Metabolism of 2,3,4′,6-tetrachlorobiphenyl: formation and tissue localization of mercapturic acid pathway metabolites in mice

Abstract

1. 2,3,4′,6-Tetrachlorobiphenyl (tetraCB) and the corresponding ¹⁴C-labelled compound (¹⁴C-TetraCB) were synthesized. Two reference compounds, 4-methylthio- and 4-methylsulphonyl-2,3,4′,6-tetrachlorobiphenyl were also prepared and characterized.

2. TetraCB and ³⁵S-cysteine were given to groups of female mice. Formation of methyl[³⁵S]sulphonyl-tetraCB was indicated by the presence of extractable sulphuric acid-soluble radioactivity in lung, liver, kidney and fat of the tetraCB-treated mice.

3. As demonstrated by gel permeation chromatography followed by gas chromatography-mass spectrometry, the tissues of the tetraCB-treated mice contained mainly methylsulphonyl-tetraCB, minor amounts of TetraCB and traces of methylthio-TetraCB.

4. The major compound present in lung was 4-methylsulphonyl-tetraCB, indicating the presence of specific binding sites for this metabolite in lung tissue. According to autoradiography of mice injected with ¹⁴C-tetraCB, these binding sites were present mainly in the tracheo-bronchial mucosa.