Methyltestosterone


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:18PPARα activation in utero leading to impaired fertility in malesReproductive system diseaseUnder ReviewHuman, Rat, Mouse0.12KE:1690Decrease, circulating testosterone levels
AOP:41Sustained AhR Activation leading to Rodent Liver TumoursCancer; Gastrointestinal system diseaseUnder ReviewRattus sp. ABTC 42503, Mus sp. 20000820.2KE:854Alterations, Cellular proliferation / hyperplasia
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:73Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundityUnclassified-0.15KE:10059Decreased LH surge for 24 hours
KE:531Decreased, LH Surge
AOP:99Histamine (H2) receptor antagonism leading to reduced survivalUnclassified-Zebrafish0.14KE:635Decreased, locomotion
AOP:102Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transitionReproductive system disease-Goldfish, Human, Rat, Mouse0.1KE:690Reduced, Luteinizing hormone (LH), plasma
AOP:103Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpointReproductive system disease-Goldfish, Human, Rat, Mouse0.1KE:690Reduced, Luteinizing hormone (LH), plasma
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:1023Increased, Thyroid-stimulating hormone (TSH)
AOP:112Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)Reproductive system disease; Cancer-Rattus norvegicus0.17KE:111Agonism, Estrogen receptor
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:1023Increased, Thyroid-stimulating hormone (TSH)
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:124HMG-CoA reductase inhibition leading to decreased fertilityReproductive system disease-Rattus rattus0.33KE:807Decreased, cholesterol
KE:1690Decrease, circulating testosterone levels
AOP:126Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulationUnclassified-0.15KE:10059Decreased LH surge for 24 hours
KE:531Decreased, LH Surge
AOP:136Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal TumorsBenign neoplasm; Respiratory system diseaseUnder Review0.14KE:868Increase, Tissue Degeneration, Necrosis & Atrophy
AOP:155Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflationUnclassifiedWPHA/WNT EndorsedFathead minnow, Zebrafish0.17KE:1003Decreased, Triiodothyronine (T3)
AOP:156Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflationUnclassifiedWPHA/WNT EndorsedZebrafish, Fathead minnow0.17KE:1003Decreased, Triiodothyronine (T3)
AOP:157Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflationUnclassifiedWPHA/WNT EndorsedZebrafish, Fathead minnow0.17KE:1003Decreased, Triiodothyronine (T3)
AOP:158Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflationUnclassifiedWPHA/WNT EndorsedZebrafish, Fathead minnow0.17KE:1003Decreased, Triiodothyronine (T3)
AOP:159Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflationUnclassifiedWPHA/WNT EndorsedZebrafish, Fathead minnow0.12KE:1003Decreased, Triiodothyronine (T3)
AOP:189Type I iodothyronine deiodinase (DIO1) inhibition leading to altered amphibian metamorphosisUnclassified-African clawed frog0.5KE:1116Decreased, Triiodothyronine (T3) in tissues
KE:1003Decreased, Triiodothyronine (T3)
AOP:190Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosisUnclassified-African clawed frog0.5KE:1828Increased, Thyroxine (T4) in serum
KE:1116Decreased, Triiodothyronine (T3) in tissues
KE:1023Increased, Thyroid-stimulating hormone (TSH)
AOP:207NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegansReproductive system disease-Caenorhabditis elegans0.25KE:1281Increased, DNA Damage-Repair
KE:1262Apoptosis
AOP:209Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOPGastrointestinal system disease-0.12KE:1289Perturbation of cholesterol
AOP:218Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activityUnclassified-Japanese quail, Cynops pyrrhogaster0.17KE:1389Locomotor activity, decreased
AOP:287Mitochondrial complex III antagonism leading to growth inhibition (2)Unclassified-Lemna minor, Daphnia magna, Danio rerio0.25KE:1825Increase, Cell death
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:291Mitochondrial ATP synthase antagonism leading to growth inhibition (2)Unclassified-Daphnia magna0.25KE:1825Increase, Cell death
AOP:3055α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspringUnclassifiedUnder DevelopmentRat, Human, Mouse0.4KE:286Altered, Transcription of genes by the androgen receptor
KE:1614Decrease, androgen receptor activation
AOP:323PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-KetotestosteroneUnclassified-Teleost fish0.33KE:1758Impaired, Spermatogenesis
KE:807Decreased, cholesterol
AOP:330Excessive reactive oxygen species production leading to mortality (4)Unclassified-Daphnia magna0.2KE:1365Increase, Apoptosis
AOP:348Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectoryUnclassifiedUnder DevelopmentFish0.2KE:1758Impaired, Spermatogenesis
AOP:349Inhibition of 11β-hydroxylase leading to decresed population trajectoryUnclassifiedUnder DevelopmentFish0.12KE:1798Decreased spermatogenesis
AOP:362Immune mediated hepatitisGastrointestinal system disease; Immune system disease-Homo sapiens, Rat0.12KE:1817Apoptotic cell death
AOP:363Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structureUnclassifiedUnder ReviewZebrafish0.12KE:1003Decreased, Triiodothyronine (T3)
AOP:364Thyroperoxidase inhibition leading to altered visual function via decreased eye sizeUnclassifiedUnder Development0.12KE:1003Decreased, Triiodothyronine (T3)
AOP:365Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterningUnclassifiedUnder Development0.12KE:1003Decreased, Triiodothyronine (T3)
AOP:366Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosisUnclassified-0.14KE:959Increased, Free serum thyroxine (T4)
AOP:367Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosisUnclassified-0.14KE:959Increased, Free serum thyroxine (T4)
AOP:368Cytochrome oxidase inhibition leading to increased nasal lesionsUnclassified-Rodents, Human0.33KE:1825Increase, Cell death
AOP:388Deposition of ionising energy leading to population decline via programmed cell deathReproductive system disease-Lemna minor0.2KE:1864Increase, Programmed cell death
AOP:410GSK3beta inactivation leading to increased mortality via defects in developing inner earUnclassified-Zebrafish0.1KE:1825Increase, Cell death
AOP:418Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathwayRespiratory system disease-0.2KE:1825Increase, Cell death
AOP:419Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathwayRespiratory system disease-0.25KE:1262Apoptosis
AOP:439Activation of the AhR leading to metastatic breast cancerThoracic disease; CancerUnder DevelopmentHumans, Mice0.11KE:1262Apoptosis
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, Yeast0.1KE:112Antagonism, Estrogen receptor
AOP:444Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchabilityUnclassified-0.22KE:1798Decreased spermatogenesis
KE:1365Increase, Apoptosis
AOP:446PM-related Adverse outcome pathway frameworks on various systemsRespiratory system disease-0.05KE:1262Apoptosis
AOP:447Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathwaysUrinary system disease-0.08KE:1365Increase, Apoptosis
AOP:452Adverse outcome pathway of PM-induced respiratory toxicityRespiratory system disease-0.09KE:1262Apoptosis
AOP:460Antagonism of Smoothened receptor leading to orofacial cleftingUnclassifiedUnder DevelopmentMouse0.11KE:1262Apoptosis
AOP:463The AOP framwork on silica nanopariticles induced hepatoxicityGastrointestinal system disease-0.09KE:1262Apoptosis
AOP:464Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficitsNervous system disease-0.05KE:1825Increase, Cell death
AOP:465Alcohol dehydrogenase leading to reproductive dysfunctionUnclassified-0.12KE:748Increased, Estrogen receptor (ER) activity
AOP:468Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)Unclassified-0.12KE:1825Increase, Cell death
AOP:472DNA adduct formation leading to kidney failureUrinary system disease-0.11KE:1825Increase, Cell death
AOP:482Deposition of energy leading to occurrence of bone lossMusculoskeletal system diseaseUnder ReviewHuman, Mouse, Rat, Rhesus monkeys0.14KE:1825Increase, Cell death
AOP:491Decrease, GLI1/2 target gene expression leads to orofacial cleftingUnclassifiedUnder DevelopmentMouse0.17KE:1262Apoptosis
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 sapiens0.14KE:1262Apoptosis
AOP:509Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunctionCardiovascular system disease-0.14KE:1365Increase, Apoptosis
AOP:521Essential element imbalance leads to reproductive failure via oxidative stressUnclassified-Murinae gen. sp.0.29KE:2206Increased, histomorphological alteration of testis
KE:1758Impaired, Spermatogenesis
AOP:529Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosisGastrointestinal system disease; Inherited metabolic disorder-Vertebrates, Mouse, Rat, Zebrafish0.12KE:2225Disrupted Lipid Storage
AOP:535Binding and activation of GPER leading to learning and memory impairmentsDevelopmental disorder of mental health-Mouse, Human0.11KE:1262Apoptosis
AOP:540Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin ProductionUnclassified-0.11KE:1262Apoptosis
AOP:563Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosisReproductive system disease; Endocrine system disease-Rat, Mouse, Zebra fish, Human0.17KE:1262Apoptosis
AOP:573Inhibition, cytochrome oxidase leads to Increased, pulmonary edemaRespiratory system disease-Rodents, Humans0.33KE:1825Increase, Cell death
AOP:574Inhibition, cytochrome oxidase leads to Loss of olfactory functionUnclassified-Rodents, Humans0.33KE:1825Increase, 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:205AOP from chemical insult to cell deathUnclassified-Vertebrates0.17KE:1262Apoptosis
AOP:212Histone deacetylase inhibition leading to testicular atrophyReproductive system diseaseWPHA/WNT EndorsedRat, Human, Mouse0.33KE:1506Testicular atrophy
KE:1262Apoptosis
AOP:270Elevated ATP demand for detoxification and repair mechanisms leading to impaired locomotor activityUnclassified-0.12KE:10016Impaired locomotor activity
AOP:322Alkylation of DNA leading to reduced sperm countReproductive system disease-0.4KE:1365Increase, Apoptosis
KE:1757Reduce, Sperm count
AOP:423Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathwayUnclassified-0.17KE:1817Apoptotic cell death
AOP:504SULT1E1 inhibition leading to uterine adenocarcinoma via increased estrogen availability at target organ levelUnclassified-Mammals0.33KE:1065Activation, estrogen receptor alpha
AOP:532Retinoic acid receptor agonism during cerebellar development leading to impaired locomotor functionUnclassified-0.2KE:2231Locomotor function. Impaired
AOP:561Aromatase induction leading to estrogen receptor alpha activation via increased estradiolUnclassified-Vertebrates0.2KE:1065Activation, estrogen receptor alpha

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:19Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)Reproductive system disease-0.4KE:286Altered, Transcription of genes by the androgen receptor
KE:26Antagonism, Androgen receptor
AOP:23Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)UnclassifiedWPHA/WNT EndorsedPimephales promelas0.1KE:25Agonism, Androgen receptor
AOP:30Estrogen receptor antagonism leading to reproductive dysfunctionUnclassifiedUnder ReviewZebra danio, Fathead minnow, Medaka0.17KE:112Antagonism, Estrogen receptor
AOP:91Sodium channel inhibition leading to reduced survivalUnclassified-Medaka, Gammarus pulex, Hydra0.17KE:584Inhibition, sodium channel
AOP:93sodium channel inhibition leading to increased predationUnclassified-0.25KE:584Inhibition, sodium channel
AOP:94Sodium channel inhibition leading to congenital malformationsUnclassified-Human, Rat, Mouse0.17KE:584Inhibition, sodium channel
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:117Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal system diseaseUnder DevelopmentMus musculus, Rattus norvegicus0.25KE:25Agonism, Androgen receptor
AOP:167Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.Reproductive system disease; Cancer-Mouse, Homo sapiens0.43KE:1065Activation, estrogen receptor alpha
KE:1064prepubertal increase, Estrogen receptor (ER) activity
KE:1069Increased, Hyperplasia (glandular epithelial cells of endometrium)
AOP:306Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspringUnclassifiedUnder DevelopmentRat, Human, Mouse0.75KE:286Altered, Transcription of genes by the androgen receptor
KE:1614Decrease, androgen receptor activation
KE:26Antagonism, Androgen receptor
AOP:314Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE)Immune system disease; Musculoskeletal system diseaseUnder DevelopmentHomo sapiens0.2KE:1710Binding to estrogen receptor (ER)-α in immune cells
AOP:344Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspringUnclassifiedUnder Development0.75KE:286Altered, Transcription of genes by the androgen receptor
KE: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 DevelopmentMammals0.5KE:286Altered, Transcription of genes by the androgen receptor
KE:1614Decrease, androgen receptor activation
KE:26Antagonism, Androgen receptor
AOP:372Androgen receptor antagonism leading to testicular cancerEndocrine system disease; Reproductive system disease; Cancer-0.6KE:286Altered, Transcription of genes by the androgen receptor
KE:1614Decrease, androgen receptor activation
KE:26Antagonism, Androgen receptor
AOP:376Androgen receptor agonism leading to male-biased sex ratioUnclassifiedWPHA/WNT EndorsedZebrafish, Medaka, Fathead minnow, Channel catfish, Oreochromis niloticus, Chinook salmon0.25KE:25Agonism, Androgen receptor
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, Mice0.22KE:1046Suppression, Estrogen receptor (ER) activity
KE:1973Increased, estrogens
AOP:445Estrogen Receptor Alpha Agonism leads to Impaired ReproductionReproductive system disease-0.12KE:1065Activation, estrogen receptor alpha
AOP:477Androgen receptor (AR) antagonism leading to hypospadias in male (mammalian) offspringPhysical disorder-0.67KE:1614Decrease, androgen receptor activation
KE:26Antagonism, Androgen receptor
AOP:493ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesityAcquired metabolic disease-Mus musculus, Homo sapiens0.1KE:2126Estrogen receptor alpha inactivation
AOP:495Androgen receptor activation leading to prostate cancerReproductive system disease; Cancer-0.33KE:854Alterations, Cellular proliferation / hyperplasia
KE:286Altered, Transcription of genes by the androgen receptor
KE:25Agonism, Androgen receptor
AOP:496Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)Unclassified-Zebrafish0.3KE:286Altered, Transcription of genes by the androgen receptor
KE:25Agonism, Androgen receptor
KE:1690Decrease, circulating testosterone levels
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-0.12KE:2126Estrogen receptor alpha inactivation
AOP:503Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulationReproductive system disease; CancerUnder ReviewHuman, Mouse0.17KE:1065Activation, estrogen receptor alpha
AOP:525Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memoryDevelopmental disorder of mental health-0.23KE:2217Binding of antagonist to glucocorticoid hormone receptor
KE:2115Altered, cholesterol metabolism
KE:2220Antagonism, Glucocorticoid hormone receptor
AOP:536Estrogen receptor agonism leading to reduced survival and population growth due to renal failureUnclassified-0.17KE:111Agonism, Estrogen receptor
AOP:537Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liverUnclassified-0.2KE:111Agonism, Estrogen receptor
AOP:553Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failureCardiovascular system disease-Human, Rodents, Dogs, Pigs, Insects, Fish0.25KE:584Inhibition, sodium channel

No associated AOPs with Level of Relevance 5

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