1,4-Benzenediamine

1,4-Benzenediamine



Associated curated AOPs from AOP-Wiki
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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: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 Endorsed0.2KE:1493
Increased Pro-inflammatory mediators
KE:1392
Oxidative Stress
AOP:27Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)Gastrointestinal System DiseaseUnder Development0.12KE:149
Increase, Inflammation
AOP:38Protein Alkylation leading to Liver FibrosisGastrointestinal System DiseaseWPHA/WNT Endorsed0.14KE:1493
Increased Pro-inflammatory mediators
AOP:41Sustained AhR Activation leading to Rodent Liver TumoursCancer; Gastrointestinal System DiseaseUnder Review0.2KE:853
Changes/Inhibition, Cellular Homeostasis and Apoptosis
AOP:64Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male FertilityReproductive System Disease-0.29KE:496
Increased apoptosis, decreased fetal/adult Leydig Cells
KE:520
Decreased sperm quantity or quality in the adult, Decreased fertility
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:114HPPD inhibition leading to corneal papillomas and carcinomas (in rat)Cancer-0.17KE:777
Increase, Inflammation (corneal cells)
AOP:115Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)Cancer-0.2KE:149
Increase, Inflammation
AOP:128Kidney dysfunction by decreased thyroid hormoneUrinary System DiseaseUnder Development0.09KE:825
Decreased, Renal ability to dilute urine
AOP:144Endocytic lysosomal uptake leading to liver fibrosisGastrointestinal System DiseaseUnder Review0.11KE:1493
Increased Pro-inflammatory mediators
AOP:173Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosisMusculoskeletal System Disease; Respiratory System DiseaseWPHA/WNT Endorsed0.12KE:1497
Increased, recruitment of inflammatory cells
AOP:206Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosisMusculoskeletal System Disease; Respiratory System DiseaseUnder Development0.17KE:149
Increase, Inflammation
AOP:207NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegansReproductive System Disease-0.12KE:1262
Apoptosis
AOP:220Cyp2E1 Activation Leading to Liver CancerCancer; Gastrointestinal System DiseaseWPHA/WNT Endorsed0.2KE:1392
Oxidative Stress
AOP:260CYP2E1 activation and formation of protein adducts leading to neurodegenerationNervous System Disease-0.14KE:1392
Oxidative Stress
AOP:272Deposition of energy leading to lung cancerCancerWPHA/WNT Endorsed0.14KE:1636
Increase, Chromosomal aberrations
AOP:280α-diketone-induced bronchiolitis obliteransMusculoskeletal System Disease; Respiratory System Disease-0.14KE:149
Increase, Inflammation
AOP:293Increased DNA damage leading to increased risk of breast cancerGenetic Disease; Thoracic Disease; CancerUnder Development0.11KE:1493
Increased Pro-inflammatory mediators
AOP:294Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancerGenetic Disease; Thoracic Disease; CancerUnder Development0.11KE:1493
Increased Pro-inflammatory mediators
AOP:303Frustrated phagocytosis-induced lung cancerCancerUnder Development0.14KE:1497
Increased, recruitment of inflammatory cells
AOP:409Frustrated phagocytosis leads to malignant mesotheliomaCancer-0.12KE:1497
Increased, recruitment of inflammatory cells
AOP:413Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failureUnclassified-0.17KE:1607
Increase, Necrosis
AOP:419Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathwayRespiratory System Disease-0.25KE:1262
Apoptosis
AOP:420Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathwayCancer-0.25KE:1917
Altered gene expression, NRF2 dependent antioxidant pathway
AOP:432Deposition of Energy by Ionizing Radiation leading to Acute Myeloid LeukemiaHematopoietic System Disease; Cancer-0.09KE:1493
Increased Pro-inflammatory mediators
AOP:437Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicityUrinary System DiseaseUnder Development0.2KE:1392
Oxidative Stress
AOP:438reactive oxygen species generation leading to increased cardiovascular morbidity and mortalityCardiovascular System Disease-0.08KE:1392
Oxidative Stress
AOP:439Activation of the AhR leading to metastatic breast cancerThoracic Disease; CancerUnder Development0.22KE:149
Increase, Inflammation
KE:1262
Apoptosis
AOP:441Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiationCongenital Nervous System Abnormality; Nervous System Disease-0.14KE:1262
Apoptosis
AOP:443DNA damage and mutations leading to Metastatic Breast CancerThoracic Disease; CancerUnder Development0.1KE:1554
Increase Chromosomal Aberrations
AOP:444Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchabilityUnclassified-0.11KE:1392
Oxidative Stress
AOP:446PM-related Adverse outcome pathway frameworks on various systemsRespiratory System Disease-0.2KE:149
Increase, Inflammation
KE:1262
Apoptosis
KE:1497
Increased, recruitment of inflammatory cells
KE:1392
Oxidative Stress
AOP:448ROS, inflammation, and activation of nAChR lead to increased incidence of cardiovascular morbidity and mortalityCardiovascular System Disease-0.06KE:1392
Oxidative Stress
AOP:450Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortalityNervous System Disease-0.14KE:1392
Oxidative Stress
AOP:451Interaction with lung resident cell membrane components leads to lung cancerCancer-0.11KE:1497
Increased, recruitment of inflammatory cells
AOP:452Adverse outcome pathway of PM-induced respiratory toxicityRespiratory System Disease-0.18KE:1262
Apoptosis
KE:1392
Oxidative Stress
AOP:453Reactive oxygen species and subsequent oxidative stress lead to increased incidence of digestive morbidity and mortality in the general populationGastrointestinal System Disease-0.08KE:1392
Oxidative Stress
AOP:457Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxineInherited Metabolic Disorder-0.17KE:1392
Oxidative Stress
AOP:459AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.11KE:1392
Oxidative Stress
AOP:460Antagonism of Smoothened receptor leading to orofacial cleftingUnclassifiedUnder Development0.11KE:1262
Apoptosis
AOP:463The AOP framwork on silica nanopariticles induced hepatoxicityGastrointestinal System Disease-0.27KE:149
Increase, Inflammation
KE:1262
Apoptosis
KE:1392
Oxidative Stress
AOP:464Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficitsNervous System Disease-0.05KE:1392
Oxidative Stress
AOP:465Alcohol dehydrogenase leading to reproductive dysfunctionUnclassified-0.12KE:748
Increased, Estrogen receptor (ER) activity
AOP:469Reactive oxygen speicies overproduction leading to increased digestive morbidity and mortality in generation populationGastrointestinal System Disease-0.08KE:1392
Oxidative Stress
AOP:470Deposition of energy leads to abnormal vascular remodelingCardiovascular System DiseaseUnder Review0.38KE:2244
Altered Stress Response Signaling
KE:1493
Increased Pro-inflammatory mediators
KE:1392
Oxidative Stress
AOP:478Deposition of energy leading to occurrence of cataractsNervous System Disease; Monogenic DiseaseUnder Review0.2KE:1636
Increase, Chromosomal aberrations
KE:1392
Oxidative Stress
AOP:479Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stressCardiovascular System Disease; Thoracic DiseaseUnder Development0.14KE:1392
Oxidative Stress
AOP:482Deposition of energy leading to occurrence of bone lossMusculoskeletal System DiseaseUnder Review0.14KE:1392
Oxidative Stress
AOP:483Deposition of Energy Leading to Learning and Memory ImpairmentDevelopmental Disorder Of Mental HealthUnder Review0.25KE:2244
Altered Stress Response Signaling
KE:1392
Oxidative Stress
AOP:488Increased reactive oxygen species production leading to decreased cognitive functionCognitive Disorder-0.14KE:1392
Oxidative Stress
AOP:491Decrease, GLI1/2 target gene expression leads to orofacial cleftingUnclassifiedUnder Development0.17KE:1262
Apoptosis
AOP:493ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesityAcquired Metabolic Disease-0.1KE:1497
Increased, recruitment of inflammatory cells
AOP:495Androgen receptor activation leading to prostate cancerReproductive System Disease; Cancer-0.11KE:1183
Decreased, Apoptosis (Epithelial 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:1392
Oxidative Stress
AOP:500Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosisDevelopmental Disorder Of Mental Health-0.14KE:1262
Apoptosis
AOP:501Excessive iron accumulation leading to neurological disordersNervous System Disease-0.25KE:1392
Oxidative Stress
AOP:505Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathwayCancer-0.4KE:149
Increase, Inflammation
KE:1392
Oxidative Stress
AOP:507Nrf2 inhibition leading to vascular disrupting effects via inflammation pathwayCardiovascular System Disease-0.17KE:1392
Oxidative Stress
AOP:509Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunctionCardiovascular System Disease-0.14KE:1392
Oxidative Stress
AOP:510Demethylation of PPAR promotor leading to vascular disrupting effectsCardiovascular System Disease-0.1KE:1392
Oxidative Stress
AOP:511The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effectsCardiovascular System Disease-0.06KE:1392
Oxidative Stress
AOP:521Essential element imbalance leads to reproductive failure via oxidative stressUnclassified-0.29KE:2206
Increased, histomorphological alteration of testis
KE:1392
Oxidative Stress
AOP:534Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stressCancer-0.17KE:1392
Oxidative Stress
AOP:535Binding and activation of GPER leading to learning and memory impairmentsDevelopmental Disorder Of Mental Health-0.22KE:1262
Apoptosis
KE:1392
Oxidative Stress
AOP:540Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin ProductionUnclassified-0.22KE:1262
Apoptosis
KE:1392
Oxidative Stress
AOP:541Excessive ROS generation leading to increased incidence of vascular calcification by VSMC phenotype switchingCardiovascular System Disease-0.15KE:1493
Increased Pro-inflammatory mediators
KE:1392
Oxidative Stress
AOP:544Inhibition of neuropathy target esterase leading to delayed neuropathy via increased inflammationNervous System Disease-0.17KE:149
Increase, Inflammation
AOP:563Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosisReproductive System Disease; Endocrine System Disease-0.17KE:1262
Apoptosis

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:40Covalent Protein binding leading to Skin SensitisationIntegumentary System DiseaseWPHA/WNT Endorsed0.2KE:827
sensitisation, skin
AOP:196Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary IrritationRespiratory System Disease-0.11KE:1226
Increased Respiratory irritability and Chronic Cough,
AOP:205AOP from chemical insult to cell deathUnclassified-0.33KE:1263
Necrosis
KE:1262
Apoptosis
AOP:212Histone deacetylase inhibition leading to testicular atrophyReproductive System DiseaseWPHA/WNT Endorsed0.33KE:1506
Testicular atrophy
KE:1262
Apoptosis
AOP:296Oxidative DNA damage leading to chromosomal aberrations and mutationsGenetic Disease; Chromosomal DiseaseWPHA/WNT Endorsed0.2KE:1636
Increase, Chromosomal aberrations
AOP:322Alkylation of DNA leading to reduced sperm countReproductive System Disease-0.2KE:1757
Reduce, Sperm count
AOP:392Decreased fibrinolysis and activated bradykinin system leading to hyperinflammationUnclassifiedUnder Development0.4KE:1868
Hyperinflammation
KE:1497
Increased, recruitment of inflammatory cells
AOP:406SARS-CoV-2 infection leading to hyperinflammationUnclassified-0.17KE:1868
Hyperinflammation
AOP:468Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)Unclassified-0.25KE:1868
Hyperinflammation
KE:1497
Increased, recruitment of inflammatory cells

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:42Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive DisorderWPHA/WNT Endorsed0.12KE:279
Thyroperoxidase, Inhibition
AOP:62AKT2 activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.25KE:486
systemic inflammation leading to hepatic steatosis
AOP:119Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)Cancer; Endocrine System Disease-0.14KE:279
Thyroperoxidase, Inhibition
AOP:159Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflationUnclassifiedWPHA/WNT Endorsed0.12KE:279
Thyroperoxidase, Inhibition
AOP:175Thyroperoxidase inhibition leading to altered amphibian metamorphosisUnclassified-0.25KE:279
Thyroperoxidase, Inhibition
AOP:271Inhibition of thyroid peroxidase leading to impaired fertility in fishUnclassifiedUnder Development0.2KE:279
Thyroperoxidase, Inhibition
AOP:363Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structureUnclassifiedUnder Review0.12KE:279
Thyroperoxidase, Inhibition
AOP:364Thyroperoxidase inhibition leading to altered visual function via decreased eye sizeUnclassifiedUnder Development0.12KE:279
Thyroperoxidase, Inhibition
AOP:365Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterningUnclassifiedUnder Development0.12KE:279
Thyroperoxidase, Inhibition
AOP:411Oxidative stress Leading to Decreased Lung FunctionRespiratory System Disease-0.25KE:1392
Oxidative Stress
AOP:424Oxidative stress Leading to Decreased Lung Function via CFTR dysfunctionRespiratory System Disease-0.17KE:1392
Oxidative Stress
AOP:425Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1Respiratory System Disease-0.17KE:1392
Oxidative Stress
AOP:447Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathwaysUrinary System Disease-0.17KE:1917
Altered gene expression, NRF2 dependent antioxidant pathway
KE:1392
Oxidative Stress
AOP:472DNA adduct formation leading to kidney failureUrinary System Disease-0.22KE:149
Increase, Inflammation
KE:1392
Oxidative Stress

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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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.