Immature rat uterotrophic assay of bisphenol A.
We used the immature rat uterotrophic assay to determine the estrogenicity of bisphenol A (BPA). We administered BPA (in sesame oil) to rats subcutaneously (sc; 0, 8, 40, and 160 mg/kg/day) or orally (0, 40, 160, and 800 mg/kg/day) for 3 days beginning on postnatal day (PND) 18; rats were sacrificed 24 hr after the last administration. Uterine wet, blotted, and relative weights increased in all groups given BPA sc. After oral administration, uterine relative weight increased in 160 and 800 mg/kg BPA groups, and wet and blotted weights increased in the 800 mg/kg BPA group. Plasma concentrations of BPA at 1 hr after the last administration were detected in all groups given BPA sc and in groups given 160 and 800 mg/kg BPA orally, with a dose-response effect. The study was then reproduced under the same conditions. After sc injections, uterine wet and blotted weights increased in the 40 and 160 mg/kg BPA groups, and relative weight increased in all groups given BPA sc. By contrast, uterine wet, blotted, and relative weights increased only in the 160 and 800 mg/kg oral BPA groups. Also, to examine time-course changes in uterine weight, we administered BPA (in sesame oil) sc from PND 18 to PND 20 for 3 days at doses of 0, 8, 40, and 160 mg/kg/day; uterine weights were then measured at 6, 12, 18, and 24 hr after the last administration. Uterine wet, blotted, and relative weights increased in all BPA groups at 6 and 24 hr and in 40 and 160 mg/kg BPA groups at 12 hr. By contrast, at 18 hr, uterine wet, blotted, and relative blotted weights increased in all BPA groups and relative wet weight increased in 40 and 160 mg/kg BPA groups. The percentage increases in uterine wet and relative weights of 40 and 160 mg/kg BPA groups at 6 hr were higher than those at 24 hr relative to the controls, but the coefficient of variation in these weights in the group given 8 mg/kg BPA at 24 hr was smaller than that at 6 hr. These findings demonstrate BPA-induced uterotrophy in the immature uterotrophic assay in rats administered 8 mg/kg/day sc and in rats given 160 mg/kg/day orally, and suggest that the autopsy at 24 hr after the last administration is suitable.
Yamasaki
K
K
Chemicals Assessment Center, Chemicals Evaluation and Research Institute, Oita, Japan. yamasaki-kanji@hita.cerij.or.jp
Sawaki
M
M
Takatsuki
M
M
D000284:Administration, Oral; D000818:Animals; D001559:Benzhydryl Compounds; D001681:Biological Assay; D004305:Dose-Response Relationship, Drug; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005260:Female; D006984:Hypertrophy; D007279:Injections, Subcutaneous; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D014599:Uterus / Q000187:drug effects* / Q000473:pathology; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004968:Estrogens, Non-Steroidal; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds