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Toxicological Sciences 68, 339-348 (2002)
Copyright © 2002 by the Society of Toxicology

ENDOCRINE TOXICOLOGY

Normal Sexual Development of Two Strains of Rat Exposed in Utero to Low Doses of Bisphenol A

H. Tinwell*, J. Haseman{dagger}, P. A. Lefevre*, N. Wallis* and J. Ashby*,1

* Syngenta Central Toxicology Laboratory, Alderley Park, Cheshire, SK10 4TJ, United Kingdom; and {dagger} National Institute of Environmental Health Sciences, Alexander Drive, Research Triangle Park, North Carolina 27709

Pregnant Sprague-Dawley (SD) and Alderley Park (Wistar derived) rats were exposed by gavage during gestation days 6–21 to 20 µg/kg, 100 µg/kg, or 50 mg/kg body weight of BPA with ethinylestradiol (EE; 200 µg/kg) acting as a positive control agent. The sexual development of the derived pups was monitored until termination at postnatal day 90–98. The endpoints evaluated were litter size and weight, anogenital distance at birth, days of vaginal opening, first estrus and prepuce separation, weights of the liver, seminal vesicles, epididimydes, testes, ventral prostate, uterus, vagina, cervix and ovaries, and daily sperm production. Males were terminated at postnatal day 90 and females at postnatal day 98. The only statistically significant effects observed for any dose of BPA were a decrease in daily sperm production and an increase in the age of vaginal opening for the Alderley Park animals at the highest dose evaluated (50 mg/kg). The dose of EE evaluated proved to be maternally toxic in our laboratory, but provided gross evidence of endocrine disruption in the treated dams. These results diverge from those of Chahoud and his colleagues who indicated disturbances to the sexual development of both male and female SD rat pups administered the same 3 doses of BPA. This failure to confirm low dose endocrine effects for BPA is discussed within the context of similar divergent conclusions derived from other assessments of the endocrine toxicity of this agent to rats.

Key Words: bisphenol A; Sprague-Dawley rats; Alderley Park rats; sexual development; in utero exposure.


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