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:27Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)Gastrointestinal System DiseaseUnder Development0.12KE:288
Activation of specific nuclear receptors, Transcriptional change
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-0.14KE:496
Increased apoptosis, decreased fetal/adult Leydig Cells
AOP:112Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)Reproductive System Disease; Cancer-0.17KE:111
Agonism, Estrogen receptor
AOP:167Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.Reproductive System Disease; Cancer-0.14KE:1065
Activation, estrogen receptor alpha
AOP:207NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegansReproductive System Disease-0.12KE:1262
Apoptosis
AOP:212Histone deacetylase inhibition leading to testicular atrophyReproductive System DiseaseWPHA/WNT Endorsed0.17KE:1262
Apoptosis
AOP:419Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathwayRespiratory System Disease-0.25KE:1262
Apoptosis
AOP:439Activation of the AhR leading to metastatic breast cancerThoracic Disease; CancerUnder Development0.11KE:1262
Apoptosis
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 Development0.11KE:1973
Increased, estrogens
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:446PM-related Adverse outcome pathway frameworks on various systemsRespiratory System Disease-0.05KE:1262
Apoptosis
AOP:452Adverse outcome pathway of PM-induced respiratory toxicityRespiratory System Disease-0.09KE:1262
Apoptosis
AOP:460Antagonism of Smoothened receptor leading to orofacial cleftingUnclassifiedUnder Development0.11KE:1262
Apoptosis
AOP:463The AOP framwork on silica nanopariticles induced hepatoxicityGastrointestinal System Disease-0.09KE:1262
Apoptosis
AOP:465Alcohol dehydrogenase leading to reproductive dysfunctionUnclassified-0.12KE:748
Increased, Estrogen receptor (ER) activity
AOP:491Decrease, GLI1/2 target gene expression leads to orofacial cleftingUnclassifiedUnder Development0.17KE:1262
Apoptosis
AOP:495Androgen receptor activation leading to prostate cancerReproductive System Disease; Cancer-0.11KE:1183
Decreased, Apoptosis (Epithelial Cells)
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:535Binding and activation of GPER leading to learning and memory impairmentsDevelopmental Disorder Of Mental Health-0.11KE:1262
Apoptosis
AOP:540Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin ProductionUnclassified-0.11KE:1262
Apoptosis
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:205AOP from chemical insult to cell deathUnclassified-0.17KE:1262
Apoptosis
AOP:279Microtubule interacting drugs lead to peripheral neuropathyNervous System Disease-0.25KE:1583
Sensory axonal peripheral neuropathy
AOP:450Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortalityNervous System Disease-0.14KE:1583
Sensory axonal peripheral neuropathy
AOP:498Increased LCN2/iron complex leading to neurological disordersNervous System Disease-0.25KE:2150
Neurological disorder
AOP:501Excessive iron accumulation leading to neurological disordersNervous System Disease-0.25KE:2150
Neurological disorder
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 Development0.11KE:239
Activation, Pregnane-X receptor, NR1l2
AOP:60NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.08KE:245
Activation, PXR/SXR
AOP:445Estrogen Receptor Alpha Agonism leads to Impaired ReproductionReproductive System Disease-0.12KE:1065
Activation, estrogen receptor alpha
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:520Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memoryDevelopmental Disorder Of Mental Health-0.2KE:2201
Agonism, Retinoic acid receptor
AOP:523Retinoic acid receptor agonism during neurodevelopment leading to microcephalyCongenital Nervous System Abnormality; Nervous System Disease-0.2KE:2201
Agonism, Retinoic acid receptor
AOP:532Retinoic acid receptor agonism during cerebellar development leading to impaired locomotor functionUnclassified-0.2KE:2201
Agonism, Retinoic acid receptor
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.