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EFFECTS OF PERFLUOROOCTANOIC ACID (PFOA) ON MICE EXPOSED IN UTERO AT SPECIFIC GESTATIONAL STAGES
Citation:
ABBOTT, B. D., CYNTHIAJ J. WOLF, K. DAS, AND C. S. LAU. EFFECTS OF PERFLUOROOCTANOIC ACID (PFOA) ON MICE EXPOSED IN UTERO AT SPECIFIC GESTATIONAL STAGES. Presented at Society of Toxicology, San Diego, CA, March 05 - 09, 2006.
Description:
Perfluorooctanoic acid is developmentally toxic resulting in embryonic and postnatal deaths and growth retardation. Previous studies showed that dosing mice from gestation day (GD)2-18 with 5 mg PFOA/kg body weight impacts the growth and development of the fetus and newborns. The present study evaluates whether there is a sensitive period during gestation critical to producing these effects. Pregnant CD-1 mice were dosed orally with 5 mg PFOA/kg body weight on either GD8-18, 11-18, 14-18, or 16-18. Litter size was adjusted to 10 and pups were weighed on postnatal days (PND) 1, 2, 3, 4, 7, 10, 14, 17, 22, and 43. At weaning the dam and one pup of each sex per litter were killed, liver was weighed and uterine implantation sites counted. Weight gain during pregnancy was not altered by PFOA. Liver/body weight ratios were significantly increased, but the numbers of implantation sites, live pups at birth, % dead per litter, and survival from PND1-22 were not significantly affected. A trend for decreasing birth weight with increasing exposure duration was significant for male pups. Male birth weights were significantly reduced by exposure on GD8-18 and 11-18. By PND4, all groups had significantly decreased pup weights that persisted to weaning. After weaning, males exposed on GD8-18 or 11-18 had significantly reduced body weights on PND43, but females were similar to controls. The effects of PFOA on weight gain may be due to exposure of particular developmental stages, but interpretation is confounded by the different total doses in each group. Exposure earlier in gestation (and thus to a greater total dose) was associated with more severe growth reduction at earlier ages that persisted post-weaning. Exposure limited to late gestation did not affect birth weights, but by PND4 growth was reduced. However, exposure early in development (GD2-7) was not required to reduce body weight. In conclusion, PFOA affects in utero and postnatal growth and exposure during late gestation may be sufficient for this response. This abstract does not necessarily reflect U.S. EPA policy.