Maternal and neonatal effects of in utero exposure to perfluoroalkyl ether acids in the Sprague-Dawley rat

This is an invited presentation/webinar for the Collaborative for Health and the Environment and no abstract was submitted for presentation acceptance.

Impact/Purpose

Per- and poly-fluoroalkyl substance (PFAS) research is an area of critical need due to the relatively long environmental persistence, widespread occurrence, long biological half-lives, and nearly ubiquitous human and environmental exposure to this chemical class. Perfluoroalkyl ether acids (PFEAs) are a sub-class of PFAS and include the compounds hexafluoropropylene oxide dimer acid (GenX), Nafion byproduct 2 (NBP2), and perfluoro-2-methoxyacetic acid (PFMOAA). PFEAs are currently used in the production of fluoropolymers following the phase-out of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), presumably due to more favorable fate and toxicity profiles. However, monitoring studies have detected GenX, NBP2, PFMOAA, and others in a wide range of matrices including surface water, drinking water, and/or human serum. Little to no published research is available regarding the potential toxicity of these compounds compared to the legacy PFAS or cumulative effects of exposure to PFAS mixtures. We hypothesized that in utero exposure to GenX would impact the maternal liver during gestation and potentially lead to some adverse neonatal effects, similar to other PFAS, however at considerably higher doses than the more potent, long-chain PFAS (e.g., PFOS, PFOA) and that mixture exposures would produce dose additive effects. The data from this project will be useful to state, federal, and other regulatory agencies in the development of hazard assessments for GenX and NBP2, among other PFAS and combined exposure to multiple PFAS. This study characterizes the toxic effects of oral GenX, NBP2, and a PFAS mixture exposure during pregnancy to both the mother and the offspring (fetal and newborn) using a laboratory rat model. We found multiple, severe effects for GenX and NBP2 that were consistent with other PFAS, such as PFOA and PFOS. Importantly, it appears that NBP2 is only slightly less potent than PFOS and GenX is only slightly less potent than PFOA based on the orally administered dose. Further, combined exposure to multiple PFAS produce dose additive effects. Continuation of this work will focus on characterizing the internal serum and liver doses for NBP2 and GenX because toxicokinetics appears to be a major factor in the oral toxicity. The data presented here will be highly valuable for regulators to make scientifically based decisions on the potential adverse effects of NBP2 on human health and informing future toxicity studies of additional PFAS.

Citation

Conley, J. Maternal and neonatal effects of in utero exposure to perfluoroalkyl ether acids in the Sprague-Dawley rat. Virtual-Collaborative for Health and the Environment Webinar, N/A, N/A, January 15, 2020.