Citation:

Hartig, P., J. Conley, C. Lambright, N. Evans, M. Cardon, V. Wilson, M. Strynar, J. McCord, B. Mcintyre, G. Travlos, AND E. Gray. GenX (FRD-902, ammonium (2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoate) Does Not Display Estrogenic, (anti)androgenic or Glucocorticoid-like Activity In Vitro Whereas In Utero Exposure Induces Dose-related Maternal And Fetal Rat Liver PPAR Pathway Gene Expression Without Affecting Fetal Testis Testosterone Production. SOT 2018 Annual Meeting, San Antonio, TX, March 11 - 15, 2018.

Impact/Purpose:

The data from these studies will provide novel developmental toxicity information on the in utero effects on GenX, a PFAS chemical of concern in NC, among other places. These data begin to fill some of the data gaps on this persistent unregluated water contaminant

Description:

GenX (CAS 13252-13-6) is an unregulated, persistent contaminant that has been found in both the Cape Fear River and in Wilmington NC drinking water. Concerns exist about the potential health effects of GenX exposure because it is not removed using traditional water treatment methods and little is known about the toxicity of it or other associated per/polyfluoroalkyl substances (PFAS). Our objective was to evaluate the in vitro hormone receptor activity of GenX and the potential to disrupt growth, viability and reproductive development in rats exposed in utero during sexual differentiation. In vitro, GenX did not display estrogenic, androgenic, antiandrogenic or glucocorticoid-like activity at any concentration (100pM to 10uM). When administered from gestational days (GD)14 to 18 of pregnancy by oral gavage at dosage levels of 0, 1, 3, 10, 30, 62.5, 125, 250 and 500 mg/kg/d, GenX reduced maternal weight gain (from 32g in controls to 21g at 250 mg and 11g at 500 mg), increased liver weight (30 mg and above) and induced mRNA for PPAR-specific genes in the liver (NOEL to be determined (N-TBD). Maternal serum was collected on GD18 for determination of GenX and T4 levels and a lipid profile (TBD). Fetal viability and body weight at GD18 were not reduced, whereas liver mRNA for PPAR-specific genes were dramatically increased (N-TBD). In addition to the fetal study, we are examining the in utero effects of in utero GenX on the development of the offspring using a one-generation screening protocol which uses a single dose level (125 mg) and small sample sizes. Thus far there have been no adverse effects from birth to 50 days of age on growth, viability, or reproductive indices (neonatal anogenital distance, nipple retention, age at puberty) in the pilot study. The prenatal-postnatal study will be repeated with multiple dosage levels administered throughout gestation. When completed, these studies will enable us to link the internal GenX exposure levels to effects in the dam, fetus and offspring which will enhance the utility of the data for human health risk assessment. This abstract does not reflect Agency policy.

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