Bisphenol A (BPA) is active in inmaur AP rat uterotrphic asa when evduated using either the oral or the subcutaneous (sc) injection routes of eposure (de daily ta of 400-800 mg/kg BPA). Prmatue vaginal opening was sen for 8 of 14 animals eposed to 600 and 800 nm/kg BPA by sc injection. Vaginal openng was not produced by BPA in the gavage studies. Thes results are consistent with those ofDodds and Lawson [Nawue 137:96 (1936)1 who found that BPA induces persistent vain comnfication in ovariectomized rats exposd to the twice-daily injections of85 mg/kg BPA (totl daily dose 170 mg/kg), but they conflict with the reported inctivity of BPA in the imm mouse uterorophicaay. The uterotroplicacvity ofdiehilbestrol in the rat is also estabbished (0.04 mg/kg/day for three days). Key word bisphenol A, endocrine, estrogen, uterus.Despite extensive interest in the endocrine toxicity of bisphenol A (BPA) to mammals (1-5), only one report of its activity in the rodent uterotrophic assay exists (4). In that study, Coldham et al. (4) exposed immature (18-day-old) CFLP mice to 0.05, 0.5, and 5 mg BPA per mouse by subcutaneous (sc) injection on 3 successive days. The 5 mg dose of BPA was toxic, and the treated mice were withdrawn from the study. No uterotrophic activity was observed for the two lower dose levels, and it was concluded that BPA was inactive in the mouse uetrotrophic assay. This condusion is important, given that reliance is currently placed on the rat/mouse uterotrophic assay as a primary screen for estrogens. We therefore decided to evaluate this chemical in the immature rat uterotrophic assay with a view to establishing if it is inactive in this assay using both species of rodent. Materials and MethodsBPA was obtained from Aldrich Chemical Company (Poole, Dorset, UK) and diethylstilbestrol (DES) from Sigma Chemical Company (Poole, Dorset, UK). The vehicle, arachis oil, was as previously described (6). Immature female Alpk:AP rats (21-22 days old), with body weights in the range 38-48 g, were obtained from the breeding unit at Zeneca, Alderley Park. Animals were housed in wire mesh cages with solid bottoms. Humidity was controlled and a 12 hr/12 hr light/dark cycle was maintained.Animals were weaned on R&M no. 1 diet at 19-21 days old and maintained on R&M no. 3 diet from 21 days onward (both diets obtained from Special Diet Services Ltd., Witham, Essex, UK). Diet and water were available ad libitum. All animals were acclimatized for 24 hr before being dosed. The uterotrophic activities of BPA and DES were evaluated in three separate experiments using the test protocol described earlier (6). The test agents were dissolved (DES) or homogeneously suspended (BPA) (6) in arachis oil and dosed by either oral gavage or sc injection. The dosing volume for both routes of exposure was 5 ml/kg body weight. Animals received three daily doses of the test compound and were killed by an overdose of Fluothane (Zeneca Pharmaceuticals) 24 hr after the final dose. The dose levels shown in Table 1 are the daily dose levels. Presence or ...