The relevance of 4,5-dihydroxy-2-hexanone in the excretion kinetics of n-hexane metabolites in rat and man.

Male Wistar rats were exposed to n-hexane concentrations between 50 and 3000 ppm for 8 h, and urinary excretion kinetics of the n-hexane metabolites 1-hexanol, 2-hexanol, 3-hexanol, 2-hexanone, 2,5-hexanedione, and 4,5-dihydroxy-2-hexanone were assessed. The amounts of metabolites excreted were linearly dependent on the n-hexane exposure concentration, up to an exposure of about 300 ppm. Above 300 ppm exposure the metabolite excretion indicated saturation kinetics in the metabolism of n-hexane. In its quantity, the newly described 4,5-dihydroxy-2-hexanone was the second metabolite, its amount in the urine being about ten times higher than that of excreted 2,5-hexanedione. Using gas chromatography-mass spectrometry the occurrence of 4,5-dihydroxy-2-hexanone as an n-hexane metabolite in urine of man was confirmed after exposure of a male volunteer to a mean of 217 ppm n-hexane for 4 h (laboratory exposure). Twenty-six hours after starting this exposure the excretion of 4,5-dihydroxy-2-hexanone (as a result of the n-hexane exposure) reached a level which was four times higher than the excretion of 2,5-hexanedione. The results in both rat and man indicate the relevance of 4,5-dihydroxy-2-hexanone as a metabolite of n-hexane metabolism. Formation of this metabolite may be viewed as a route of detoxification.