Normal reproductive organ development in CF-1 mice following prenatal exposure to bisphenol A

Abstract

Bisphenol A (BPA) is a monomer used in the manufacture of a multitude of chemical products, including epoxy resins and polycarbonate. The objective of this study was to evaluate the effects of BPA on male sexual development. This study, performed in CF-1 mice, was limited to the measurement of sex-organ weights, daily sperm production (DSP), epididymal sperm count, and testis histopathology in the offspring of female mice exposed to low doses of BPA (0, 0.2, 2, 20, or 200 microg/kg/day), by deposition in the mouth on gestation days 11-17. Male sexual development determinations were made in offspring at 90 days-of-age. Since this study was conducted to investigate and clarify low-dose effects reported by S. C. Nagel et al., 1997, Environ. Health Perspect. 105, 70-76, and F. S. vom Saal et al., 1998, Toxicol. Indust. Health 14, 239-260, our study protocol purposely duplicated the referenced studies for all factors indicated as critical by those investigators. An additional group was dosed orally with 0.2 microg/kg/day of diethylstilbestrol (DES), which was selected based on the maternal dose reported to have maximum effect on the prostate of developing offspring, by F. S. vom Saal (1996, personal communication), vom Saal et al. (1997, Proc. Natl. Acad. Sci. U S A 94, 2056-2061). Tocopherol-stripped corn oil was used as the vehicle for BPA and DES, and was administered alone to control animals. No treatment-related effects on clinical observations, body weight, or food consumption were observed in adult females administered any dose of BPA or DES. Similarly, no treatment-related effects on growth or survival of offspring from dams treated with BPA or DES were observed. The total number of pups born per litter was slightly lower in the 200-microg/kg/day BPA group when compared to controls, but this change was not considered treatment-related since the litter size was within the normal range of historical controls. There were no treatment-related effects of BPA or DES on testes histopathology, daily sperm production, or sperm count, or on prostate, preputial gland, seminal vesicle, or epididymis weights at doses previously reported to affect these organs or at doses an order of magnitude higher or lower. In conclusion, under the conditions of this study, the effects of low doses of BPA reported by S. C. Nagel et al., 1997 (see above) and F. S. vom Saal et al., 1998 (see above), or of DES reported by F. S. vom Saal et al., 1997 (see above) were not observed. The absence of adverse findings in the offspring of dams treated orally with DES challenges the "low-dose hypothesis" of a special susceptibility of mammals exposed perinatally to ultra-low doses of even potent estrogenic chemicals. Based on the data in the present study and the considerable body of literature on effects of BPA at similar and much higher doses, BPA should not be considered as a selective reproductive or developmental toxicant.