Toxicokinetic Profiling and Developmental Neurotoxicity of Long-Chain PFAS Exposure in Zebrafish as a Model for Human Health

This thesis is concerned with the investigation of the health effects and toxicokinetic behavior of perfluorooctane sulfonate (PFOS), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), three legacy, long-chain per- and polyfluoroalkyl substances (PFAS). These substances are known to be highly persistent in the environment and generally believed to be highly bioaccumulative. Despite being phased out of production in favor of theoretically safer short-chain alternatives in the 2000s, a study found that many Americans are still being exposed to a number of long-chain PFAS, primarily PFOS, PFDA, and PFUnDA, to a substantial degree through the consumption of freshwater fish. In this thesis, zebrafish were used as a model organism to characterize toxicokinetics of these three PFAS and as a model for potential human developmental neurotoxicity, specifically as it pertains to dysregulation of dopamine. Mass spectrometer quantification of both water and tissue samples revealed that all three PFAS were rapidly absorbed by zebrafish during the early developmental window and bioconcentrated in the tissue to a substantial degree. Locomotor behavioral analysis of exposed larvae revealed a number of significant abnormalities, especially in PFDA and PFUnDA. ELISA quantification of dopamine indicated that these compounds induced significant changes in dopamine regulation at nearly every exposure concentration for each compound down to the lowest test concentration used in this study at 0.004 ppb (µg/L). These findings indicate that PFOS, PFDA, and PFUnDA all exhibit a substantial capacity for bioaccumulation. The present findings also demonstrate a need for further research into how developmental exposure to long-chain PFAS can impact neurological health, as well as further consideration for the legal regulation of this class of environmental pollutants.