Topiramate


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 Taxonomic applicability Coverage Score ⓘ The fraction of KEs within the AOP, that are mapped to the chemical-associated toxicological endpoints. KE Identifier KE Name
AOP:4Ecdysone receptor agonism leading to incomplete ecdysis associated mortalityUnclassified-Insects, Crustaceans0.1KE:1268Decrease, Excitatory postsynaptic potential
AOP:10Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brainNervous system diseaseWPHA/WNT EndorsedHuman, Mouse, Rat, Bobwhite quail, Zebrafish0.17KE:682Generation, Amplified excitatory postsynaptic potential (EPSP)
AOP:37PPARα activation leading to hepatocellular adenomas and carcinomas in rodentsCancer; Gastrointestinal system diseaseUnder DevelopmentMouse, Rat0.2KE:716Increase, cell proliferation (hepatocytes)
AOP:39Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity ResponseRespiratory system diseaseUnder DevelopmentHuman, Mouse0.2KE:272Activation/Proliferation, T-cells
AOP:40Covalent Protein binding leading to Skin SensitisationIntegumentary system diseaseWPHA/WNT EndorsedMouse, Human0.2KE:272Activation/Proliferation, T-cells
AOP:41Sustained AhR Activation leading to Rodent Liver TumoursCancer; Gastrointestinal system diseaseUnder ReviewRattus sp. ABTC 42503, Mus sp. 20000820.2KE:854Alterations, Cellular proliferation / hyperplasia
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 EndorsedHuman, Mouse, Rat0.11KE:352N/A, Neurodegeneration
AOP:105Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)Cancer; Urinary system disease-Rattus norvegicus0.17KE:710Increase, 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 ReviewRattus norvegicus, Mus musculus0.2KE:716Increase, cell proliferation (hepatocytes)
AOP:109Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)Cancer; Respiratory system disease-Mus musculus0.2KE:734Increase, 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-Rattus norvegicus, Mus musculus0.14KE:739Increase, Hypertrophy and proliferation (follicular cell)
AOP:112Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)Reproductive system disease; Cancer-Rattus norvegicus0.17KE:749Decreased, Progesterone from corpus luteum
AOP:114HPPD inhibition leading to corneal papillomas and carcinomas (in rat)Cancer-Rattus norvegicus0.17KE:778Increase, Regenerative cell proliferation (corneal cells)
AOP:115Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)Cancer-Mus musculus, Rattus norvegicus0.2KE:781Increase, Regenerative cell proliferation (forestomach epithelial cells)
AOP:116Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)Cancer; Urinary system disease-Rattus norvegicus0.25KE:710Increase, Regenerative cell proliferation (tubular epithelial cells)
AOP:117Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal system diseaseUnder DevelopmentMus musculus, Rattus norvegicus0.25KE:716Increase, cell proliferation (hepatocytes)
AOP:118Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal system disease-Mus musculus, Rattus norvegicus0.25KE:787Increase, Regenerative cell proliferation (hepatocytes)
AOP:119Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)Cancer; Endocrine system disease-Rattus norvegicus, Mus musculus0.14KE:739Increase, Hypertrophy and proliferation (follicular cell)
AOP:121Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)Cancer; Urinary system disease-Mus musculus, Rattus norvegicus0.2KE:795Increase, Regenerative cell proliferation (urothelial cells)
AOP:136Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal TumorsBenign neoplasm; Respiratory system diseaseUnder Review0.14KE:870Increase, Cell Proliferation
AOP:149Peptide Oxidation Leading to HypertensionCardiovascular system diseaseUnder DevelopmentHuman, Mouse, Rat, Cow0.1KE:937KE7 : Impaired, Vasodilation
AOP:164Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouseCancer; Reproductive system disease-CD-1 mouse, SD rat0.17KE:1042Proliferation/Clonal Expansion, smooth muscle
AOP:167Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.Reproductive system disease; Cancer-Mouse, Homo sapiens0.14KE:1067Proliferation/Clonal Expansion, aberrant basal cells
AOP:263Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferationUnclassifiedWPHA/WNT EndorsedZebrafish, Mouse, Rat, Lemna minor, Human, Caenorhabditis elegans0.25KE:1821Decrease, Cell proliferation
AOP:267Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletionUnclassifiedUnder Development0.2KE:1821Decrease, Cell proliferation
AOP:272Deposition of energy leading to lung cancerCancerWPHA/WNT EndorsedHuman, Rat, Mouse0.14KE:870Increase, Cell Proliferation
AOP:286Mitochondrial complex III antagonism leading to growth inhibition (1)Unclassified-Lemna minor, Daphnia magna, Danio rerio0.25KE:1821Decrease, Cell proliferation
AOP:290Mitochondrial ATP synthase antagonism leading to growth inhibition (1)Unclassified-Daphnia magna0.25KE:1821Decrease, Cell proliferation
AOP:293Increased DNA damage leading to increased risk of breast cancerGenetic disease; Thoracic disease; CancerUnder DevelopmentRattus rattus, Mus musculus0.11KE:1182Increase, Cell Proliferation (Epithelial Cells)
AOP:294Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancerGenetic disease; Thoracic disease; CancerUnder Development0.11KE:1182Increase, Cell Proliferation (Epithelial Cells)
AOP:303Frustrated phagocytosis-induced lung cancerCancerUnder DevelopmentMammals0.14KE:870Increase, Cell Proliferation
AOP:309Luteinizing hormone receptor antagonism leading to reproductive dysfunctionUnclassified-Fish0.29KE:1693Reduction, Plasma progesterone concentration
KE:1692Reduction, Progesterone synthesis
AOP:327Excessive reactive oxygen species production leading to mortality (1)Unclassified-Daphnia magna0.2KE:1769Increase, Body fluid overload
AOP:331Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and reduced cell proliferationUnclassified-Daphnia magna, Daphnia middendorffiana, Daphnia pulex, Daphnia pulicaria, Daphnia parvula0.17KE:1821Decrease, Cell proliferation
AOP:332Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferationUnclassified-0.2KE:1821Decrease, Cell proliferation
AOP:333Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylationUnclassified-0.2KE:1821Decrease, Cell proliferation
AOP:335AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairmentCancer; Urinary system disease-Rat0.2KE:795Increase, Regenerative cell proliferation (urothelial cells)
AOP:349Inhibition of 11β-hydroxylase leading to decresed population trajectoryUnclassifiedUnder DevelopmentFish0.25KE:1835Cortisol and 11β-(OH) testosterone decreased
KE:1836Decreased plasma Cortisol level
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 DevelopmentHuman0.25KE:352N/A, Neurodegeneration
AOP:399Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)Unclassified-Zebrafish0.12KE:1821Decrease, Cell proliferation
AOP:409Frustrated phagocytosis leads to malignant mesotheliomaCancer-0.12KE:870Increase, Cell Proliferation
AOP:420Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathwayCancer-0.25KE:870Increase, Cell Proliferation
AOP:432Deposition of Energy by Ionizing Radiation leading to Acute Myeloid LeukemiaHematopoietic system disease; Cancer-Homo sapiens, Mus musculus0.09KE:870Increase, Cell Proliferation
AOP:450Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortalityNervous system disease-Rattus norvegicus, Mus musculus, Homo sapiens0.14KE:352N/A, Neurodegeneration
AOP:451Interaction with lung resident cell membrane components leads to lung cancerCancer-Human0.11KE:870Increase, Cell Proliferation
AOP:460Antagonism of Smoothened receptor leading to orofacial cleftingUnclassifiedUnder DevelopmentMouse0.11KE:1821Decrease, Cell proliferation
AOP:478Deposition of energy leading to occurrence of cataractsNervous system disease; Monogenic diseaseUnder ReviewHuman, Mouse, Rat, Rhesus monkeys, Rabbit, Guinea pig0.1KE:870Increase, Cell Proliferation
AOP:491Decrease, GLI1/2 target gene expression leads to orofacial cleftingUnclassifiedUnder DevelopmentMouse0.17KE:1821Decrease, Cell proliferation
AOP:495Androgen receptor activation leading to prostate cancerReproductive system disease; Cancer-0.11KE:854Alterations, Cellular proliferation / hyperplasia
AOP:498Increased LCN2/iron complex leading to neurological disordersNervous system disease-Homo sapiens0.25KE:191Neuronal dysfunction
AOP:500Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosisDevelopmental disorder of mental health-Rattus norvegicus, Mus musculus, Homo sapiens0.14KE:352N/A, Neurodegeneration
AOP:569Decreased DNA methylation of FAM50B/PTCHD3 leading to IQ loss of children via PI3K-Akt pathwayDevelopmental disorder of mental health-0.17KE:2195Increase, 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 Taxonomic applicability Coverage Score ⓘ The fraction of KEs within the AOP, that are mapped to the chemical-associated toxicological endpoints. KE Identifier KE Name
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 EndorsedMonkey, Rat, Human, Mouse, Zebrafish0.12KE:352N/A, Neurodegeneration
AOP:220Cyp2E1 Activation Leading to Liver CancerCancer; Gastrointestinal system diseaseWPHA/WNT EndorsedRodents, Homo sapiens0.2KE:1395Liver Cancer
AOP:260CYP2E1 activation and formation of protein adducts leading to neurodegenerationNervous system disease-Human0.14KE:1514Neurodegeneration
AOP:281Acetylcholinesterase Inhibition Leading to NeurodegenerationNervous system disease-0.1KE:352N/A, Neurodegeneration
AOP:463The AOP framwork on silica nanopariticles induced hepatoxicityGastrointestinal system disease-0.09KE:2034liver dysfunction

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 Taxonomic applicability Coverage Score ⓘ The fraction of KEs within the AOP, that are mapped to the chemical-associated toxicological endpoints. KE Identifier KE Name
AOP:392Decreased fibrinolysis and activated bradykinin system leading to hyperinflammationUnclassifiedUnder DevelopmentHumans0.2KE:1867Bradykinin system, hyperactivated

No associated AOPs with Level of Relevance 5
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