Characterization of New Bisphenol A Metabolites Produced by CD1 Mice Liver Microsomes and S9 Fractions

Abstract

Bisphenol A [2,2-bis(4-hydroxyphenyl)propane] (BPA) is a widely used industrial chemical resulting in occupational and consumer exposure. BPA possesses weak estrogenomimetic activity and can be cytotoxic, though the underlying mechanisms of its toxicity toward cells are not completely understood. The metabolism of BPA by CD1 mice liver microsomal and S9 fractions was investigated. Nine metabolites were isolated and characterized using HPLC and mass spectrometry. Many of these metabolites were characterized for the first time in mammals, namely isopropyl-hydroxyphenol (produced by the cleavage of BPA), a bisphenol A glutathione conjugate, glutathionyl-phenol, glutathionyl 4-isopropylphenol, and BPA dimers. Most of these metabolites apparently share a common metabolic pathway, for which considerable evidence supports the hypothesis of the production of a reactive intermediate, and also helps explain BPA cytotoxicity.

Genotoxic and endocrine activities of bis(hydroxyphenyl)methane (bisphenol F) and its derivatives in the HepG2 cell line

“…In the present study, BPF-OH was neither cytotoxic nor genotoxic when HepG2 cells were exposed up to the concentration of 10 −7 M. Ortho-Hydroxylated-BPA (catechol-BPA) is a metabolite of BPA formed in mice liver microsomes (Jaeg et al, 2004) but also in vivo (Zalko et al, 2003). Catechol-BPA exhibits a high cytoxicity on freshly isolated rat hepatocytes .…”

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

“…Additional details of this study are included in Section 2.1.2.2. Jaeg et al (2004) reported metabolites observed following incubation of CD-1 mouse liver microsomes or S9 fractions with bisphenol A at 20-500 mM [4.6-114 mg/L]. The metabolites included isopropyl-hydroxyphenol, bisphenol A glutathione conjugate, glutythionylphenol, glutathionyl 4-isopropylphenol, 2,2-bis-(4-hydroxyphenyl)1-propanol, 5-hydroxy bisphenol A, and bisphenol A dimers.…”

Atmospheric pressure photoionization mass spectrometry as a tool for the investigation of the hydrolysis reaction mechanisms of phosphite antioxidants

“…Ionization mechanisms taking place in the ion source were investigated in the latter case and were similar to those previously reported for related structures [23]. Other applications involved the analysis of common antioxidants, slip agents and light stabilizers by SFC/APCI/MS [17] and HPLC/APCI/MS [15,19]. A few applications in the field also deal with the characterization of additives and their degradation pathways [20,21,[24][25][26][27].…”

“…So far, ESI and APCI have been the methods of choice for additive analysis [13][14][15][16][17][18][19][20][21]. Brominated flame retardants, used in a variety of consumer and industrial products, have been successfully analyzed by HPLC/ESI/MS in biological fluids [16] and tissue samples [13,14].…”