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:15Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutationsGenetic DiseaseWPHA/WNT Endorsed0.25KE:155
Inadequate DNA repair
AOP:41Sustained AhR Activation leading to Rodent Liver TumoursCancer; Gastrointestinal System DiseaseUnder Review0.2KE:139
N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects
AOP:80Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failureUnclassified-0.12KE:664
Overwhelmed, Mitochondrial DNA repair mechanisms
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:207NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegansReproductive System Disease-0.12KE:1281
Increased, DNA Damage-Repair
AOP:220Cyp2E1 Activation Leading to Liver CancerCancer; Gastrointestinal System DiseaseWPHA/WNT Endorsed0.2KE:1393
Hepatocytotoxicity
AOP:296Oxidative DNA damage leading to chromosomal aberrations and mutationsGenetic Disease; Chromosomal DiseaseWPHA/WNT Endorsed0.2KE:155
Inadequate DNA repair
AOP:322Alkylation of DNA leading to reduced sperm countReproductive System Disease-0.2KE:155
Inadequate DNA repair
AOP:397Bulky DNA adducts leading to mutationsGenetic DiseaseUnder Development0.33KE:155
Inadequate DNA repair
AOP:432Deposition of Energy by Ionizing Radiation leading to Acute Myeloid LeukemiaHematopoietic System Disease; Cancer-0.09KE:155
Inadequate DNA repair
AOP:443DNA damage and mutations leading to Metastatic Breast CancerThoracic Disease; CancerUnder Development0.1KE:155
Inadequate DNA repair
AOP:478Deposition of energy leading to occurrence of cataractsNervous System Disease; Monogenic DiseaseUnder Review0.1KE:155
Inadequate DNA repair

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:139Alkylation of DNA leading to cancer 1Cancer-0.5KE:885
Increase, Cancer
KE:155
Inadequate DNA repair
AOP:272Deposition of energy leading to lung cancerCancerWPHA/WNT Endorsed0.29KE:1556
Increase, lung cancer
KE:155
Inadequate DNA repair
AOP:293Increased DNA damage leading to increased risk of breast cancerGenetic Disease; Thoracic Disease; CancerUnder Development0.11KE:1193
N/A, Breast Cancer
AOP:294Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancerGenetic Disease; Thoracic Disease; CancerUnder Development0.11KE:1193
N/A, Breast Cancer
AOP:303Frustrated phagocytosis-induced lung cancerCancerUnder Development0.14KE:1670
Lung cancer
AOP:416Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathwayCancer-0.17KE:1670
Lung cancer
AOP:417Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathwayCancer-0.2KE:1670
Lung cancer
AOP:420Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathwayCancer-0.25KE:1670
Lung cancer
AOP:451Interaction with lung resident cell membrane components leads to lung cancerCancer-0.11KE:1670
Lung cancer
AOP:463The AOP framwork on silica nanopariticles induced hepatoxicityGastrointestinal System Disease-0.09KE:2034
liver dysfunction
AOP:474Succinate dehydrogenase inactivation leads to cancer by promoting EMTCancerUnder Development0.2KE:885
Increase, Cancer
AOP:505Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathwayCancer-0.2KE:885
Increase, Cancer
AOP:513Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathwayCancer-0.2KE:885
Increase, Cancer
AOP:534Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stressCancer-0.17KE:885
Increase, Cancer
AOP:546Succinate dehydrogenase inactivation leads to cancer through hypoxic-like mechanismsCancer-0.2KE:885
Increase, Cancer

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 Development0.11KE:239
Activation, Pregnane-X receptor, NR1l2
AOP:118Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal System Disease-0.25KE:786
Increase, Cytotoxicity (hepatocytes)
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

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.