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:16Acetylcholinesterase inhibition leading to acute mortalityUnclassifiedUnder Development0.14KE:445
Respiratory distress/arrest
AOP:21Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2UnclassifiedWPHA/WNT Endorsed0.2KE:317
Altered, Cardiovascular development/function
AOP:27Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)Gastrointestinal System DiseaseUnder Development0.25KE:149
Increase, Inflammation
KE:1115
Increase, Reactive oxygen species
AOP:37PPARα activation leading to hepatocellular adenomas and carcinomas in rodentsCancer; Gastrointestinal System DiseaseUnder Development0.2KE:716
Increase, cell proliferation (hepatocytes)
AOP:38Protein Alkylation leading to Liver FibrosisGastrointestinal System DiseaseWPHA/WNT Endorsed0.14KE:1493
Increased Pro-inflammatory mediators
AOP:39Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity ResponseRespiratory System DiseaseUnder Development0.4KE:1496
Increased, secretion of proinflammatory mediators
KE:272
Activation/Proliferation, T-cells
AOP:41Sustained AhR Activation leading to Rodent Liver TumoursCancer; Gastrointestinal System DiseaseUnder Review0.6KE:854
Alterations, Cellular proliferation / hyperplasia
KE:853
Changes/Inhibition, Cellular Homeostasis and Apoptosis
KE:139
N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects
AOP:58NR1I3 (CAR) suppression leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.06KE:454
Increased, Triglyceride formation
AOP:60NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.08KE:454
Increased, Triglyceride formation
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:77Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1Unclassified-0.14KE:341
Impairment, Learning and memory
AOP:78Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1Unclassified-0.12KE:341
Impairment, Learning and memory
AOP:87Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failureUnclassified-0.12KE:341
Impairment, Learning and memory
AOP:88Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within casteUnclassified-0.14KE:341
Impairment, Learning and memory
AOP:89Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failureUnclassified-0.12KE:341
Impairment, Learning and memory
AOP:90Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2Unclassified-0.12KE:341
Impairment, Learning and memory
AOP:94Sodium channel inhibition leading to congenital malformationsUnclassified-0.17KE:445
Respiratory distress/arrest
AOP:96Axonal sodium channel modulation leading to acute mortalityUnclassified-0.17KE:602
Increased, Ataxia, paralysis, or hyperactivity
AOP:99Histamine (H2) receptor antagonism leading to reduced survivalUnclassified-0.14KE:341
Impairment, Learning and memory
AOP:102Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transitionReproductive System Disease-0.1KE:693
Increased, cyclic adenosine monophosphate
AOP:104Altered ion channel activity leading impaired heart functionUnclassified-0.25KE:698
Altered, Action Potential
AOP:105Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)Cancer; Urinary System Disease-0.17KE:710
Increase, Regenerative cell proliferation (tubular epithelial cells)
AOP:107Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the ratCancer; Gastrointestinal System DiseaseUnder Review0.2KE:716
Increase, cell proliferation (hepatocytes)
AOP:109Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)Cancer; Respiratory System Disease-0.2KE:734
Increase, Regenerative cell proliferation (terminal bronchiolar epithelial cells)
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:113Glutamate-gated chloride channel activation leading to acute mortalityUnclassified-0.17KE:764
N/A, Ataxia, paralysis, or hyperactivity
AOP:114HPPD inhibition leading to corneal papillomas and carcinomas (in rat)Cancer-0.33KE:777
Increase, Inflammation (corneal cells)
KE:778
Increase, Regenerative cell proliferation (corneal cells)
AOP:115Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)Cancer-0.4KE:149
Increase, Inflammation
KE:781
Increase, Regenerative cell proliferation (forestomach epithelial cells)
AOP:116Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)Cancer; Urinary System Disease-0.25KE:710
Increase, Regenerative cell proliferation (tubular 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:136Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal TumorsBenign Neoplasm; Respiratory System DiseaseUnder Review0.14KE:870
Increase, Cell Proliferation
AOP:144Endocytic lysosomal uptake leading to liver fibrosisGastrointestinal System DiseaseUnder Review0.11KE:1493
Increased Pro-inflammatory mediators
AOP:150Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGFUnclassifiedWPHA/WNT Endorsed0.14KE:317
Altered, Cardiovascular development/function
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-0.14KE:1067
Proliferation/Clonal Expansion, aberrant basal cells
AOP:173Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosisMusculoskeletal System Disease; Respiratory System DiseaseWPHA/WNT Endorsed0.25KE:1497
Increased, recruitment of inflammatory cells
KE:1496
Increased, secretion of proinflammatory mediators
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-0.25KE: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:245Reduction in photophosphorylation leading to growth inhibition in aquatic plantsUnclassified-0.09KE:40
Decrease, Mitochondrial ATP production
AOP:272Deposition of energy leading to lung cancerCancerWPHA/WNT Endorsed0.29KE:870
Increase, Cell Proliferation
KE:1636
Increase, Chromosomal aberrations
AOP:276Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndromeUrinary System Disease-0.17KE:1562
Decreased Na/K ATPase activity
AOP:280α-diketone-induced bronchiolitis obliteransMusculoskeletal System Disease; Respiratory System Disease-0.14KE:149
Increase, Inflammation
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:293Increased DNA damage leading to increased risk of breast cancerGenetic Disease; Thoracic Disease; CancerUnder Development0.22KE:1493
Increased Pro-inflammatory mediators
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:1493
Increased Pro-inflammatory mediators
KE:1182
Increase, Cell Proliferation (Epithelial Cells)
AOP:299Deposition of energy leading to population decline via DNA oxidation and follicular atresiaUnclassified-0.14KE:1115
Increase, Reactive oxygen species
AOP:303Frustrated phagocytosis-induced lung cancerCancerUnder Development0.43KE:1115
Increase, Reactive oxygen species
KE:1497
Increased, recruitment of inflammatory cells
KE:870
Increase, Cell Proliferation
AOP:311Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosisUnclassified-0.14KE:1115
Increase, Reactive oxygen species
AOP:320Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortalityUnclassifiedUnder Development0.11KE:1496
Increased, secretion of proinflammatory mediators
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:362Immune mediated hepatitisGastrointestinal System Disease; Immune System Disease-0.12KE:1818
Immune cell activation
AOP:374Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on brain cells (neuronal and non-neuronal) leads to neuroinflammation resulting in encephalitisNervous System DiseaseUnder Development0.25KE:352
N/A, Neurodegeneration
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 Development0.33KE:1115
Increase, Reactive oxygen species
KE:1496
Increased, secretion of proinflammatory mediators
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:399Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)Unclassified-0.12KE:1821
Decrease, Cell proliferation
AOP:409Frustrated phagocytosis leads to malignant mesotheliomaCancer-0.5KE:1115
Increase, Reactive oxygen species
KE:870
Increase, Cell Proliferation
KE:1497
Increased, recruitment of inflammatory cells
KE:1496
Increased, secretion of proinflammatory mediators
AOP:413Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failureUnclassified-0.17KE:1115
Increase, Reactive oxygen species
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:1493
Increased Pro-inflammatory mediators
AOP:433hERG channel blockade leading to sudden cardiac deathCardiovascular System Disease-0.33KE:1962
Prolongation of QT interval
KE:1963
Torsades de Pointes
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:447Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathwaysUrinary System Disease-0.17KE:1097
Occurrence, renal proximal tubular necrosis
KE:814
Occurrence, Kidney toxicity
AOP:451Interaction with lung resident cell membrane components leads to lung cancerCancer-0.44KE:1115
Increase, Reactive oxygen species
KE:870
Increase, Cell Proliferation
KE:1497
Increased, recruitment of inflammatory cells
KE:1496
Increased, secretion of proinflammatory mediators
AOP:452Adverse outcome pathway of PM-induced respiratory toxicityRespiratory System Disease-0.09KE:1262
Apoptosis
AOP:456Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicityUnclassifiedUnder Review0.17KE:317
Altered, Cardiovascular development/function
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:389
Increased, Intracellular Calcium overload
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:470Deposition of energy leads to abnormal vascular remodelingCardiovascular System DiseaseUnder Review0.12KE:1493
Increased Pro-inflammatory mediators
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: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-0.22KE:854
Alterations, Cellular proliferation / hyperplasia
KE:1183
Decreased, Apoptosis (Epithelial Cells)
AOP:521Essential element imbalance leads to reproductive failure via oxidative stressUnclassified-0.14KE:1115
Increase, Reactive oxygen species
AOP:534Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stressCancer-0.33KE:1115
Increase, Reactive oxygen species
KE:1446
Decrease, Coupling of oxidative phosphorylation
AOP:544Inhibition of neuropathy target esterase leading to delayed neuropathy via increased inflammationNervous System Disease-0.17KE:149
Increase, Inflammation
AOP:559Inhibition of acetylcholinesterase (AChE) leading to arrhythmiasSymptom-0.2KE:698
Altered, Action Potential
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-0.33KE:1115
Increase, Reactive oxygen species
KE:2195
Increase, CNS Neural cell death

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: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 Endorsed0.25KE:341
Impairment, Learning and memory
KE:352
N/A, Neurodegeneration
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:341
Impairment, Learning and memory
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:341
Impairment, Learning and memory
AOP:19Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)Reproductive System Disease-0.2KE:337
N/A, Impairment of reproductive capacity
AOP:34LXR activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.08KE:345
N/A, Liver Steatosis
AOP:40Covalent Protein binding leading to Skin SensitisationIntegumentary System DiseaseWPHA/WNT Endorsed0.6KE:827
sensitisation, skin
KE:826
Activation, Keratinocytes
KE:272
Activation/Proliferation, T-cells
AOP:42Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive DisorderWPHA/WNT Endorsed0.12KE:402
Cognitive function, decreased
AOP:48Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.Developmental Disorder Of Mental HealthWPHA/WNT Endorsed0.33KE:389
Increased, Intracellular Calcium overload
KE:341
Impairment, Learning and memory
KE:352
N/A, Neurodegeneration
AOP:54Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairmentDevelopmental Disorder Of Mental HealthWPHA/WNT Endorsed0.1KE:341
Impairment, Learning and memory
AOP:124HMG-CoA reductase inhibition leading to decreased fertilityReproductive System Disease-0.33KE:330
Decrease, Fertility
KE:807
Decreased, cholesterol
AOP:128Kidney dysfunction by decreased thyroid hormoneUrinary System DiseaseUnder Development0.09KE:814
Occurrence, Kidney toxicity
AOP:134Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.11KE:402
Cognitive function, decreased
AOP:149Peptide Oxidation Leading to HypertensionCardiovascular System DiseaseUnder Development0.2KE:952
Hypertension
KE:933
KE6 : Depletion, Nitric Oxide
AOP:196Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary IrritationRespiratory System Disease-0.11KE:1226
Increased Respiratory irritability and Chronic Cough,
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-0.17KE:1262
Apoptosis
AOP:220Cyp2E1 Activation Leading to Liver CancerCancer; Gastrointestinal System DiseaseWPHA/WNT Endorsed0.6KE:1393
Hepatocytotoxicity
KE:1394
Induction, persistent proliferation/sustained proliferation
KE:1395
Liver Cancer
AOP:237Substance interaction with lung resident cell membrane components leading to atherosclerosisCardiovascular System DiseaseUnder Development0.4KE:1443
Atherosclerosis
KE:1496
Increased, secretion of proinflammatory mediators
AOP:256Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicityUrinary System DiseaseUnder Development0.2KE:814
Occurrence, Kidney toxicity
AOP:257Receptor mediated endocytosis and lysosomal overload leading to kidney toxicityUrinary System DiseaseUnder Development0.2KE:814
Occurrence, Kidney toxicity
AOP:258Renal protein alkylation leading to kidney toxicityUrinary System DiseaseUnder Development0.4KE:40
Decrease, Mitochondrial ATP production
KE:814
Occurrence, Kidney toxicity
AOP:260CYP2E1 activation and formation of protein adducts leading to neurodegenerationNervous System Disease-0.14KE:1514
Neurodegeneration
AOP:270Elevated ATP demand for detoxification and repair mechanisms leading to impaired locomotor activityUnclassified-0.12KE:10016
Impaired locomotor activity
AOP:279Microtubule interacting drugs lead to peripheral neuropathyNervous System Disease-0.25KE:1583
Sensory axonal peripheral neuropathy
AOP:281Acetylcholinesterase Inhibition Leading to NeurodegenerationNervous System Disease-0.2KE:389
Increased, Intracellular Calcium overload
KE:352
N/A, Neurodegeneration
AOP:296Oxidative DNA damage leading to chromosomal aberrations and mutationsGenetic Disease; Chromosomal DiseaseWPHA/WNT Endorsed0.2KE:1636
Increase, Chromosomal aberrations
AOP:300Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive DisorderUnder Development0.2KE:402
Cognitive function, decreased
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:392Decreased fibrinolysis and activated bradykinin system leading to hyperinflammationUnclassifiedUnder Development0.6KE:1868
Hyperinflammation
KE:1497
Increased, recruitment of inflammatory cells
KE:1496
Increased, secretion of proinflammatory mediators
AOP:405Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive functionCognitive Disorder-0.2KE:402
Cognitive function, decreased
AOP:406SARS-CoV-2 infection leading to hyperinflammationUnclassified-0.33KE:1868
Hyperinflammation
KE:1869
Diminished protective oxidative stress response
AOP:431Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)Inherited Metabolic Disorder-0.4KE:1953
Gestational diabetes mellitus
KE:1952
Abnormal, Glucose homeostasis
AOP:437Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicityUrinary System DiseaseUnder Development0.2KE:814
Occurrence, Kidney toxicity
AOP:442Binding to voltage gate sodium channels during development leads to cognitive impairmentCognitive DisorderUnder Review0.14KE:402
Cognitive function, decreased
AOP:450Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortalityNervous System Disease-0.29KE:1583
Sensory axonal peripheral neuropathy
KE:352
N/A, Neurodegeneration
AOP:457Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxineInherited Metabolic Disorder-0.17KE:2119
Insulin resistance, increased
AOP:458AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.12KE:402
Cognitive function, decreased
AOP:459AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.11KE:402
Cognitive function, decreased
AOP:468Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)Unclassified-0.38KE:1868
Hyperinflammation
KE:1497
Increased, recruitment of inflammatory cells
KE:1496
Increased, secretion of proinflammatory mediators
AOP:475Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neuronsDevelopmental Disorder Of Mental HealthUnder Development0.25KE:389
Increased, Intracellular Calcium overload
KE:341
Impairment, Learning and memory
AOP:478Deposition of energy leading to occurrence of cataractsNervous System Disease; Monogenic DiseaseUnder Review0.3KE:870
Increase, Cell Proliferation
KE:1636
Increase, Chromosomal aberrations
KE:2083
Occurrence of Cataracts
AOP:483Deposition of Energy Leading to Learning and Memory ImpairmentDevelopmental Disorder Of Mental HealthUnder Review0.12KE:341
Impairment, Learning and memory
AOP:485Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognitionCognitive Disorder-0.14KE:402
Cognitive function, decreased
AOP:486Binding to the extracellular protein laminin leading to decreased cognitive functionCognitive Disorder-0.14KE:402
Cognitive function, decreased
AOP:490Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanismsDevelopmental Disorder Of Mental Health-0.09KE:341
Impairment, Learning and memory
AOP:493ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesityAcquired Metabolic Disease-0.4KE:2129
Metabolically unhealthy Obesity
KE:1497
Increased, recruitment of inflammatory cells
KE:2125
Increased fat mass
KE:2119
Insulin resistance, increased
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-0.38KE:1115
Increase, Reactive oxygen species
KE:2145
Metabolic syndrome
KE:2119
Insulin resistance, increased
AOP:498Increased LCN2/iron complex leading to neurological disordersNervous System Disease-0.5KE:191
Neuronal dysfunction
KE:2150
Neurological disorder
AOP:499Activation of MEK-ERK1/2 leads to deficits in learning and cognition via disrupted neurotransmitter releaseDevelopmental Disorder Of Mental Health-0.25KE:341
Impairment, Learning and memory
AOP:500Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosisDevelopmental Disorder Of Mental Health-0.57KE:1115
Increase, Reactive oxygen species
KE:1262
Apoptosis
KE:341
Impairment, Learning and memory
KE:352
N/A, Neurodegeneration
AOP:501Excessive iron accumulation leading to neurological disordersNervous System Disease-0.25KE:2150
Neurological disorder
AOP:520Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memoryDevelopmental Disorder Of Mental Health-0.4KE:2204
Altered brain morphology
KE:341
Impairment, Learning and memory
AOP:525Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memoryDevelopmental Disorder Of Mental Health-0.08KE:341
Impairment, Learning and memory
AOP:532Retinoic acid receptor agonism during cerebellar development leading to impaired locomotor functionUnclassified-0.2KE:2231
Locomotor function. Impaired
AOP:533Retinoic acid receptor antagonism during neurodevelopment leading to impaired learning and memoryDevelopmental Disorder Of Mental Health-0.17KE:341
Impairment, Learning and memory
AOP:535Binding and activation of GPER leading to learning and memory impairmentsDevelopmental Disorder Of Mental Health-0.33KE:389
Increased, Intracellular Calcium overload
KE:341
Impairment, Learning and memory
KE:1262
Apoptosis
AOP:550Increased LMNA gene mutation leading to heart failureCardiovascular System Disease-0.2KE:1535
Heart failure
AOP:553Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failureCardiovascular System Disease-0.75KE:698
Altered, Action Potential
KE: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-0.4KE:1962
Prolongation of QT interval
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:62AKT2 activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.25KE:486
systemic inflammation leading to hepatic steatosis
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:121Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)Cancer; Urinary System Disease-0.4KE:795
Increase, Regenerative cell proliferation (urothelial cells)
KE:793
Increase, Urinary bladder calculi
AOP:209Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOPGastrointestinal System Disease-0.25KE:1287
Glutathione synthesis
KE:1286
Down Regulation, GSS and GSTs gene
AOP:263Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferationUnclassifiedWPHA/WNT Endorsed0.5KE:1821
Decrease, Cell proliferation
KE:1446
Decrease, Coupling of oxidative phosphorylation
AOP:264Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell deathUnclassifiedUnder Development0.25KE: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:1562
Decreased Na/K ATPase activity
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: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: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-0.2KE:1115
Increase, Reactive oxygen species
AOP:329Excessive reactive oxygen species production leading to mortality (3)Unclassified-0.2KE:1115
Increase, Reactive oxygen species
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-0.6KE:1821
Decrease, Cell proliferation
KE:1115
Increase, Reactive oxygen species
KE:1446
Decrease, Coupling of oxidative phosphorylation
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-0.08KE:1115
Increase, Reactive oxygen species
AOP:446PM-related Adverse outcome pathway frameworks on various systemsRespiratory System Disease-0.25KE:1262
Apoptosis
KE:149
Increase, Inflammation
KE:1496
Increased, secretion of proinflammatory mediators
KE:1115
Increase, Reactive oxygen species
KE:1497
Increased, recruitment of inflammatory cells
AOP:448ROS, inflammation, and activation of nAChR lead to increased incidence of cardiovascular morbidity and mortalityCardiovascular System Disease-0.12KE:1443
Atherosclerosis
KE:1115
Increase, Reactive oxygen species
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-0.27KE:149
Increase, Inflammation
KE: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:472DNA adduct formation leading to kidney failureUrinary System Disease-0.44KE:149
Increase, Inflammation
KE:1816
Mitochondrial dysfunction EMPTY
KE:1115
Increase, Reactive oxygen species
KE:1097
Occurrence, renal proximal tubular necrosis
AOP:492Glutathione conjugation leading to reproductive dysfunction via oxidative stressReproductive System Disease-0.4KE:1115
Increase, Reactive oxygen species
KE:2131
Conjugation, GSH
AOP:505Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathwayCancer-0.4KE:149
Increase, Inflammation
KE:1115
Increase, Reactive oxygen species
AOP:511The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effectsCardiovascular System Disease-0.06KE:1115
Increase, Reactive oxygen species
AOP:513Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathwayCancer-0.2KE:1115
Increase, Reactive oxygen species
AOP:540Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin ProductionUnclassified-0.22KE:1115
Increase, Reactive oxygen species
KE:1262
Apoptosis
AOP:541Excessive ROS generation leading to increased incidence of vascular calcification by VSMC phenotype switchingCardiovascular System Disease-0.23KE:1115
Increase, Reactive oxygen species
KE:1493
Increased Pro-inflammatory mediators
KE:1816
Mitochondrial dysfunction EMPTY

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:261L-type calcium channel blockade leading to heart failure via decrease in cardiac contractilityCardiovascular System DiseaseUnder Development0.38KE:1529
Blockade, L-Type Calcium Channels
KE:1532
Decrease, Cardiac contractility
KE:1535
Heart failure
AOP:488Increased reactive oxygen species production leading to decreased cognitive functionCognitive Disorder-0.43KE:1115
Increase, Reactive oxygen species
KE:1869
Diminished protective oxidative stress response
KE:402
Cognitive function, decreased
AOP:539Decreased Sodium/Potassium ATPase activity leads to Heart failureCardiovascular System Disease-0.29KE:1562
Decreased Na/K ATPase activity
KE: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-1.0KE:698
Altered, Action Potential
KE:2281
Increased uncoordinated cardiac contraction
KE:1529
Blockade, L-Type Calcium Channels
KE:1963
Torsades de Pointes
KE:1535
Heart failure
KE:1962
Prolongation of QT interval
AOP:556Decreased Na/K ATPase activity leading to heart failureCardiovascular System Disease-1.0KE:389
Increased, Intracellular Calcium overload
KE:1532
Decrease, Cardiac contractility
KE:1321
Increased, intracellular sodium (Na+)
KE:1562
Decreased Na/K ATPase activity
KE:2287
Impaired Sodium-Calcium Exchange
KE:1535
Heart failure
AOP:558Phosphodiesterase inhibition leading to heart failureCardiovascular System Disease-1.0KE:389
Increased, Intracellular Calcium overload
KE:1532
Decrease, Cardiac contractility
KE:2289
Hyperphosphorylation of ryanodine receptor (RyR2)
KE:2288
Phosphodiesterase inhibition
KE:1535
Heart failure
KE:693
Increased, cyclic adenosine monophosphate
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.