Transcriptomics-based points of departure for Daphnia magna exposed to 18 per- and polyfluoroalkyl substances

Per- and polyfluoroalkyl substances (PFAS) are a large chemical group of concern for both human and ecological health. While a few PFAS are well studied with respect to potential ecological effects, hazard data are lacking for most PFAS and collecting traditional toxicity data for thousands of PFAS would take decades. A growing body of evidence indicates that chemical concentrations that do not elicit concerted changes in gene expression in short term exposures are not toxic, even after much longer exposures. Consequently, this study examined whole body gene expression in Daphnia magna, a widely used invertebrate model organism in ecotoxicology, exposed for 24 hour, in a 96-well plate format, to identify concentrations of 18 structurally diverse PFAS that would not be expected to long-term adverse effects to aquatic invertebrates. Comparison with available toxicity data for several of the tested PFAS suggests the gene-expression based points of departure (termed tPODs) were generally protective. At the same time, Daphnia were often much more sensitive than human cells. With appropriate caveats (for example consideration of potential bioaccumulation), the resulting tPODs can potentially be used for risk-based screening and prioritization to help identify whether water concentrations of the tested PFAS would be likely to cause adverse ecological effects. This study contributes to on-going efforts to support integration of data from new approach methodologies employing global gene expression measurements into chemical safety decision-making practices.