In Japan it was about 1955 when partial substitution of nitroglycol was initiated for nitroglycerine as a staple ingredient of dynamite, and in 1960 the mixing rate rose up to 60%. In the summer of 1960 six fatal cases from nitroglycol poisoning in two dynamite factories were reported and roused keen social concern. At that time the concentration of nitroglycol in the air of cartridge-making, wrapping, or packing rooms was often above 0.5 ppm. But at present the concentration has been notably decreased through such means as improvement of exhaust ventilation, suppression of the elevation of material temperature, and especially keeping the mixing rate of nitroglycol below 30%. At present there are almost no working room where the concentration of nitroglycol is above 0.25 ppm, which is MAC in the air as adviced desirable by the Ministry of Labor for the control of nitroglycol poisoning in December 1960 and in May 1961. However, it still remains as a problem that protection of the skin of the workers in the above stated working rooms is not yet satisfactory. On the other hand, many clinical as well as experimental investigations have been made in order to provide adequate curative as well as preventive measures for nitroglycol workers. Some of them are attacked with characteristic paroxysms simulating angina pectoris often on holidays or on its next days. Although the pathologic mechanism is not yet clear, we have found ischemic changes in the patient's hearts by necropsy and in the heart muscle of rabbits experiment. At present, it is impossible exactly to predict and to prevent these paroxysms. But, on account of the fact that such paroxysms occur among workers employed for a long time, we think it is advisable to transfer to other jobs those workers with one or more clinically abnormal findings by continuous observation on long-time workers. As clinical abnormal findings in this case the Ministry of Labor is suggesting such items as fits simulating angina pectoris, chest pain, digestive disorder, headache, etc., i.e. subjective symptoms, as well as abnormality in the specific gravity of the whole blood, blood pressure, electrocardiogram, and liver functions, i.e. abnormal results by clinical tests and observations. We are suspecting further those who show abnormality by the cold pressor test, increase of fatty acids in the blood, relative increase of globulin against albumin in the blood, i.e. decrease of the ratio albumin/globulin, anesthesia of fingers, and central scotoma. (The above is a summary of the knowledge as advanced by the Committee for the Control of Nitroglycol Poisoning established in Japan Industrial Explosive Association in the autumn of 1960.)

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Since 1959 there have been four fatal, eight non-fatal, and twelve suspective cases of nitroglycol poisoning among workers in the plant to which author's hospital belongs. Of the fatal cases, two engaged in press-extending work, one in packing aged between 35 and 50, employed for 12 to 22 years. Of 27 stenocardiac paroxysms in all, 18 occured 36 to 60 hours after cessation of works and in the eary morning in most of them, preferring summer season to others. The duration of the fit were between 20 and 40 minutes. Main symptoms of the fit were acute general debility, pressure or suffocating feeling and pain in the chest, acceleration of pulse rate, and fainting. In the non-fatal cases, the process of recovery was prompt and the workers could resume the daily work as usual. Nitroglycerine was ineffective for treatment as well as for prevention of the fit, while ATP seemed to be somewhat effective for prevention. As to ECG no special finding was confirmed except atrial fibrillation in one case. On necropsies of two cases, slight hypertrophia of the left ventricle, minor sclerophia of the left ventricle, minor sclerosis of the coronary arteries, edema and transversal bands in the heart muscle, decrease of lipoids content in the adrenals, and inflammatory findings in the kidneys were observed. Although findings peculiar to the nitroglycol poisoning by tests and measurements were not confirmed in all the cases, the time relation of the occurrence of the fit to nitroglycol exposure, its duration, and its symptome made it very probable to be due to the nitoroglycol poisoning. This causal relation were made more probable by the correlations of the length of employment and the following items. That is to say, higher diastolic blood pressures at rest, decrease of the increment of systolic blood pressures on the attack of fit, decreased counts of erythrocytes, leucocytes, and eosinophils, decrease of the increment of the blood sugar level by food intake, decrease of the ratio albumin/globulin of the blood serum, increase of the concentrating capacity of the kidneys, increase of the increment of the blood pressure by adrenaline injection, all of these were marked in the employees over ten years of employment. The author discussed also the mechanism of the attack of paroxysm due to nitroglycol poisoning.

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Since August 1960 fatal cases with paroxysm of angina pectoris due to nitroglycol poisoning have been reported. By means of Heines-Brown's cold-pressor tests we have ascertained a relationship between the tone of blood vessels and nitroglycol poisoning. Subjects were workers engaged in press-extending and kneading materials containing nitroglycol. Clerical workers in the same plant were used as controls. Features in common among subjects in question were: Abnormally marked increase of diastolic pressure with little increase of systolic pressure, and decrease of pulsse pressure as a result, during exposure to cold, and delayed arrival of the maximum value of blood pressures. Those who had had paroxysms of angina pectoris showed similar results. Therefore, continued exposure to nitroglycol decreases reactivity to cold stimuli. This fact may be exlained on assuming that elevated vasoconstrictor tone leaves little space for further vasoconstriction by some provoking factors and that this state has been realized in persons exposed to nitroglycol.

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The Paralysis occurs in the hand in most of the cases, and it occurs after midnight while the patients are asleep or in the early morning after they get up. Disorders of the autonomic nervous functions have been found in 40% of the paralyzed cases by means of the pressure methods after Ashner and Czermak. Decrease of the pulse pressure has been confirmed in 61.9% of the cases by the cold-pressor test after Hines-Brown. This may serve to understand the turning pale of the fingers by exposure to cold wind outdoors. Fragility of capilaries has been ascertained by Delta-petechiometer, which revealed in 56% of the paralyzed and in 30% of the non-paralyzed 10 and more petechie at negative pressure 200mmHg of for one minute. Anemia combined with has been found in 24 of the cases, suggesting no special relation with anemia. Central relative scotoma for red has been found in 47% of the paralyzed, and dilatation or winding of the retinal in 53% of the cases. The diastolic pressure in such cases is decreases·These findings may serve to understand drug narcosis and hypotension which are common among them. There are no abnormality in the leucocyte counts and in the percentage of their classification.

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In nitroglycol workers in an explosives factory, the mean of the specific gravity of their whole blood was found to be nearly at the lowest margin of the physiologically distributed values. Even after improvements in the environmental conditions and enforced health supervision, the recovery was not yet satisfactory. Even in workers working in the place where the concentration of nitroglycol wasat about the threshold limit, the decrease of the blood specific gravity was noticed. This fact must be considered in regards the threshold limit as to chronic poisoning.

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A survey was made by means of questionnaire papers on items: age at the initiation of menstruation, age at which the menstruation become regular, states before as well as after the employment as to regularity, duration of bleeding in days, amount of the blood during one period, and subjective symptoms. Comparing the state the employment with that before it and comparing nitroglycol workers with the control, no evidence was detected that menstrual disorders were involved as a result of exposure to nitroglycol.

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From 1961 on workers in the washing, kneading, or press-extending rooms are wearing air-spouting masks, rubber gloves, and rubber aprons, and both of the latter are being worn also by those working in the room for mixing-gelatinizing. Workers in the wrapping room are using protective cream and nylon gloves, while in the packing room workers are wearing air-spouting masks and gloves, arm covers, aprons and boots all made of rubber. As preventive medicaments, calcium pantothenate, methionine, thiamine, and ascorbic acid being used. According to Tamai's experiment on mice, calcium pantothenate was found most effective, and methionine came to the next, compared with the effect of thioctic acid or thiamine, as regards change of the body weight and pathologic findings in the heart and the liver.

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Pathological findings were investigated histologically in the tissues of several organs of full-grown rabbits which had received 0.4-3.0g of nitroglycol and nitroglycerine respectively 1-30 times by subcutaneous injections. The findings were as follows. 1. Relative weight of the heart in respect to the body weight showed an increase in general, and histologically, vacuolization of the heart muscle fibre was seen in and around the nucleous or in the protoplasm. In the case in which larger amounts were administered at a time, fat degeneration and formation of hyaline transverse bands in the heart muscle were observed. These changes are thought to be due to anoxemia caused by circulatory disorders. 2. Any remarkable morphological change in the cardiac arteries was not ascertained. 3. In the liver, a decrease of glycogen content, vacuolization, and fat degeneration of liver cells were noticed. 4. In the bone marrow as well as in the spleen, fairly intensive hemosiderosis was found. 5. In the kidney, slight glomerulonephritis was obserbed.

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Nitroglycol and nitroglycerine were injected subcutaneously to dogs in an amount of 0.5g per kg of the body weight, and a marked decrease of circulating blood amount in the coronary vessels with significantly lowered blood pressure were observed 10-20 minutes after the injection. In the heart muscle, decreases of oxygen consumption as well as its utilization and metabolic impairments of carbohydrates as well as fats occurred. Especially the last disorders were marked. No metabolic change was noticed as to K, Na, Cl, or Ca. Nearly similar changes were observed in the case in which 0.05g of the substance per kg of the body weight was injected at a time every week, but the impairment of fat metabolism was more severe, being suppressed almost to nil. Therefore, decrease of cardiac function caused by nitroglycerine and nitroglycol are thought to be due to impairment of coronary circulation and of gas exchange as well as carbohydrate and fat metabolisms in the cardiac muscle.

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In order to see the effect of nitroglycerine and nitroglycol absorbed through the skin, each auricle of rabbits was smeared by 3 grams of the substance, i.e. 6 grams were used for each rabbit. And, the smeared surface was covered tight by cellophane tape and left for 1-2 months, during which appearance of Heinz bodies in the peripheral circulation was examined. After this period the animals were killed and post mortem histological changes were examined. 1. The same changes as in the case of subcutaneous injection, i.e., vacuolization and formation of hyaline transverse bands of the cardiac muscle were noticed. 2. Local skin smeared by the substance showed hyperkeratinization, acantosis and nail-leg elongation and roundcell infiltration, mainly of plasma cells. 3. Hypoplasia of the bone marrow, roundcell infiltration in the Glisson's sheath of the liver, hyperemia of the spleen, etc were noticed. 3. Two weeks after the smearing, red cells with Heinz bodies were observed in the circulating blood.

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