POTENTIAL ESTROGENIC EFFECTS OF BISPHENOL : A ESTIMATED BY IN VITRO AND IN VIVO COMBINATION ASSAYS

概要

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The potential estrogenic activities of bisphenol-A were investigated in vitro (E-screen and estrogen receptor competitive binding bioassays) and in vivo (uterotrophic assay). Uterotrophic responses were evaluated using mature ovariectomized Sprague-Dawley female rats treated subcutaneously with bisphenol A (1, 5, 10, 50, and 100 mg/kg/day), E2 (0.3 μg/kg), and DES (0.3 μg/kg) for 3 consecutive days. In a MCF-7 cell proliferation assay, E2 and DES used as positive estrogens induced maximum proliferation of MCF-7 cells at 1.0 nM, whereas BPA slightly induced MCF-7 cell proliferation at a higher level of 0.1 μM and maximum proliferation at 10μM. In a competitive binding assay, E2 and DES showed inhibition of 17 β-[^3H]estradiol binding to the rat utcrus ER with an IC_<50> of 1.0 nM and 0.5 nM, respectively. However, BPA had an IC_<50> of 5μM, which was approximately 5,000 or 10,000-fold greater than the IC_<50> of E2 and DES. In uterotrophic assays, uterus (wet and blotted) and vagina weights were significantly increased at the dose of BPA 100 mg/kg/day in OVX Sprague-Dawley rats. These studies demonstrate that BPA exhibits weak estrogenic activity in all experimental systems, and thus its migration from epoxy resins or polycarbonate products should be controlled not to exceed a safety levels for humans.
日本トキシコロジー学会の論文
2001-08-07