Selection of tests for genotoxicity assessment: Sensitivity and specificity considerations

The appropriate strategy for a genotoxicity assessment depends on the purpose of the study. If the purpose is research-oriented (for example, to understand mechanisms of gene-mutation events or chromosomal aberrations), the tests should meet the researcher's scientific goals. However, to make regulatory decisions with confidence, the genotoxicity strategy must cover all necessary endpoints. Thus, it is crucial to standardize the relevant test methods and to certify reproducible experimental processes. A battery system, which is often used for genotoxicity evaluation, consists of several tests that complementarily detect different endpoints. Numerous genotoxicity tests are available, employing various organisms and methodologies, and it is therefore crucial to select the appropriate tests for the battery system. Sensitivity and specificity are essential considerations. These are inversely correlated, and we cannot maximize them simultaneously; our interest tends to lie more with sensitivity than specificity; that is, we want to avoid false negatives. We also discuss the issues arising in parallel from a statistical perspective, namely type I and II errors. Genotoxicity is a crucial endpoint for decision-making in human safety assessment, and the issues mentioned above must be thoroughly understood and considered.