Novel metabolites of trichloroethylene through dechlorination reactions in rats, mice and humans

Abstract

The excretion and biotransformation of [14C]trichloroethylene (Tri) has been studied in female rats and mice. Seventy-two hours after a single oral dose of 200 mg/kg, rats exhaled 52% and mice 11% of the recovered radioactivity as unchanged Tri, and 1.9% and 6%, respectively, as 14CO2. Rats excreted 41.2% of the recovered radioactivity in the urine, in contrast to mice where urinary activity amounted to 76%. The isolation of urinary metabolites was accomplished by reversed-phase HPLC, using a water-methanol gradient. After chemical derivatization, a combination of radio-GC and GC/MS was used for identification. The metabolites identified in rat urine were: trichloroacetic acid (15.3%); trichloroethanol, free (11.7%) and as the glucuronide (61.9%); dichloroacetic acid (2.0%); oxalic acid (1.3%) and N-(hydroxyacetyl)-aminoethanol (HAAE) (7.2%). In mice, trichloroethanol (free and in several conjugated forms) is the main metabolite of Tri (94.3%), but small amounts of HAAE (4.1%) and oxalic acid (0.7%) are also excreted. Only traces of dichloro- and trichloroacetic acids were found in this species. In human male subjects, HAAE was also identified as a urinary metabolite of Tri after exposure of two volunteers to 200 ppm Tri for 6 hr. The identification of HAAE and oxalic acid as metabolites indicates hydrolytic dechlorination reactions in the metabolism of Tri.