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:3Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficitsNervous System DiseaseWPHA/WNT Endorsed0.29KE:188
Neuroinflammation
KE:887
Inhibition, NADH-ubiquinone oxidoreductase (complex I)
AOP:4Ecdysone receptor agonism leading to incomplete ecdysis associated mortalityUnclassified-0.1KE:993
Decrease, Abdominal muscle contraction
AOP:8Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in MammalsNervous System DiseaseUnder Development0.22KE:757
Hippocampal anatomy, Altered
KE:758
Hippocampal Physiology, Altered
AOP:10Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brainNervous System DiseaseWPHA/WNT Endorsed0.17KE:669
Reduction, Neuronal synaptic inhibition
AOP:15Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutationsGenetic DiseaseWPHA/WNT Endorsed0.25KE:155
Inadequate DNA repair
AOP:16Acetylcholinesterase inhibition leading to acute mortalityUnclassifiedUnder Development0.14KE:1703
Dysregulation of heart rate and vascular tone
AOP:18PPARα activation in utero leading to impaired fertility in malesReproductive System DiseaseUnder Review0.12KE:1690
Decrease, circulating testosterone levels
AOP:36Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to SteatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.12KE:327
Accumulation, Fatty acid
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:40Covalent Protein binding leading to Skin SensitisationIntegumentary System DiseaseWPHA/WNT Endorsed0.4KE:826
Activation, Keratinocytes
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-0.19KE:327
Accumulation, Fatty acid
KE:454
Increased, Triglyceride formation
KE:458
Increased, De Novo FA synthesis
AOP:60NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.17KE:327
Accumulation, Fatty acid
KE:454
Increased, Triglyceride formation
AOP:64Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male FertilityReproductive System Disease-0.29KE:1690
Decrease, circulating testosterone levels
KE: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: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: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:444
Increased, Atrioventricular block and bradycardia
AOP:96Axonal sodium channel modulation leading to acute mortalityUnclassified-0.33KE:602
Increased, Ataxia, paralysis, or hyperactivity
KE:600
Overactivation, Neuronotransmitter release
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:104Altered ion channel activity leading impaired heart functionUnclassified-0.25KE:699
Increased, cardiac arrthymia
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: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: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:120Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)Cancer; Reproductive System Disease-0.2KE:1690
Decrease, circulating testosterone levels
AOP:136Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal TumorsBenign Neoplasm; Respiratory System DiseaseUnder Review0.43KE:768
Increase, Cytotoxicity
KE:870
Increase, Cell Proliferation
KE:868
Increase, Tissue Degeneration, Necrosis & Atrophy
AOP:154Inhibition of Calcineurin Activity Leading to Impaired T-Cell Dependent Antibody ResponseImmune System DiseaseWPHA/WNT Endorsed0.2KE:981
Reduction, NFAT/AP-1 complex formation
AOP:160Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortalityUnclassified-0.14KE:1015
Increased, Neuronal synaptic inhibition
AOP:161Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortalityUnclassified-0.14KE:1015
Increased, Neuronal synaptic inhibition
AOP:164Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouseCancer; Reproductive System Disease-0.33KE:1043
Hypertrophy/hyperplasia, smooth muscle
KE: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 Endorsed0.38KE:68
Accumulation, Collagen
KE:1497
Increased, recruitment of inflammatory cells
KE:1496
Increased, secretion of proinflammatory mediators
AOP:1955-hydroxytryptamine transporter (5-HTT) inhibition leading to population increaseUnclassified-0.12KE:1161
Increased, oocyte maturation
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-0.38KE: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 Endorsed0.33KE:1262
Apoptosis
KE:1503
Histone acetylation, increase
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:219Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behaviorUnclassified-0.17KE:1390
Sexual behavior, decreased
AOP:241Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosisMusculoskeletal System Disease; Respiratory System Disease-0.17KE:68
Accumulation, Collagen
AOP:276Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndromeUrinary System Disease-0.17KE:887
Inhibition, NADH-ubiquinone oxidoreductase (complex I)
AOP:280α-diketone-induced bronchiolitis obliteransMusculoskeletal System Disease; Respiratory System Disease-0.14KE:149
Increase, Inflammation
AOP:288Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)Endocrine System Disease-0.12KE:1690
Decrease, circulating testosterone levels
AOP:296Oxidative DNA damage leading to chromosomal aberrations and mutationsGenetic Disease; Chromosomal DiseaseWPHA/WNT Endorsed0.2KE:155
Inadequate DNA repair
AOP:297Inhibition of retinaldehyde dehydrogenase leads to population declineUnclassifiedUnder Development0.17KE:1643
Altered, Visual function
AOP:299Deposition of energy leading to population decline via DNA oxidation and follicular atresiaUnclassified-0.14KE:1115
Increase, Reactive oxygen species
AOP:311Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosisUnclassified-0.14KE:1115
Increase, Reactive oxygen species
AOP:315Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody ResponseImmune System DiseaseUnder Development0.2KE:1716
Blockade of STAT5 phosphorylation
AOP:318Glucocorticoid Receptor activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.2KE:291
Accumulation, Triglyceride
AOP:320Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortalityUnclassifiedUnder Development0.22KE:1847
Increased SARS-CoV-2 production
KE:1496
Increased, secretion of proinflammatory mediators
AOP:321Reduced environmental pH leading to thinner shells in Mytilus edulisUnclassified-0.18KE:592
Reduced, survival
KE:10042
Abnormal development
AOP:323PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-KetotestosteroneUnclassified-0.17KE:807
Decreased, cholesterol
AOP:334Glucocorticoid Receptor Agonism Leading to Impaired Fin RegenerationUnclassified-0.33KE:2089
Altered Bone Cell Homeostasis
KE:2245
Altered Cell Differentiation Signaling
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:363Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structureUnclassifiedUnder Review0.12KE:1643
Altered, Visual function
AOP:364Thyroperoxidase inhibition leading to altered visual function via decreased eye sizeUnclassifiedUnder Development0.25KE:1643
Altered, Visual function
KE:1878
Decreased, Eye size
AOP:365Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterningUnclassifiedUnder Development0.12KE:1643
Altered, Visual function
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 Development0.5KE:188
Neuroinflammation
KE:352
N/A, Neurodegeneration
AOP:382Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosisMusculoskeletal System Disease; Respiratory System DiseaseUnder Development0.67KE:1115
Increase, Reactive oxygen species
KE:68
Accumulation, Collagen
KE:1496
Increased, secretion of proinflammatory mediators
KE:1172
Increased activation, Nuclear factor kappa B (NF-kB)
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-0.38KE:1821
Decrease, Cell proliferation
KE:1643
Altered, Visual function
KE:1878
Decreased, Eye size
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-0.33KE:1115
Increase, Reactive oxygen species
KE:1607
Increase, Necrosis
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:422Binding of SARS-CoV-2 to ACE2 in enterocytes leads to intestinal barrier disruptionGastrointestinal System DiseaseUnder Development0.2KE:1847
Increased SARS-CoV-2 production
AOP:432Deposition of Energy by Ionizing Radiation leading to Acute Myeloid LeukemiaHematopoietic System Disease; Cancer-0.27KE:870
Increase, Cell Proliferation
KE:1493
Increased Pro-inflammatory mediators
KE:155
Inadequate DNA repair
AOP:437Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicityUrinary System DiseaseUnder Development0.2KE:1392
Oxidative Stress
AOP:439Activation of the AhR leading to metastatic breast cancerThoracic Disease; CancerUnder Development0.44KE:149
Increase, Inflammation
KE:1971
Increased, tumor growth
KE:1262
Apoptosis
KE:1241
Increased, Motility
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 Development0.3KE:1554
Increase Chromosomal Aberrations
KE:155
Inadequate DNA repair
KE:1172
Increased activation, Nuclear factor kappa B (NF-kB)
AOP:444Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchabilityUnclassified-0.11KE:1392
Oxidative Stress
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:1392
Oxidative Stress
AOP:452Adverse outcome pathway of PM-induced respiratory toxicityRespiratory System Disease-0.27KE:2011
Emphysema
KE:1262
Apoptosis
KE: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-0.11KE:1512
Unfolded Protein Response
KE:1392
Oxidative Stress
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 Review0.38KE:2244
Altered Stress Response Signaling
KE:1493
Increased Pro-inflammatory mediators
KE:1392
Oxidative Stress
AOP:491Decrease, GLI1/2 target gene expression leads to orofacial cleftingUnclassifiedUnder Development0.33KE:1821
Decrease, Cell proliferation
KE:1262
Apoptosis
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-0.3KE:1497
Increased, recruitment of inflammatory cells
KE:2125
Increased fat mass
KE:2119
Insulin resistance, increased
AOP:494AhR activation leading to liver fibrosisGastrointestinal System Disease-0.17KE:265
Activation, Stellate cells
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:496Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)Unclassified-0.1KE:1690
Decrease, circulating testosterone levels
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:517Pregnane X Receptor (PXR) activation leads to liver steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.2KE:291
Accumulation, Triglyceride
AOP:518Liver X Receptor (LXR) activation leads to liver steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.4KE:291
Accumulation, Triglyceride
KE:89
Synthesis, De Novo Fatty Acid (FA)
AOP:521Essential element imbalance leads to reproductive failure via oxidative stressUnclassified-0.29KE:1115
Increase, Reactive oxygen species
KE:1392
Oxidative Stress
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:291
Accumulation, Triglyceride
AOP:539Decreased Sodium/Potassium ATPase activity leads to Heart failureCardiovascular System Disease-0.14KE:2261
Decreased, blood plasma volume
AOP:544Inhibition of neuropathy target esterase leading to delayed neuropathy via increased inflammationNervous System Disease-0.17KE:149
Increase, Inflammation
AOP:550Increased LMNA gene mutation leading to heart failureCardiovascular System Disease-0.4KE:2066
Altered Signaling Pathways
KE:1924
Increased,Cardiac fibrosis
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

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 Endorsed0.38KE:188
Neuroinflammation
KE: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 Endorsed0.4KE:1493
Increased Pro-inflammatory mediators
KE:188
Neuroinflammation
KE:341
Impairment, Learning and memory
KE:1392
Oxidative Stress
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:21Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2UnclassifiedWPHA/WNT Endorsed0.4KE:317
Altered, Cardiovascular development/function
KE:947
Increase, Early Life Stage Mortality
AOP:27Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)Gastrointestinal System DiseaseUnder Development0.38KE:357
Cholestasis, Pathology
KE:1115
Increase, Reactive oxygen species
KE:149
Increase, Inflammation
AOP:34LXR activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.23KE:291
Accumulation, Triglyceride
KE:89
Synthesis, De Novo Fatty Acid (FA)
KE:345
N/A, Liver Steatosis
AOP:37PPARα activation leading to hepatocellular adenomas and carcinomas in rodentsCancer; Gastrointestinal System DiseaseUnder Development0.4KE:719
Increase, hepatocellular adenomas and carcinomas
KE:716
Increase, cell proliferation (hepatocytes)
AOP:42Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive DisorderWPHA/WNT Endorsed0.38KE:757
Hippocampal anatomy, Altered
KE:758
Hippocampal Physiology, Altered
KE:402
Cognitive function, decreased
AOP:43Disruption of VEGFR Signaling Leading to Developmental DefectsUnclassifiedWPHA/WNT Endorsed0.4KE:28
Reduction, Angiogenesis
KE:1001
Increased, Developmental Defects
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:188
Neuroinflammation
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:91Sodium channel inhibition leading to reduced survivalUnclassified-0.17KE:592
Reduced, survival
AOP:95Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survivalUnclassified-0.17KE:592
Reduced, survival
AOP:99Histamine (H2) receptor antagonism leading to reduced survivalUnclassified-0.29KE:636
Decreased, survival
KE:341
Impairment, Learning and memory
AOP:107Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the ratCancer; Gastrointestinal System DiseaseUnder Review0.4KE:719
Increase, hepatocellular adenomas and carcinomas
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-0.33KE:768
Increase, Cytotoxicity
KE:719
Increase, hepatocellular adenomas and carcinomas
AOP:117Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal System DiseaseUnder Development0.5KE:719
Increase, hepatocellular adenomas and carcinomas
KE:716
Increase, cell proliferation (hepatocytes)
AOP:124HMG-CoA reductase inhibition leading to decreased fertilityReproductive System Disease-0.5KE:330
Decrease, Fertility
KE:1690
Decrease, circulating testosterone levels
KE:807
Decreased, cholesterol
AOP:134Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.33KE:757
Hippocampal anatomy, Altered
KE:758
Hippocampal Physiology, Altered
KE:402
Cognitive function, decreased
AOP:139Alkylation of DNA leading to cancer 1Cancer-0.5KE:885
Increase, Cancer
KE:155
Inadequate DNA repair
AOP:148EGFR Activation Leading to Decreased Lung FunctionRespiratory System DiseaseUnder Development0.25KE:1250
Decrease, Lung function
AOP:149Peptide Oxidation Leading to HypertensionCardiovascular System DiseaseUnder Development0.4KE:927
KE1 : S-Glutathionylation, eNOS
KE:937
KE7 : Impaired, Vasodilation
KE:952
Hypertension
KE: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:947
Increase, Early Life Stage Mortality
AOP:196Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary IrritationRespiratory System Disease-0.11KE:1226
Increased Respiratory irritability and Chronic Cough,
AOP:220Cyp2E1 Activation Leading to Liver CancerCancer; Gastrointestinal System DiseaseWPHA/WNT Endorsed0.8KE:1393
Hepatocytotoxicity
KE:1394
Induction, persistent proliferation/sustained proliferation
KE:1395
Liver Cancer
KE:1392
Oxidative Stress
AOP:227NSAID induced PTGS1 inactivation to gastric ulcerGastrointestinal System Disease-0.14KE:1385
Activated, gastric ulcer formation
AOP:228NSAID induced PTGS2 inactivation to gastric ulcerGastrointestinal System Disease-0.2KE:1385
Activated, gastric ulcer formation
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:242Inhibition of lysyl oxidase leading to enhanced chronic fish toxicityUnclassified-0.12KE:636
Decreased, survival
AOP:245Reduction in photophosphorylation leading to growth inhibition in aquatic plantsUnclassified-0.18KE:40
Decrease, Mitochondrial ATP production
KE:1521
Decrease, Growth
AOP:269Elevated ATP demand for detoxification and repair mechanisms leading to impaired growth and developmentUnclassified-0.17KE:10013
Impaired growth and development
AOP:270Elevated ATP demand for detoxification and repair mechanisms leading to impaired locomotor activityUnclassified-0.12KE:10016
Impaired locomotor activity
AOP:272Deposition of energy leading to lung cancerCancerWPHA/WNT Endorsed0.43KE:870
Increase, Cell Proliferation
KE:1556
Increase, lung cancer
KE:155
Inadequate DNA repair
AOP:274Histone deacetylase inhibition leads to impeded craniofacial developmentMusculoskeletal System Disease-0.5KE:1559
Facial cartilage structures are reduced in size and morphologically distorted
KE:1557
Neural crest cell migration, reduced
AOP:275Histone deacetylase inhibition leads to neural tube defectsNeural Tube Defect-0.4KE:1561
Neural tube defects
KE:1503
Histone acetylation, increase
AOP:278IKK complex inhibition leading to liver injuryUnclassified-0.12KE:1549
Liver Injury
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:352
N/A, Neurodegeneration
KE:1350
Increased, glutamate
AOP:286Mitochondrial complex III antagonism leading to growth inhibition (1)Unclassified-0.75KE:1821
Decrease, Cell proliferation
KE:1771
Decrease, Adenosine triphosphate pool
KE:1521
Decrease, Growth
AOP:287Mitochondrial complex III antagonism leading to growth inhibition (2)Unclassified-0.5KE:1771
Decrease, Adenosine triphosphate pool
KE:1521
Decrease, Growth
AOP:290Mitochondrial ATP synthase antagonism leading to growth inhibition (1)Unclassified-0.75KE:1821
Decrease, Cell proliferation
KE:1771
Decrease, Adenosine triphosphate pool
KE:1521
Decrease, Growth
AOP:291Mitochondrial ATP synthase antagonism leading to growth inhibition (2)Unclassified-0.5KE:1771
Decrease, Adenosine triphosphate pool
KE:1521
Decrease, Growth
AOP:293Increased DNA damage leading to increased risk of breast cancerGenetic Disease; Thoracic Disease; CancerUnder Development0.33KE:1493
Increased Pro-inflammatory mediators
KE: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 Development0.33KE:1493
Increased Pro-inflammatory mediators
KE:1193
N/A, Breast Cancer
KE:1182
Increase, Cell Proliferation (Epithelial Cells)
AOP:300Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive DisorderUnder Development0.6KE:757
Hippocampal anatomy, Altered
KE:758
Hippocampal Physiology, Altered
KE:402
Cognitive function, decreased
AOP:302Lung surfactant function inhibition leading to decreased lung functionRespiratory System DiseaseUnder Development0.2KE:1250
Decrease, Lung function
AOP:303Frustrated phagocytosis-induced lung cancerCancerUnder Development0.57KE:1115
Increase, Reactive oxygen species
KE:870
Increase, Cell Proliferation
KE:1497
Increased, recruitment of inflammatory cells
KE:1670
Lung cancer
AOP:304TBX1 inhibition leading to congenital cardiac conotruncal anomaliesCardiovascular System Disease-0.33KE:1682
Disruption, Progenitor cells of second heart field
KE:1685
Anomalies, Congenital cardiac conotruncal
AOP:322Alkylation of DNA leading to reduced sperm countReproductive System Disease-0.4KE:1757
Reduce, Sperm count
KE:155
Inadequate DNA repair
AOP:362Immune mediated hepatitisGastrointestinal System Disease; Immune System Disease-0.12KE:1820
Immune mediated hepatitis
AOP:379Binding to ACE2 leading to thrombosis and disseminated intravascular coagulationCardiovascular System DiseaseUnder Development0.43KE:1847
Increased SARS-CoV-2 production
KE:1869
Diminished protective oxidative stress response
KE:1846
Thrombosis and Disseminated Intravascular Coagulation
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 Development0.29KE:1847
Increased SARS-CoV-2 production
KE:1873
impaired olfactory function (anosmia)
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-0.5KE:1868
Hyperinflammation
KE:1847
Increased SARS-CoV-2 production
KE:1869
Diminished protective oxidative stress response
AOP:416Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathwayCancer-0.33KE:1115
Increase, Reactive oxygen species
KE:1670
Lung cancer
AOP:417Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathwayCancer-0.2KE:1670
Lung cancer
AOP:418Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathwayRespiratory System Disease-0.4KE:1115
Increase, Reactive oxygen species
KE:1250
Decrease, Lung function
AOP:419Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathwayRespiratory System Disease-0.5KE:1250
Decrease, Lung function
KE:1262
Apoptosis
AOP:420Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathwayCancer-0.5KE:870
Increase, Cell Proliferation
KE:1670
Lung cancer
AOP:430Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferationViral Infectious DiseaseUnder Development0.4KE:1847
Increased SARS-CoV-2 production
KE:1939
Viral infection and host-to-host transmission, proliferated
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:442Binding to voltage gate sodium channels during development leads to cognitive impairmentCognitive DisorderUnder Review0.43KE:757
Hippocampal anatomy, Altered
KE:758
Hippocampal Physiology, Altered
KE:402
Cognitive function, decreased
AOP:449Ceramide synthase inhibition leading to neural tube defectsNeural Tube Defect-0.14KE:1561
Neural tube defects
AOP:450Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortalityNervous System Disease-0.43KE:1583
Sensory axonal peripheral neuropathy
KE:352
N/A, Neurodegeneration
KE:1392
Oxidative Stress
AOP:451Interaction with lung resident cell membrane components leads to lung cancerCancer-0.56KE:870
Increase, Cell Proliferation
KE:1670
Lung cancer
KE:1496
Increased, secretion of proinflammatory mediators
KE:1115
Increase, Reactive oxygen species
KE:1497
Increased, recruitment of inflammatory cells
AOP:455Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial developmentMusculoskeletal System DiseaseUnder Review0.33KE:1559
Facial cartilage structures are reduced in size and morphologically distorted
KE:947
Increase, Early Life Stage Mortality
AOP:456Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicityUnclassifiedUnder Review0.33KE:317
Altered, Cardiovascular development/function
KE:947
Increase, Early Life Stage Mortality
AOP:457Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxineInherited Metabolic Disorder-0.33KE:2119
Insulin resistance, increased
KE:1392
Oxidative Stress
AOP:458AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.25KE:758
Hippocampal Physiology, Altered
KE:402
Cognitive function, decreased
AOP:459AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.33KE:758
Hippocampal Physiology, Altered
KE:402
Cognitive function, decreased
KE:1392
Oxidative Stress
AOP:466Doda decarboxylase leading to mortalityIntegumentary System Disease-0.11KE:2055
Increase, pigmentation
AOP:468Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)Unclassified-0.5KE:1847
Increased SARS-CoV-2 production
KE:1868
Hyperinflammation
KE:1497
Increased, recruitment of inflammatory cells
KE:1496
Increased, secretion of proinflammatory mediators
AOP:474Succinate dehydrogenase inactivation leads to cancer by promoting EMTCancerUnder Development0.2KE:885
Increase, Cancer
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 Development0.12KE:341
Impairment, Learning and memory
AOP:478Deposition of energy leading to occurrence of cataractsNervous System Disease; Monogenic DiseaseUnder Review0.4KE:870
Increase, Cell Proliferation
KE:155
Inadequate DNA repair
KE:1392
Oxidative Stress
KE:2083
Occurrence of Cataracts
AOP:479Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stressCardiovascular System Disease; Thoracic DiseaseUnder Development0.43KE:2215
Decrease Left Ventricular function
KE:2084
Increase, Cardiac remodelling
KE:1392
Oxidative Stress
AOP:480Mitochondrial complexes inhibition leading to heart failure via decreased ATP productionCardiovascular System Disease; Thoracic DiseaseUnder Development0.4KE:2215
Decrease Left Ventricular function
KE:40
Decrease, Mitochondrial ATP production
AOP:482Deposition of energy leading to occurrence of bone lossMusculoskeletal System DiseaseUnder Review0.57KE:2089
Altered Bone Cell Homeostasis
KE:2245
Altered Cell Differentiation Signaling
KE:2091
Occurrence, Bone Loss
KE:1392
Oxidative Stress
AOP:483Deposition of Energy Leading to Learning and Memory ImpairmentDevelopmental Disorder Of Mental HealthUnder Review0.38KE:2244
Altered Stress Response Signaling
KE:341
Impairment, Learning and memory
KE:1392
Oxidative Stress
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-0.45KE:2121
decreased, Intellectual Quotient
KE:758
Hippocampal Physiology, Altered
KE:188
Neuroinflammation
KE:1350
Increased, glutamate
KE:341
Impairment, Learning and memory
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-0.5KE:1115
Increase, Reactive oxygen species
KE:2145
Metabolic syndrome
KE:2119
Insulin resistance, increased
KE:1392
Oxidative Stress
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-0.5KE:2150
Neurological disorder
KE:1392
Oxidative Stress
AOP:520Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memoryDevelopmental Disorder Of Mental Health-0.2KE:341
Impairment, Learning and memory
AOP:525Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memoryDevelopmental Disorder Of Mental Health-0.15KE:2115
Altered, cholesterol metabolism
KE: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:534Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stressCancer-0.67KE:1115
Increase, Reactive oxygen species
KE:885
Increase, Cancer
KE:1446
Decrease, Coupling of oxidative phosphorylation
KE:1392
Oxidative Stress
AOP:535Binding and activation of GPER leading to learning and memory impairmentsDevelopmental Disorder Of Mental Health-0.44KE:1262
Apoptosis
KE:188
Neuroinflammation
KE:341
Impairment, Learning and memory
KE:1392
Oxidative Stress
AOP:546Succinate dehydrogenase inactivation leads to cancer through hypoxic-like mechanismsCancer-0.2KE:885
Increase, Cancer
AOP:551Increased Muscarinic M2 Receptor leading to ArrhythmiaSymptom-0.2KE:1106
Occurrence, cardiac arrhythmia
AOP:554β-adrenergic receptor agonists leading to arrhythmias.Symptom-0.25KE:1106
Occurrence, cardiac arrhythmia
AOP:559Inhibition of acetylcholinesterase (AChE) leading to arrhythmiasSymptom-0.2KE:1106
Occurrence, cardiac arrhythmia
AOP:560Inhibition of Funny current (If) leading to ArrhythmiasSymptom-0.25KE:1106
Occurrence, cardiac arrhythmia
AOP:562HCN Channel Inhibition leading to ArrhythmiasSymptom-0.2KE:1106
Occurrence, cardiac arrhythmia
AOP:569Decreased DNA methylation of FAM50B/PTCHD3 leading to IQ loss of children via PI3K-Akt pathwayDevelopmental Disorder Of Mental Health-0.5KE:2121
decreased, Intellectual Quotient
KE:1115
Increase, Reactive oxygen species
KE:2195
Increase, CNS Neural cell death
AOP:572Imidacloprid-Induced BMP4 inhibition Leading to Neural Tube Closure DefectsNeural Tube Defect-0.2KE:1561
Neural tube defects
AOP:573Inhibition, cytochrome oxidase leads to Increased, pulmonary edemaRespiratory System Disease-0.33KE:2316
Increased, pulmonary edema

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:38Protein Alkylation leading to Liver FibrosisGastrointestinal System DiseaseWPHA/WNT Endorsed0.57KE:68
Accumulation, Collagen
KE:1493
Increased Pro-inflammatory mediators
KE:265
Activation, Stellate cells
KE:244
Alkylation, Protein
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:112Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)Reproductive System Disease; Cancer-0.17KE:746
Increase, Dopaminergic activity
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:144Endocytic lysosomal uptake leading to liver fibrosisGastrointestinal System DiseaseUnder Review0.44KE:68
Accumulation, Collagen
KE:1493
Increased Pro-inflammatory mediators
KE:265
Activation, Stellate cells
KE:1539
Endocytotic lysosomal uptake
AOP:209Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOPGastrointestinal System Disease-0.5KE:1287
Glutathione synthesis
KE:1289
Perturbation of cholesterol
KE:1286
Down Regulation, GSS and GSTs gene
KE:1285
Up Regulation, Unsaturated fatty acid
AOP:258Renal protein alkylation leading to kidney toxicityUrinary System DiseaseUnder Development0.4KE:40
Decrease, Mitochondrial ATP production
KE:244
Alkylation, Protein
AOP:282Adverse outcome pathway on photochemical toxicity initiated by light exposureUnclassifiedUnder Review0.25KE:1115
Increase, Reactive oxygen species
AOP:327Excessive reactive oxygen species production leading to mortality (1)Unclassified-0.4KE:1115
Increase, Reactive oxygen species
KE:1769
Increase, Body fluid overload
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:398Decreased ALDH1A (RALDH) activity leading to decreased fertility via disrupted meiotic initiation of fetal oogoniaReproductive System DiseaseUnder Development0.33KE:1880
Decreased, ALDH1A (RALDH) enzyme activity
KE:1881
Decreased, all-trans retinoic acid (atRA) concentration
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-0.33KE:1115
Increase, Reactive oxygen species
KE:1919
Increased, Cardiac Dysregulation
KE:1924
Increased,Cardiac fibrosis
KE:1392
Oxidative Stress
AOP:446PM-related Adverse outcome pathway frameworks on various systemsRespiratory System Disease-0.4KE:1262
Apoptosis
KE:1392
Oxidative Stress
KE:149
Increase, Inflammation
KE:1496
Increased, secretion of proinflammatory mediators
KE:1115
Increase, Reactive oxygen species
KE:1250
Decrease, Lung function
KE:1497
Increased, recruitment of inflammatory cells
KE:1198
Activation, Macrophages
AOP:448ROS, inflammation, and activation of nAChR lead to increased incidence of cardiovascular morbidity and mortalityCardiovascular System Disease-0.41KE:2001
Cardiac hypertrophy
KE:1392
Oxidative Stress
KE:2002
Ventricular remodeling
KE:1443
Atherosclerosis
KE:1115
Increase, Reactive oxygen species
KE:1924
Increased,Cardiac fibrosis
KE:1198
Activation, Macrophages
AOP:453Reactive oxygen species and subsequent oxidative stress lead to increased incidence of digestive morbidity and mortality in the general populationGastrointestinal System Disease-0.31KE:1995
Abnormal lipid metabolism
KE:1115
Increase, Reactive oxygen species
KE:1198
Activation, Macrophages
KE:1392
Oxidative Stress
AOP:469Reactive oxygen speicies overproduction leading to increased digestive morbidity and mortality in generation populationGastrointestinal System Disease-0.31KE:1995
Abnormal lipid metabolism
KE:1115
Increase, Reactive oxygen species
KE:1198
Activation, Macrophages
KE:1392
Oxidative Stress
AOP:472DNA adduct formation leading to kidney failureUrinary System Disease-0.44KE:149
Increase, Inflammation
KE:1115
Increase, Reactive oxygen species
KE:1097
Occurrence, renal proximal tubular necrosis
KE:1392
Oxidative Stress
AOP:511The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effectsCardiovascular System Disease-0.12KE:1115
Increase, Reactive oxygen species
KE:1392
Oxidative Stress
AOP:530Endocytotic lysosomal uptake leads to intestinal barrier disruptionGastrointestinal System Disease-0.2KE:1539
Endocytotic lysosomal uptake
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:1392
Oxidative Stress
AOP:541Excessive ROS generation leading to increased incidence of vascular calcification by VSMC phenotype switchingCardiovascular System Disease-0.31KE:1115
Increase, Reactive oxygen species
KE:1493
Increased Pro-inflammatory mediators
KE:1198
Activation, Macrophages
KE:1392
Oxidative Stress

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:118Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal System Disease-0.75KE:719
Increase, hepatocellular adenomas and carcinomas
KE:786
Increase, Cytotoxicity (hepatocytes)
KE:787
Increase, Regenerative cell proliferation (hepatocytes)
AOP:205AOP from chemical insult to cell deathUnclassified-0.5KE:1259
narcosis
KE:1262
Apoptosis
KE:1263
Necrosis
AOP:260CYP2E1 activation and formation of protein adducts leading to neurodegenerationNervous System Disease-1.0KE:1508
CYP2E1 Activation
KE:1509
Protein Adduct Formation
KE:1392
Oxidative Stress
KE:1511
Lipid Peroxidation
KE:1512
Unfolded Protein Response
KE:1514
Neurodegeneration
KE:1513
General Apoptosis
AOP:263Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferationUnclassifiedWPHA/WNT Endorsed1.0KE:1821
Decrease, Cell proliferation
KE:1771
Decrease, Adenosine triphosphate pool
KE:1446
Decrease, Coupling of oxidative phosphorylation
KE:1521
Decrease, Growth
AOP:264Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell deathUnclassifiedUnder Development0.75KE:1771
Decrease, Adenosine triphosphate pool
KE:1446
Decrease, Coupling of oxidative phosphorylation
KE:1521
Decrease, Growth
AOP:265Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calciumUnclassifiedUnder Development0.5KE:1521
Decrease, Growth
KE:1446
Decrease, Coupling of oxidative phosphorylation
AOP:266Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activityUnclassifiedUnder Development0.5KE:1771
Decrease, Adenosine triphosphate pool
KE:1446
Decrease, Coupling of oxidative phosphorylation
KE:1521
Decrease, Growth
AOP:267Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletionUnclassifiedUnder Development0.6KE:1821
Decrease, Cell proliferation
KE:1521
Decrease, Growth
KE:1446
Decrease, Coupling of oxidative phosphorylation
AOP:268Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swellingUnclassifiedUnder Development0.5KE:1521
Decrease, Growth
KE:1446
Decrease, Coupling of oxidative phosphorylation
AOP:298Increase in reactive oxygen species (ROS) leading to human treatment-resistant gastric cancer via chronic ROSCancer; Gastrointestinal System DiseaseUnder Review0.5KE:1651
Treatment-resistant gastric cancer
KE: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-0.5KE:1115
Increase, Reactive oxygen species
KE:1521
Decrease, Growth
AOP:325Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and cell deathUnclassified-0.5KE:1115
Increase, Reactive oxygen species
KE:1521
Decrease, Growth
AOP:326Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell deathUnclassified-0.5KE:1115
Increase, Reactive oxygen species
KE:1521
Decrease, Growth
AOP:331Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and reduced cell proliferationUnclassified-0.5KE:1821
Decrease, Cell proliferation
KE:1115
Increase, Reactive oxygen species
KE:1521
Decrease, Growth
AOP:332Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferationUnclassified-0.6KE:1821
Decrease, Cell proliferation
KE:1115
Increase, Reactive oxygen species
KE:1521
Decrease, Growth
AOP:333Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylationUnclassified-1.0KE:1521
Decrease, Growth
KE:1115
Increase, Reactive oxygen species
KE:1771
Decrease, Adenosine triphosphate pool
KE:1446
Decrease, Coupling of oxidative phosphorylation
KE:1821
Decrease, Cell proliferation
AOP:392Decreased fibrinolysis and activated bradykinin system leading to hyperinflammationUnclassifiedUnder Development0.8KE:1868
Hyperinflammation
KE:1867
Bradykinin system, hyperactivated
KE:1496
Increased, secretion of proinflammatory mediators
KE:1497
Increased, recruitment of inflammatory cells
AOP:411Oxidative stress Leading to Decreased Lung FunctionRespiratory System Disease-0.5KE:1250
Decrease, Lung function
KE:1392
Oxidative Stress
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
AOP:436Inhibition of RALDH2 causes reduced all-trans retinoic acid levels, leading to transposition of the great arteriesCardiovascular System Disease-1.0KE:1880
Decreased, ALDH1A (RALDH) enzyme activity
KE:1557
Neural crest cell migration, reduced
KE:1970
transposition of the great arteries
KE:1881
Decreased, all-trans retinoic acid (atRA) concentration
KE:1682
Disruption, Progenitor cells of second heart field
AOP:463The AOP framwork on silica nanopariticles induced hepatoxicityGastrointestinal System Disease-0.45KE:1262
Apoptosis
KE:1392
Oxidative Stress
KE:149
Increase, Inflammation
KE:1115
Increase, Reactive oxygen species
KE:2034
liver dysfunction
AOP:488Increased reactive oxygen species production leading to decreased cognitive functionCognitive Disorder-0.57KE:1115
Increase, Reactive oxygen species
KE:1869
Diminished protective oxidative stress response
KE:402
Cognitive function, decreased
KE:1392
Oxidative Stress
AOP:505Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathwayCancer-1.0KE:1392
Oxidative Stress
KE:149
Increase, Inflammation
KE:1115
Increase, Reactive oxygen species
KE:885
Increase, Cancer
KE:1513
General Apoptosis
AOP:513Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathwayCancer-0.8KE:1513
General Apoptosis
KE:1115
Increase, Reactive oxygen species
KE:1060
Alteration, lipid metabolism
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.