Genetic Toxicology: Basics and Practical Insights into Its Appropriate Application

Abstract

Genetic toxicology data play an important role in a variety of regulatory applications. Thus, industrial hygienists and toxicologists need a basic understanding of the principles and testing approaches for the evaluation of genotoxicity. Genetox tests are used for hazard assessment, to support the classification of chemicals as carcinogens or mutagens, and to support the evaluation of modes of action for tumor induction. Genetic toxicology has primarily been used in the evaluation of potential carcinogens, and for predicting potential germ cell and heritable risk. More recent considerations include using genetic damage as a standalone adverse outcome. Many genetox tests are recommended for regulatory use, with OECD test guidelines that describe conduct and data interpretation. Since these recommendations have evolved over the years, data from older studies must be carefully evaluated before accepting study conclusions. In silico models now contribute by complementing the biological tests. This chapter includes our insights into strategies for selecting appropriate tests and generating optimal data sets to address specific questions and advice for conducting weight of the evidence evaluations on information from multiple endpoints and tests. Genetic toxicology data provide not only qualitative results, but with careful study design, can also provide information useful to address dose–response issues.