EXPERIMENTAL STUDIES ON MODIFICATION AND MECHANISM OF N-HEXANE NEUROTOXICITY BY CO-EXPOSURE OF OTHER SOLVENTS.

接触有机溶剂的工人经常接触到它们的混合物。众所周知，正己烷的神经毒性会因MEK的共同暴露而增强。甲苯共暴露可降低正己烷的神经毒性。研究了其他溶剂联合暴露对正己烷神经毒性的修饰作用及其机制，结果表明：1)MEK联合暴露可使尿液中正己烷代谢产物2，5-己二酮的排泄量与MEK浓度成比例减少，血液中的2，5-己二酮也显著减少。MEK共暴露促进正己烷代谢并增加2，5-己二酮的产生从而增强正己烷的神经毒性的假设从我们的结果看来似乎是值得怀疑的。2)为了评估溶剂联合暴露的长期影响，设计了一种用于小型实验动物的自动溶剂暴露系统。正己烷和甲苯…的单一和混合暴露更多的人在一天暴露和长期暴露下成功地进行了NE。但在长期接触MEK的情况下，暴露系统被发现效果不佳。因此，中断了正己烷和MEK的长期共暴露实验，并对系统进行了改进，再次开始了长期共暴露，现在仍在继续。3)以周围神经、大脑、小脑、脑干的神经系统特异性蛋白、分析蛋白和S-100蛋白作为有机溶剂神经毒性的指标。结果表明，这些神经系统特异性蛋白是反映神经系统功能的有用指标。4)建立了尿液中2，5-己二酮的检测方法，以便更准确、更特异地检测尿液中2，5-己二酮。结果表明，要获得稳定的2，5-己二酮，样品前尿液的pH值应降至1以下，未接触正己烷的人尿中几乎检测不到2，5-己二酮，选择合适的色谱柱，正己烷接触量与尿2，5-己二酮的相关性良好。较少

The workers handling organic solvents are often exposed to mixture of them. Neurotoxicity of n-hexane is well known to be enhanced by co-exposure of MEK. We made clear that neurotoxicity of n-hexane was decreased be co- exposure of toluene. The modification and mechanism of neurotoxicity of n-hexane by co-exposure of other solvents were studied and the results are as follows;1) Urinary 2,5-hexanedione, one of n-hexane metabolites, was decreased by co-exposure of MEK in proportion to the concentration of MEK, 2,5-hexanedione in blood was remarkably decreased by co-exposure of MEK, too. The hypothesis that co-exposure of MEK facilitates metabolism of n- hexane and increase, of production of 2,5-hexanedione resulting in enhancement of neurotoxicity of n-hexane seems doubtful from our results.2) In order to evaluate the long-term effects of co-exposure of solvents, an automated solvent exposure system for small laboratory animals was devised. Single and mixed exposure of n-hexane and tolue … More ne were successfully conducted for one day exposure and for long-term exposure. But the exposure system was found not to work well in the long-term exposure of MEK. Therefore, the experiment of the long-term co-exposure of n-hexane and MEK was interrupted and the system was improved.The long-term co-exposure started again and continues now. 3) As indices for neurotoxicity of organic solvents, nervous system specific proteins, analysis and S-100 proteins were determined in the peripheral nerves, cerebrum, cerebellum and brain stem. The results showed that these nervous system specific proteins were useful indices of the effects on the nervous system. 4) The method to determine urinary 2,5-hexanedione was established by us in order to determine it more exactly and specifically. It was revealed that pH of sample urine should be decreased to less than 1 at the pretreatment in order to obtain a stable 2,5-hexanedione, and 2,5- hexanedione was hardly detected in the urine of the person unexposed to n- hexane and the good co-relation between n-hexane exposure and urinary 2,5- hexanedione was obtained using the appropriate column. Less