The Neurodevelopmental Effects of PFAS Exposure through Drinking Water

Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants that have become globally ubiquitous in the environment and in humans. One local population facing disproportionate PFAS exposure risk through their drinking water was Pittsboro, NC residents. In utero PFAS exposure is associated with an array of long-term health effects; however, the mechanism of toxicity is poorly understood. The aim of this study is to determine the causal relationship between in utero PFAS mixture exposure and cognitive deficits, emotional dysfunction, and behavioral dysregulation in rats. Using animal models, this study addresses the neurodevelopmental effects of gestational exposure to clearly defined PFAS concentrations seen in Pittsboro’s drinking water and a 5,000-fold concentration as the positive control. To quantitatively assess toxicity, animal subjects exposed to PFAS-laden drinking water during fetal development underwent a battery of assessments from an established behavioral testing framework. Dams exposed to the high-dose mixture yielded smaller litters on average. Offspring in the low-dose group of environmental relevance demonstrated significantly smaller weights (p<0.05) and smaller anogenital distances on average just prior to weaning (PND 21). In the behavioral battery, low and high-dose-exposed rats made fewer attempts to explore different arms of the elevated plus maze, indicating a heightened anxiety response. In the figure-8 maze, males in the high-dose group displayed hyperactivity compared to the other groups. These findings suggest that maternal PFAS exposure may be able to cause diminished fertility, small pup size, increased anxiety, and hyperactivity in rats. However, continued investigation is necessary to obtain sufficient statistical power.