Products of aqueous chlorination of bisphenol A and their estrogenic activity.
To assess the estrogenic activity potentially stemming from bisphenol A (BPA) in drinking water, APCI/LC/MS and NMR were used to identify the products of its aqueous chlorination under the following conditions: 500 microg/L bisphenol A and 1.46 mg/L sodium hypochlorite (pH 7.5) at 25 degrees C. The 13 products (4-chloro-BPA; 2,6'-dichloro-BPA; 2,6-dichloro-BPA; 2,2',6'-trichloro-BPA; 2,2',6,6'-tetrachloro-BPA; trichlorophenol; 4-isopropyl-2'-hydroxylphenol; and six kinds of polychlorinated phenoxyphenols (PCPPs)) were found in the chlorinated BPA solution. Three main pathways are proposed: (1) chlorine-substitution reactions on the aromatic ring, followed by dehydration to form the chlorine-substituted BPA, (2) chlorine substitution reactions followed by cleavage of the alpha-C on the isopropyl moiety with positive partial charge and beta'-C on the benzene moiety with a negative partial charge to form trichlorophenol and 4-isopropyl-2'-hydroxylphenol, and (3) the formation of PCPPs. Especially for pathway 2, the reaction mechanism was clarified based on semiempirical quantum mechanical calculations. The reaction proceeded by attack of the OH and Cl (from HOCl) on the alpha-C on the isopropyl moiety with a positive partial charge and on the beta'-C with a negative partial charge on the benzene moiety. The activation energies forthe HOCl/4-chloro-BPA and 2,2',6,6'-tetrachloro-BPA reactions were 0.14 and 0.15 kcal/mol, respectively. Finally, the estrogenic activity of the aqueous chlorinated BPA solution was assessed by an estrogen receptor binding assay and a yeast two-hybrid system. It was found that the binding affinity of the chlorinated aqueous BPA at 60 min was 24 times that before chlorination. The transcriptional activation-induced by products were detected by a yeast two-hybrid system based on the ligand-dependent interaction of two proteins, a human ER and a coactivator, suggesting that the chlorinated BPA solution elicits an ability to mimic the effect of the estrogen hormone.
Hu
Jian-Ying
JY
Department of Urban and Environmental Science, Peking University, Beijing, China. hujy@urban.pku.edu.cn
Aizawa
Takako
T
Ookubo
Shinji
S
D001559:Benzhydryl Compounds; D017606:Chlorine Compounds / Q000737:chemistry*; D004968:Estrogens, Non-Steroidal / Q000737:chemistry* / Q000494:pharmacology*; D010636:Phenols / Q000737:chemistry* / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000502:physiology; D018508:Water Purification; D014881:Water Supply; D015003:Yeasts; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D017606:Chlorine Compounds; D004968:Estrogens, Non-Steroidal; D010636:Phenols; D011960:Receptors, Estrogen; C006780:bisphenol A; D000098826:Bisphenol A Compounds