3,3'-Dimethylbenzidine

3,3'-Dimethylbenzidine



Associated High Confidence AOPs
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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 Coverage Score KE Identifier KE Name
AOP:60NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.08KE:474
Down Regulation, HMGCS2
AOP:107Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the ratCancer; Gastrointestinal System DiseaseUnder Review0.2KE:1214
Altered gene expression specific to CAR activation, Hepatocytes
AOP:112Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)Reproductive System Disease; Cancer-0.17KE:111
Agonism, Estrogen receptor
AOP:136Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal TumorsBenign Neoplasm; Respiratory System DiseaseUnder Review0.14KE:768
Increase, Cytotoxicity
AOP:194Hepatic nuclear receptor activation leading to altered amphibian metamorphosisUnclassified-0.17KE:295
Induction, Upregulation of glucuronyltransferase activity
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:1614
Decrease, androgen receptor activation
AOP:303Frustrated phagocytosis-induced lung cancerCancerUnder Development0.14KE:1669
Increased, DNA damage and mutation
AOP:331Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and reduced cell proliferationUnclassified-0.17KE:1505
Cell cycle, disrupted
AOP:332Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferationUnclassified-0.2KE:1505
Cell cycle, disrupted
AOP:409Frustrated phagocytosis leads to malignant mesotheliomaCancer-0.12KE:1669
Increased, DNA damage and mutation
AOP:446PM-related Adverse outcome pathway frameworks on various systemsRespiratory System Disease-0.1KE:18
Activation, AhR
KE:165
Activation, Long term AHR receptor driven direct and indirect gene expression changes
AOP:449Ceramide synthase inhibition leading to neural tube defectsNeural Tube Defect-0.14KE:1502
Histone deacetylase inhibition
AOP:451Interaction with lung resident cell membrane components leads to lung cancerCancer-0.11KE:1669
Increased, DNA damage and mutation
AOP:465Alcohol dehydrogenase leading to reproductive dysfunctionUnclassified-0.12KE:748
Increased, Estrogen receptor (ER) activity
AOP:495Androgen receptor activation leading to prostate cancerReproductive System Disease; Cancer-0.11KE:286
Altered, Transcription of genes by the androgen receptor
AOP:496Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）Unclassified-0.1KE:286
Altered, Transcription of genes by the androgen receptor
AOP:510Demethylation of PPAR promotor leading to vascular disrupting effectsCardiovascular System Disease-0.1KE:2165
Activation of PPAR

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 Coverage Score KE Identifier KE Name
AOP:504SULT1E1 inhibition leading to uterine adenocarcinoma via increased estrogen availability at target organ levelUnclassified-0.33KE:1065
Activation, estrogen receptor alpha
AOP:561Aromatase induction leading to estrogen receptor alpha activation via increased estradiolUnclassified-0.2KE:1065
Activation, 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 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:295
Induction, Upregulation of glucuronyltransferase activity
KE:239
Activation, Pregnane-X receptor, NR1l2
AOP:18PPARα activation in utero leading to impaired fertility in malesReproductive System DiseaseUnder Review0.12KE:227
Activation, PPARα
AOP:19Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)Reproductive System Disease-0.4KE:26
Antagonism, Androgen receptor
KE:286
Altered, Transcription of genes by the androgen receptor
AOP:21Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2UnclassifiedWPHA/WNT Endorsed0.2KE:18
Activation, AhR
AOP:27Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)Gastrointestinal System DiseaseUnder Development0.12KE:41
Inhibition, Bile Salt Export Pump (ABCB11)
AOP:30Estrogen receptor antagonism leading to reproductive dysfunctionUnclassifiedUnder Review0.17KE:112
Antagonism, Estrogen receptor
AOP:37PPARα activation leading to hepatocellular adenomas and carcinomas in rodentsCancer; Gastrointestinal System DiseaseUnder Development0.2KE:227
Activation, PPARα
AOP:41Sustained AhR Activation leading to Rodent Liver TumoursCancer; Gastrointestinal System DiseaseUnder Review0.2KE:165
Activation, Long term AHR receptor driven direct and indirect gene expression changes
AOP:64Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male FertilityReproductive System Disease-0.14KE:494
Glucocorticoid Receptor Agonist, Activation
AOP:108Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal System Disease-0.33KE:768
Increase, Cytotoxicity
KE:724
Inhibition, Pyruvate dehydrogenase kinase (PDK) enzyme
AOP:111Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)Cancer; Reproductive System Disease-0.2KE:1614
Decrease, androgen receptor activation
AOP:120Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)Cancer; Reproductive System Disease-0.2KE:1617
Inhibition, 5α-reductase
AOP:131Aryl hydrocarbon receptor activation leading to uroporphyriaInherited Metabolic DisorderWPHA/WNT Endorsed0.33KE:18
Activation, AhR
KE:850
Induction, CYP1A2/CYP1A5
AOP:150Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGFUnclassifiedWPHA/WNT Endorsed0.14KE:18
Activation, AhR
AOP:151AhR activation leading to preeclampsiaCardiovascular System DiseaseUnder Development0.14KE:18
Activation, AhR
AOP:167Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.Reproductive System Disease; Cancer-0.29KE:1064
prepubertal increase, Estrogen receptor (ER) activity
KE:1065
Activation, estrogen receptor alpha
AOP:212Histone deacetylase inhibition leading to testicular atrophyReproductive System DiseaseWPHA/WNT Endorsed0.33KE:1502
Histone deacetylase inhibition
KE:1505
Cell cycle, disrupted
AOP:274Histone deacetylase inhibition leads to impeded craniofacial developmentMusculoskeletal System Disease-0.25KE:1502
Histone deacetylase inhibition
AOP:275Histone deacetylase inhibition leads to neural tube defectsNeural Tube Defect-0.2KE:1502
Histone deacetylase inhibition
AOP:289Inhibition of 5α-reductase leading to impaired fecundity in female fishUnclassifiedUnder Development0.17KE:1617
Inhibition, 5α-reductase
AOP:3055α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspringUnclassifiedUnder Development0.6KE:1617
Inhibition, 5α-reductase
KE:1614
Decrease, androgen receptor activation
KE:286
Altered, Transcription of genes by the androgen receptor
AOP:306Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspringUnclassifiedUnder Development0.75KE:1614
Decrease, androgen receptor activation
KE:26
Antagonism, Androgen receptor
KE:286
Altered, Transcription of genes by the androgen receptor
AOP:310Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHRUnclassified-0.08KE:18
Activation, AhR
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:1710
Binding to estrogen receptor (ER)-α in immune cells
AOP:318Glucocorticoid Receptor activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.2KE:122
Activation, Glucocorticoid Receptor
AOP:323PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-KetotestosteroneUnclassified-0.17KE:227
Activation, PPARα
AOP:334Glucocorticoid Receptor Agonism Leading to Impaired Fin RegenerationUnclassified-0.17KE:122
Activation, Glucocorticoid Receptor
AOP:344Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspringUnclassifiedUnder Development0.75KE:1614
Decrease, androgen receptor activation
KE:26
Antagonism, Androgen receptor
KE:286
Altered, 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:1614
Decrease, androgen receptor activation
KE:26
Antagonism, Androgen receptor
KE:286
Altered, Transcription of genes by the androgen receptor
AOP:372Androgen receptor antagonism leading to testicular cancerEndocrine System Disease; Reproductive System Disease; Cancer-0.6KE:1614
Decrease, androgen receptor activation
KE:26
Antagonism, Androgen receptor
KE:286
Altered, Transcription of genes by the androgen receptor
AOP:414Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathwayMusculoskeletal System Disease; Respiratory System Disease-0.2KE:18
Activation, AhR
AOP:415Aryl hydrocarbon receptor activation leading to lung fibrosis through IL-6 toxicity pathwayMusculoskeletal System Disease; Respiratory System Disease-0.2KE:18
Activation, AhR
AOP:416Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathwayCancer-0.33KE:18
Activation, AhR
KE:1669
Increased, DNA damage and mutation
AOP:417Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathwayCancer-0.6KE:18
Activation, AhR
KE:17
Altered gene expression, AHR nuclear translocator (ARNT)-dependent pathway
KE:1669
Increased, DNA damage and mutation
AOP:418Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathwayRespiratory System Disease-0.4KE:18
Activation, AhR
KE:17
Altered gene expression, AHR nuclear translocator (ARNT)-dependent pathway
AOP:419Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathwayRespiratory System Disease-0.25KE:18
Activation, AhR
AOP:420Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathwayCancer-0.25KE:18
Activation, AhR
AOP:439Activation of the AhR leading to metastatic breast cancerThoracic Disease; CancerUnder Development0.11KE:18
Activation, AhR
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:1973
Increased, estrogens
KE:1046
Suppression, Estrogen receptor (ER) activity
AOP:443DNA damage and mutations leading to Metastatic Breast CancerThoracic Disease; CancerUnder Development0.2KE:1669
Increased, DNA damage and mutation
KE:112
Antagonism, Estrogen receptor
AOP:445Estrogen Receptor Alpha Agonism leads to Impaired ReproductionReproductive System Disease-0.12KE:1065
Activation, estrogen receptor alpha
AOP:455Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial developmentMusculoskeletal System DiseaseUnder Review0.17KE:18
Activation, AhR
AOP:456Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicityUnclassifiedUnder Review0.17KE:18
Activation, AhR
AOP:458AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.25KE:18
Activation, AhR
KE:295
Induction, Upregulation of glucuronyltransferase activity
AOP:459AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.22KE:18
Activation, AhR
KE:850
Induction, CYP1A2/CYP1A5
AOP:477Androgen receptor (AR) antagonism leading to hypospadias in male (mammalian) offspringPhysical Disorder-0.67KE:1614
Decrease, androgen receptor activation
KE:26
Antagonism, Androgen receptor
AOP:493ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesityAcquired Metabolic Disease-0.1KE:2126
Estrogen receptor alpha inactivation
AOP:494AhR activation leading to liver fibrosisGastrointestinal System Disease-0.17KE:18
Activation, 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-0.12KE:2126
Estrogen receptor alpha inactivation
AOP:503Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulationReproductive System Disease; CancerUnder Review0.17KE:1065
Activation, estrogen receptor alpha
AOP:517Pregnane X Receptor (PXR) activation leads to liver steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.2KE:239
Activation, Pregnane-X receptor, NR1l2
AOP:536Estrogen receptor agonism leading to reduced survival and population growth due to renal failureUnclassified-0.17KE:111
Agonism, Estrogen receptor
AOP:537Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liverUnclassified-0.2KE:111
Agonism, Estrogen receptor
AOP:545Activation, Pregnane-X receptor, NR1l2 leads to increased plasma low-density lipoprotein (LDL) cholesterol via increased cholesterol synthesisUnclassified-0.2KE:239
Activation, 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:239
Activation, Pregnane-X receptor, NR1l2
AOP:563Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosisReproductive System Disease; Endocrine System Disease-0.17KE:18
Activation, AhR

No associated AOPs with Level of Relevance 5
Glossary of Terms
AOP
Adverse Outcome Pathway
MIE
Molecular Initiating Event
KE
Key Event
AO
Adverse Outcome
Coverage score
The fraction of KEs within the AOP, that are mapped to the chemical-associated toxicological endpoints
Level of relevance
Qualitative rank based on the kind of associated KEs within the corresponding AOP
AO classification
The disease category corresponding to the AO in the AOP obtained from Disease Ontology
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DISCLAIMER

TICToK is a knowledgebase of chemicals found in tattoo inks, compiled from publicly available regulatory and scientific resources. The chemical classifications presented in this knowledgebase are derived from multiple publicly available resources and are provided solely for informational purposes, and they are neither authoritative nor binding. The chemical-AOP mappings compiled in this knowledgebase serve as plausible hypotheses for research, and further experimental validation is required to definitively establish these potential toxicity mechanisms. The authors bear no responsibility for any errors, omissions, or inconsistencies originating from these external sources. Users are advised to exercise independent judgment when interpreting chemical classifications and any other data provided 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.