Identification of the n-heptane metabolites in rat and human urine

Abstract

Numerous n-heptane metabolites have been identified and quantified by gas chromatography and mass spectrometry in some tissues and in the urine of Sprague Dawley rats exposed for 6 h to 1800 ppm n-heptane. 2-Heptanol and 3-heptanol were the main biotransformation products of the solvent. 2-Heptanone, 3-heptanone, 4-heptanol, 2,5-heptanedione, gamma-valerolactone, 2-ethyl-5-methyl-2,3-dihydrofuran and 2,6-dimethyl-2,5-dihydropyran were also found as metabolites of n-heptane. In five shoe factory workers and in three rubber factory workers the mean exposure to technical heptane was measured (n-heptane ranged between 5 and 196 mg/m3). In the urine collected at the end of their work shift some n-heptane biotransformation products were found: 2-heptanol, 3-heptanol, 2-heptanone, 4-heptanone and 2,5-heptanedione. 2-Heptanol was the main n-heptane metabolite and its urinary concentrations ranged between 0.1 and 1.9 mg/l. Urinary 2,5-heptanedione was detectable only in some samples and at very low concentration (0.1-0.4 mg/l). These data suggest that n-heptane can be considered as a neurotoxic product, since it gives rise to 2,5-heptanedione, but the small amount of the urinary metabolite is very unlikely to cause clinical damage to the peripheral nervous system.