دورية أكاديمية
Scientific Opinion of the Scientific Panel on Plant Protection Products and their Residues (PPR Panel) on testing and interpretation of comparative in vitro metabolism studies
| العنوان: | Scientific Opinion of the Scientific Panel on Plant Protection Products and their Residues (PPR Panel) on testing and interpretation of comparative in vitro metabolism studies |
|---|---|
| المؤلفون: | EFSA Panel on Plant Protection Products and their Residues (EFSA PPR Panel), Antonio F Hernandez‐Jerez, Paulien Adriaanse, Annette Aldrich, Philippe Berny, Tamara Coja, Sabine Duquesne, Andreas Focks, Marina Marinovich, Maurice Millet, Olavi Pelkonen, Silvia Pieper, Aaldrik Tiktak, Christopher J Topping, Anneli Widenfalk, Martin Wilks, Gerrit Wolterink, Ursula Gundert‐Remy, Jochem Louisse, Serge Rudaz, Emanuela Testai, Alfonso Lostia, Jean‐Lou Dorne, Juan Manuel Parra Morte |
| المصدر: | EFSA Journal, Vol 19, Iss 12, Pp n/a-n/a (2021) |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Nutrition. Foods and food supply LCC:Chemical technology |
| مصطلحات موضوعية: | xenobiotic, reactive metabolites, interspecies metabolism, suspension/plated hepatocytes, clearance, PBK, Nutrition. Foods and food supply, TX341-641, Chemical technology, TP1-1185 |
| الوصف: | Abstract EFSA asked the Panel on Plant Protection Products and their residues to deliver a Scientific Opinion on testing and interpretation of comparative in vitro metabolism studies for both new active substances and existing ones. The main aim of comparative in vitro metabolism studies of pesticide active substances is to evaluate whether all significant metabolites formed in the human in vitro test system, as a surrogate of the in vivo situation, are also present at comparable level in animal species tested in toxicological studies and, therefore, if their potential toxicity has been appropriately covered by animal studies. The studies may also help to decide which animal model, with regard to a particular compound, is the most relevant for humans. In the experimental strategy, primary hepatocytes in suspension or culture are recommended since hepatocytes are considered the most representative in vitro system for prediction of in vivo metabolites. The experimental design of 3 × 3 × 3 (concentrations, time points, technical replicates, on pooled hepatocytes) will maximise the chance to identify unique (UHM) and disproportionate (DHM) human metabolites. When DHM and UHM are being assessed, test item‐related radioactivity recovery and metabolite profile are the most important parameters. Subsequently, structural characterisation of the assigned metabolites is performed with appropriate analytical techniques. In toxicological assessment of metabolites, the uncertainty factor approach is the first alternative to testing option, followed by new approach methodologies (QSAR, read‐across, in vitro methods), and only if these fail, in vivo animal toxicity studies may be performed. Knowledge of in vitro metabolites in human and animal hepatocytes would enable toxicological evaluation of all metabolites of concern, and, furthermore, add useful pieces of information for detection and evaluation of metabolites in different matrices (crops, livestock, environment), improve biomonitoring efforts via better toxicokinetic understanding, and ultimately, develop regulatory schemes employing physiologically based or physiology‐mimicking in silico and/or in vitro test systems to anticipate the exposure of humans to potentially hazardous substances in plant protection products. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1831-4732 |
| Relation: | https://doaj.org/toc/1831-4732 |
| DOI: | 10.2903/j.efsa.2021.6970 |
| URL الوصول: | https://doaj.org/article/8a45cbb641404c6b8e714a9e89daa8c1 |
| رقم الأكسشن: | edsdoj.8a45cbb641404c6b8e714a9e89daa8c1 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 18314732 |
|---|---|
| DOI: | 10.2903/j.efsa.2021.6970 |