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WINDOW OF SUSCEPTIBILITY TO PERFLUOROOCTANE SULFONATE (PFOS)-INDUCED NEONATAL MORTALITY IN THE RAT
Citation:
Grasty, R. C., B E. Grey, C S. Lau, AND J M. Rogers. WINDOW OF SUSCEPTIBILITY TO PERFLUOROOCTANE SULFONATE (PFOS)-INDUCED NEONATAL MORTALITY IN THE RAT. Presented at Teratology Society Meeting, Philadelphia, PA, June 21-26, 2003.
Description:
GRASTY1, 2, R.C., B.E. GREY1, C.S. LAU1 and J.M. ROGERS1, 2. 1Reproductive Toxicology Division, NHEERL, ORD, US EPA, Research Triangle Park, NC; and 2Curriculum in Toxicology, UNC Chapel Hill, Chapel Hill, NC. Window of susceptibility to perfluorooctane sulfonate (PFOS)-induced neonatal mortality in the rat.
The widely used perfluorinated chemical, PFOS, increases neonatal lethality in rodents following gestational exposure. We have previously demonstrated the critical window for this toxicity occurs between gestation days (GD) 17-20 in the rat. Here, we utilized a 2-day dosing regimen to further narrow the window of susceptibility. Timed-pregnant Sprague-Dawley rats were treated by oral gavage with 0, 25, or 50 mg/kg/d PFOS/K+ on GD 19-20. Maternal and neonatal toxicity paralleled those described previously. Dam weight gain was suppressed in both PFOS groups following dosing. Control dams gained 29 g over 2 days, whereas the high dose group lost 12 g. Litter size and pup weight on GD 21 were not different between groups. However, the number of live pups born was reduced in the 50 mg/kg group and average pup weight was significantly lower in both treatment groups. While no control pups died on postnatal day (PND) 0, the 25 and 50 mg PFOS/kg groups experienced 6 and 71% mortality, respectively, within the first 12 hours. Pup survival continued to be significantly lower in PFOS treated groups through PND 5, where the survival rates were 98, 66, and 3% for the 0, 25, and 50 mg/kg groups, respectively. Pup weight was also significantly reduced in the dosed groups on these days. Histological examination of lungs revealed differences in maturation between control and treated animals on PND 0. From these data, we conclude that exposure to PFOS on 2 days late in gestation is sufficient to induce 100% pup mortality and that PFOS-induced neonatal mortality may involve inhibition of perinatal lung maturation. This abstract does not reflect EPA policy.