In vitro and in vivo estrogenic activity of chlorinated derivatives of bisphenol A

The estrogenic activity of bisphenol A (BPA) and its chlorinated derivatives, 2-(3-chloro-4-hydroxyphenyl)-2-(4-hydroxyphenyl)propane (3-ClBPA) and 2,2-bis(3-chloro-4-hydroxyphenyl)propane (3,3′-diClBPA) was assessed by determining their relative binding affinity for the human estrogen receptor-α and -β (ERα and ERβ) and also their uterotrophic activity in ovariectomized female rats. BPA and its chlorinated derivatives were active in competing with [3H]17β-estradiol for their binding to the human ERα and ERβ proteins. While 3-ClBPA and 3,3′-diClBPA competed more effectively for ERα binding than BPA (IC50 values of 2.48 × 10−5, 1.28 × 10−5, and 1.08 × 10−4 M, respectively), they had similar activity as BPA for competing the binding to ERβ (IC50 values of 1.43 × 10−5, 1.87 × 10−5, and 2.59 × 10−5 M, respectively). To determine the uterotropic activity, three doses (10, 50 and 100 mg/kg/day) of BPA and its derivatives were given to mature ovariectomized Sprague-Dawley rats for 3 consecutive days. Treatment of animals with 50 and 100 mg/kg/day of BPA or its chlorinated derivatives caused a significant increase in the uterine wet weight and the endometrial area. The results of our present study demonstrated that the affinities of 3-ClBPA and 3,3′-diClBPA for ERα were higher than the affinity of BPA, although the in vivo estrogenic activity of the two chlorinated BPAs in ovariectomized female Sprague-Dawley rats appeared to be comparable to that of BPA.