ToxSci Advance Access published online on January 16, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfj105
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1 Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC
* To whom correspondence should be addressed. Perfluorooctanoic acid (PFOA), a member of the perfluoroalkyl acids that have wide commercial applications, has recently been detected in humans and wildlife. The current study characterizes the developmental toxicity of PFOA in the mouse. Timed pregnant CD-1 mice were given 1, 3, 5, 10, 20 or 40 mg/kg PFOA by oral gavage daily from gestational day (GD) 1 to 17; controls received an equivalent volume (10 ml/kg) of water. PFOA treatment produced dose-dependent full-litter resorptions; all dams in the 40 mg/kg group resorbed their litters. Weight gain in dams that carried pregnancy to term was significantly lower in the 20 mg/kg group. At GD 18, some dams were sacrificed for maternal and fetal examinations (group A), and the rest were treated once more with PFOA and allowed to give birth (group B). Postnatal survival, growth and development of the offspring were monitored. PFOA induced enlarged liver in group A dams at all dosages, but did not alter the number of implantations. The percent of live fetuses was lower only in the 20 mg/kg group (74% vs. 94% in controls), and fetal weight was also significantly lower in this group. However, no significant increase in malformations was noted in any treatment group. The incidence of live birth in group B mice was significantly lowered by PFOA: ca. 70% for the 10 and 20 mg/kg groups compared to 96% for controls. Postnatal survival was severely compromised at 10 or 20 mg/kg, and moderately so at 5 mg/kg. Dose-dependent growth deficits were detected in all PFOA-treated litters except the 1 mg/kg group. Significant delays in eye-opening (up to 2-3 days) were noted at 5 mg/kg and higher dosages. Accelerated sexual maturation was observed in male offspring, but not in females. These data indicate maternal and developmental toxicity of PFOA in the mouse, leading to early pregnancy loss, compromised postnatal survival, delays in general growth and development, and sex-specific alterations in pubertal maturation.
Received October 29, 2005
Accepted December 20, 2005
Reproductive and Developmental Toxicology
Effects of Perfluorooctanoic Acid Exposure during Pregnancy in the Mouse
Christopher Lau 1 *,
Julie R. Thibodeaux 1,
Roger G. Hanson 1,
Michael G. Narotsky 1,
John M. Rogers 1,
Andrew B. Lindstrom 2,
and
Mark J. Strynar 2
2 Human Exposure and Atmospheric Science Division, National Exposure Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC
Christopher Lau, E-mail: lau.christopher{at}epa.gov
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