METABOLIC INTERACTION BETWEEN TOLUENE, TRICHLOROETHYLENE AND N-HEXANEIN HUMANS

Objectives This human experimental study describes the mutual metaboli c interaction between toluene, trichloroethylene, and n-hexane. Method s Eight healthy male volunteers were exposed to combinations of toluen e (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 m easured before and up to 240 min after the start of exposure. The urin ary excretion of hippuric acid, o-cresol, trichloroethanol, trichloroa cetic acid, and 2,5-hexanedione was measured before and up to 270 min after the start of the exposures. Results When the low dose rates were combined, the end exhaled concentrations were at or below the detecti on limit, while an increase in the dose rate of toluene increased the area under the end exhaled air concentration curve (AUG) of toluene, t richloroethylene, and n-hexane by factors of 44 (16-117) [geometric me an and 95% confidence interval], 12.8 (4.1-40.0), and 2.2 (1.2-4.1), r espectively. 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 corr esponding 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 on ly interaction measured in the metabolite excretion. No correlation oc curred between the individual measures of the end exhaled concentratio ns or the excretion of metabolites. Conclusions The study shows that t he threshold for the flow-limited metabolism of the 3 solvents in huma ns is exceeded at liver dose rates corresponding to inhalation exposur e at occupational exposure limits. At these levels there are metabolic interactions between the 3 solvents.