Methylcholanthrene


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:15Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutationsGenetic diseaseWPHA/WNT EndorsedMus musculus, Drosophila melanogaster, Oryzias latipes, Syrian golden hamster0.25KE:155Inadequate DNA repair
AOP:17Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memoryDevelopmental disorder of mental healthWPHA/WNT EndorsedRat, Mouse, Human0.1KE:1392Oxidative Stress
AOP:18PPARα activation in utero leading to impaired fertility in malesReproductive system diseaseUnder ReviewHuman, Rat, Mouse0.12KE:1690Decrease, circulating testosterone levels
AOP:23Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)UnclassifiedWPHA/WNT EndorsedPimephales promelas0.2KE:219Reduction, Plasma 17beta-estradiol concentrations
KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:37PPARα activation leading to hepatocellular adenomas and carcinomas in rodentsCancer; Gastrointestinal system diseaseUnder DevelopmentMouse, Rat0.2KE:716Increase, cell proliferation (hepatocytes)
AOP:39Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity ResponseRespiratory system diseaseUnder DevelopmentHuman, Mouse0.2KE:272Activation/Proliferation, T-cells
AOP:40Covalent Protein binding leading to Skin SensitisationIntegumentary system diseaseWPHA/WNT EndorsedMouse, Human0.2KE:272Activation/Proliferation, T-cells
AOP:58NR1I3 (CAR) suppression leading to hepatic steatosisGastrointestinal system disease; Inherited metabolic disorder-Human, Mouse, Rat0.06KE:454Increased, Triglyceride formation
AOP:60NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosisGastrointestinal system disease; Inherited metabolic disorder-0.08KE:454Increased, Triglyceride formation
AOP:64Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male FertilityReproductive system disease-Rattus norvegicus0.43KE:520Decreased sperm quantity or quality in the adult, Decreased fertility
KE:496Increased apoptosis, decreased fetal/adult Leydig Cells
KE:1690Decrease, circulating testosterone levels
AOP:80Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failureUnclassified-Honey bee0.12KE:664Overwhelmed, Mitochondrial DNA repair mechanisms
AOP:105Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)Cancer; Urinary system disease-Rattus norvegicus0.17KE:710Increase, Regenerative cell proliferation (tubular epithelial cells)
AOP:107Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the ratCancer; Gastrointestinal system diseaseUnder ReviewRattus norvegicus, Mus musculus0.4KE:1214Altered gene expression specific to CAR activation, Hepatocytes
KE:716Increase, cell proliferation (hepatocytes)
AOP:109Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)Cancer; Respiratory system disease-Mus musculus0.2KE:734Increase, Regenerative cell proliferation (terminal bronchiolar epithelial cells)
AOP:110Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse)Cancer; Endocrine system disease-Rattus norvegicus, Mus musculus0.14KE:739Increase, Hypertrophy and proliferation (follicular cell)
AOP:114HPPD inhibition leading to corneal papillomas and carcinomas (in rat)Cancer-Rattus norvegicus0.17KE:778Increase, Regenerative cell proliferation (corneal cells)
AOP:115Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)Cancer-Mus musculus, Rattus norvegicus0.4KE:149Increase, Inflammation
KE:781Increase, Regenerative cell proliferation (forestomach epithelial cells)
AOP:116Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)Cancer; Urinary system disease-Rattus norvegicus0.25KE:710Increase, Regenerative cell proliferation (tubular epithelial cells)
AOP:117Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal system diseaseUnder DevelopmentMus musculus, Rattus norvegicus0.25KE:716Increase, cell proliferation (hepatocytes)
AOP:118Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal system disease-Mus musculus, Rattus norvegicus0.25KE:787Increase, Regenerative cell proliferation (hepatocytes)
AOP:119Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)Cancer; Endocrine system disease-Rattus norvegicus, Mus musculus0.14KE:739Increase, Hypertrophy and proliferation (follicular cell)
AOP:120Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)Cancer; Reproductive system disease-Rattus norvegicus, Mus musculus0.2KE:1690Decrease, circulating testosterone levels
AOP:121Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)Cancer; Urinary system disease-Mus musculus, Rattus norvegicus0.2KE:795Increase, Regenerative cell proliferation (urothelial cells)
AOP:122Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formationUnclassified-Pimephales promelas0.3KE:800Decreased, Aromatase (Cyp19a1) mRNA
KE:219Reduction, Plasma 17beta-estradiol concentrations
KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:123Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcriptionUnclassified-Pimephales promelas0.27KE:800Decreased, Aromatase (Cyp19a1) mRNA
KE:219Reduction, Plasma 17beta-estradiol concentrations
KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:124HMG-CoA reductase inhibition leading to decreased fertilityReproductive system disease-Rattus rattus0.33KE:807Decreased, cholesterol
KE:1690Decrease, circulating testosterone levels
AOP:136Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal TumorsBenign neoplasm; Respiratory system diseaseUnder Review0.14KE:870Increase, Cell Proliferation
AOP:149Peptide Oxidation Leading to HypertensionCardiovascular system diseaseUnder DevelopmentHuman, Mouse, Rat, Cow0.1KE:927KE1 : S-Glutathionylation, eNOS
AOP:164Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouseCancer; Reproductive system disease-CD-1 mouse, SD rat0.17KE:1042Proliferation/Clonal Expansion, smooth muscle
AOP:167Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.Reproductive system disease; Cancer-Mouse, Homo sapiens0.14KE:1067Proliferation/Clonal Expansion, aberrant basal cells
AOP:206Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosisMusculoskeletal system disease; Respiratory system diseaseUnder DevelopmentHomo sapiens0.17KE:149Increase, Inflammation
AOP:207NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegansReproductive system disease-Caenorhabditis elegans0.38KE:1115Increase, Reactive oxygen species
KE:1281Increased, DNA Damage-Repair
KE:1262Apoptosis
AOP:213Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)Gastrointestinal system disease; Inherited metabolic disorder-Vertebrates0.17KE:1115Increase, Reactive oxygen species
AOP:220Cyp2E1 Activation Leading to Liver CancerCancer; Gastrointestinal system diseaseWPHA/WNT EndorsedRodents, Homo sapiens0.4KE:1392Oxidative Stress
KE:1394Induction, persistent proliferation/sustained proliferation
AOP:260CYP2E1 activation and formation of protein adducts leading to neurodegenerationNervous system disease-Human0.14KE:1392Oxidative Stress
AOP:263Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferationUnclassifiedWPHA/WNT EndorsedZebrafish, Mouse, Rat, Lemna minor, Human, Caenorhabditis elegans0.25KE:1821Decrease, Cell proliferation
AOP:267Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletionUnclassifiedUnder Development0.4KE:1821Decrease, Cell proliferation
KE:2071Decrease, Glucose pool
AOP:271Inhibition of thyroid peroxidase leading to impaired fertility in fishUnclassifiedUnder DevelopmentFish0.2KE:219Reduction, Plasma 17beta-estradiol concentrations
AOP:275Histone deacetylase inhibition leads to neural tube defectsNeural tube defect-0.2KE:1503Histone acetylation, increase
AOP:280α-diketone-induced bronchiolitis obliteransMusculoskeletal system disease; Respiratory system disease-0.14KE:149Increase, Inflammation
AOP:286Mitochondrial complex III antagonism leading to growth inhibition (1)Unclassified-Lemna minor, Daphnia magna, Danio rerio0.25KE:1821Decrease, Cell proliferation
AOP:288Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)Endocrine system disease-Human, Rat0.25KE:1614Decrease, androgen receptor activation
KE:1690Decrease, circulating testosterone levels
AOP:289Inhibition of 5α-reductase leading to impaired fecundity in female fishUnclassifiedUnder DevelopmentFish0.17KE:219Reduction, Plasma 17beta-estradiol concentrations
AOP:290Mitochondrial ATP synthase antagonism leading to growth inhibition (1)Unclassified-Daphnia magna0.25KE:1821Decrease, Cell proliferation
AOP:299Deposition of energy leading to population decline via DNA oxidation and follicular atresiaUnclassified-0.14KE:1115Increase, Reactive oxygen species
AOP:3055α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspringUnclassifiedUnder DevelopmentRat, Human, Mouse0.2KE:1614Decrease, androgen receptor activation
AOP:311Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosisUnclassified-Daphnia magna, Fish0.14KE:1115Increase, Reactive oxygen species
AOP:315Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody ResponseImmune system diseaseUnder DevelopmentHomo sapiens, Mus musculus0.2KE:1716Blockade of STAT5 phosphorylation
AOP:321Reduced environmental pH leading to thinner shells in Mytilus edulisUnclassified-0.09KE:10042Abnormal development
AOP:323PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-KetotestosteroneUnclassified-Teleost fish0.5KE:1756Decreased, plasma 11-ketotestosterone level
KE:1758Impaired, Spermatogenesis
KE:807Decreased, cholesterol
AOP:335AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairmentCancer; Urinary system disease-Rat0.2KE:795Increase, Regenerative cell proliferation (urothelial cells)
AOP:348Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectoryUnclassifiedUnder DevelopmentFish0.4KE:1756Decreased, plasma 11-ketotestosterone level
KE:1758Impaired, Spermatogenesis
AOP:349Inhibition of 11β-hydroxylase leading to decresed population trajectoryUnclassifiedUnder DevelopmentFish0.25KE:1798Decreased spermatogenesis
KE:1756Decreased, plasma 11-ketotestosterone level
AOP:362Immune mediated hepatitisGastrointestinal system disease; Immune system disease-Homo sapiens, Rat0.12KE:1633Increase in inflammation
AOP:376Androgen receptor agonism leading to male-biased sex ratioUnclassifiedWPHA/WNT EndorsedZebrafish, Medaka, Fathead minnow, Channel catfish, Oreochromis niloticus, Chinook salmon0.25KE:1790Increased, Differentiation to Testis
AOP:379Binding to ACE2 leading to thrombosis and disseminated intravascular coagulationCardiovascular system diseaseUnder DevelopmentHomo sapiens0.14KE:1869Diminished protective oxidative stress response
AOP:382Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosisMusculoskeletal system disease; Respiratory system diseaseUnder Development0.17KE:1115Increase, Reactive oxygen species
AOP:383Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosisGastrointestinal system diseaseUnder Development0.17KE:1115Increase, Reactive oxygen species
AOP:384Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney diseaseUrinary system disease-0.17KE:1115Increase, Reactive oxygen species
AOP:386Deposition of ionizing energy leading to population decline via inhibition of photosynthesisReproductive system disease-Lemna minor, Chlamydomonas reinhardtii0.12KE:1115Increase, Reactive oxygen species
AOP:387Deposition of ionising energy leading to population decline via mitochondrial dysfunctionReproductive system disease-Lemna minor0.12KE:1115Increase, Reactive oxygen species
AOP:397Bulky DNA adducts leading to mutationsGenetic diseaseUnder Development0.33KE:155Inadequate DNA repair
AOP:399Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)Unclassified-Zebrafish0.12KE:1821Decrease, Cell proliferation
AOP:409Frustrated phagocytosis leads to malignant mesotheliomaCancer-0.25KE:870Increase, Cell Proliferation
KE:1115Increase, Reactive oxygen species
AOP:413Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failureUnclassified-Fish, Mice0.17KE:1115Increase, Reactive oxygen species
AOP:431Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)Inherited metabolic disorder-Human0.2KE:1952Abnormal, Glucose homeostasis
AOP:432Deposition of Energy by Ionizing Radiation leading to Acute Myeloid LeukemiaHematopoietic system disease; Cancer-Homo sapiens, Mus musculus0.18KE:155Inadequate DNA repair
KE:870Increase, Cell Proliferation
AOP:437Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicityUrinary system diseaseUnder Development0.2KE:1392Oxidative Stress
AOP:441Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiationCongenital nervous system abnormality; Nervous system disease-Homo sapiens, Mus musculus musculus, Rattus norvegicus0.14KE:1262Apoptosis
AOP:443DNA damage and mutations leading to Metastatic Breast CancerThoracic disease; CancerUnder DevelopmentHuman and other cells in culture, Human, Mice, Rat, Canine heartworm nematode, Yeast0.3KE:155Inadequate DNA repair
KE:112Antagonism, Estrogen receptor
KE:1554Increase Chromosomal Aberrations
AOP:444Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchabilityUnclassified-0.22KE:1392Oxidative Stress
KE:1798Decreased spermatogenesis
AOP:450Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortalityNervous system disease-Rattus norvegicus, Mus musculus, Homo sapiens0.14KE:1392Oxidative Stress
AOP:452Adverse outcome pathway of PM-induced respiratory toxicityRespiratory system disease-0.18KE:1392Oxidative Stress
KE:1262Apoptosis
AOP:457Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxineInherited metabolic disorder-Human0.17KE:1392Oxidative Stress
AOP:460Antagonism of Smoothened receptor leading to orofacial cleftingUnclassifiedUnder DevelopmentMouse0.22KE:1821Decrease, Cell proliferation
KE:1262Apoptosis
AOP:464Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficitsNervous system disease-0.05KE:1392Oxidative Stress
AOP:470Deposition of energy leads to abnormal vascular remodelingCardiovascular system diseaseUnder ReviewHuman, Rat, Mouse, Rabbit0.25KE:1392Oxidative Stress
KE:2244Altered Stress Response Signaling
AOP:478Deposition of energy leading to occurrence of cataractsNervous system disease; Monogenic diseaseUnder ReviewHuman, Mouse, Rat, Rhesus monkeys, Rabbit, Guinea pig0.4KE:1392Oxidative Stress
KE:155Inadequate DNA repair
KE:870Increase, Cell Proliferation
KE:1636Increase, Chromosomal aberrations
AOP:479Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stressCardiovascular system disease; Thoracic diseaseUnder Development0.14KE:1392Oxidative Stress
AOP:482Deposition of energy leading to occurrence of bone lossMusculoskeletal system diseaseUnder ReviewHuman, Mouse, Rat, Rhesus monkeys0.14KE:1392Oxidative Stress
AOP:483Deposition of Energy Leading to Learning and Memory ImpairmentDevelopmental disorder of mental healthUnder ReviewMouse, Rat, Rabbit, Dog, Pigs, Cow, Human0.25KE:1392Oxidative Stress
KE:2244Altered Stress Response Signaling
AOP:491Decrease, GLI1/2 target gene expression leads to orofacial cleftingUnclassifiedUnder DevelopmentMouse0.33KE:1821Decrease, Cell proliferation
KE:1262Apoptosis
AOP:492Glutathione conjugation leading to reproductive dysfunction via oxidative stressReproductive system disease-Mammals, Fish0.2KE:1115Increase, Reactive oxygen species
AOP:495Androgen receptor activation leading to prostate cancerReproductive system disease; Cancer-0.22KE:854Alterations, Cellular proliferation / hyperplasia
KE:1183Decreased, Apoptosis (Epithelial Cells)
AOP:496Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)Unclassified-Zebrafish0.2KE:219Reduction, Plasma 17beta-estradiol concentrations
KE:1690Decrease, circulating testosterone levels
AOP:500Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosisDevelopmental disorder of mental health-Rattus norvegicus, Mus musculus, Homo sapiens0.29KE:1115Increase, Reactive oxygen species
KE:1262Apoptosis
AOP:501Excessive iron accumulation leading to neurological disordersNervous system disease-Homo sapiens0.25KE:1392Oxidative Stress
AOP:507Nrf2 inhibition leading to vascular disrupting effects via inflammation pathwayCardiovascular system disease-Mouse, Zebrafish, Human0.17KE:1392Oxidative Stress
AOP:509Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunctionCardiovascular system disease-0.14KE:1392Oxidative Stress
AOP:510Demethylation of PPAR promotor leading to vascular disrupting effectsCardiovascular system disease-Human, Mouse, Zebrafish0.1KE:1392Oxidative Stress
AOP:521Essential element imbalance leads to reproductive failure via oxidative stressUnclassified-Murinae gen. sp.0.57KE:1392Oxidative Stress
KE:2206Increased, histomorphological alteration of testis
KE:1758Impaired, Spermatogenesis
KE:1115Increase, Reactive oxygen species
AOP:525Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memoryDevelopmental disorder of mental health-0.08KE:2115Altered, cholesterol metabolism
AOP:535Binding and activation of GPER leading to learning and memory impairmentsDevelopmental disorder of mental health-Mouse, Human0.33KE:1392Oxidative Stress
KE:2233Decreased, ERαβ heterodimers
KE:1262Apoptosis
AOP:544Inhibition of neuropathy target esterase leading to delayed neuropathy via increased inflammationNervous system disease-Homo sapiens, Mus musculus0.17KE:149Increase, Inflammation
AOP:569Decreased DNA methylation of FAM50B/PTCHD3 leading to IQ loss of children via PI3K-Akt pathwayDevelopmental disorder of mental health-0.17KE:1115Increase, Reactive oxygen species

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:6Antagonist binding to PPARα leading to body-weight lossSymptomWPHA/WNT EndorsedMus musculus, Homo sapiens, Pimephales promelas, Colinus virginianus, Rattus norvegicus0.12KE:864Decreased, Body Weight
AOP:27Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)Gastrointestinal system diseaseUnder DevelopmentHumans0.38KE:357Cholestasis, Pathology
KE:149Increase, Inflammation
KE:1115Increase, Reactive oxygen species
AOP:139Alkylation of DNA leading to cancer 1Cancer-Homo sapiens, Mus musculus0.5KE:885Increase, Cancer
KE:155Inadequate DNA repair
AOP:205AOP from chemical insult to cell deathUnclassified-Vertebrates0.17KE:1262Apoptosis
AOP:212Histone deacetylase inhibition leading to testicular atrophyReproductive system diseaseWPHA/WNT EndorsedRat, Human, Mouse0.5KE:1506Testicular atrophy
KE:1503Histone acetylation, increase
KE:1262Apoptosis
AOP:237Substance interaction with lung resident cell membrane components leading to atherosclerosisCardiovascular system diseaseUnder DevelopmentHuman, Mouse0.2KE:1443Atherosclerosis
AOP:269Elevated ATP demand for detoxification and repair mechanisms leading to impaired growth and developmentUnclassified-0.17KE:10013Impaired growth and development
AOP:272Deposition of energy leading to lung cancerCancerWPHA/WNT EndorsedHuman, Rat, Mouse0.57KE:155Inadequate DNA repair
KE:870Increase, Cell Proliferation
KE:1636Increase, Chromosomal aberrations
KE:1556Increase, lung cancer
AOP:278IKK complex inhibition leading to liver injuryUnclassified-0.12KE:1549Liver Injury
AOP:293Increased DNA damage leading to increased risk of breast cancerGenetic disease; Thoracic disease; CancerUnder DevelopmentRattus rattus, Mus musculus0.22KE:1193N/A, Breast Cancer
KE:1182Increase, Cell Proliferation (Epithelial Cells)
AOP:294Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancerGenetic disease; Thoracic disease; CancerUnder Development0.22KE:1193N/A, Breast Cancer
KE:1182Increase, Cell Proliferation (Epithelial Cells)
AOP:296Oxidative DNA damage leading to chromosomal aberrations and mutationsGenetic disease; Chromosomal diseaseWPHA/WNT EndorsedHuman, Mice, Rat, Fish0.4KE:155Inadequate DNA repair
KE:1636Increase, Chromosomal aberrations
AOP:303Frustrated phagocytosis-induced lung cancerCancerUnder DevelopmentMammals0.43KE:870Increase, Cell Proliferation
KE:1115Increase, Reactive oxygen species
KE:1670Lung cancer
AOP:322Alkylation of DNA leading to reduced sperm countReproductive system disease-0.4KE:155Inadequate DNA repair
KE:1757Reduce, Sperm count
AOP:392Decreased fibrinolysis and activated bradykinin system leading to hyperinflammationUnclassifiedUnder DevelopmentHumans0.2KE:1868Hyperinflammation
AOP:406SARS-CoV-2 infection leading to hyperinflammationUnclassified-0.33KE:1869Diminished protective oxidative stress response
KE:1868Hyperinflammation
AOP:451Interaction with lung resident cell membrane components leads to lung cancerCancer-Human0.33KE:870Increase, Cell Proliferation
KE:1115Increase, Reactive oxygen species
KE:1670Lung cancer
AOP:468Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)Unclassified-0.12KE:1868Hyperinflammation
AOP:474Succinate dehydrogenase inactivation leads to cancer by promoting EMTCancerUnder DevelopmentHuman and other cells in culture0.2KE:885Increase, Cancer
AOP:534Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stressCancer-Vertebrates0.5KE:1392Oxidative Stress
KE:885Increase, Cancer
KE:1115Increase, Reactive oxygen species
AOP:545Activation, Pregnane-X receptor, NR1l2 leads to increased plasma low-density lipoprotein (LDL) cholesterol via increased cholesterol synthesisUnclassified-Mammals0.2KE:2271Increased, plasma low-density lipoprotein (LDL) cholesterol
AOP:546Succinate dehydrogenase inactivation leads to cancer through hypoxic-like mechanismsCancer-Human and other cells in culture0.2KE:885Increase, Cancer
AOP:548Activation, Pregnane-X receptor, NR1l2 leads to increased plasma low-density lipoprotein (LDL) cholesterol via increased PCSK9 protein expressionUnclassified-Mammals0.2KE:2271Increased, plasma low-density lipoprotein (LDL) cholesterol

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:7Aromatase (Cyp19a1) reduction leading to impaired fertility in adult femaleReproductive system disease; Endocrine system disease; Reproductive system diseaseUnder ReviewRat, Mouse, Human0.6KE:408reduction in ovarian granulosa cells, Aromatase (Cyp19a1)
KE:219Reduction, Plasma 17beta-estradiol concentrations
KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:19Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)Reproductive system disease-0.2KE:26Antagonism, Androgen receptor
AOP:21Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2UnclassifiedWPHA/WNT EndorsedZebrafish, Medaka, Gallus gallus0.2KE:18Activation, AhR
AOP:25Aromatase inhibition leading to reproductive dysfunctionUnclassifiedWPHA/WNT EndorsedFathead minnow, Medaka, Zebrafish0.38KE:36Inhibition, Aromatase
KE:219Reduction, Plasma 17beta-estradiol concentrations
KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:30Estrogen receptor antagonism leading to reproductive dysfunctionUnclassifiedUnder ReviewZebra danio, Fathead minnow, Medaka0.17KE:112Antagonism, Estrogen receptor
AOP:38Protein Alkylation leading to Liver FibrosisGastrointestinal system diseaseWPHA/WNT EndorsedHuman, Rat0.14KE:244Alkylation, Protein
AOP:41Sustained AhR Activation leading to Rodent Liver TumoursCancer; Gastrointestinal system diseaseUnder ReviewRattus sp. ABTC 42503, Mus sp. 20000820.6KE:854Alterations, Cellular proliferation / hyperplasia
KE:165Activation, Long term AHR receptor driven direct and indirect gene expression changes
KE:853Changes/Inhibition, Cellular Homeostasis and Apoptosis
AOP:69Modulation of Adult Leydig Cell Function Subsequent to Decreased Cholesterol Synthesis or Transport in the Adult Leydig CellReproductive system disease-Rattus norvegicus, Homo sapiens0.4KE:645Decreased Cholesterol, Decreased Testosterone Production by Adult Leydig Cells
KE:642Decreased Cholesterol, Decreased De Novo Biosynthesis of Choleseterol
AOP:111Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)Cancer; Reproductive system disease-Rattus norvegicus0.2KE:1614Decrease, androgen receptor activation
AOP:131Aryl hydrocarbon receptor activation leading to uroporphyriaInherited metabolic disorderWPHA/WNT EndorsedMouse, Rat, Human, Japanese quail, Chicken, Herring gull, Common Starling0.17KE:18Activation, AhR
AOP:150Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGFUnclassifiedWPHA/WNT EndorsedChicken, Zebrafish, Mouse, Rattus norvegicus0.14KE:18Activation, AhR
AOP:151AhR activation leading to preeclampsiaCardiovascular system diseaseUnder DevelopmentHomo sapiens, Mus musculus0.14KE:18Activation, AhR
AOP:209Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOPGastrointestinal system disease-0.25KE:1289Perturbation of cholesterol
KE:1286Down Regulation, GSS and GSTs gene
AOP:258Renal protein alkylation leading to kidney toxicityUrinary system diseaseUnder DevelopmentHuman, Rat, Mouse0.2KE:244Alkylation, Protein
AOP:282Adverse outcome pathway on photochemical toxicity initiated by light exposureUnclassifiedUnder ReviewHuman0.25KE:1115Increase, Reactive oxygen species
AOP:298Increase in reactive oxygen species (ROS) leading to human treatment-resistant gastric cancer via chronic ROSCancer; Gastrointestinal system diseaseUnder ReviewHomo sapiens0.33KE:1753Chronic reactive oxygen species
KE:1115Increase, Reactive oxygen species
AOP:306Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspringUnclassifiedUnder DevelopmentRat, Human, Mouse0.5KE:1614Decrease, androgen receptor activation
KE:26Antagonism, Androgen receptor
AOP:310Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHRUnclassified-Zebrafish0.25KE:18Activation, AhR
KE:219Reduction, Plasma 17beta-estradiol concentrations
KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:324Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and cell deathUnclassified-Fish0.25KE:1115Increase, Reactive oxygen species
AOP:325Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and cell deathUnclassified-Fish0.25KE:1115Increase, Reactive oxygen species
AOP:326Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell deathUnclassified-Fish0.25KE:1115Increase, Reactive oxygen species
AOP:327Excessive reactive oxygen species production leading to mortality (1)Unclassified-Daphnia magna0.4KE:1115Increase, Reactive oxygen species
KE:1769Increase, Body fluid overload
AOP:328Excessive reactive oxygen species production leading to mortality (2)Unclassified-Daphnia magna0.2KE:1115Increase, Reactive oxygen species
AOP:329Excessive reactive oxygen species production leading to mortality (3)Unclassified-Daphnia magna, Paracyclopina nana0.2KE:1115Increase, Reactive oxygen species
AOP:330Excessive reactive oxygen species production leading to mortality (4)Unclassified-Daphnia magna0.2KE:1115Increase, Reactive oxygen species
AOP:331Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and reduced cell proliferationUnclassified-Daphnia magna, Daphnia middendorffiana, Daphnia pulex, Daphnia pulicaria, Daphnia parvula0.33KE:1821Decrease, Cell proliferation
KE:1115Increase, Reactive oxygen species
AOP:332Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferationUnclassified-0.4KE:1821Decrease, Cell proliferation
KE:1115Increase, Reactive oxygen species
AOP:333Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylationUnclassified-0.4KE:1821Decrease, Cell proliferation
KE:1115Increase, Reactive oxygen species
AOP:344Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspringUnclassifiedUnder Development0.5KE:1614Decrease, androgen receptor activation
KE:26Antagonism, Androgen receptor
AOP:345Androgen receptor (AR) antagonism leading to decreased fertility in femalesEndocrine system disease; Reproductive system disease; Reproductive system diseaseUnder DevelopmentMammals0.33KE:1614Decrease, androgen receptor activation
KE:26Antagonism, Androgen receptor
AOP:346Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiationUnclassifiedWPHA/WNT EndorsedZebrafish, Oreochromis niloticus, Chinook salmon, Fathead minnow, European sea bass0.6KE:1789Reduction, 17beta-estradiol synthesis by the undifferentiated gonad
KE:36Inhibition, Aromatase
KE:1790Increased, Differentiation to Testis
AOP:372Androgen receptor antagonism leading to testicular cancerEndocrine system disease; Reproductive system disease; Cancer-0.4KE:1614Decrease, androgen receptor activation
KE:26Antagonism, Androgen receptor
AOP:411Oxidative stress Leading to Decreased Lung FunctionRespiratory system disease-Homo sapiens0.25KE:1392Oxidative Stress
AOP:414Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathwayMusculoskeletal system disease; Respiratory system disease-0.2KE:18Activation, AhR
AOP:415Aryl hydrocarbon receptor activation leading to lung fibrosis through IL-6 toxicity pathwayMusculoskeletal system disease; Respiratory system disease-0.2KE:18Activation, AhR
AOP:418Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathwayRespiratory system disease-0.6KE:18Activation, AhR
KE:17Altered gene expression, AHR nuclear translocator (ARNT)-dependent pathway
KE:1115Increase, Reactive oxygen species
AOP:419Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathwayRespiratory system disease-0.5KE:18Activation, AhR
KE:1262Apoptosis
AOP:423Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathwayUnclassified-0.17KE:1115Increase, Reactive oxygen species
AOP:424Oxidative stress Leading to Decreased Lung Function via CFTR dysfunctionRespiratory system disease-Human0.17KE:1392Oxidative Stress
AOP:425Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1Respiratory system disease-Human0.17KE:1392Oxidative Stress
AOP:438reactive oxygen species generation leading to increased cardiovascular morbidity and mortalityCardiovascular system disease-0.17KE:1392Oxidative Stress
KE:1115Increase, Reactive oxygen species
AOP:439Activation of the AhR leading to metastatic breast cancerThoracic disease; CancerUnder DevelopmentHumans, Mice0.44KE:18Activation, AhR
KE:1971Increased, tumor growth
KE:149Increase, Inflammation
KE:1262Apoptosis
AOP:440Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasiaBenign neoplasm; Endocrine system disease; Reproductive system disease; Reproductive system disease; Cancer; Endocrine system diseaseUnder DevelopmentHuman, Rat, Mice0.11KE:1046Suppression, Estrogen receptor (ER) activity
AOP:446PM-related Adverse outcome pathway frameworks on various systemsRespiratory system disease-0.3KE:1115Increase, Reactive oxygen species
KE:165Activation, Long term AHR receptor driven direct and indirect gene expression changes
KE:1392Oxidative Stress
KE:18Activation, AhR
KE:149Increase, Inflammation
KE:1262Apoptosis
AOP:447Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathwaysUrinary system disease-0.25KE:1392Oxidative Stress
KE:1917Altered gene expression, NRF2 dependent antioxidant pathway
KE:1633Increase in inflammation
AOP:448ROS, inflammation, and activation of nAChR lead to increased incidence of cardiovascular morbidity and mortalityCardiovascular system disease-0.18KE:1392Oxidative Stress
KE:1443Atherosclerosis
KE:1115Increase, Reactive oxygen species
AOP:453Reactive oxygen species and subsequent oxidative stress lead to increased incidence of digestive morbidity and mortality in the general populationGastrointestinal system disease-0.15KE:1392Oxidative Stress
KE:1115Increase, Reactive oxygen species
AOP:455Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial developmentMusculoskeletal system diseaseUnder ReviewZebrafish, Mouse, Human, Sebastiscus marmoratus, Salmo salar, Chicken0.17KE:18Activation, AhR
AOP:456Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicityUnclassifiedUnder ReviewZebrafish, Mouse, Human, Chicken0.17KE:18Activation, AhR
AOP:458AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive disorder-Rat, Mouse, Monkey, Human0.12KE:18Activation, AhR
AOP:459AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive disorder-Human, Mouse, Rat0.22KE:18Activation, AhR
KE:1392Oxidative Stress
AOP:469Reactive oxygen speicies overproduction leading to increased digestive morbidity and mortality in generation populationGastrointestinal system disease-0.15KE:1392Oxidative Stress
KE:1115Increase, Reactive oxygen species
AOP:472DNA adduct formation leading to kidney failureUrinary system disease-0.33KE:1392Oxidative Stress
KE:149Increase, Inflammation
KE:1115Increase, Reactive oxygen species
AOP:477Androgen receptor (AR) antagonism leading to hypospadias in male (mammalian) offspringPhysical disorder-0.67KE:1614Decrease, androgen receptor activation
KE:26Antagonism, Androgen receptor
AOP:488Increased reactive oxygen species production leading to decreased cognitive functionCognitive disorder-Human0.43KE:1392Oxidative Stress
KE:1869Diminished protective oxidative stress response
KE:1115Increase, Reactive oxygen species
AOP:493ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesityAcquired metabolic disease-Mus musculus, Homo sapiens0.2KE:2126Estrogen receptor alpha inactivation
KE:1633Increase in inflammation
AOP:494AhR activation leading to liver fibrosisGastrointestinal system disease-Mus musculus, Homo sapiens0.17KE:18Activation, AhR
AOP:497ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndromeInherited metabolic disorder; Disease of metabolism-0.38KE:1392Oxidative Stress
KE:2126Estrogen receptor alpha inactivation
KE:1115Increase, Reactive oxygen species
AOP:511The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effectsCardiovascular system disease-Human, Mouse, Zebrafish0.12KE:1392Oxidative Stress
KE:1115Increase, Reactive oxygen species
AOP:540Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin ProductionUnclassified-0.44KE:1392Oxidative Stress
KE:1115Increase, Reactive oxygen species
KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
KE:1262Apoptosis
AOP:541Excessive ROS generation leading to increased incidence of vascular calcification by VSMC phenotype switchingCardiovascular system disease-0.15KE:1392Oxidative Stress
KE:1115Increase, Reactive oxygen species
AOP:549Aromatase inhibition leads to reproductive toxicity (including growth and developmental toxicity) in adult female zebrafishUnclassified-0.25KE:36Inhibition, Aromatase
KE:219Reduction, Plasma 17beta-estradiol concentrations
AOP:563Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosisReproductive system disease; Endocrine system disease-Rat, Mouse, Zebra fish, Human0.33KE:18Activation, AhR
KE:1262Apoptosis

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:416Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathwayCancer-0.5KE:18Activation, AhR
KE:1115Increase, Reactive oxygen species
KE:1670Lung cancer
AOP:417Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathwayCancer-0.6KE:18Activation, AhR
KE:17Altered gene expression, AHR nuclear translocator (ARNT)-dependent pathway
KE:1670Lung cancer
AOP:420Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathwayCancer-1.0KE:18Activation, AhR
KE:1917Altered gene expression, NRF2 dependent antioxidant pathway
KE:870Increase, Cell Proliferation
KE:1670Lung cancer
AOP:463The AOP framwork on silica nanopariticles induced hepatoxicityGastrointestinal system disease-0.45KE:1115Increase, Reactive oxygen species
KE:1392Oxidative Stress
KE:2034liver dysfunction
KE:149Increase, Inflammation
KE:1262Apoptosis
AOP:505Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathwayCancer-Human, Mouse, Rat0.8KE:1392Oxidative Stress
KE:885Increase, Cancer
KE:149Increase, Inflammation
KE:1115Increase, Reactive oxygen species
AOP:513Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathwayCancer-Human, Mouse, Rat0.4KE:885Increase, Cancer
KE:1115Increase, Reactive oxygen species

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.