Toxicokinetic Profiling and Developmental Toxicity of Long-Chain Per- and Polyfluoroalkyl Substances in Zebrafish

Perfluorooctanesulfonate (PFOS), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnA) are three legacy long-chain per-/polyfluoroalkyl substances (PFAS). Although phased out of production, recent studies indicate substantial exposure can occur through consumption of contaminated freshwater fish, with minimal information known on the potential for developmental toxicity, especially for PFDA and PFUnA. In this study, zebrafish were used to characterize the toxicokinetics of these three PFAS as a model for developmental neurotoxicity, specifically behavior and dopamine (DA) dysregulation. Mass spectrometer quantification of water and tissue samples revealed that all three PFAS were rapidly absorbed during the early developmental window and bioconcentrated in tissue to a substantial degree. The visual motor response assay revealed altered behavioral patterns in the larvae, especially for PFDA and PFUnA. Enzyme-linked immunosorbent assay (ELISA) quantification of DA indicated these compounds induced elevations in total DA at nearly every exposure concentration for each compound down to the lowest test concentration used in this study at 0.004 ppb (ppb, μg/L) (equivalent to 4 ppb, US EPA drinking water regulation for PFOS). These findings confirm that PFOS, PFDA, and PFUnA exhibit a substantial capacity for bioaccumulation and demonstrate a need for further research into how developmental exposure impacts neurological health.