Behavior Effects of Structurally Diverse Per- and Polyfluoroalkyl Substances in Zebrafish

Per- and polyfluoroalkyl substances (PFAS) are ubiquitously detected in the environment, and some pose significant human and environmental health concerns globally. While some PFAS induce adverse health effects, relatively few toxicological studies adequately address the broad structural diversity of this chemical class. In the current study, we evaluated 58 individual PFAS spanning 14 structural subclasses and 2 mixtures at single concentrations for developmental toxicity in zebrafish using highly sensitive behavior endpoints. Following developmental exposure to PFAS, zebrafish were assessed for mortality and challenged with an embryonic photomotor response (EPR) assay at 24 h postfertilization (hpf) and with larval photomotor response (LPR) and larval startle response assays at 120 hpf. We found that none of the tested PFAS exposures elicited significant mortality or aberrant EPR; however, exposure to 21 individual PFAS from multiple structural subclasses and 1 mixture induced aberrant larval behavior. We then evaluated developmental toxicity across a concentration range of 0-100 μM for 10 perfluoroalkyl carboxylic acids (PFCAs; 4-carbon perfluorobutanoic acid through the 13-carbon perfluorotridecanoic acid). Exposure to the PFCAs did not cause significant mortality or morphological effects, with the exception of perfluorooctanoic acid and perfluorononanoic acid, and did not induce aberrant EPR. All PFCAs, except for longer-chain perfluorododecanoic acid caused abnormal LPR following exposure to at least one concentration. In this study, we evaluated a broad set of PFAS not previously assessed for in vivo sublethal behavior endpoints and confirmed previous findings that exposure to some PFAS induces abnormal behavior in developing zebrafish. The data from this study will guide the selection of PFAS for which to investigate modes of toxic action.