Toxicological Sciences, Vol 50, 36-44, Copyright © 1999 by Society of Toxicology
SZ Cagen, JM Waechter Jr, SS Dimond, WJ Breslin, JH Butala, FW Jekat, RL Joiner, RN Shiotsuka, GE Veenstra and LR Harris
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.
ARTICLES
Normal reproductive organ development in CF-1 mice following prenatal exposure to bisphenol A
Shell Chemical Co., Houston, Texas, USA.
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