Perspectives on the Drosophila melanogaster Model for Advances in Toxicological Science

The use of Drosophila melanogaster for studies of toxicology has grown considerably in the last decade. The Drosophila model has long been appreciated as a versatile and powerful model for developmental biology and genetics because of its ease of handling, short life cycle, low cost of maintenance, molecular genetic accessibility, and availability of a wide range of publicly available strains and data resources. These features, together with recent unique developments in genomics and metabolomics, make the fly model especially relevant and timely for the development of new approach methodologies and movements toward precision toxicology. Here, we offer a perspective on how flies can be leveraged to identify risk factors relevant to environmental exposures and human health. First, we review and discuss fundamental toxicologic principles for experimental design with Drosophila. Next, we describe quantitative and systems genetics approaches to resolve the genetic architecture and candidate pathways controlling susceptibility to toxicants. Finally, we summarize the current state and future promise of the emerging field of Drosophila metabolomics for elaborating toxic mechanisms. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.