Validation of the performance of TIMES genotoxicity models with EFSA pesticide data
| العنوان: | Validation of the performance of TIMES genotoxicity models with EFSA pesticide data |
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| المؤلفون: | Ovanes G. Mekenyan, Takashi Yamada, Elena Kaloyanova, Petko I. Petkov, Masamitsu Honma, Terry W Schultz |
| المصدر: | Mutagenesis. 34:83-90 |
| بيانات النشر: | Oxford University Press (OUP), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Food Safety, Databases, Factual, Health, Toxicology and Mutagenesis, Biology, Toxicology, medicine.disease_cause, Mice, 03 medical and health sciences, Genetics, medicine, Animals, Tissue metabolism, Food science, Pesticides, Genetics (clinical), 030304 developmental biology, Chromosome Aberrations, 0303 health sciences, Micronucleus Tests, Mutagenicity Tests, Mouse Lymphoma, 030311 toxicology, Pesticide, Micronucleus test, Carcinogens, Genotoxicity, DNA Damage |
| الوصف: | This study validates the performance of the TIssue MEtabolism Simulator (TIMES) genotoxicity models with data on pesticide chemicals included in a recently released European Food Safety Authority (EFSA) genotoxicity database. The EFSA database is biased towards negative chemicals. A comparison of substances included in the EFSA database and TIMES genotoxicity databases showed that the majority of the EFSA pesticides is not included in the TIMES genotoxicity databases and, thus, out of the applicability domains of the current TIMES models. However, the EFSA genotoxicity database provides an opportunity to expand the TIMES models. Where there is overlap of substances, consistency between EFSA and TIMES databases for the chemicals with documented data is found to be high (>80%) with respect to the Ames data and lower than the Ames data with respect to chromosomal aberration (CA) and mouse lymphoma assay (MLA) data. No conclusion for consistency with respect to micronucleus test and comet genotoxicity data can be provided due to the limited number of overlapping substances. Specificity of the models is important, given the prevalence of negative genotoxicity data in the EFSA database. High specificity (>80%) is obtained for prediction of the EFSA pesticides with Ames data. Moreover, this high specificity of the TIMES Ames models is not dependant on pesticides being within the domains. Specificity of the TIMES CA and MLA models is lower (>40%) to pesticides for out of domain. Sensitivity of TIMES in vitro and in vivo models cannot be properly estimated due to the small number of positive chemicals in the EFSA database. |
| تدمد: | 1464-3804 0267-8357 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6cdeb9fbce4bf4f1c1a8dbf6c1c9bc38 https://doi.org/10.1093/mutage/gey035 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....6cdeb9fbce4bf4f1c1a8dbf6c1c9bc38 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14643804 02678357 |
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