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

处理有机溶剂的工人经常接触到有机溶剂的混合物。众所周知，正己烷的神经毒性会因MEK的共暴露而增强。我们清楚地表明，正己烷的神经毒性降低，共同暴露于甲苯。研究了正己烷与其他溶剂共暴露对其神经毒性的修饰作用及其机制，结果如下：1)尿中正己烷代谢物之一2,5-己二酮与MEK浓度成比例降低，血液中2,5-己二酮也显著降低。从我们的结果来看，MEK的共暴露促进了正己烷的代谢，增加了2,5-己二酮的产生，从而增强了正己烷的神经毒性的假设似乎是值得怀疑的。2)为了评价溶剂共暴露的长期影响，设计了小型实验动物溶剂自动暴露系统。正己烷和甲苯的单一和混合暴露…更多的试验成功地进行了一天暴露和长期暴露。但暴露系统在MEK的长期暴露中表现不佳。因此，中断了正己烷与MEK长期共暴露实验，对体系进行了改进。长期的共同暴露又开始了，现在还在继续。3)测定周围神经、大脑、小脑和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神经系统作用的有用指标。4)为了更准确、特异地测定尿中2,5-己二酮，我们建立了测定尿中2,5-己二酮的方法。结果表明，为了获得稳定的2,5-己二酮，预处理时应将尿样pH降至1以下，未暴露于正己烷的人的尿液中几乎检测不到2,5-己二酮，使用合适的色谱柱可获得正己烷暴露与尿液中2,5-己二酮的良好相关性。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