Characterization of new bisphenol a metabolites produced by CD1 mice liver microsomes and S9 fractions

J Agric Food Chem. 2004 Jul 28;52(15):4935-42. doi: 10.1021/jf049762u.


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.

MeSH terms

  • Animals
  • Anisoles / metabolism*
  • Cell Fractionation
  • Chromatography, High Pressure Liquid
  • Female
  • Liver / metabolism
  • Liver / ultrastructure*
  • Male
  • Mice
  • Microsomes, Liver / metabolism*
  • Spectrometry, Mass, Electrospray Ionization
  • Subcellular Fractions / metabolism


  • Anisoles
  • methoxybisphenol A