ノルマルヘキサンの末梢神経毒性に関する電気生理学的研究

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n-Hexane (hexyl hydride, caproyl hydride) is an ingredient of petroleum, and volatile. It is widely used as a safe solvent in the industrial fields. Rcently 17 cases of peripheral neuropathy caused by industrial use of n-Hexane have been reported in Japan. In these cases, n-Hexane vapour concentrations in the work rooms were 500 to 1,000 p.p.m. and local concentrations near the sources were 1,000 to 2,000 p.p.m.. The aim of this experiment was to study the neurotoxicity of n-Hexane through animal experiments, and to confirm the critical level of the vapour concentration of n-Hexane which just causes these pathological states. The animals used in this experiment were SMA strain male mice, and were separated into 6 groups of 10 mice each. Each gorup of animals was housed in a gas-chamber. These groups were kept in n-Hexane vapour for 24 hours a day, 6 days a week, and for one year. The vapour concentrations of n-Hexane in these chambers were as follows; (the values outside the parenthesis indicate the planned concentrations and those inside indicate the mean vapour concentrations which were measured throughout the total experiment period of one year.) group 1:100 (98.6) p.p.m., group 2:250 (272.0) p.p.m., group 3:500 (551.9) p.p.m., group 4:1,000 (1030.1) p.p.m., group 5:2,000 (1903.6) p.p.m., and group 6: the control. The examinations were made on the distal part of the lower extremities of the animals. The examinations used were electromyography, stregthdurations curves, electrical reaction time, and flexor / extensor chronaxy ratio. Other investigations performed were that on gait posture and measurement of the grade of muscle atrophy of the lower extremities. Histological examinations of the distal muscles of the lower extremities were performed in some of the animals. The results of these examinations were as follows; 1) Electromyography: Complex N.M.U. voltages were observed frequently in NO. 3, 4, and NO. 5 groups and less frequently in NO.2 groups. Fibrillation voltages were observed in NO. 4 and NO 5 groups. Low voltages were rarely observed. 2) Strength-duration curves: in most of the animals of NO.4 and NO.5 groups the curves showed "denervation" type. The curves showed "mixed denervation" (incomplete denervation) types in most of the animals of NO. 2 and 3 groups an in some of the NO. 4 group. 3) Electrical reaction time: it was clearly longer in NO. 4 and 5 groups. 4) Flexor/extensor chronaxy ratio: it was significantly lower than 1.0 in NO. 4 and 5 groups, while it was near 2.0 in the control group. 5) Gait posture: in NO.4 and 5 groups animals showed abnormal gait posture which might be understood as the result of muscle weakness caused by n-Hexane. 6) Muscle atrophy: decreased muscle volumes of the lower extremities were seen more or less than in the animals of NO.4 and 5 groups. 7) Histological examinations: histological specimens of distal muscles of the lower extremities of NO.5 group animals showed neural muscular atrophy. The diagnosis was made in each animal according to the results of these examinations. The results of the examinations mentioned above might lead to a conclusion that peripheral nerve disorders of the animals were brought about through one year exposure of n-Hexane and that the effective toxic concentration of n-Hexane was 250 p.p.m. or more. Far more study might be necessary to discuss about the effects of n-Hexane on the central nervous system including the spinal cord. In view of the fact that man is several times more sensitive concerning the toxicological nervous changes than the mice, which were used in these experimental studies, the results of this sutdy might lead to the conclusion that the vapour concentration of n-Hexane in the work room should be 100 p.p.m. or less. The electrophysiological examinations mentioned above might be interesting methods to investigate the biological effects of industrial organic solvents.
社団法人日本産業衛生学会の論文
1967-08-20

著者

宮垣仁実
名古屋大学医学部衛生学教室

ノルマルヘキサンの末梢神経毒性に関する電気生理学的研究

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