Genetic Toxicity Assessment: Employing the Best Science for Human Safety Evaluation Part VI: When Salt and Sugar and Vegetables Are Positive, How Can Genotoxicity Data Serve to Inform Risk Assessment?

Abstract

This opinion piece examines the current approaches in the design and evaluation of genotoxicity data and recommends an alternative that would provide information that could be more useful to human risk assessment. It is suggested that genotoxicity studies, both in vitro and in vivo, be designed similar to other traditional toxicology studies, such that a dose-response relationship is characterized, including identification of a "no-observed-adverse-effect-level" dose. It is further suggested that genotoxicity tests should no longer be designed or interpreted in isolation but should be examined in the context of other available data including toxicokinetics, mechanism of genotoxicity, and relevant exposure information. The answer to improving genetic toxicology testing does not lie in coming up with better, "more sensitive" genotoxicity test systems but rather in the incorporation of contextual improvements in both the experimental design and the interpretation of data collected using the current models. Such a strategy will better position the toxicology and risk assessment communities to cope with the current intellectually uncomfortable dichotomy that directs disproportionate scientific resource to addressing genetic toxicity findings of anthropogenic substances, regardless of dose-exposure context, while at the same time ignoring the plethora and comparatively large amounts of genotoxic and toxic substances that are inescapably present in what are otherwise regarded as healthy foods (salt, sugar, and vegetables).