Lack of effects for low dose levels of bisphenol A and diethylstilbestrol on the prostate gland of CF1 mice exposed in utero.
vom Saal et al. (Proc. Natl. Acad. Sci. 94, 2056-2061, 1997) have reported that low dose exposure (0.02-2 microg/kg/day) of CF1 mice to diethylstilbestrol (DES) in utero led to increases in the prostate gland weight when the pups reached 8 months of age. Nagel et al. (Environ. Health Perspect. 105, 70-76, 1997) reported similar effects in CF1 mice at 6 months of age after exposure in utero to low dose levels (2 and 20 microg/kg/day) of bisphenol A (BPA). vom Saal et al. (Toxicol. Indust. Health 14(1/2) 239-260, 1998) subsequently reported reduced sperm efficiency (daily sperm production per gram testes) in a subset of the BPA animals for which enlarged prostates had been observed. These three experiments have been repeated in a single experiment that was terminated when the offspring reached 6 months of age. No statistically significant effects on prostate weight or sperm efficiency were recorded for offspring of animals exposed to either DES (0.2 microg/kg/day) or BPA (2 and 20 microg/kg/day) in utero. Significant dam effects were seen for several of the assay parameters indicating that the litter, as opposed to the individual, should be considered as the statistical unit in such experiments. A statistically significant increase in body weight was recorded for the low dose BPA male offspring. Females from the study underwent normal sexual maturation and showed no significant differences in reproductive tissue weights at termination and the mean day of vaginal opening. The possible reasons for this failure to confirm the earlier reported effects for DES and BPA at these low doses are discussed.
Ashby
J
J
AstraZeneca Central Toxicology Laboratory, Alderley Park, Cheshire, SK10 4TJ, United Kingdom. John.Ashby@CTL.AstraZeneca.com
Tinwell
H
H
Haseman
J
J
D000818:Animals; D000831:Animals, Newborn; D001559:Benzhydryl Compounds; D001835:Body Weight / Q000187:drug effects; D004054:Diethylstilbestrol / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004822:Epididymis / Q000187:drug effects; D005260:Female; D005836:Genitalia, Female / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011467:Prostate / Q000187:drug effects*; D012669:Seminal Vesicles / Q000187:drug effects; D012741:Sexual Maturation / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000187:drug effects; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004054:Diethylstilbestrol; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds