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

Bisphenol A (BPA) is a monomer used in the manufacture of a multitude of ch emical 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-o rgan weights, daily sperm production (DSP), epididymal sperm count, and tes tis histopathology in the offspring of female mice exposed to low doses of BPA (0, 0.2, 2, 20, or 200 mu g/kg/day), by deposition in the mouth on gest ation days 11-17. Male sexual development determinations were made in offsp ring at 90 days-of-age. Since this study was conducted to investigate and c larify low-dose effects reported by S. C. Nagel et al., 1997, Environ. Heal th Perspect. 105, 70-76, and F. S. vom Saal et at, 1998, Toxicol. Indust. H ealth 14, 239-260, our study protocol purposely duplicated the referenced s tudies for all factors indicated as critical by those investigators. An add itional group was dosed orally with 0.2 mu g/kg/day of diethylstilbestrol ( DES), which was selected based on the maternal dose reported to have maximu m 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-re lated effects on clinical observations, body weight, or food consumption we re 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 l itter Was slightly lower in the 200-mu g/kg/day BPA group when compared to controls, but this change was not considered treatment-related since the li tter size was within the normal range of historical controls. There were no treatment-related effects of BPA or DES on testes histopathology, daily sp erm production, or sperm count, or on prostate, preputial gland, seminal ve sicle, or epididymis weights at doses previously reported to affect these o rgans or at doses an order of magnitude higher or lower. In conclusion, und er the conditions of this study, the effects of low doses of BPA reported b y S. C. Nagel et al. 1997 (see above) and F. S. vom Saal et at, 1998 (see a bove), or of DES reported by F. S. vom Saal ef al., 1997 (see above) were n ot observed. The absence of adverse findings in the offspring of dams treat ed orally with DES challenges the "low-dose hypothesis" of a special suscep tibility of mammals exposed perinatally to ultra-low doses of even potent e strogenic chemicals. Based on the data in the present study and the conside rable body of literature on effects of EPA at similar and much higher doses , BPA should not be considered as a selective reproductive or developmental toxicant.