The role of mouse intestinal microflora in the metabolism of trichloroethylene, an in vivo study

Abstract

1 Both trichloroethylene and its metabolite, dichloroa cetic acid, produce liver tumors peroxisome prolifera tion and other adverse cellular alterations in rodents. 2 The hepatic mechanism by which dichloroacetic acid is formed is not conclusively demonstrated, but pharmacokinetic models have successfully associated its formation with trichloroacetic acid as immediate precursor. 3 Previous investigations have shown that dichloroace tic acid is formed from trichloroacetic acid by gut microflora isolated in vitro. 4 To determine the impact of gut microflora on dichlor oacetic acid formation from a trichloroethylene dose in vivo, we developed a procedure which reduced gut microflora some 3 orders of magnitude below pub lished levels. 5 The administration of trichloroethylene to control mice and to mice whose gut was practically sterile resulted in equivalent concentrations of dichloroace tic acid and other metabolites in blood and liver, but significantly different content of these metabolites in cecum contents. 6 These data indicate that gut microflora contribute minimally, if at all, to the formation of circulating dichloroacetic acid under these conditions.