基于计算毒理学的遗传毒性评价研究进展

Research Progress of Genotoxicity Assessment Based on Computational Toxicology

计算毒理学是一种使用计算方法分析、模拟、可视化或预测化学品毒性的毒性评估方法,在时间、成本和动物福利方面具有明显优势。近年来,使用计算工具预测遗传毒性正受到监管机构更多的关注,ICH M7指南表明在药品监管中认可应用(Q)SAR模型预测药物杂质的Ames致突变性。本文讨论了经典的遗传毒性计算评估方法及其原理,总结目前常用的遗传毒性评价模型及模型的构建现状,回顾计算毒理学在药物杂质、纳米材料和化妆品成分的遗传毒性评价中的应用,旨在为评价遗传毒性的计算模型的构建和优化提供一定参考,进一步促进计算毒理学在国家遗传毒性监管中的应用。

Computational toxicology,a toxicity assessment method that uses computational methods to analyze,simulate,visualize or predict the toxicity of chemicals,has obvious advantages in time,cost and animal welfare.In recent years,the use of computational tools to predict genotoxicity is gaining more attention from the regulatory agencies,the ICH M7 guideline indicates that(Q)SAR predictions for the Ames mutagenicity of drug impurities can be used for drug regulatory purposes.On this basis,the classical genotoxicity computational evaluation methods and their principles were discussed,the status of commonly used genotoxicity evaluation models and the model building was summarized,and the application of computational toxicology in genotoxicity assessment of drug impurities,nanomaterials and cosmetic components was reviewed in this paper,in order to provide references for the development and optimization of computational models for evaluating genotoxicity and promote the application of computational toxicology in national genotoxicity regulation.