Urinary 2,5-hexanedione increases with potentiation of neurotoxicity in chronic coexposure to n-hexane and methyl ethyl ketone

• Published in: International archives of occupational and environmental health 1998-03, Vol.71 (2), p.100-104
• Main Authors: ICHIHARA, G, SAITO, T, KAMIJIMA, M, XIAOZHONG YU, SHIBATA, E, TOIDA, M, TAKEUCHI, Y
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Butanones - pharmacology; Butanones - toxicity; Chemical and industrial products toxicology. Toxic occupational diseases; Drug Interactions; Hexanes - pharmacology; Hexanes - toxicity; Hexanones - metabolism; Hexanones - urine; Inhalation Exposure; Male; Medical sciences; Rats; Rats, Wistar; Solvents; Solvents - pharmacology; Solvents - toxicity; Toxicology
• ISSN: 0340-0131; 1432-1246
• DOI: 10.1007/s004200050255

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. 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. 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. 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.