Thibodeaux, J; Hanson, RG; Rogers, JM; Lau, C
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. CD-1 mice were mated overnight and the day on which copulatory plugs were found was designated as GD 1. Animals were given 1, 3, 5, 10, 20, or 40 mg/kg PFOA by oral gavage daily from GD2 to GD 18; controls received an equivalent volume (10 ml/kg) of water. PFOA treatment produced early, full-litter resorptions in a dose-dependent manner, leading to 100% loss in the 40 mg/kg group. Significant deficits in maternal weight gains were detected in dams of the 20 mg/kg group that carried pregnancy to term. On GD 18, some dams were sacrificed for maternal and fetal examinations while the rest were allowed to give birth for monitoring of postnatal survival, growth, and development of the pups. PFOA induced liver enlargement in the dams at all doses, but did not alter the number of implantations. In the 20 mg/kg group, the percent of live fetuses was reduced to 74% (compared to 97% in controls) the day before birth, and fetal weight (0.86 ? 0.11 g) was significantly lower than that of controls (1.05 ? 0.02 g). However, no discernable anatomical malformations were noted in any of the treatment groups. The incidence of live births was significantly lowered by PFOA in the 10 and 20 mg/kg groups (70% compared to 93% in the control group), and postnatal survival of the neonates was severely compromised in these treatment groups. Dose-dependent deficits of weight gains were detected in all PFOA-treated pups. Significant delays in eye-opening (by about 2 days) were noted in the 10 and 20 mg/kg groups, and pubertal indices were significantly delayed (by about 3 days in males and females) in the 20 mg/kg group. These data indicate maternal and developmental toxicities of PFOA in the mouse measured as early pregnancy loss, compromised postnatal survival, and delays in postnatal growth and maturation.