Changes in urinary n-hexane metabolites by co-exposure to various concentrations of methyl ethyl ketone and fixed n-hexane levels.
To make clear how the n-hexane metabolism is modified by co-exposure with MEK, rats were exposed to various concentrations of MEK mixed with a fixed concentration of n-hexane. Twenty-four male Wistar rats were divided into four equal groups. Each group was exposed for 8 h to 2000 ppm n-hexane, 2000 ppm n-hexane plus 200 ppm MEK, 2000 ppm n-hexane plus 630 ppm MEK and 2000 ppm n-hexane plus 2000 ppm MEK, respectively. Free metabolites and the sum of free and conjugated metabolites of n-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 inverse proportion to the co-exposed MEK concentrations. The results suggest that augmentation of n-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 of n-hexane exposure. However, one should be careful to evaluate the exposed n-hexane concentration by urinary 2,5-HD, because n-hexane metabolism could be largely modified by co-exposure with MEK.
Shibata
E
E
Department of Hygiene, Nagoya University School of Medicine, Japan.
Huang
J
J
Ono
Y
Y
Hisanaga
N
N
Iwata
M
M
Saito
I
I
Takeuchi
Y
Y
D000280:Administration, Inhalation; D000818:Animals; D002074:Butanones / Q000494:pharmacology*; D002849:Chromatography, Gas; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006586:Hexanes / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D002074:Butanones; D006586:Hexanes; C026385:n-hexane; C005222:methylethyl ketone