Changes in urinaryn-hexane metabolites by co-exposure to various concentrations of methyl ethyl ketone and fixedn-hexane levels

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Abstract
To make clear how then-hexane metabolism is modified by co-exposure with MEK, rats were exposed to various concentrations of MEK mixed with a fixed concentration ofn-hexane. Twenty-four male Wistar rats were divided into four equal groups. Each group was exposed for 8 h to 2000 ppmn-hexane, 2000 ppmn-hexane plus 200 ppm MEK, 2000 ppmn-hexane plus 630 ppm MEK and 2000 ppmn-hexane plus 2000 ppm MEK, respectively. Free metabolites and the sum of free and conjugated metabolites ofn-hexane were analyzed by gas chromatography. The main metabolite was 2-hexanol during the exposure and 2,5-hexanedione (2,5-HD) after the exposure in any group. The main metabolites, 2-hexanol and 2,5 HD, decreased in iverse proportion to the co-exposed MEK concentrations. The results suggest that augmentation ofn-hexane neurotoxicity by MEK co-exposure could not be explained only by 2,5-HD. In addition, 2,5-HD is recommended as an index for biological monitoring ofn-hexane exposure. However, one should be careful to evaluate the exposedn-hexane concentration by urinary 2,5-HD, becausen-hexane metabolism could be largely modified by co-exposure with MEK.