The metabolism of higher chlorinated benzene isomers

The metabolism of the isomeric tri- and tetrachlorobenzene isomers, penta- and hexachlorobenzene was investigated in the rabbit. The major urinary metabolites of the isomeric tri- and tetrachlorobenzenes were identified as the corresponding tri- and tetrachlorophenols whose structures were confirmed by chromatographic analyses. The genesis of the formation of metabolites is discussed in terms of their possible arene oxide intermediates in which the NIH shift of a chlorine atom is observed in the oxidation of many of the isomers. Pentachlorobenzene is metabolized to give both pentachlorophenol and a dechlorination-hydroxylation product which was identified as 2,3,4,5-tetrachlorophenol. The hexachlorobenzene substrate did not give any phenolic metabolites.