A study on the mechanism and biomarker of neurotoxicity of organic solvents.

1.为阐明甲苯对大鼠中枢神经系统(CNS)的影响，对大鼠脑内胺进行了研究。用微透析法测定各组胺的含量。甲苯暴露增加了大鼠的活动，纹状体中的多巴胺却没有增加。结果表明，甲苯对中枢神经系统的作用机制可能与苯乙胺不同，甲苯和苯乙胺可能是研究有机溶剂对中枢神经系统毒性作用的有用生物标志物。对一名甲苯嗅探者的大脑进行了磁共振成像(MRI)检查，发现有脑萎缩和脑白质病变。在工作场所接触甲苯的工人身上也发现了类似但较轻微的大脑发现。这些结果表明，脑的MRI表现可能是阐明有机溶剂对中枢神经系统影响的有用的生物标志物。研究了己烷及其代谢产物对培养的雪旺细胞的毒性，发现2，5-二甲基呋喃毒性最大。结果表明，除2，5-己二酮是公认的主要神经毒性物质外，2，5-二甲基呋喃可能还参与了己烷的神经毒性。4.对日本现有的工业神经毒性化学品及其神经毒性危害进行了调查，并提出了相应的预防措施。

1. Amines in the brain was investigated to clarify the effects of toluene on the central nervous system (CNS) in the rat. The amines were measured with microdialysis method. Toluene exposure increased activity of rat without dopamin increase in the striatum. The results showed that toluene might have effects on CNS through different mechanism from amphethamine and the amines might be useful biomarkers for research of neurotoxic effects of organic solvents on CNS.2. The brain of a toluene sniffer was investigated with magnetic resonance imaging (MRI) and atrophy of the brain and leukoencephalopathy were found. The similar but slighter findings of the brain was found in a worker exposed to toluene in the workplace. These results showed that the findings of the brain with MRI method might be useful biomarkers to clarify the effects of organic solvents on CNS.3. The toxicity of hexane and its metabolites on the cultivated Schwann cells was investigated and 2,5-dimethylfuran was found the most toxic among them. The results showed that in addition to 2,5-hexanedione which is well known as a main causative neurotoxicant, 2,5-dimethylfuran might be involved in neurotoxicity of hexane. 4. The available industrial neurotoxic chemicals and neurotoxic hazards due to them in Japan were investigated and proposed some preventive measures against them.