrenergic receptor agonists leading to arrhythmias.	Symptom	-	Human and other cells in culture, Rodents, Macaca mulatta, Zebrafish, Gallus gallus	0.25	KE:1106	Occurrence, cardiac arrhythmia
AOP:560	Inhibition of Funny current (If) leading to Arrhythmias	Symptom	-	Human and other cells in culture, Rodents, Dogs, Zebrafish	0.25	KE:1106	Occurrence, cardiac arrhythmia
AOP:562	HCN Channel Inhibition leading to Arrhythmias	Symptom	-	Human and other cells in culture, Dogs, Zebrafish, Rodents, Pigs	0.2	KE:1106	Occurrence, cardiac arrhythmia

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:16	Acetylcholinesterase inhibition leading to acute mortality	Unclassified	Under Development		0.14	KE:12	Acetylcholinesterase (AchE) Inhibition
AOP:60	NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-		0.08	KE:245	Activation, PXR/SXR
AOP:93	sodium channel inhibition leading to increased predation	Unclassified	-		0.25	KE:584	Inhibition, sodium channel
AOP:94	Sodium channel inhibition leading to congenital malformations	Unclassified	-	Human, Rat, Mouse	0.17	KE:584	Inhibition, sodium channel
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:786	Increase, Cytotoxicity (hepatocytes)
AOP:118		Cancer; Gastrointestinal system disease	-	Mus musculus, Rattus norvegicus	0.5	KE:787	Increase, Regenerative cell proliferation (hepatocytes)
AOP:123	Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription	Unclassified	-	Pimephales promelas	0.27	KE:801	modulation, Unknown
						KE:802	Increased, HIF-1 alpha transcription
						KE:799	Increased, HIF-1 heterodimer
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:1753	Chronic reactive oxygen species
AOP:312	Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement	Unclassified	-		0.17	KE:12	Acetylcholinesterase (AchE) Inhibition
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:12	Acetylcholinesterase (AchE) Inhibition
AOP:450		Nervous system disease	-	Rattus norvegicus, Mus musculus, Homo sapiens	0.29	KE:352	N/A, Neurodegeneration
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
AOP:553	Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure	Cardiovascular system disease	-	Human, Rodents, Dogs, Pigs, Insects, Fish	0.25	KE:584	Inhibition, sodium channel

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:91	Sodium channel inhibition leading to reduced survival	Unclassified	-	Medaka, Gammarus pulex, Hydra	0.33	KE:592	Reduced, survival
AOP:91	Sodium channel inhibition leading to reduced survival	Unclassified	-	Medaka, Gammarus pulex, Hydra	0.33	KE:584	Inhibition, sodium channel
AOP:281	Acetylcholinesterase Inhibition Leading to Neurodegeneration	Nervous system disease	-		0.2	KE:12	Acetylcholinesterase (AchE) Inhibition
AOP:281		Nervous system disease	-		0.2	KE:352	N/A, Neurodegeneration
AOP:405	Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function	Cognitive disorder	-	Rattus norvegicus, Mus musculus, Homo sapiens	0.4	KE:12	Acetylcholinesterase (AchE) Inhibition
AOP:405		Cognitive disorder	-	Rattus norvegicus, Mus musculus, Homo sapiens	0.4	KE:402	Cognitive function, decreased
AOP:559	Inhibition of acetylcholinesterase (AChE) leading to arrhythmias	Symptom	-	Human and other cells in culture, Rattus norvegicus, Dogs, Sus scrofa, Zebrafish, Insecta sp. BOLD:AAN5199	0.4	KE:12	Acetylcholinesterase (AchE) Inhibition
AOP:559		Symptom	-		0.4	KE:1106	Occurrence, cardiac arrhythmia

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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.