A series of studies was made to clarify the relationship of the chemical structures of 2, 3-butanedione (2, 3-BDione), 2, 4-pentanedione (2, 4-PDione) and 2, 5-hexanedione (2, 5-HDione) to neurotoxicity in terms of n-hexane neuropathy and relative neurotoxic potentials, using electrophysiological methods. These compounds are all molecularly symmetrical diketones with 4, 5 and 6 carbons respectively. A 200 mg/kg dose of each compound was administered subcutaneously five days a week to one of three groups of eight rats. This program continued for 40 weeks in the case of 2, 3-BDione and 2, 4-PDione and for 14 weeks in the case of 2, 5-HDione. Electrophysiological studies of the effects of the compounds on the peripheral nerve were performed by measuring maximum motor conduction velocities (MCV) and sensory conduction velocities (SCV) in the tail nerve of the rats. Residual latencies (RL), motor distal latencies (DL), amplitudes of the muscle action potentials (MAP), and amplitudes of the nerve action potentials (NAP) were also estimated. A significant slowing of MCV began to be observed in the 2, 5-HDione group at the 6th week and in the 2, 4-PDione group at 10th week. At 8th week, a significant decrease in SCV was also observed in these two groups. The degree of reduction in both MCV and SCV was more pronounced in the 2, 5-HDione group than in the 2, 4-PDione group. In the 2, 5-HDione group, the MCV values were more strongly affected than the SCV values. On the other hand, in the 2, 4-PDione group the SCV values were slowed more than the MCV values. The amplitudes of MAP and NAP in the 2, 5-HDione group decreased significantly at 12th week and at 10th week, respectively. In the 2, 4-PDione group, a significant decrease in NAP amplitudes was observed at 16th week and that in MAP amplitudes at 28th week. The 2, 3-BDione group showed a decrease in MAP amplitudes at 28th week. The RL and DL were markedly prolonged at an early stage only in the 2, 5-HDione group. The γ-diketone of 6, 7 and 8 normal chains of the aliphatic hydrocarbons has been reported to cause peripheral distal axonopathy with giant axonal degeneration. This disorder is named γ-diketone neuropathy. In this study, neurotoxic evidence was revealed by 2, 4-PDione, which is 5-carbon and symmetrical β-diketone. However, between the 2, 4-PDione group and the 2, 5-HDione group, some differences exist in clinical and electrophysiological features, suggesting that the mechanisms of neurotoxic action in these two compounds may differ. The compound 2, 3-BDione gave no other peripheral neurological findings than a temporal decrease in MAP amplitudes, and therefore may be considered to be non-neurotoxic.

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To investigate the dose-response relationship and the relationships among symptoms related to the vibration syndrome, 266 chain saw operators were examined. The subjects were classified into four groups according to total operating time (TOT): Group E₁ (below 2, 000 hrs, n=39), Group E₂ (2, 000-5, 000 hrs, n=76), Group E₃ (5, 000-8, 000 hrs, n=51), and Group E₄ (over 8, 000 hrs, n=100). The control group (Group O) consisted of 46 healthy subjects with very brief employment period as bush cleaners. The subjective symptoms and clinical findings were divided into four major symptom categories: circulatory disturbances, sensory disturbances, damage to muscles and joints, and general symptoms such as autonomic nerve disturbances. Each major symptom category was rated from 0 to 25 according to the severity of the symptoms observed (Table 2). The mean scores in the four major symptom categories were compared for the four TOT groups in order to study the dose-response relationship. The relationship among symptoms was investigated by cluster analysis for the four major symptom categories of all operators in each group and inferred from the significance of partial correlation coefficients between the two of the four major symptom categories calculated for each group. 1. The mean scores in the four major categories showed a significant elevation with the increase in TOT. A dose-response relationship of the vibration syndrome was proved. 2. Each major symptom category was aggravated, not independently, but in close correlation with the symptoms. The inter-symptom relationships of the vibration syndrome were confirmed. That is, very close correlations between circulatory disturbances and sensory disturbances and between sensory disturbances and damages to muscles and joints were demonstrated.

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Recently, vibrating tools such as chain saws, pneumatic hammers, rock drills, riveters, and grinders have been widely introduced in various industries in order to increase efficiency and to reduce the burden of labor. The disease due to hand-arm vibration often causes serious damages to the operator's body, more particulary of the circulatory, peripheral nervous, osteo-articular and muscular systems. Many kinds of examinations such as roentgenography, electromyography, and sthenometry have been used to diagnose the damage to the musculoskeletal systems. Among these, the measurement of muscular strength, evaluated by grip and pinch strength, is widely used in mass examinations of vibration hazards but this is not always effective in precise recognition of the decrease in muscular strength. In the present study, therefore, in order to diagnose the severity of muscle disorders objectively, serum activities of aldolase (ALD), creatine phosphokinase (CPK) and lactate dehydrogenase (LDH), which are called "muscle enzymes, " were determined in 260 chain saw operators aged 40 to 59 years. The same tests were performed for 46 healthy subjects (controls) of a similar age-range, who had a very short experience handling bush cleaners. All chain saw operators were classified into four groups according to the total chain saw operating time (TOT): 1) 58 operators with up to 2, 500 hours' experience, 2) 70 with 2, 500-5, 000 hours' experience, 3) 74 with 5, 000-10, 000 hours' experience, and 4) 58 with over 10, 000 hours' experience. The relationships were investigated in their enzyme activities on the one hand, and their TOT, muscular strength and numbness and Pain symptoms related to muscle disorders of the upper extremities on the other hand. The following results were obtained: 1) Serum ALD and LDH activities in chain saw operators increased in proportion to the decrease in muscular strength. The activity of ALD showed a tendency to increase with increased TOT. The ALD activity in the group with over 5, 000 hours' experience was significantly higher than that in the control group. However, no relationships were observed between CPK, LDH activities and TOT. 2) In chain saw operators with numbness and pain symptoms, ALD activity in the group with 2, 500 hours' experience was significantly higher than that in the control group. However, no obvious relationships were found between CPK, LDH activities and numbness and pain symptoms. 3) In chain saw operators with muscular weakness in addition to numbness and pain symptoms, ALD activity in the group with over 2, 500 hours' experience was significantly higher than that in the control group. Moreover, the chain saw operating group with over 10, 000 hours' experience showed a remarkable increase in ALD activity. However, no significant changes occurred in CPK and LDH levels. 4) The majority of the 15 chain saw operators with high levels of ALD activity showed a decrease in muscular strength and had numbness and pain symptoms in the upper extremities as well as mobility disturbances in the elbow joints. In conclusion, the results of the present study suggest that the serum ALD determination may be useful as a diagnostic aid to estimate the severity of muscle disorders caused by vibration work, especially in subjects in which this disorder was in progress.

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ALAD activity is decreased by lead as well as by the aging of red cells. Experiments were performed to clarify the factors decreasing ALAD activity by the aging of red blood cells in rabbits. Measurements were conducted on ALAD activity and lead contents in young and old cells. Lead content in both young and old RBC groups ranged from 32 to 68 and 61 to 115 ng/10¹⁰ RBC respectively. The old cells had a higher range of lead (21 to 50 ng) than the young cells. The result revealed that the increased lead content was not the main cause of decreased ALAD activity. Fully activated ALAD activity in both groups was measured by adding zinc ion (0.25 mM) and dithiothreitol (10 mM). The activity ratio of young to old cells was 1 to 0.6, suggesting that the decrease in enzyme depended on aging. The fully activated ALAD activity and oxidation of this enzyme were compared among erythroblasts, young and old cells. The ALAD activity decreased by 5-19.6% in young red cells and by 37-67% in old ones against that of erythroblasts. Treatment of the enzyme with dithiothreitol increased the activity by 12.6-19.4% in young red cells and by 24.2-27.3% in old ones. No increase in the enzyme activity in erythroblasts with dithiothreitol treatment was observed. These results suggest that the decreased activity of ALAD by aging is due mainly to the decrease of enzyme amount, partly to the oxidation of sulfhydryl groups of this enzyme, and only slightly to the increase in the blood lead.

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