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LONG-TERM HEALTH EFFECTS FOLLOWING GESTATIONAL EXPOSURE TO PFOA IN MICE
Citation:
WHITE, S. S., E. P. HINES, J. RAYNER, C. S. LAU, J. R. THIBODEAUX, AND S. E. FENTON. LONG-TERM HEALTH EFFECTS FOLLOWING GESTATIONAL EXPOSURE TO PFOA IN MICE. Presented at Endocrine Meeting, Boston, MA, June 23 - 26, 2006.
Description:
Perfluorooctanoic acid (PFOA) is used in many commercial products as a surfactant. It has been shown to induce mammary tumors in lifetime fed adult female rats and to delay mammary gland development in mouse pups exposed to the compound prenatally. To evaluate the long-term health effects of the compound, pregnant CD-1 mice were dosed with 0, 1, 3, or 5 mg/kg/d PFOA from gestation day (GD) 2-18. Mice (n=15-20/dose group) were evaluated until 18 months of age. The body weights of the offspring were recorded throughout life and animals were examined at least monthly for abnormal development. PFOA initially suppressed body weight gain of the mouse pups. These deficits reversed during adulthood, leading to a dose-related increase in body weight by 16 months (p<0.05). Body weight of the 1 and 3 mg/kg groups ranged from 4.3-15.7% and 10.9-17.0% higher than controls, peaking in weight at 18 and 15 months, respectively. On the other hand, the 5 mg/kg group was never more than 8% heavier than controls, suggesting a bell-shaped dose response. At necropsy (18.5 mo), there was a dose-related increase in ovarian cysts (p<0.05), with 25, 47, 60, and 80% of the animals in the 0, 1, 3, 5 mg/kg PFOA groups, respectively, demonstrating either uni- or bilateral cysts. In whole mount preparations of the mammary glands, gross examination revealed nodules in the glands and the incidence of this abnormal observation increased with corresponding doses. Although PFOA is known to increase liver:body weight ratios during and immediately following dosing, there was no effect of PFOA on liver:body weight. Unexpectedly, there was a dose-dependent increase in snout whisker loss (p<0.05), with more than 30% of the animals lacking whiskers in the 3 and 5 mg/kg group. Gross tissue abnormalities were also noted in the brown adipose tissue, pancreas, liver, spleen and kidney/adrenal glands. These preliminary observations will be followed up with histopathology and extended to lower doses. (This is an abstract of a proposed presentation and does not necessarily reflect EPA policy).