دورية أكاديمية
Monte Carlo Models for Sub-Chronic Repeated-Dose Toxicity: Systemic and Organ-Specific Toxicity
| العنوان: | Monte Carlo Models for Sub-Chronic Repeated-Dose Toxicity: Systemic and Organ-Specific Toxicity |
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| المؤلفون: | Gianluca Selvestrel, Giovanna J. Lavado, Alla P. Toropova, Andrey A. Toropov, Domenico Gadaleta, Marco Marzo, Diego Baderna, Emilio Benfenati |
| المصدر: | International Journal of Molecular Sciences, Vol 23, Iss 12, p 6615 (2022) |
| بيانات النشر: | MDPI AG, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | NOAEL, LOAEL, QSAR, sub-chronic repeated-dose toxicity, organ-specific toxicity, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | The risk-characterization of chemicals requires the determination of repeated-dose toxicity (RDT). This depends on two main outcomes: the no-observed-adverse-effect level (NOAEL) and the lowest-observed-adverse-effect level (LOAEL). These endpoints are fundamental requirements in several regulatory frameworks, such as the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) and the European Regulation of 1223/2009 on cosmetics. The RDT results for the safety evaluation of chemicals are undeniably important; however, the in vivo tests are time-consuming and very expensive. The in silico models can provide useful input to investigate sub-chronic RDT. Considering the complexity of these endpoints, involving variable experimental designs, this non-testing approach is challenging and attractive. Here, we built eight in silico models for the NOAEL and LOAEL predictions, focusing on systemic and organ-specific toxicity, looking into the effects on the liver, kidney and brain. Starting with the NOAEL and LOAEL data for oral sub-chronic toxicity in rats, retrieved from public databases, we developed and validated eight quantitative structure-activity relationship (QSAR) models based on the optimal descriptors calculated by the Monte Carlo method, using the CORAL software. The results obtained with these models represent a good achievement, to exploit them in a safety assessment, considering the importance of organ-related toxicity. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 1661-6596 |
| Relation: | https://www.mdpi.com/1422-0067/23/12/6615; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067 |
| DOI: | 10.3390/ijms23126615 |
| URL الوصول: | https://doaj.org/article/e6e20d0c0e044d6794d76d7c1617ee90 |
| رقم الأكسشن: | edsdoj.6e20d0c0e044d6794d76d7c1617ee90 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 16616596 |
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| DOI: | 10.3390/ijms23126615 |