Utility of a next-generation framework for assessment of genomic damage: A case study using the pharmaceutical drug candidate etoposide

Standard batteries to test for genetic damage due to exposure to chemical substances have been relatively consistent for several decades. Existing tests are typically binary, with a yes/no outcome and not always appropriate for detecting the broad range of potential genetic damage. New approaches are needed for characterizing this range of potential damage, allowing for identification and understanding of diverse modes of action (MOAs), which may then be applied to risk assessment and regulatory decision-making.

The HESI Genetic Toxicology Technical Committee (GTTC) developed a systematic and flexible approach for assessing the risk of genetic damage due to exposure to chemical substances that was published in 2017 (Dearfield et al., 2017). This most recent paper applies the framework to etoposide, a drug used in certain types of cancer treatments, as a representative pharmaceutical case study. It places greater emphasis on estimating the potential risk of a substance if and when people are exposed, rather than applying genetic toxicity testing data only for hazard identification. This allows decision makers to discern how much benefit is critical to balance any adverse effects that may be introduced by a pharmaceutical, such as shown with this case study on etoposide.

Full text online: https://onlinelibrary.wiley.com/doi/10.1002/em.22467