Monte Carlo Models for Sub-Chronic Repeated-Dose Toxicity: Systemic and Organ-Specific Toxicity.
Int J Mol Sci
; 23(12)2022 Jun 14.
Article
em En
| MEDLINE
| ID: mdl-35743059
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Software
/
Relação Quantitativa Estrutura-Atividade
Tipo de estudo:
Health_economic_evaluation
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article