Products of Aqueous Chlorination of Bisphenol A and Their Estrogenic Activity

Abstract

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.

Estrogenic/Antiestrogenic Activities of Polycyclic Aromatic Hydrocarbons and Their Monohydroxylated Derivatives by Yeast Two-Hybrid Assay

“…18,20,21) The partial charge was related to estrogenic activity (Fig. 5A) as well as antiestrogenic activity (Fig.…”

Activation of sodium persulfate by magnetic carbon xerogels (CX/CoFe) for the oxidation of bisphenol A: Process variables effects, matrix effects and reaction pathways

“…10). Chlorine-substituted BPA derivatives have also been reported in the literature during the chlorination of BPA molecule through a chlorine-substitution reaction on the aromatic ring, followed by dehydration as the proposed mechanism (Gallard et al, 2004;Hu et al, 2002). Based on literature data (Gallard et al, 2004;Hu et al, 2002), 2-chloro-BPA, 2,6 0 -dichloro-BPA or 2,6-dichloro-BPA can be postulated.…”

NTP‐CERHR expert panel report on the reproductive and developmental toxicity of bisphenol A

“…(Gallard et al, 2004). The toxicity of these chlorinated bisphenol A congeners is unknown; however, there is some evidence that estrogenic activity and receptor binding remains after chlorination (Hu et al, 2002). 1.2.3.3 Potential migration from dental material: Bisphenol A is used in the manufacture of materials found in dental sealants or composites (i.e., fillings) (EuropeanUnion, 2003).…”