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.