Normal sexual development of two strains of rat exposed in utero to low doses of bisphenol A.
Pregnant Sprague-Dawley (SD) and Alderley Park (Wistar derived) rats were exposed by gavage during gestation days 6-21 to 20 microg/kg, 100 microg/kg, or 50 mg/kg body weight of BPA with ethinylestradiol (EE; 200 microg/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.
Tinwell
H
H
Syngenta Central Toxicology Laboratory, Alderley Park, Cheshire, SK10 4TJ, United Kingdom.
Haseman
J
J
Lefevre
P A
PA
Wallis
N
N
Ashby
J
J
D000818:Animals; D001559:Benzhydryl Compounds; D004305:Dose-Response Relationship, Drug; D004965:Estrogen Antagonists / Q000494:pharmacology; D030762:Estrous Cycle / Q000187:drug effects; D004997:Ethinyl Estradiol / Q000494:pharmacology; D005260:Female; D005835:Genitalia / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012098:Reproduction / Q000187:drug effects / Q000502:physiology; D012741:Sexual Maturation / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects / Q000502:physiology; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004965:Estrogen Antagonists; D004997:Ethinyl Estradiol; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds