Urinary 2,5-hexanedione increases with potentiation of neurotoxicity in chronic coexposure to n-hexane and methyl ethyl ketone.
OBJECTIVE
MEK (methyl ethyl ketone) is widely and frequently used as an ingredient of mixed solvents together with n-hexane. MEK is known to decrease urinary levels of 2,5-hexanedione dose-dependently in an acute or chronic coexposure with a constant level of n-hexane. This change in urinary 2,5-hexanedione appears to contradict the potentiation effect of MEK on n-hexane-induced neurotoxicity because it is believed that the toxicity of n-hexane is activated through n-hexane metabolism. We aimed to clarify how the urinary level of 2,5-hexanedione changes when MEK modifies the degree of n-hexane-induced neurotoxicity.


METHODS
A total of 32 male Wistar rats were divided into 4 groups of 8 each and were then exposed to fresh air only, 2000 ppm n-hexane only, 2000 ppm n-hexane plus 200 ppm MEK, and 2000 ppm n-hexane plus 2000 ppm MEK, respectively. Inhalation exposures were performed 12 h/day, 6 days/week, for 20 weeks. Motornerve conduction velocity (MCV), distal latency (DL), and urinary 2,5-hexanedione were measured every 4 weeks.


RESULTS
The MCV decreased, the DL increased, and urinary levels of 2,5-hexanedione increased in the 2000-ppm n-hexane plus 200 ppm MEK group in comparison with the 2000-ppm n-hexane only group following 4 weeks' exposure. On the 1st day of exposure, however, coexposure to MEK decreased urinary levels of 2,5-hexanedione dose-dependently.


CONCLUSIONS
The present study showed that urinary concentrations of 2,5-hexanedione increased with potentiation of n-hexane neurotoxicity. Urinary 2,5-hexanedione concentration does not necessarily reflect the exposure concentration of n-hexane in coexposure to n-hexane along with MEK or other solvents, but it may be useful as a marker in the assessment of neurotoxicity in coexposure to n-hexane and other solvents.
Ichihara
G
G
Department of Hygiene, Nagoya University School of Medicine, Japan. gak@tsuru.med.nagoya-u.ac.jp
Saito
I
I
Kamijima
M
M
Yu
X
X
Shibata
E
E
Toida
M
M
Takeuchi
Y
Y
D000818:Animals; D002074:Butanones / Q000494:pharmacology / Q000633:toxicity*; D004347:Drug Interactions; D006586:Hexanes / Q000494:pharmacology / Q000633:toxicity*; D006588:Hexanones / Q000378:metabolism / Q000652:urine*; D019570:Inhalation Exposure; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012997:Solvents / Q000494:pharmacology / Q000633:toxicity*
D002074:Butanones; D006586:Hexanes; D006588:Hexanones; D012997:Solvents; C026385:n-hexane; C005222:methylethyl ketone; C011269:2,5-hexanedione