Environmental fate of bisphenol A and its biological metabolites in river water and their xeno-estrogenic activity.

Monitoring of bisphenol A [BPA; 2,2-bis(4-hydroxyphenyl)propane] and its biological metabolites [4,4'-dihydroxy-alphamethylstilbene (DHMS), 2,2-bis(4-hydroxyphenyl)-1-propanol (BPA-OH), 2,2-bis(4-hydroxyphenyl)propanoic acid (BPA-COOH), and 2-(3,4-dihydroxyphenyl)-2-(4-hydroxyphenyl)propane (3-OH-BPA)] in river waters was performed by solid-phase extraction and GC/MS determination. The concentrations of BPA, BPA-COOH, BPA-OH, and 3-OH-BPA in the river water ranged from 2 to 230 (8.8 x 10(-12) to 1.0 x 10(-9) M), from 5 to 75 (1.9 x 10(-11) to 2.9 x 10(-10) M), from 3 to 16 (1.2 x 10(-11) to 6.6 x 10(-11) M), and from 3 to 11 (1.2 x 10(-11) to 4.5 x 10(-11) M) ng L(-1), respectively. DHMS, an intermediate in the main degradation pathway of BPA, was not detected in any water sample. Under the aerobic conditions in the river water, BPA disappeared within 8 d of incubation, but BPA-COOH, BPA-OH, and tetraol remained in the supernatant after 14 d of incubation. For the xeno-estrogenic activity of BPA and the metabolites, their ability to bind to recombinant human estrogen receptor alpha in competition with fluorescence-labeled 17beta-estradiol was measured. Fifty percent inhibitory concentrations (IC50) of BPA, DHMS, 3-OH-BPA, and BPA-OH were approximately 1 x 10(-5), 1 x 10(-6), 3 x 10(-5), and 1 x 10(-2) M, respectively. In human cultured MCF-7 breast cancer cells, BPA increased cell numbers in a dose-dependent manner at concentrations from 10(-7) to 10(-5) M. For the BPA metabolites, DOHMS, 3-OH-BPA, and BPA-COOH caused the cells proliferation at concentrations from 10(-9) to 10(-6), from 10(-7) to 10(-6), and from 10(-5) to 10(-4) M, respectively. BPA-OH did not cause MCF-7 cells proliferation. These results indicate that BPA is mainly metabolized through oxidative rearrangement by bacteria in the river water, and intermediate bisphenols via minor metabolic pathways exist in river water. The presence of the bisphenols having the xeno-estrogenic effect suggests the necessity of monitoring those in river water, in the effluent waters from sewage plants, or in landfill leachate.