ToxSci Advance Access originally published online on November 10, 2006
Toxicological Sciences 2007 95(2):462-473; doi:10.1093/toxsci/kfl159
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Developmental Toxicity of Perfluorooctanoic Acid in the CD-1 Mouse after Cross-Foster and Restricted Gestational Exposures
* Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711
Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia 30341
2 To whom correspondence should be addressed at National Health and Environmental Effects Research Laboratory Building, U.S. Environmental Protection Agency, 2525 East Highway 54, Durham, NC 27713. Fax: (919) 541-4017. E-mail: abbott.barbara{at}epa.gov.
Received September 5, 2006; accepted November 5, 2006
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Abstract |
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Perfluorooctanoic acid (PFOA) is a persistent pollutant and is detectable in human serum (5 ng/ml in the general population of the Unites States). PFOA is used in the production of fluoropolymers which have applications in the manufacture of a variety of industrial and commercial products (e.g., textiles, house wares, electronics). PFOA is developmentally toxic and in mice affects growth, development, and viability of offspring. This study segregates the contributions of gestational and lactational exposures and considers the impact of restricting exposure to specific gestational periods. Pregnant CD-1 mice were dosed on gestation days (GD) 1–17 with 0, 3, or 5 mg PFOA/kg body weight, and pups were fostered at birth to give seven treatment groups: unexposed controls, pups exposed in utero (3U and 5U), lactationally (3L and 5L), or in utero + lactationally (3U + L and 5U + L). In the restricted exposure (RE) study, pregnant mice received 5 mg PFOA/kg from GD7–17, 10–17, 13–17, or 15–17 or 20 mg on GD15–17. In all PFOA-treated groups, dam weight gain, number of implantations, and live litter size were not adversely affected and relative liver weight increased. Treatment with 5 mg/kg on GD1–17 increased the incidence of whole litter loss and pups in surviving litters had reduced birth weights, but effects on pup survival from birth to weaning were only affected in 5U + L litters. In utero exposure (5U), in the absence of lactational exposure, was sufficient to produce postnatal body weight deficits and developmental delay in the pups. In the RE study, birth weight and survival were reduced by 20 mg/kg on GD15–17. Birth weight was also reduced by 5 mg/kg on GD7–17 and 10–17. Although all PFOA-exposed pups had deficits in postnatal weight gain, only those exposed on GD7–17 and 10–17 also showed developmental delay in eye opening and hair growth. In conclusion, the postnatal developmental effects of PFOA are due to gestational exposure. Exposure earlier in gestation produced stronger responses, but further study is needed to determine if this is a function of higher total dose or if there is a developmentally sensitive period.
Key Words: perfluorooctanoic acid; developmental toxicity; cross-foster; prenatal sensitivity.
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