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: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:1392
Oxidative Stress
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: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:263Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferationUnclassifiedWPHA/WNT Endorsed0.25KE:1821
Decrease, Cell proliferation
AOP:267Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletionUnclassifiedUnder Development0.2KE:1821
Decrease, Cell proliferation
AOP:286Mitochondrial complex III antagonism leading to growth inhibition (1)Unclassified-0.25KE:1821
Decrease, Cell proliferation
AOP:290Mitochondrial ATP synthase antagonism leading to growth inhibition (1)Unclassified-0.25KE:1821
Decrease, Cell proliferation
AOP:331Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and reduced cell proliferationUnclassified-0.17KE:1821
Decrease, Cell proliferation
AOP:332Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferationUnclassified-0.2KE:1821
Decrease, Cell proliferation
AOP:333Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylationUnclassified-0.2KE:1821
Decrease, Cell proliferation
AOP:399Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)Unclassified-0.12KE:1821
Decrease, Cell proliferation
AOP:413Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failureUnclassified-0.17KE:1607
Increase, Necrosis
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: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: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-0.3KE:18
Activation, AhR
KE:1262
Apoptosis
KE:1458
Pulmonary fibrosis
KE:1392
Oxidative Stress
KE:165
Activation, Long term AHR receptor driven direct and indirect gene expression changes
KE:1250
Decrease, Lung function
AOP:448ROS, inflammation, and activation of nAChR lead to increased incidence of cardiovascular morbidity and mortalityCardiovascular System Disease-0.06KE:1392
Oxidative Stress
AOP:449Ceramide synthase inhibition leading to neural tube defectsNeural Tube Defect-0.14KE:1502
Histone deacetylase inhibition
AOP:450Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortalityNervous System Disease-0.14KE: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:460Antagonism of Smoothened receptor leading to orofacial cleftingUnclassifiedUnder Development0.22KE:1821
Decrease, Cell proliferation
KE:1262
Apoptosis
AOP:464Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficitsNervous System Disease-0.05KE:1392
Oxidative Stress
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 Review0.12KE:1392
Oxidative Stress
AOP:478Deposition of energy leading to occurrence of cataractsNervous System Disease; Monogenic DiseaseUnder Review0.1KE: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 Review0.12KE: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 Development0.33KE:1821
Decrease, Cell proliferation
KE:1262
Apoptosis
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: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-0.14KE: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-0.08KE:1392
Oxidative Stress

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-0.25KE:885
Increase, Cancer
AOP:148EGFR Activation Leading to Decreased Lung FunctionRespiratory System DiseaseUnder Development0.25KE:1250
Decrease, Lung function
AOP:173Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosisMusculoskeletal System Disease; Respiratory System DiseaseWPHA/WNT Endorsed0.12KE:1458
Pulmonary fibrosis
AOP:205AOP from chemical insult to cell deathUnclassified-0.33KE:1263
Necrosis
KE:1262
Apoptosis
AOP:206Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosisMusculoskeletal System Disease; Respiratory System DiseaseUnder Development0.17KE:1276
Lung fibrosis
AOP:241Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosisMusculoskeletal System Disease; Respiratory System Disease-0.17KE:1458
Pulmonary fibrosis
AOP:272Deposition of energy leading to lung cancerCancerWPHA/WNT Endorsed0.14KE:1556
Increase, lung cancer
AOP:302Lung surfactant function inhibition leading to decreased lung functionRespiratory System DiseaseUnder Development0.2KE:1250
Decrease, Lung function
AOP:303Frustrated phagocytosis-induced lung cancerCancerUnder Development0.14KE:1670
Lung cancer
AOP:347Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosisMusculoskeletal System Disease; Respiratory System Disease-0.11KE:1458
Pulmonary fibrosis
AOP:382Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosisMusculoskeletal System Disease; Respiratory System DiseaseUnder Development0.17KE:1276
Lung fibrosis
AOP:384Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney diseaseUrinary System Disease-0.17KE:1603
Chronic kidney disease
AOP:451Interaction with lung resident cell membrane components leads to lung cancerCancer-0.11KE:1670
Lung cancer
AOP:452Adverse outcome pathway of PM-induced respiratory toxicityRespiratory System Disease-0.27KE:2008
Chronic obstructive pulmonary disease
KE:1262
Apoptosis
KE:1392
Oxidative Stress
AOP:463The AOP framwork on silica nanopariticles induced hepatoxicityGastrointestinal System Disease-0.27KE:1262
Apoptosis
KE:1392
Oxidative Stress
KE: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-0.4KE:885
Increase, Cancer
KE:1392
Oxidative Stress
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-0.33KE:885
Increase, Cancer
KE:1392
Oxidative Stress
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:21Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2UnclassifiedWPHA/WNT Endorsed0.2KE:18
Activation, AhR
AOP:41Sustained AhR Activation leading to Rodent Liver TumoursCancer; Gastrointestinal System DiseaseUnder Review0.4KE:165
Activation, Long term AHR receptor driven direct and indirect gene expression changes
KE:853
Changes/Inhibition, Cellular Homeostasis and Apoptosis
AOP:131Aryl hydrocarbon receptor activation leading to uroporphyriaInherited Metabolic DisorderWPHA/WNT Endorsed0.17KE:18
Activation, AhR
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:212Histone deacetylase inhibition leading to testicular atrophyReproductive System DiseaseWPHA/WNT Endorsed0.33KE:1262
Apoptosis
KE:1502
Histone deacetylase inhibition
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:310Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHRUnclassified-0.08KE:18
Activation, AhR
AOP:439Activation of the AhR leading to metastatic breast cancerThoracic Disease; CancerUnder Development0.33KE:18
Activation, AhR
KE:1971
Increased, tumor growth
KE:1262
Apoptosis
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: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-0.12KE:18
Activation, AhR
AOP:459AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.22KE:18
Activation, AhR
KE:1392
Oxidative Stress
AOP:472DNA adduct formation leading to kidney failureUrinary System Disease-0.11KE:1392
Oxidative Stress
AOP:494AhR activation leading to liver fibrosisGastrointestinal System Disease-0.17KE:18
Activation, AhR
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:563Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosisReproductive System Disease; Endocrine System Disease-0.33KE:18
Activation, AhR
KE:1262
Apoptosis

Associated AOPs with Level of Relevance 5
AOPs with at least 1 MIE and AO associated with chemical, and there exists a directed path between that MIE and AO
AOP Identifier AOP Title AO Classification OECD Status Coverage Score KE Identifier KE Name
AOP:411Oxidative stress Leading to Decreased Lung FunctionRespiratory System Disease-0.5KE:1250
Decrease, Lung function
KE:1392
Oxidative Stress
AOP:414Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathwayMusculoskeletal System Disease; Respiratory System Disease-0.4KE:18
Activation, AhR
KE:1276
Lung fibrosis
AOP:415Aryl hydrocarbon receptor activation leading to lung fibrosis through IL-6 toxicity pathwayMusculoskeletal System Disease; Respiratory System Disease-0.4KE:18
Activation, AhR
KE:1276
Lung fibrosis
AOP:416Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathwayCancer-0.33KE:18
Activation, AhR
KE:1670
Lung cancer
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:1670
Lung cancer
AOP:418Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathwayRespiratory System Disease-0.6KE:18
Activation, AhR
KE:17
Altered gene expression, AHR nuclear translocator (ARNT)-dependent pathway
KE:1250
Decrease, Lung function
AOP:419Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathwayRespiratory System Disease-0.75KE:18
Activation, AhR
KE:1250
Decrease, Lung function
KE:1262
Apoptosis
AOP:420Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathwayCancer-0.75KE:18
Activation, AhR
KE:1917
Altered gene expression, NRF2 dependent antioxidant pathway
KE:1670
Lung cancer
AOP:424Oxidative stress Leading to Decreased Lung Function via CFTR dysfunctionRespiratory System Disease-0.33KE:1250
Decrease, Lung function
KE:1392
Oxidative Stress
AOP:425Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1Respiratory System Disease-0.33KE:1250
Decrease, Lung function
KE:1392
Oxidative Stress
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.