Trapping and identification of the dichloroacetate radical from the reductive dehalogenation of trichloroacetate by mouse and rat liver microsomes

A key question in the risk assessment of trichloroethylene (TRI) is the ext ent to which its carcinogenic effects might depend on the formation of dich loroacetate (DCA) as a metabolite. One of the metabolic pathways proposed f or the formation of DCA from TRI is by the reductive dehalogenation of tric hloroacetate (TCA), via a free radical intermediate. Although proof of this radical has been elusive, the detection of fully dechlorinated metabolites in the urine and the formation of lipid peroxidation by-products in micros omal incubations with TCA argue for its existence. We report here the trapp ing of the dichloroacetate radical with the spin-trapping agent PBN, and it s identification by GC/MS. The PBN/dichloroacetate radical adduct was found to undergo an intramolecular rearrangement during its extraction into orga nic solvent. An internal condensation reaction between the acetate and the nitroxide radical moieties is hypothesized to form a cyclic adduct with the elimination of an OH radical. The PBN/dichloroacetate radical adduct has b een identified by GC/MS in both a chemical Fenton system and in rodent micr osomal incubations with TCA as substrate. (C) 2000 Elsevier Science Inc.