An assessment of mutagenicity of chemical substances by (quantitative) structure-activity relationship

Abstract

Currently, there are more than 100,000 industrial chemicals substances produced and present in our living environments. Some of them may have adverse effects on human health. Given the rapid expansion in the number of industrial chemicals, international organizations and regulatory authorities have expressed the need for effective screening tools to promptly and accurately identify chemical substances with potential adverse effects without conducting actual toxicological studies. (Quantitative) Structure-Activity Relationship ((Q)SAR) is a promising approach to predict the potential adverse effects of a chemical on the basis of its chemical structure. Significant effort has been devoted to the development of (Q) SAR models for predicting Ames mutagenicity, among other toxicological endpoints, owing to the significant amount of the necessary Ames test data that have already been accumulated. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) M7 guideline for the assessment and control of mutagenic impurities in pharmaceuticals was established in 2014. It is the first international guideline that addresses the use of (Q) SAR instead of actual toxicological studies for human health assessment. Therefore, (Q) SAR for Ames mutagenicity now require higher predictive power for identifying mutagenic chemicals. This review introduces the advantages and features of (Q)SAR. Several (Q) SAR tools for predicting Ames mutagenicity and approaches to improve (Q) SAR models are also reviewed. Finally, I mention the future of (Q) SAR and other advanced in silico technology in genetic toxicology.