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EFFECTS OF PERFLUOROOCTANOIC ACID EXPOSURE DURING PREGNANCY IN THE MOUSE
Citation:
LAU, C. S., J. R. THIBODEAUX, R. HANSON, M. G. NAROTSKY, J. M. ROGERS, A. B. LINDSTROM, AND M. J. STRYNAR. EFFECTS OF PERFLUOROOCTANOIC ACID EXPOSURE DURING PREGNANCY IN THE MOUSE. TOXICOLOGICAL SCIENCES. Oxford University Press, Cary, NC, 90(2):510-519, (2006).
Impact/Purpose:
To characterize the developmental toxicity of perfluorooctanoic acid (PFOA) in the mouse.
Description:
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 were affected in the 40 mg/kg group. Maternal weight gains in dams that carried pregnancy to term were significantly attenuated in the 10 and 20 mg/kg groups. 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 pups were monitored. PFOA induced enlarged liver in group A dams at all doses, but did not alter number of implantations. The percent of live fetuses was reduced only in the 20 mg/kg group, to 74% (compared to 94% in controls), and fetal weight was also significantly lower in this group. However, no significant malformations were noted in any of the treatment groups. 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 pups except the 1 mg/kg group. Significant delays in eye-opening (up to 2-3 days) were noted at 5 mg/kg and higher doses. 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.