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 t o decrease urinary levels of 2,5-hexanedione dose-dependently in an ac ute or chronic coexposure with a constant level of n-hexane. This chan ge in urinary 2,5-hexanedione appears to contradict the potentiation e ffect 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.Method : 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/w eek, for 20 weeks. Motor-nerve conduction velocity (MCV), distal laten cy (DL). and urinary 2,5-hexanedione were measured every 4 weeks. Resu lts: The MCV decreased, the DL increased, and urinary levels of 2,5-he xanedione increased in the 2000-ppm n-hexane plus 2000 ppm MEK group i n comparison with the 2000-ppm n-hexane only group following 4 weeks' exposure. On the 1st day of exposure, however, coexposure to MEK decre ased urinary levels of 2,5-hexanedione dose-dependently. Conclusions: The present study showed that urinary concentrations of 2,5-hexanedion e increased with potentiation of n-hexane neurotoxicity. Urinary 2,5-h exanedione concentration does not necessarily reflect the exposure con centration of n-hexane in coexposure to n-hexane along with MEK or oth er solvents, but it may be useful as a marker in the assessment of neu rotoxicity in coexposure to n-hexane and other solvents.