4,4'-Methylenebis(o-toluidine)

4,4'-Methylenebis(o-toluidine)



Associated High Confidence AOPs
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Associated AOPs with Level of Relevance 1
AOP Identifier AOP Title AO Classification OECD Status Coverage Score KE Identifier KE Name
AOP:12Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in agingNervous System Disease; Developmental Disorder Of Mental HealthWPHA/WNT Endorsed0.12KE:55Increase, Cell injury/death
AOP:13Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilitiesDevelopmental Disorder Of Mental HealthWPHA/WNT Endorsed0.1KE:55Increase, Cell injury/death
AOP:15Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutationsGenetic DiseaseWPHA/WNT Endorsed0.25KE: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 Endorsed0.1KE:55Increase, Cell injury/death
AOP:27Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)Gastrointestinal System DiseaseUnder Development0.12KE:288Activation of specific nuclear receptors, Transcriptional change
AOP:38Protein Alkylation leading to Liver FibrosisGastrointestinal System DiseaseWPHA/WNT Endorsed0.14KE:55Increase, Cell injury/death
AOP:48Binding 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 HealthWPHA/WNT Endorsed0.11KE:55Increase, Cell injury/death
AOP:58NR1I3 (CAR) suppression leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.06KE:457Activation, SREBF1
AOP:62AKT2 activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.25KE:457Activation, SREBF1
AOP:112Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)Reproductive System Disease; Cancer-0.17KE:111Agonism, Estrogen receptor
AOP:131Aryl hydrocarbon receptor activation leading to uroporphyriaInherited Metabolic DisorderWPHA/WNT Endorsed0.17KE:850Induction, CYP1A2/CYP1A5
AOP:136Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal TumorsBenign Neoplasm; Respiratory System DiseaseUnder Review0.14KE:768Increase, Cytotoxicity
AOP:139Alkylation of DNA leading to cancer 1Cancer-0.25KE:155Inadequate DNA repair
AOP:144Endocytic lysosomal uptake leading to liver fibrosisGastrointestinal System DiseaseUnder Review0.22KE:1494Leukocyte recruitment/activation
KE:55Increase, Cell injury/death
AOP:167Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.Reproductive System Disease; Cancer-0.14KE:1065Activation, estrogen receptor alpha
AOP:173Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosisMusculoskeletal System Disease; Respiratory System DiseaseWPHA/WNT Endorsed0.12KE:1497Increased, recruitment of inflammatory cells
AOP:194Hepatic nuclear receptor activation leading to altered amphibian metamorphosisUnclassified-0.17KE:295Induction, Upregulation of glucuronyltransferase activity
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:212Histone deacetylase inhibition leading to testicular atrophyReproductive System DiseaseWPHA/WNT Endorsed0.17KE:1505Cell cycle, disrupted
AOP:264Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell deathUnclassifiedUnder Development0.25KE:55Increase, Cell injury/death
AOP:265Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calciumUnclassifiedUnder Development0.25KE:55Increase, Cell injury/death
AOP:266Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activityUnclassifiedUnder Development0.17KE:55Increase, Cell injury/death
AOP:268Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swellingUnclassifiedUnder Development0.5KE:55Increase, Cell injury/death
KE:2072Increase, Mitochondrial swelling
AOP:272Deposition of energy leading to lung cancerCancerWPHA/WNT Endorsed0.14KE:155Inadequate DNA repair
AOP:278IKK complex inhibition leading to liver injuryUnclassified-0.12KE:55Increase, Cell injury/death
AOP:281Acetylcholinesterase Inhibition Leading to NeurodegenerationNervous System Disease-0.1KE:55Increase, Cell injury/death
AOP:287Mitochondrial complex III antagonism leading to growth inhibition (2)Unclassified-0.25KE: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-0.12KE:1614Decrease, androgen receptor activation
AOP:291Mitochondrial ATP synthase antagonism leading to growth inhibition (2)Unclassified-0.25KE:1825Increase, Cell death
AOP:293Increased DNA damage leading to increased risk of breast cancerGenetic Disease; Thoracic Disease; CancerUnder Development0.11KE:1494Leukocyte recruitment/activation
AOP:294Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancerGenetic Disease; Thoracic Disease; CancerUnder Development0.11KE:1494Leukocyte recruitment/activation
AOP:296Oxidative DNA damage leading to chromosomal aberrations and mutationsGenetic Disease; Chromosomal DiseaseWPHA/WNT Endorsed0.2KE:155Inadequate DNA repair
AOP:303Frustrated phagocytosis-induced lung cancerCancerUnder Development0.29KE:1669Increased, DNA damage and mutation
KE:1497Increased, recruitment of inflammatory cells
AOP:3055α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspringUnclassifiedUnder Development0.4KE:1614Decrease, androgen receptor activation
KE:286Altered, Transcription of genes by the androgen receptor
AOP:322Alkylation of DNA leading to reduced sperm countReproductive System Disease-0.2KE:155Inadequate DNA repair
AOP:324Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and cell deathUnclassified-0.25KE:55Increase, Cell injury/death
AOP:325Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and cell deathUnclassified-0.25KE:55Increase, Cell injury/death
AOP:326Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell deathUnclassified-0.25KE:55Increase, Cell injury/death
AOP:331Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and reduced cell proliferationUnclassified-0.17KE:1505Cell cycle, disrupted
AOP:332Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferationUnclassified-0.2KE:1505Cell cycle, disrupted
AOP:368Cytochrome oxidase inhibition leading to increased nasal lesionsUnclassified-0.33KE:1825Increase, Cell death
AOP:392Decreased fibrinolysis and activated bradykinin system leading to hyperinflammationUnclassifiedUnder Development0.2KE:1497Increased, recruitment of inflammatory cells
AOP:397Bulky DNA adducts leading to mutationsGenetic DiseaseUnder Development0.33KE:155Inadequate DNA repair
AOP:409Frustrated phagocytosis leads to malignant mesotheliomaCancer-0.25KE:1669Increased, DNA damage and mutation
KE:1497Increased, recruitment of inflammatory cells
AOP:410GSK3beta inactivation leading to increased mortality via defects in developing inner earUnclassified-0.1KE:1825Increase, Cell death
AOP:416Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathwayCancer-0.17KE:1669Increased, DNA damage and mutation
AOP:417Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathwayCancer-0.2KE:1669Increased, DNA damage and mutation
AOP:418Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathwayRespiratory System Disease-0.2KE:1825Increase, Cell death
AOP:432Deposition of Energy by Ionizing Radiation leading to Acute Myeloid LeukemiaHematopoietic System Disease; Cancer-0.09KE:155Inadequate DNA repair
AOP:446PM-related Adverse outcome pathway frameworks on various systemsRespiratory System Disease-0.05KE:1497Increased, recruitment of inflammatory cells
AOP:451Interaction with lung resident cell membrane components leads to lung cancerCancer-0.22KE:1669Increased, DNA damage and mutation
KE:1497Increased, recruitment of inflammatory cells
AOP:458AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.12KE:295Induction, Upregulation of glucuronyltransferase activity
AOP:459AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.11KE:850Induction, CYP1A2/CYP1A5
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-0.25KE:1497Increased, recruitment of inflammatory cells
KE:1825Increase, Cell death
AOP:472DNA adduct formation leading to kidney failureUrinary System Disease-0.11KE:1825Increase, Cell death
AOP:478Deposition of energy leading to occurrence of cataractsNervous System Disease; Monogenic DiseaseUnder Review0.1KE:155Inadequate DNA repair
AOP:479Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stressCardiovascular System Disease; Thoracic DiseaseUnder Development0.14KE:55Increase, Cell injury/death
AOP:482Deposition of energy leading to occurrence of bone lossMusculoskeletal System DiseaseUnder Review0.14KE:1825Increase, Cell death
AOP:490Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanismsDevelopmental Disorder Of Mental Health-0.09KE:55Increase, Cell injury/death
AOP:494AhR activation leading to liver fibrosisGastrointestinal System Disease-0.17KE:55Increase, Cell injury/death
AOP:495Androgen receptor activation leading to prostate cancerReproductive System Disease; Cancer-0.11KE:286Altered, Transcription of genes by the androgen receptor
AOP:496Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）Unclassified-0.1KE:286Altered, Transcription of genes by the androgen receptor
AOP:510Demethylation of PPAR promotor leading to vascular disrupting effectsCardiovascular System Disease-0.1KE:2165Activation of PPAR
AOP:530Endocytotic lysosomal uptake leads to intestinal barrier disruptionGastrointestinal System Disease-0.2KE:55Increase, Cell injury/death
AOP:573Inhibition, cytochrome oxidase leads to Increased, pulmonary edemaRespiratory System Disease-0.33KE:1825Increase, Cell death
AOP:574Inhibition, cytochrome oxidase leads to Loss of olfactory functionUnclassified-0.33KE:1825Increase, Cell death

Associated AOPs with Level of Relevance 2
AOP Identifier AOP Title AO Classification OECD Status Coverage Score KE Identifier KE Name
AOP:37PPARα activation leading to hepatocellular adenomas and carcinomas in rodentsCancer; Gastrointestinal System DiseaseUnder Development0.2KE:719Increase, hepatocellular adenomas and carcinomas
AOP:43Disruption of VEGFR Signaling Leading to Developmental DefectsUnclassifiedWPHA/WNT Endorsed0.2KE:1001Increased, Developmental Defects
AOP:107Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the ratCancer; Gastrointestinal System DiseaseUnder Review0.4KE:719Increase, hepatocellular adenomas and carcinomas
KE:1214Altered gene expression specific to CAR activation, Hepatocytes
AOP:108Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal System Disease-0.33KE:768Increase, Cytotoxicity
KE:719Increase, hepatocellular adenomas and carcinomas
AOP:117Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal System DiseaseUnder Development0.25KE:719Increase, hepatocellular adenomas and carcinomas
AOP:118Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal System Disease-0.25KE:719Increase, hepatocellular adenomas and carcinomas
AOP:504SULT1E1 inhibition leading to uterine adenocarcinoma via increased estrogen availability at target organ levelUnclassified-0.33KE:1065Activation, estrogen receptor alpha
AOP:561Aromatase induction leading to estrogen receptor alpha activation via increased estradiolUnclassified-0.2KE:1065Activation, estrogen receptor alpha

Associated AOPs with Level of Relevance 3
AOP Identifier AOP Title AO Classification OECD Status Coverage Score 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 Development0.22KE:295Induction, Upregulation of glucuronyltransferase activity
KE:239Activation, Pregnane-X receptor, NR1l2
AOP:19Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)Reproductive System Disease-0.4KE:26Antagonism, Androgen receptor
KE:286Altered, Transcription of genes by the androgen receptor
AOP:30Estrogen receptor antagonism leading to reproductive dysfunctionUnclassifiedUnder Review0.17KE:112Antagonism, Estrogen receptor
AOP:42Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive DisorderWPHA/WNT Endorsed0.12KE:279Thyroperoxidase, Inhibition
AOP:111Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)Cancer; Reproductive System Disease-0.2KE:1614Decrease, androgen receptor activation
AOP:119Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)Cancer; Endocrine System Disease-0.14KE:279Thyroperoxidase, Inhibition
AOP:159Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflationUnclassifiedWPHA/WNT Endorsed0.12KE:279Thyroperoxidase, Inhibition
AOP:175Thyroperoxidase inhibition leading to altered amphibian metamorphosisUnclassified-0.25KE:279Thyroperoxidase, Inhibition
AOP:271Inhibition of thyroid peroxidase leading to impaired fertility in fishUnclassifiedUnder Development0.2KE:279Thyroperoxidase, Inhibition
AOP:306Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspringUnclassifiedUnder Development0.75KE:1614Decrease, androgen receptor activation
KE:26Antagonism, Androgen receptor
KE:286Altered, Transcription of genes by the 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 Development0.2KE: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:1614Decrease, androgen receptor activation
KE:26Antagonism, Androgen receptor
KE:286Altered, Transcription of genes by the androgen receptor
AOP:345Androgen receptor (AR) antagonism leading to decreased fertility in femalesEndocrine System Disease; Reproductive System Disease; Reproductive System DiseaseUnder Development0.5KE:1614Decrease, androgen receptor activation
KE:26Antagonism, Androgen receptor
KE:286Altered, Transcription of genes by the androgen receptor
AOP:363Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structureUnclassifiedUnder Review0.12KE: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-0.6KE:1614Decrease, androgen receptor activation
KE:26Antagonism, Androgen receptor
KE:286Altered, Transcription of genes by the 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 Development0.22KE:1973Increased, estrogens
KE:1046Suppression, Estrogen receptor (ER) activity
AOP:443DNA damage and mutations leading to Metastatic Breast CancerThoracic Disease; CancerUnder Development0.3KE:1669Increased, DNA damage and mutation
KE:155Inadequate DNA repair
KE:112Antagonism, Estrogen receptor
AOP:445Estrogen Receptor Alpha Agonism leads to Impaired ReproductionReproductive System Disease-0.25KE:1987Decreased, Androgen and Progestin
KE: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-0.2KE:2126Estrogen receptor alpha inactivation
KE:1497Increased, recruitment of inflammatory cells
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 Review0.17KE:1065Activation, estrogen receptor alpha
AOP:517Pregnane X Receptor (PXR) activation leads to liver steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.2KE:239Activation, Pregnane-X receptor, NR1l2
AOP:525Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memoryDevelopmental Disorder Of Mental Health-0.23KE:2115Altered, cholesterol metabolism
KE:2220Antagonism, Glucocorticoid hormone receptor
KE:2217Binding of antagonist to 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:545Activation, Pregnane-X receptor, NR1l2 leads to increased plasma low-density lipoprotein (LDL) cholesterol via increased cholesterol synthesisUnclassified-0.2KE: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-0.2KE:239Activation, Pregnane-X receptor, NR1l2

No associated AOPs with Level of Relevance 5
DISCLAIMER

TICToK is a database of tattoo ink chemicals compiled from different regulatory resources. The authors are not liable for any inaccuracies or omissions of any chemicals in this resource. Importantly, our sole goal to build this resource on tattoo ink chemicals is to enable future basic research on this topic, and it does not necessarily reflect the views or objectives of our employers or funders.