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PRENATAL AND POSTNATAL EFFECTS IN RATS OF PERFLUORONONANOIC ACID EXPOSURE IN UTERO
Citation:
GREY, B. E., R. G. ELLIS-HUTCHINGS, K. DAS, J. M. ROGERS, AND C. S. LAU. PRENATAL AND POSTNATAL EFFECTS IN RATS OF PERFLUORONONANOIC ACID EXPOSURE IN UTERO . Presented at SOT Annual Meeting, Seattle, WA, March 16 - 20, 2008.
Impact/Purpose:
Further understanding of the developmental toxicity of perfluoroalkyl acids
Description:
In recent years, our understanding of the developmental toxicity of perfluoroalkyl acids (PFAAs) has focused on the C8 compounds. Ubiquitous environmental contaminants, PFAA’s are utilized as surfactants in a variety of industrial applications. Although several PFAAs have been extensively studied, the paucity of data for perfluorononanoic acid (PFNA) led us to conduct the current study. An initial range-finding study was conducted with timed pregnant Sprague-Dawley (SD) rats dosed by oral gavage with 0, 1, 10, or 30 mg/kg PFNA from gestation day (GD) 2-21. On GD 8, rats dosed with 30 mg/kg PFNA were euthanized due to overt maternal toxicity. Three of seven rats in the 10 mg/kg PFNA dose group were also euthanized on GD 11 due to excessive toxicity. Remaining dams in the 10 mg/kg group had reduced maternal body weight gain throughout gestation and reduced pup weights, compared to controls. Based on these initial findings, a larger study was conducted with timed pregnant SD rats dosed with 0, 1, 3, or 5 mg/kg PFNA from GD 2-21 (n=12 per group). Maternal body weight gain and food intake were monitored throughout gestation. On GD 21, Caesarean sections were performed on half of the dams. Maternal body weight, percent live fetuses per litter, and litter size and weight were similar between the groups. However, dams exposed to 5 mg/kg PFNA had significantly higher liver weights compared to controls (11%). The fetuses were examined for external malformations but none were observed. Remaining dams were allowed to deliver and were monitored for pup survival, weight gain, and postnatal development. Postnatally, pups exposed to 5 mg/kg PFNA had significantly lower birth weight than controls (16%), which remained lower than controls through early postnatal development. Postnatal survival through day 7 was not affected by PFNA exposure. These data indicate that exposure of pregnant rats to PFNA may elicit developmental toxicity at doses of 5 mg/kg or above.