Effects of MEK on kinetics of n-hexane metabolites in serum.
The neurotoxicity of n-hexane is thought to be caused ultimately by 2,5-hexanedione (2,5-HD), one of the n-hexane metabolites. The potentiation of n-hexane neurotoxicity by co-exposure with MEK, therefore, is suspected to be related to kinetics of 2,5-HD in blood. To clarify the kinetics of n-hexane metabolites in the mixed exposure of n-hexane and MEK, rats were exposed to 2000 ppm n-hexane or a mixture of 2000 ppm n-hexane and 2000 ppm MEK, and the time courses of serum n-hexane metabolites were determined. 2,5-HD in serum increased until 2 h after the end of exposure, when serum 2,5-HD concentration reached a peak of 16.35 micrograms/ml in the n-hexane-alone group. In contrast, 2,5-HD in the mixed exposure group increased much more slowly during and after exposure than in the n-hexane-alone group. It reached a peak of 2.12 micrograms/ml at 8 h after the end of exposure. Serum MBK, a precursor of 2,5-HD in the co-exposure group, was about half in the n-hexane-alone group during exposure. However, MBK decreased more slowly in the co-exposure group than in the n-hexane-alone group after the end of the exposure. The results suggest that co-exposed MEK might inhibit oxidation of n-hexane and decrease clearance of n-hexane metabolites. Co-exposed MEK did not increase serum 2,5-HD, which was considered a main neurotoxic metabolite. Therefore the enhancement of neurotoxicity could not be attributed to increased serum 2,5-HD in the co-exposed group.(ABSTRACT TRUNCATED AT 250 WORDS)
Shibata
E
E
Department of Hygiene, Nagoya University School of Medicine, Japan.
Huang
J
J
Hisanaga
N
N
Ono
Y
Y
Saito
I
I
Takeuchi
Y
Y
D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects; D002074:Butanones / Q000494:pharmacology* / Q000633:toxicity; D006586:Hexanes / Q000097:blood / Q000378:metabolism*; D006588:Hexanones / Q000097:blood / Q000378:metabolism; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D002074:Butanones; D006586:Hexanes; D006588:Hexanones; C026385:n-hexane; C005222:methylethyl ketone; C011269:2,5-hexanedione