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.
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References
Abdel-Rahman MS, Hetland LB, Couri D (1976) Toxicity and metabolism of methyln-butyl ketone. Am Ind Hyg Assoc J 37: 95–102
ACGIH (1988) Threshold limit values and biological exposure indices for 1988–1989. American Conference of Governmental Industrial Hygienists, Cincinnati, Ohio, USA, pp 57
Altenkirch H, Stoltenberg G, Wagner HN (1978) Experimental studies on hydrocarbon neuropathies induced by methylethyl-ketone (MEK). J Neurol 219: 159–170
Couri D, Abdel-Rahman MS, Hetland LB (1978) Biotransformation ofn-hexane and methyln-butyl ketone in guinea pigs and mice. Am Ind Hyg Assoc J 39: 295–300
Iwata M, Takeuchi Y, Hisanaga N, Ono Y (1983) Changes ofn-hexane metabolites in urine of rats exposed to various concentrations ofn-hexane and to its mixture with toluene or MEK. Int Arch Occup Environ Health 53: 1–8
Iwata M, Takeuchi Y, Hisanaga N, Ono Y (1984) Changes ofn-hexane neurotoxicity and its urinary metabolites by longterm co-exposure with MEK or toluene. Int Arch Occup Environ Health 54: 273–281
Fedtke N, Bolt HM (1987) The relevance of 4,5-dihydroxy-2-hexanone in the excretion kinetics ofn-hexane metabolites in rat and man. Arch Toxicol 61: 131–137
Maeda K (1968) Gas chambers for the exposure of animals to organic solvents. Jpn J Ind Health (in Japanese) 10: 427–432
Perbellini L, Burgnone F, Fagginato G (1981) Urinary excretion of the metabolites ofn-hexane and its isomers during occupational exposure. Br J Ind Med 38: 20–26
Ralston WH, Hilderbrand RL, Uddin DE, Andersen ME, Gardier RW (1985) Potentiation of 2,5-hexanedione neurotoxicity by methyl ethyl ketone. Toxicol Appl Pharmacol 81: 319–327
Takeuchi Y, Ono Y, Hisanaga N, Iwata M, Aoyama M, Kitoh J, Sugiura Y (1983) An experimental study of the combined effects ofn-hexane and methyl ethyl ketone. Br J Ind Med 40: 199–203
Williams DA (1970) A test for differences between treatment means when several dose levels are compared with a zero dose control. Biometrics 27: 103–117
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Shibata, E., Huang, J., Ono, Y. et al. Changes in urinaryn-hexane metabolites by co-exposure to various concentrations of methyl ethyl ketone and fixedn-hexane levels. Arch Toxicol 64, 165–168 (1990). https://doi.org/10.1007/BF01974405
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DOI: https://doi.org/10.1007/BF01974405