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:4Ecdysone receptor agonism leading to incomplete ecdysis associated mortalityUnclassified-0.2KE:1264
Increase, Nuclear receptor E75b gene expression
KE:1265
Increase, Fushi tarazu factor-1 gene expression
AOP:8Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in MammalsNervous System DiseaseUnder Development0.11KE:756
Hippocampal gene expression, Altered
AOP:12Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in agingNervous System Disease; Developmental Disorder Of Mental HealthWPHA/WNT Endorsed0.12KE:381
Reduced levels of BDNF
AOP:13Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilitiesDevelopmental Disorder Of Mental HealthWPHA/WNT Endorsed0.1KE:381
Reduced levels of BDNF
AOP:15Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutationsGenetic DiseaseWPHA/WNT Endorsed0.25KE:155
Inadequate DNA repair
AOP:18PPARα activation in utero leading to impaired fertility in malesReproductive System DiseaseUnder Review0.25KE:266
Decrease, Steroidogenic acute regulatory protein (STAR)
KE:289
Decrease, Translocator protein (TSPO)
AOP:21Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2UnclassifiedWPHA/WNT Endorsed0.4KE:317
Altered, Cardiovascular development/function
KE:1269
Increase, COX-2 expression
AOP:23Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)UnclassifiedWPHA/WNT Endorsed0.1KE:285
Reduction, Vitellogenin synthesis in liver
AOP:25Aromatase inhibition leading to reproductive dysfunctionUnclassifiedWPHA/WNT Endorsed0.12KE:285
Reduction, Vitellogenin synthesis in liver
AOP:27Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)Gastrointestinal System DiseaseUnder Development0.25KE:1115
Increase, Reactive oxygen species
KE:288
Activation of specific nuclear receptors, Transcriptional change
AOP:30Estrogen receptor antagonism leading to reproductive dysfunctionUnclassifiedUnder Review0.17KE:285
Reduction, Vitellogenin synthesis in liver
AOP:34LXR activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.15KE:54
Up Regulation, CD36
KE:258
Activation, SCD-1
AOP:36Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to SteatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.25KE:327
Accumulation, Fatty acid
KE:140
Decreased, HSD17B10 expression
AOP:37PPARα activation leading to hepatocellular adenomas and carcinomas in rodentsCancer; Gastrointestinal System DiseaseUnder Development0.2KE:716
Increase, cell proliferation (hepatocytes)
AOP:39Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity ResponseRespiratory System DiseaseUnder Development0.2KE:272
Activation/Proliferation, T-cells
AOP:40Covalent Protein binding leading to Skin SensitisationIntegumentary System DiseaseWPHA/WNT Endorsed0.2KE:272
Activation/Proliferation, T-cells
AOP:41Sustained AhR Activation leading to Rodent Liver TumoursCancer; Gastrointestinal System DiseaseUnder Review0.4KE:853
Changes/Inhibition, Cellular Homeostasis and Apoptosis
KE:139
N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects
AOP:42Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive DisorderWPHA/WNT Endorsed0.12KE:756
Hippocampal gene expression, Altered
AOP:54Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairmentDevelopmental Disorder Of Mental HealthWPHA/WNT Endorsed0.1KE:381
Reduced levels of BDNF
AOP:58NR1I3 (CAR) suppression leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.25KE:462
Up Regulation, SCD-1
KE:327
Accumulation, Fatty acid
KE:463
Up Regulation, FAS
KE:54
Up Regulation, CD36
AOP:60NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.42KE:54
Up Regulation, CD36
KE:462
Up Regulation, SCD-1
KE:327
Accumulation, Fatty acid
KE:474
Down Regulation, HMGCS2
KE:472
Down Regulation, CPT1A
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: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:100Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behaviorReproductive System Disease-0.14KE:672
Reduced, Prostaglandin F2alpha synthesis, ovary
AOP:101Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone releaseReproductive System Disease-0.14KE:681
Decreased, Prostaglandin F2alpha synthesis, ovary
AOP:107Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the ratCancer; Gastrointestinal System DiseaseUnder Review0.4KE:1214
Altered gene expression specific to CAR activation, Hepatocytes
KE:716
Increase, cell proliferation (hepatocytes)
AOP:108Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal System Disease-0.17KE:768
Increase, Cytotoxicity
AOP:110Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse)Cancer; Endocrine System Disease-0.14KE:739
Increase, Hypertrophy and proliferation (follicular cell)
AOP:114HPPD inhibition leading to corneal papillomas and carcinomas (in rat)Cancer-0.17KE:778
Increase, Regenerative cell proliferation (corneal cells)
AOP:115Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)Cancer-0.2KE:781
Increase, Regenerative cell proliferation (forestomach epithelial cells)
AOP:117Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal System DiseaseUnder Development0.25KE:716
Increase, cell proliferation (hepatocytes)
AOP:119Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)Cancer; Endocrine System Disease-0.14KE:739
Increase, Hypertrophy and proliferation (follicular cell)
AOP:121Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)Cancer; Urinary System Disease-0.2KE:795
Increase, Regenerative cell proliferation (urothelial cells)
AOP:122Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formationUnclassified-0.2KE:799
Increased, HIF-1 heterodimer
KE:285
Reduction, Vitellogenin synthesis in liver
AOP:123Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcriptionUnclassified-0.27KE:799
Increased, HIF-1 heterodimer
KE:802
Increased, HIF-1 alpha transcription
KE:285
Reduction, Vitellogenin synthesis in liver
AOP:131Aryl hydrocarbon receptor activation leading to uroporphyriaInherited Metabolic DisorderWPHA/WNT Endorsed0.17KE:850
Induction, CYP1A2/CYP1A5
AOP:134Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.11KE:756
Hippocampal gene expression, Altered
AOP:136Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal TumorsBenign Neoplasm; Respiratory System DiseaseUnder Review0.29KE:768
Increase, Cytotoxicity
KE:870
Increase, Cell Proliferation
AOP:148EGFR Activation Leading to Decreased Lung FunctionRespiratory System DiseaseUnder Development0.25KE:962
Increase, Mucin production
AOP:149Peptide Oxidation Leading to HypertensionCardiovascular System DiseaseUnder Development0.1KE:933
KE6 : Depletion, Nitric Oxide
AOP:150Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGFUnclassifiedWPHA/WNT Endorsed0.29KE:317
Altered, Cardiovascular development/function
KE:948
reduced production, VEGF
AOP:151AhR activation leading to preeclampsiaCardiovascular System DiseaseUnder Development0.14KE:948
reduced production, VEGF
AOP:164Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouseCancer; Reproductive System Disease-0.17KE:1042
Proliferation/Clonal Expansion, smooth muscle
AOP:167Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.Reproductive System Disease; Cancer-0.29KE:1066
Promotion, SIX-1 postive basal-type progenitor cells
KE:1067
Proliferation/Clonal Expansion, aberrant basal cells
AOP:201Juvenile hormone receptor agonism leading to male offspring induction associated population declineUnclassified-0.17KE:1206
Induction, Doublesex1 gene
AOP:207NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegansReproductive System Disease-0.38KE:1281
Increased, DNA Damage-Repair
KE:1115
Increase, Reactive oxygen species
KE:1262
Apoptosis
AOP:212Histone deacetylase inhibition leading to testicular atrophyReproductive System DiseaseWPHA/WNT Endorsed0.17KE:1262
Apoptosis
AOP:213Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)Gastrointestinal System Disease; Inherited Metabolic Disorder-0.17KE:1115
Increase, Reactive oxygen species
AOP:218Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activityUnclassified-0.17KE:1141
Decreased, Reproductive Success
AOP:219Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behaviorUnclassified-0.17KE:1141
Decreased, Reproductive Success
AOP:220Cyp2E1 Activation Leading to Liver CancerCancer; Gastrointestinal System DiseaseWPHA/WNT Endorsed0.4KE:1393
Hepatocytotoxicity
KE:1394
Induction, persistent proliferation/sustained proliferation
AOP:245Reduction in photophosphorylation leading to growth inhibition in aquatic plantsUnclassified-0.09KE:40
Decrease, Mitochondrial ATP production
AOP:258Renal protein alkylation leading to kidney toxicityUrinary System DiseaseUnder Development0.2KE:40
Decrease, Mitochondrial ATP production
AOP:272Deposition of energy leading to lung cancerCancerWPHA/WNT Endorsed0.29KE:870
Increase, Cell Proliferation
KE:155
Inadequate DNA repair
AOP:275Histone deacetylase inhibition leads to neural tube defectsNeural Tube Defect-0.2KE:1239
Altered, Gene Expression
AOP:286Mitochondrial complex III antagonism leading to growth inhibition (1)Unclassified-0.5KE:1821
Decrease, Cell proliferation
KE:1771
Decrease, Adenosine triphosphate pool
AOP:287Mitochondrial complex III antagonism leading to growth inhibition (2)Unclassified-0.25KE:1771
Decrease, Adenosine triphosphate pool
AOP:290Mitochondrial ATP synthase antagonism leading to growth inhibition (1)Unclassified-0.5KE:1821
Decrease, Cell proliferation
KE:1771
Decrease, Adenosine triphosphate pool
AOP:291Mitochondrial ATP synthase antagonism leading to growth inhibition (2)Unclassified-0.25KE:1771
Decrease, Adenosine triphosphate pool
AOP:296Oxidative DNA damage leading to chromosomal aberrations and mutationsGenetic Disease; Chromosomal DiseaseWPHA/WNT Endorsed0.2KE:155
Inadequate DNA repair
AOP:299Deposition of energy leading to population decline via DNA oxidation and follicular atresiaUnclassified-0.14KE:1115
Increase, Reactive oxygen species
AOP:300Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive DisorderUnder Development0.2KE:756
Hippocampal gene expression, Altered
AOP:303Frustrated phagocytosis-induced lung cancerCancerUnder Development0.29KE:1115
Increase, Reactive oxygen species
KE:870
Increase, Cell Proliferation
AOP:3055α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspringUnclassifiedUnder Development0.2KE:286
Altered, Transcription of genes by the androgen receptor
AOP:306Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspringUnclassifiedUnder Development0.25KE: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:285
Reduction, Vitellogenin synthesis in liver
AOP:311Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosisUnclassified-0.14KE:1115
Increase, Reactive oxygen species
AOP:321Reduced environmental pH leading to thinner shells in Mytilus edulisUnclassified-0.09KE:10042
Abnormal development
AOP:323PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-KetotestosteroneUnclassified-0.17KE:807
Decreased, cholesterol
AOP:335AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairmentCancer; Urinary System Disease-0.2KE:795
Increase, Regenerative cell proliferation (urothelial cells)
AOP:344Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspringUnclassifiedUnder Development0.25KE: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 Development0.17KE:286
Altered, Transcription of genes by the androgen receptor
AOP:372Androgen receptor antagonism leading to testicular cancerEndocrine System Disease; Reproductive System Disease; Cancer-0.2KE:286
Altered, Transcription of genes by the androgen receptor
AOP:379Binding to ACE2 leading to thrombosis and disseminated intravascular coagulationCardiovascular System DiseaseUnder Development0.14KE:1869
Diminished protective oxidative stress response
AOP:382Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosisMusculoskeletal System Disease; Respiratory System DiseaseUnder Development0.17KE:1115
Increase, Reactive oxygen species
AOP:383Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosisGastrointestinal System DiseaseUnder Development0.17KE:1115
Increase, Reactive oxygen species
AOP:386Deposition of ionizing energy leading to population decline via inhibition of photosynthesisReproductive System Disease-0.12KE:1115
Increase, Reactive oxygen species
AOP:387Deposition of ionising energy leading to population decline via mitochondrial dysfunctionReproductive System Disease-0.25KE:40
Decrease, Mitochondrial ATP production
KE:1115
Increase, Reactive oxygen species
AOP:397Bulky DNA adducts leading to mutationsGenetic DiseaseUnder Development0.33KE:155
Inadequate DNA repair
AOP:399Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)Unclassified-0.12KE:1821
Decrease, Cell proliferation
AOP:406SARS-CoV-2 infection leading to hyperinflammationUnclassified-0.17KE:1869
Diminished protective oxidative stress response
AOP:409Frustrated phagocytosis leads to malignant mesotheliomaCancer-0.25KE:1115
Increase, Reactive oxygen species
KE:870
Increase, Cell Proliferation
AOP:414Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathwayMusculoskeletal System Disease; Respiratory System Disease-0.2KE:1920
Altered gene expression, TGF-β dependent fibrosis pathway
AOP:416Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathwayCancer-0.17KE:1115
Increase, Reactive oxygen species
AOP:418Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathwayRespiratory System Disease-0.2KE:1115
Increase, Reactive oxygen species
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:870
Increase, Cell Proliferation
AOP:432Deposition of Energy by Ionizing Radiation leading to Acute Myeloid LeukemiaHematopoietic System Disease; Cancer-0.18KE:870
Increase, Cell Proliferation
KE:155
Inadequate DNA repair
AOP:439Activation of the AhR leading to metastatic breast cancerThoracic Disease; CancerUnder Development0.11KE: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:155
Inadequate DNA repair
AOP:451Interaction with lung resident cell membrane components leads to lung cancerCancer-0.22KE:1115
Increase, Reactive oxygen species
KE:870
Increase, Cell Proliferation
AOP:452Adverse outcome pathway of PM-induced respiratory toxicityRespiratory System Disease-0.09KE:1262
Apoptosis
AOP:455Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial developmentMusculoskeletal System DiseaseUnder Review0.33KE:2020
Decrease, sox9 expression
KE:2021
Increase, slincR expression
AOP:456Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicityUnclassifiedUnder Review0.5KE:2020
Decrease, sox9 expression
KE:317
Altered, Cardiovascular development/function
KE:2021
Increase, slincR expression
AOP:458AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.12KE:756
Hippocampal gene expression, Altered
AOP:459AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.22KE:756
Hippocampal gene expression, Altered
KE:850
Induction, CYP1A2/CYP1A5
AOP:460Antagonism of Smoothened receptor leading to orofacial cleftingUnclassifiedUnder Development0.33KE:1821
Decrease, Cell proliferation
KE:1262
Apoptosis
KE:2040
Decrease, GLI1/2 target gene expression
AOP:465Alcohol dehydrogenase leading to reproductive dysfunctionUnclassified-0.12KE:2050
Increase, developmental abnormalities
AOP:467Knickkopf leading to mortalityUnclassified-0.11KE:2050
Increase, developmental abnormalities
AOP:478Deposition of energy leading to occurrence of cataractsNervous System Disease; Monogenic DiseaseUnder Review0.2KE:870
Increase, Cell Proliferation
KE:155
Inadequate DNA repair
AOP:479Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stressCardiovascular System Disease; Thoracic DiseaseUnder Development0.14KE:1532
Decrease, Cardiac contractility
AOP:480Mitochondrial complexes inhibition leading to heart failure via decreased ATP productionCardiovascular System Disease; Thoracic DiseaseUnder Development0.4KE:40
Decrease, Mitochondrial ATP production
KE:1532
Decrease, Cardiac contractility
AOP:492Glutathione conjugation leading to reproductive dysfunction via oxidative stressReproductive System Disease-0.2KE:1115
Increase, Reactive oxygen species
AOP:493ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesityAcquired Metabolic Disease-0.1KE:2125
Increased fat mass
AOP:495Androgen receptor activation leading to prostate cancerReproductive System Disease; Cancer-0.22KE:1183
Decreased, Apoptosis (Epithelial Cells)
KE: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:500Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosisDevelopmental Disorder Of Mental Health-0.29KE:1115
Increase, Reactive oxygen species
KE:1262
Apoptosis
AOP:517Pregnane X Receptor (PXR) activation leads to liver steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.2KE:54
Up Regulation, CD36
AOP:521Essential element imbalance leads to reproductive failure via oxidative stressUnclassified-0.14KE:1115
Increase, Reactive oxygen species
AOP:529Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.25KE:327
Accumulation, Fatty acid
KE:2224
Dysregulation of transcriptional expression within PPAR signaling network
AOP:533Retinoic acid receptor antagonism during neurodevelopment leading to impaired learning and memoryDevelopmental Disorder Of Mental Health-0.17KE:1239
Altered, Gene Expression
AOP:535Binding and activation of GPER leading to learning and memory impairmentsDevelopmental Disorder Of Mental Health-0.11KE:1262
Apoptosis
AOP:536Estrogen receptor agonism leading to reduced survival and population growth due to renal failureUnclassified-0.17KE:307
Increase, Vitellogenin synthesis in liver
AOP:537Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liverUnclassified-0.2KE:307
Increase, Vitellogenin synthesis in liver
AOP:563Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosisReproductive System Disease; Endocrine System Disease-0.17KE:1262
Apoptosis
AOP:564DBDPE-induced inhibition of mitochondrial complex Ⅰ leading to population decline via neurotoxicity and metabotoxicity.Unclassified-0.09KE:40
Decrease, Mitochondrial ATP production
AOP:569Decreased DNA methylation of FAM50B/PTCHD3 leading to IQ loss of children via PI3K-Akt pathwayDevelopmental Disorder Of Mental Health-0.17KE:1115
Increase, Reactive oxygen species

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:6Antagonist binding to PPARα leading to body-weight lossSymptomWPHA/WNT Endorsed0.12KE:864
Decreased, Body Weight
AOP:19Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)Reproductive System Disease-0.4KE:286
Altered, Transcription of genes by the androgen receptor
KE:337
N/A, Impairment of reproductive capacity
AOP:124HMG-CoA reductase inhibition leading to decreased fertilityReproductive System Disease-0.33KE:330
Decrease, Fertility
KE:807
Decreased, cholesterol
AOP:139Alkylation of DNA leading to cancer 1Cancer-0.5KE:885
Increase, Cancer
KE:155
Inadequate DNA repair
AOP:2035-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population declineReproductive System Disease-0.12KE:1141
Decreased, Reproductive Success
AOP:205AOP from chemical insult to cell deathUnclassified-0.33KE:1263
Necrosis
KE:1262
Apoptosis
AOP:261L-type calcium channel blockade leading to heart failure via decrease in cardiac contractilityCardiovascular System DiseaseUnder Development0.25KE:1532
Decrease, Cardiac contractility
KE:1535
Heart failure
AOP:293Increased DNA damage leading to increased risk of breast cancerGenetic Disease; Thoracic Disease; CancerUnder Development0.22KE:1193
N/A, Breast Cancer
KE:1182
Increase, Cell Proliferation (Epithelial Cells)
AOP:294Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancerGenetic Disease; Thoracic Disease; CancerUnder Development0.22KE:1193
N/A, Breast Cancer
KE:1182
Increase, Cell Proliferation (Epithelial Cells)
AOP:322Alkylation of DNA leading to reduced sperm countReproductive System Disease-0.4KE:1757
Reduce, Sperm count
KE:155
Inadequate DNA repair
AOP:384Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney diseaseUrinary System Disease-0.33KE:1115
Increase, Reactive oxygen species
KE:1603
Chronic kidney disease
AOP:394SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)Endocrine System DiseaseUnder Development0.14KE:1873
impaired olfactory function (anosmia)
AOP:431Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)Inherited Metabolic Disorder-0.2KE:1953
Gestational diabetes mellitus
AOP:447Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathwaysUrinary System Disease-0.08KE:759
Increased, Kidney Failure
AOP:474Succinate dehydrogenase inactivation leads to cancer by promoting EMTCancerUnder Development0.2KE:885
Increase, Cancer
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-0.25KE:1115
Increase, Reactive oxygen species
KE:2145
Metabolic syndrome
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:534Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stressCancer-0.5KE:1115
Increase, Reactive oxygen species
KE:885
Increase, Cancer
KE:1446
Decrease, Coupling of oxidative phosphorylation
AOP:539Decreased Sodium/Potassium ATPase activity leads to Heart failureCardiovascular System Disease-0.14KE:1535
Heart failure
AOP:546Succinate dehydrogenase inactivation leads to cancer through hypoxic-like mechanismsCancer-0.2KE:885
Increase, Cancer
AOP:550Increased LMNA gene mutation leading to heart failureCardiovascular System Disease-0.2KE:1535
Heart failure
AOP:552Inhibiton of L-Type Calcium Channels leading to heart failure via QT interval prolongation and Torsades de Pointes (TdP)Cardiovascular System Disease-0.17KE:1535
Heart failure
AOP:553Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failureCardiovascular System Disease-0.5KE:1532
Decrease, Cardiac contractility
KE:1535
Heart failure
AOP:555Inhibition, Ether-a-go-go (ERG) Voltage-Gated Potassium Channel leading to heart failureCardiovascular System Disease-0.2KE:1535
Heart failure
AOP:556Decreased Na/K ATPase activity leading to heart failureCardiovascular System Disease-0.33KE:1532
Decrease, Cardiac contractility
KE:1535
Heart failure
AOP:558Phosphodiesterase inhibition leading to heart failureCardiovascular System Disease-0.33KE:1532
Decrease, Cardiac contractility
KE:1535
Heart failure

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:16Acetylcholinesterase inhibition leading to acute mortalityUnclassifiedUnder Development0.14KE:12
Acetylcholinesterase (AchE) Inhibition
AOP:69Modulation of Adult Leydig Cell Function Subsequent to Decreased Cholesterol Synthesis or Transport in the Adult Leydig CellReproductive System Disease-0.2KE:642
Decreased Cholesterol, Decreased De Novo Biosynthesis of Choleseterol
AOP:118Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal System Disease-0.5KE:786
Increase, Cytotoxicity (hepatocytes)
KE:787
Increase, Regenerative cell proliferation (hepatocytes)
AOP:209Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOPGastrointestinal System Disease-0.38KE:1287
Glutathione synthesis
KE:1286
Down Regulation, GSS and GSTs gene
KE:1284
Up Regulation, SREBF2
AOP:263Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferationUnclassifiedWPHA/WNT Endorsed0.75KE:1821
Decrease, Cell proliferation
KE:1771
Decrease, Adenosine triphosphate pool
KE:1446
Decrease, Coupling of oxidative phosphorylation
AOP:264Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell deathUnclassifiedUnder Development0.5KE:1771
Decrease, Adenosine triphosphate pool
KE:1446
Decrease, Coupling of oxidative phosphorylation
AOP:265Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calciumUnclassifiedUnder Development0.25KE:1446
Decrease, Coupling of oxidative phosphorylation
AOP:266Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activityUnclassifiedUnder Development0.33KE:1771
Decrease, Adenosine triphosphate pool
KE:1446
Decrease, Coupling of oxidative phosphorylation
AOP:267Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletionUnclassifiedUnder Development0.4KE:1821
Decrease, Cell proliferation
KE:1446
Decrease, Coupling of oxidative phosphorylation
AOP:268Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swellingUnclassifiedUnder Development0.25KE:1446
Decrease, Coupling of oxidative phosphorylation
AOP:281Acetylcholinesterase Inhibition Leading to NeurodegenerationNervous System Disease-0.1KE:12
Acetylcholinesterase (AchE) Inhibition
AOP:282Adverse outcome pathway on photochemical toxicity initiated by light exposureUnclassifiedUnder Review0.25KE:1115
Increase, Reactive oxygen species
AOP:298Increase in reactive oxygen species (ROS) leading to human treatment-resistant gastric cancer via chronic ROSCancer; Gastrointestinal System DiseaseUnder Review0.33KE:1115
Increase, Reactive oxygen species
KE:1753
Chronic reactive oxygen species
AOP:312Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement​Unclassified-0.17KE:12
Acetylcholinesterase (AchE) Inhibition
AOP:324Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and cell deathUnclassified-0.25KE:1115
Increase, Reactive oxygen species
AOP:325Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and cell deathUnclassified-0.25KE:1115
Increase, Reactive oxygen species
AOP:326Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell deathUnclassified-0.25KE:1115
Increase, Reactive oxygen species
AOP:327Excessive reactive oxygen species production leading to mortality (1)Unclassified-0.2KE:1115
Increase, Reactive oxygen species
AOP:328Excessive reactive oxygen species production leading to mortality (2)Unclassified-0.4KE:1115
Increase, Reactive oxygen species
KE:1771
Decrease, Adenosine triphosphate pool
AOP:329Excessive reactive oxygen species production leading to mortality (3)Unclassified-0.4KE:1115
Increase, Reactive oxygen species
KE:1771
Decrease, Adenosine triphosphate pool
AOP:330Excessive reactive oxygen species production leading to mortality (4)Unclassified-0.2KE:1115
Increase, Reactive oxygen species
AOP:331Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and reduced cell proliferationUnclassified-0.33KE:1821
Decrease, Cell proliferation
KE:1115
Increase, Reactive oxygen species
AOP:332Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferationUnclassified-0.4KE:1821
Decrease, Cell proliferation
KE:1115
Increase, Reactive oxygen species
AOP:333Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylationUnclassified-0.8KE:1821
Decrease, Cell proliferation
KE:1115
Increase, Reactive oxygen species
KE:1771
Decrease, Adenosine triphosphate pool
KE:1446
Decrease, Coupling of oxidative phosphorylation
AOP:405Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive functionCognitive Disorder-0.2KE:12
Acetylcholinesterase (AchE) Inhibition
AOP:413Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failureUnclassified-0.67KE:1115
Increase, Reactive oxygen species
KE:926
Oxidation, Glutathione (To be considered with MIE)
KE:1607
Increase, Necrosis
KE:759
Increased, Kidney Failure
AOP:423Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathwayUnclassified-0.17KE:1115
Increase, Reactive oxygen species
AOP:438reactive oxygen species generation leading to increased cardiovascular morbidity and mortalityCardiovascular System Disease-0.17KE:1115
Increase, Reactive oxygen species
KE:1919
Increased, Cardiac Dysregulation
AOP:446PM-related Adverse outcome pathway frameworks on various systemsRespiratory System Disease-0.15KE:1115
Increase, Reactive oxygen species
KE:1262
Apoptosis
KE:1239
Altered, Gene Expression
AOP:448ROS, inflammation, and activation of nAChR lead to increased incidence of cardiovascular morbidity and mortalityCardiovascular System Disease-0.06KE:1115
Increase, Reactive oxygen species
AOP:450Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortalityNervous System Disease-0.14KE:12
Acetylcholinesterase (AchE) Inhibition
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:1115
Increase, Reactive oxygen species
AOP:463The AOP framwork on silica nanopariticles induced hepatoxicityGastrointestinal System Disease-0.18KE:1115
Increase, Reactive oxygen species
KE:1262
Apoptosis
AOP:469Reactive oxygen speicies overproduction leading to increased digestive morbidity and mortality in generation populationGastrointestinal System Disease-0.08KE:1115
Increase, Reactive oxygen species
AOP:488Increased reactive oxygen species production leading to decreased cognitive functionCognitive Disorder-0.29KE:1115
Increase, Reactive oxygen species
KE:1869
Diminished protective oxidative stress response
AOP:491Decrease, GLI1/2 target gene expression leads to orofacial cleftingUnclassifiedUnder Development0.5KE:1821
Decrease, Cell proliferation
KE:1262
Apoptosis
KE:2040
Decrease, GLI1/2 target gene expression
AOP:511The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effectsCardiovascular System Disease-0.06KE:1115
Increase, Reactive oxygen species
AOP:540Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin ProductionUnclassified-0.33KE:1115
Increase, Reactive oxygen species
KE:1262
Apoptosis
KE:285
Reduction, Vitellogenin synthesis in liver
AOP:541Excessive ROS generation leading to increased incidence of vascular calcification by VSMC phenotype switchingCardiovascular System Disease-0.08KE:1115
Increase, Reactive oxygen species
AOP:559Inhibition of acetylcholinesterase (AChE) leading to arrhythmiasSymptom-0.2KE:12
Acetylcholinesterase (AchE) Inhibition

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:472DNA adduct formation leading to kidney failureUrinary System Disease-0.22KE:1115
Increase, Reactive oxygen species
KE:759
Increased, Kidney Failure
AOP:505Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathwayCancer-0.4KE:1115
Increase, Reactive oxygen species
KE:885
Increase, Cancer
AOP:513Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathwayCancer-0.4KE:1115
Increase, Reactive oxygen species
KE:885
Increase, Cancer
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.