Citation:

Conley, J., C. Lambright, N. Evans, M. Strynar, J. McCord, B. McIntyre, G. Travlos, M. Cardon, E. MedlockKakaley, P. Hartig, V. Wilson, AND E. Gray. Adverse maternal, fetal, and postnatal effects of Hexafluoropropylene oxide dimer acid (GenX) from oral gestational exposure in Sprague Dawley rats. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, , 1-13, (2019). https://doi.org/10.1289/EHP4372

Impact/Purpose:

GenX is a PFAS chemical that has contaminated water systems for decades, including the Cape Fear River Basin in NC among others. However, there a few published data on this PFAS and there are no industry or peer-reviewed multigenerational or one-generational reproduction studies on GenX in spite of the fact that other PFAS induced adverse effects on rodent offspring, exposed in utero. We anticipate the EPA OW and other program offices, the state of NC and other states and countries with GenX contaminated water sources will use the data in their evaluations of Human Health Hazard Identification.

Description:

ABSTRACT Background: GenX (CAS: 62037-80-3) is a member of the per- and polyfluoroalkyl substances (PFAS) chemical class and a high-profile contaminant of emerging concern. Recent environmental monitoring efforts have identified elevated levels of GenX in surface water, air, and treated drinking water in the United States and Europe indicating the potential for human exposure. Objectives: Our goal was to determine if GenX activates peroxisome proliferator activated receptor (PPAR) signaling pathways and alters male reproductive tract development in laboratory rats. Methods: We conducted a set of three assays in order to evaluate maternal, fetal, and early postnatal effects of GenX utilizing oral exposure to Sprague Dawley rat dams. Two assays involved dosing during the critical window for male reproductive development (gestation day (GD) 14-18) and the third incorporated a broader dosing timeframe from GD8 to postnatal day (PND) 3. A range of endpoints related to the reproductive development of offspring were evaluated along with effects on the maternal and fetal liver. Results: We found that dosing from GD14-18 at 1-500 mg/kg/d resulted in dose-responsive increases in maternal liver weight, reduced maternal weight gain, reduced maternal serum thyroid hormone and lipid profiles, and highly upregulated gene expression related to the PPAR signaling pathway in maternal and fetal livers. Dosing from GD8-PND3 at 10-250 mg/kg/d resulted in dose-responsive reduction in maternal weight gain, increases in neonatal pup mortality, and reduced surviving pup body weight. Overall, GenX exposure produced multiple adverse effects consistent with a PPAR agonism mode of action and similar to prior PFAS toxicity evaluations.

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