Identification of S-(1,2-dichlorovinyl)glutathione in the blood of human volunteers exposed to trichloroethylene

Healthy male and female human volunteers were exposed to 50 ppm or 100 ppm trichloroethylene (Tri) by inhalation for 4 h. Blood and urine samples were taken at various times before, during, and after the exposure period for a nalysis of glutathione (GSH), related thiols and disulfides, and GSH-derive d metabolites of Tri. The GSH conjugate of Tri, S-(1,2-dichlorovinyl)glutat hione (DCVG), was found in the blood of all subjects from 30 min after the start of the 4-h exposure to Tri to 1 to 8 h after the end of the exposure period, depending on the dose of Tri and the sex of the subject Male subjec ts exposed to 100 ppm Tri exhibited a maximal content of DCVG in the blood at 2 h after the start of the exposure of 46.1 +/- 14.2 nmol/ml (n = 8), wh ereas female subjects exposed to 100 ppm Tri exhibited a maximal content of DCVG; in the blood at 4 h after the start of the exposure of only 13.4 +/- 6.6 nmol/ml (n = 8). Pharmacokinetic analysis of blood DCVG concentrations showed that the area under the curve value was 3.4-fold greater in males t han in females, while the t(1/2) values for systemic clearance of DCVG were similar in the two sexes. Analysis of the distribution of individual value s indicated a possible sorting, irrespective of gender, into a high and a l ow-activity population, which suggests the possibility of a polymorphism. T he mercapturates N-acetyl-1,2-DCVG and N-acetyl-2,2-DCVG were only observed in the urine of 1 male subject exposed to 100 ppm Tri. Higher contents of glutamate were generally found in the blood of females, but no marked diffe rences between sexes were observed in contents of cyst(e)ine or GSH or in G SH redox status in the blood. Urinary GSH output exhibited a diurnal variat ion with no apparent sex- or Tri exposure-dependent differences. These resu lts provide direct, in vivo evidence of GSH conjugation of Tri in humans ex posed to Tri and demonstrate markedly higher amounts of DCVG formation in m ales, suggesting that their potential risk to Tri-induced renal toxicity ma y be greater than that of females.