Abstract
Objectives. Animal studies demonstrate that the formation of the neurotoxic metabolite, 2,5-hexanedione (HD) decreases during co-exposure to methyl ethyl ketone (MEK). The aim of the present study was to describe the influence of co-exposure to MEK on n-hexane toxicokinetics in humans.
Methods. Four healthy male volunteers were exposed, on different occasions, to three different combinations of vapor of these solvents, namely: 50 ppm n-hexane alone, and in combination with 100 and 200 ppm MEK, for 2 h during light physical exercise (50 W). Arterialized capillary blood, venous blood, and urine were sampled at scheduled intervals before, during, and up to 24 h after the onset of the exposure. HD in venous blood and urine was analyzed by gas chromatography with electron capture detector after derivatization with O-(pentafluorobenzyl) hydroxylamine.
Results. Serum HD decreased with increasing exposure to MEK at 2 h after the onset of the exposure, from an average concentration of 2.2 µmol/l in the n-hexane-alone condition to 1.2 and 0.44 µmol/l in the 100 and 200-ppm MEK conditions, respectively. The area under the concentration–time curve of HD in venous blood and the concentration of HD at 2 and 4 h after the end of exposure decreased with increasing MEK. These results suggest that combined exposure to MEK and n-hexane at occupationally realistic levels depresses the metabolism of n-hexane in a dose-dependent fashion.
Conclusion. The internal exposure to the toxic metabolite of n-hexane decreased with co-exposure to MEK in a dose-dependent fashion. Estimation of external exposure by HD in serum or urine could be confounded by the co-exposure to MEK.
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Shibata, E., Johanson, G., Löf, A. et al. Changes in n-hexane toxicokinetics in short-term single exposure due to co-exposure to methyl ethyl ketone in volunteers. Int Arch Occup Environ Health 75, 399–405 (2002). https://doi.org/10.1007/s00420-002-0325-5
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DOI: https://doi.org/10.1007/s00420-002-0325-5