Lamotrigine


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:7Aromatase (Cyp19a1) reduction leading to impaired fertility in adult femaleReproductive system disease; Endocrine system disease; Reproductive system diseaseUnder ReviewRat, Mouse, Human0.2KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:18PPARα activation in utero leading to impaired fertility in malesReproductive system diseaseUnder ReviewHuman, Rat, Mouse0.12KE:1690Decrease, circulating testosterone levels
AOP:23Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)UnclassifiedWPHA/WNT EndorsedPimephales promelas0.1KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:25Aromatase inhibition leading to reproductive dysfunctionUnclassifiedWPHA/WNT EndorsedFathead minnow, Medaka, Zebrafish0.12KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:41Sustained AhR Activation leading to Rodent Liver TumoursCancer; Gastrointestinal system diseaseUnder ReviewRattus sp. ABTC 42503, Mus sp. 20000820.2KE:139N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects
AOP:64Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male FertilityReproductive system disease-Rattus norvegicus0.14KE:1690Decrease, circulating testosterone levels
AOP:120Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)Cancer; Reproductive system disease-Rattus norvegicus, Mus musculus0.2KE:1690Decrease, circulating testosterone levels
AOP:122Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formationUnclassified-Pimephales promelas0.1KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:123Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcriptionUnclassified-Pimephales promelas0.09KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:124HMG-CoA reductase inhibition leading to decreased fertilityReproductive system disease-Rattus rattus0.17KE:1690Decrease, circulating testosterone levels
AOP:288Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)Endocrine system disease-Human, Rat0.12KE:1690Decrease, circulating testosterone levels
AOP:310Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHRUnclassified-Zebrafish0.08KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:346Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiationUnclassifiedWPHA/WNT EndorsedZebrafish, Oreochromis niloticus, Chinook salmon, Fathead minnow, European sea bass0.2KE:1789Reduction, 17beta-estradiol synthesis by the undifferentiated gonad
AOP:496Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）Unclassified-Zebrafish0.1KE:1690Decrease, circulating testosterone levels
AOP:540Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin ProductionUnclassified-0.11KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells

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:40Covalent Protein binding leading to Skin SensitisationIntegumentary system diseaseWPHA/WNT EndorsedMouse, Human0.2KE:827sensitisation, skin
AOP:220Cyp2E1 Activation Leading to Liver CancerCancer; Gastrointestinal system diseaseWPHA/WNT EndorsedRodents, Homo sapiens0.4KE:1395Liver Cancer
KE:1393Hepatocytotoxicity
AOP:278IKK complex inhibition leading to liver injuryUnclassified-0.12KE:1549Liver Injury
AOP:498Increased LCN2/iron complex leading to neurological disordersNervous system disease-Homo sapiens0.25KE:2150Neurological disorder
AOP:501Excessive iron accumulation leading to neurological disordersNervous system disease-Homo sapiens0.25KE:2150Neurological disorder

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:118Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal system disease-Mus musculus, Rattus norvegicus0.25KE:786Increase, Cytotoxicity (hepatocytes)

No associated AOPs with Level of Relevance 5
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