Butylated hydroxytoluene


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:27Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)Gastrointestinal system diseaseUnder DevelopmentHumans0.12KE:288Activation of specific nuclear receptors, Transcriptional change
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:41Sustained AhR Activation leading to Rodent Liver TumoursCancer; Gastrointestinal system diseaseUnder ReviewRattus sp. ABTC 42503, Mus sp. 20000820.6KE:854Alterations, Cellular proliferation / hyperplasia
KE:853Changes/Inhibition, Cellular Homeostasis and Apoptosis
KE:139N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects
AOP:64Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male FertilityReproductive system disease-Rattus norvegicus0.14KE:496Increased apoptosis, decreased fetal/adult Leydig Cells
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:112Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)Reproductive system disease; Cancer-Rattus norvegicus0.17KE:111Agonism, Estrogen receptor
AOP:167Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.Reproductive system disease; Cancer-Mouse, Homo sapiens0.14KE:1065Activation, estrogen receptor alpha
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:1287Glutathione synthesis
AOP:212Histone deacetylase inhibition leading to testicular atrophyReproductive system diseaseWPHA/WNT EndorsedRat, Human, Mouse0.17KE:1262Apoptosis
AOP:219Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behaviorUnclassified-Japanese quail, Cynops pyrrhogaster0.17KE:1390Sexual behavior, decreased
AOP:288Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)Endocrine system disease-Human, Rat0.12KE:1614Decrease, androgen receptor activation
AOP:296Oxidative DNA damage leading to chromosomal aberrations and mutationsGenetic disease; Chromosomal diseaseWPHA/WNT EndorsedHuman, Mice, Rat, Fish0.2KE:155Inadequate DNA repair
AOP:322Alkylation of DNA leading to reduced sperm countReproductive system disease-0.2KE:155Inadequate DNA repair
AOP:379Binding to ACE2 leading to thrombosis and disseminated intravascular coagulationCardiovascular system diseaseUnder DevelopmentHomo sapiens0.14KE:1869Diminished protective oxidative stress response
AOP:397Bulky DNA adducts leading to mutationsGenetic diseaseUnder Development0.33KE:155Inadequate DNA repair
AOP:406SARS-CoV-2 infection leading to hyperinflammationUnclassified-0.17KE:1869Diminished protective oxidative stress response
AOP:413Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failureUnclassified-Fish, Mice0.17KE:1607Increase, Necrosis
AOP:414Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathwayMusculoskeletal system disease; Respiratory system disease-0.2KE:1920Altered gene expression, TGF-β dependent fibrosis pathway
AOP:419Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathwayRespiratory system disease-0.25KE:1262Apoptosis
AOP:432Deposition of Energy by Ionizing Radiation leading to Acute Myeloid LeukemiaHematopoietic system disease; Cancer-Homo sapiens, Mus musculus0.09KE:155Inadequate DNA repair
AOP:439Activation of the AhR leading to metastatic breast cancerThoracic disease; CancerUnder DevelopmentHumans, Mice0.22KE:1971Increased, tumor growth
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:1973Increased, estrogens
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:155Inadequate DNA repair
AOP:446PM-related Adverse outcome pathway frameworks on various systemsRespiratory system disease-0.1KE:1262Apoptosis
KE:1993Increase, Pneumonia
AOP:447Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathwaysUrinary system disease-0.08KE:1097Occurrence, renal proximal tubular necrosis
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:465Alcohol dehydrogenase leading to reproductive dysfunctionUnclassified-0.12KE:748Increased, Estrogen receptor (ER) activity
AOP:472DNA adduct formation leading to kidney failureUrinary system disease-0.11KE:1097Occurrence, renal proximal tubular necrosis
AOP:478Deposition of energy leading to occurrence of cataractsNervous system disease; Monogenic diseaseUnder ReviewHuman, Mouse, Rat, Rhesus monkeys, Rabbit, Guinea pig0.1KE:155Inadequate DNA repair
AOP:488Increased reactive oxygen species production leading to decreased cognitive functionCognitive disorder-Human0.14KE:1869Diminished protective oxidative stress response
AOP:491Decrease, GLI1/2 target gene expression leads to orofacial cleftingUnclassifiedUnder DevelopmentMouse0.17KE:1262Apoptosis
AOP:495Androgen receptor activation leading to prostate cancerReproductive system disease; Cancer-0.22KE:854Alterations, Cellular proliferation / hyperplasia
KE:1183Decreased, Apoptosis (Epithelial Cells)
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:510Demethylation of PPAR promotor leading to vascular disrupting effectsCardiovascular system disease-Human, Mouse, Zebrafish0.1KE:2165Activation of PPAR
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

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:107Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the ratCancer; Gastrointestinal system diseaseUnder ReviewRattus norvegicus, Mus musculus0.4KE:716Increase, cell proliferation (hepatocytes)
KE:719Increase, hepatocellular adenomas and carcinomas
AOP:108Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal system disease-Mus musculus, Rattus norvegicus0.17KE:719Increase, hepatocellular adenomas and carcinomas
AOP:117Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal system diseaseUnder DevelopmentMus musculus, Rattus norvegicus0.5KE:716Increase, cell proliferation (hepatocytes)
KE:719Increase, hepatocellular adenomas and carcinomas
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-Vertebrates0.33KE:1263Necrosis
KE:1262Apoptosis
AOP:220Cyp2E1 Activation Leading to Liver CancerCancer; Gastrointestinal system diseaseWPHA/WNT EndorsedRodents, Homo sapiens0.6KE:1395Liver Cancer
KE:1393Hepatocytotoxicity
KE:1394Induction, persistent proliferation/sustained proliferation
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, Mouse0.29KE:155Inadequate DNA repair
KE:1556Increase, lung cancer
AOP:278IKK complex inhibition leading to liver injuryUnclassified-0.12KE:1549Liver Injury
AOP:303Frustrated phagocytosis-induced lung cancerCancerUnder DevelopmentMammals0.14KE:1670Lung cancer
AOP:3055α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspringUnclassifiedUnder DevelopmentRat, Human, Mouse0.4KE:1614Decrease, androgen receptor activation
KE:1688anogenital distance (AGD), decreased
AOP:384Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney diseaseUrinary system disease-0.17KE:1603Chronic kidney disease
AOP:416Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathwayCancer-0.17KE:1670Lung cancer
AOP:417Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathwayCancer-0.2KE:1670Lung cancer
AOP:420Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathwayCancer-0.25KE:1670Lung cancer
AOP:451Interaction with lung resident cell membrane components leads to lung cancerCancer-Human0.11KE:1670Lung cancer
AOP:463The AOP framwork on silica nanopariticles induced hepatoxicityGastrointestinal system disease-0.18KE:2034liver dysfunction
KE:1262Apoptosis
AOP:474Succinate dehydrogenase inactivation leads to cancer by promoting EMTCancerUnder DevelopmentHuman and other cells in culture0.2KE:885Increase, Cancer
AOP:498Increased LCN2/iron complex leading to neurological disordersNervous system disease-Homo sapiens0.25KE:2150Neurological disorder
AOP:501Excessive iron accumulation leading to neurological disordersNervous system disease-Homo sapiens0.25KE:2150Neurological disorder
AOP:504SULT1E1 inhibition leading to uterine adenocarcinoma via increased estrogen availability at target organ levelUnclassified-Mammals0.67KE:1065Activation, estrogen receptor alpha
KE:2251Estradiol availability, increased
AOP:505Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathwayCancer-Human, Mouse, Rat0.2KE:885Increase, Cancer
AOP:513Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathwayCancer-Human, Mouse, Rat0.2KE:885Increase, Cancer
AOP:534Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stressCancer-Vertebrates0.17KE:885Increase, Cancer
AOP:546Succinate dehydrogenase inactivation leads to cancer through hypoxic-like mechanismsCancer-Human and other cells in culture0.2KE:885Increase, Cancer
AOP:561Aromatase induction leading to estrogen receptor alpha activation via increased estradiolUnclassified-Vertebrates0.6KE:2294Plasma estradiol, increased
KE:1065Activation, estrogen receptor alpha
KE:2251Estradiol availability, increased

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:8Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in MammalsNervous system diseaseUnder DevelopmentRat0.11KE:239Activation, Pregnane-X receptor, NR1l2
AOP:18PPARα activation in utero leading to impaired fertility in malesReproductive system diseaseUnder ReviewHuman, Rat, Mouse0.12KE:227Activation, PPARα
AOP:19Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)Reproductive system disease-0.2KE:26Antagonism, Androgen receptor
AOP:42Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive disorderWPHA/WNT EndorsedHuman, Rat, Mouse0.12KE:279Thyroperoxidase, Inhibition
AOP:60NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosisGastrointestinal system disease; Inherited metabolic disorder-0.08KE:245Activation, PXR/SXR
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:119Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)Cancer; Endocrine system disease-Rattus norvegicus, Mus musculus0.14KE:279Thyroperoxidase, Inhibition
AOP:121Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)Cancer; Urinary system disease-Mus musculus, Rattus norvegicus0.2KE:793Increase, Urinary bladder calculi
AOP:159Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflationUnclassifiedWPHA/WNT EndorsedZebrafish, Fathead minnow0.12KE:279Thyroperoxidase, Inhibition
AOP:175Thyroperoxidase inhibition leading to altered amphibian metamorphosisUnclassified-African clawed frog0.25KE:279Thyroperoxidase, Inhibition
AOP:271Inhibition of thyroid peroxidase leading to impaired fertility in fishUnclassifiedUnder DevelopmentFish0.2KE:279Thyroperoxidase, Inhibition
AOP:298Increase in reactive oxygen species (ROS) leading to human treatment-resistant gastric cancer via chronic ROSCancer; Gastrointestinal system diseaseUnder ReviewHomo sapiens0.17KE:1753Chronic reactive oxygen species
AOP:323PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-KetotestosteroneUnclassified-Teleost fish0.17KE:227Activation, PPARα
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:363Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structureUnclassifiedUnder ReviewZebrafish0.12KE:279Thyroperoxidase, Inhibition
AOP:364Thyroperoxidase inhibition leading to altered visual function via decreased eye sizeUnclassifiedUnder Development0.12KE:279Thyroperoxidase, Inhibition
AOP:365Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterningUnclassifiedUnder Development0.12KE:279Thyroperoxidase, Inhibition
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: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:503Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulationReproductive system disease; CancerUnder ReviewHuman, Mouse0.17KE:1065Activation, estrogen receptor alpha
AOP:517Pregnane X Receptor (PXR) activation leads to liver steatosisGastrointestinal system disease; Inherited metabolic disorder-Vertebrates0.2KE:239Activation, Pregnane-X receptor, NR1l2
AOP:520Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memoryDevelopmental disorder of mental health-Mouse, Rat, Human0.2KE:2201Agonism, Retinoic acid receptor
AOP:523Retinoic acid receptor agonism during neurodevelopment leading to microcephalyCongenital nervous system abnormality; Nervous system disease-0.2KE:2201Agonism, Retinoic acid receptor
AOP:532Retinoic acid receptor agonism during cerebellar development leading to impaired locomotor functionUnclassified-0.2KE:2201Agonism, Retinoic acid receptor
AOP:533Retinoic acid receptor antagonism during neurodevelopment leading to impaired learning and memoryDevelopmental disorder of mental health-0.17KE:2232Antagonism, Retinoic acid receptors
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:545Activation, Pregnane-X receptor, NR1l2 leads to increased plasma low-density lipoprotein (LDL) cholesterol via increased cholesterol synthesisUnclassified-Mammals0.2KE:239Activation, Pregnane-X receptor, NR1l2
AOP:548Activation, Pregnane-X receptor, NR1l2 leads to increased plasma low-density lipoprotein (LDL) cholesterol via increased PCSK9 protein expressionUnclassified-Mammals0.2KE:239Activation, Pregnane-X receptor, NR1l2

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:37PPARα activation leading to hepatocellular adenomas and carcinomas in rodentsCancer; Gastrointestinal system diseaseUnder DevelopmentMouse, Rat0.6KE:716Increase, cell proliferation (hepatocytes)
KE:227Activation, PPARα
KE:719Increase, hepatocellular adenomas and carcinomas
AOP:118Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal system disease-Mus musculus, Rattus norvegicus0.5KE:719Increase, hepatocellular adenomas and carcinomas
KE:786Increase, Cytotoxicity (hepatocytes)
AOP:306Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspringUnclassifiedUnder DevelopmentRat, Human, Mouse0.75KE:1614Decrease, androgen receptor activation
KE:1688anogenital distance (AGD), decreased
KE:26Antagonism, Androgen receptor

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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.