Metabolic interaction between toluene, trichloroethylene and n-hexane in humans

This human experimental study describes the mutual metabolic interaction between toluene, trichloroethylene, and n-hexane.

Eight healthy male volunteers were exposed to combinations of toluene (1.5 or 4 mg/min), trichloroethylene (1.5 or 4 mg/min), and n-hexane (0.3 or 1.0 mg/min) for 60 min. End exhaled air concentrations were measured before and up to 240 min after the start of exposure. The urinary excretion of hippuric acid, o-cresol, trichloroethanol, trichloroacetic acid, and 2,5-hexanedione was measured before and up to 270 min after the start of the exposures.

When the low dose rates were combined, the end exhaled concentrations were at or below the detection limit, while an increase in the dose rate of toluene increased the area under the end exhaled air concentration curve (AUC) of toluene, trichloroethylene, and n-hexane by factors of 44 (16-117) [geometric mean and 95% confidence interval], 12.8 (4.1-40.0), and 2.2 (1.2-4.1), respectively. Trichloroethylene, in turn, increased the AUC 5.0 (1.9-13.4), 25.8 (8.2-80.8) and 2.9 (1.6-5.4), respectively, whereas the corresponding values for n-hexane were 1.9 (0.7-5.1), 1.5 (0.5-4.6), and 3.2 (1.8-5.9). An 18 (range 2-34)% decrease in hippuric acid was the only interaction measured in the metabolite excretion. No correlation occurred between the individual measures of the end exhaled concentrations or the excretion of metabolites.

The study shows that the threshold for the flow-limited metabolism of the 3 solvents in humans is exceeded at liver dose rates corresponding to inhalation exposure at occupational exposure limits. At these levels there are metabolic interactions between the 3 solvents.