Recent development in toxicological study of styrene is summarized from the viewpoint of occupational health. The topics discussed are : 1) pyhsico-chemical properties, 2) industrial use, work place environments and exposure control, 3) metabolism and biological monitoring of exposure, 4) general toxicity with special reference to dose-effect/response relationship in humans, and 5) in vitro and in vivo mutagenicity, mammalian teratogenicity and human/subhuman carcinogenicity. With 137 references.

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Of fifteen dogs each five of them inhaled 1, 1, 1-trichloroethane (1, 1, 1-TCE) at the levels of 700, 1500, and 2, 000 ppm respectively for one hour. Changes in 1, 1, 1-TCE concentrations in the expired air, arterial blood and venous blood of dogs were measured from the beginning of exposure until one hour after the end of exposure. The results obtained were as follows. 1. Cumulative uptakes of 1, 1, 1-TCE in one hour exposure were 27.3 mg/kg at 700ppm, 44.7 mg/kg at 1, 500 ppm and 71.2 mg/kg at 2, 000 ppm. 2. Excretion ratios of 1, 1, 1-TCE in hour after the exposure were 66-71% at all the three levels of exposure. 3. During the exposure, highly significant negative corrrelation was seen between arterial/venous blood concentration ratio and expired/inspired air concentration ratio. In the post-exposure period, highly significant positive correlations were seen between expired air concentration and venous or arterial blood concentration. 4. The mean ratio of the total absorption value to the total inspired value was 14% at all the three levels of exposure. 5. From these results, the authors examined the multiple regression equations with two independent variables x and z which are shown as follows. a) During the exposure period, Y₁: Cumulative absorption solvent by the dog (mg/kg) X₁: Time of exposure (min) Z₁: Level of the solvent value in the ambient air (μg/ml) logY₁=-0.526+0.622logX₁+0.905logZ₁ b) Post exposure period, Y₂: Cumulative excreted solvent value by the dog (mg/kg) X₂: Time after the end of exposure (min) Z₂: Cumulative absorbed solvent value by the dog at the end of exposure (mg/kg) logY₂=-2.300+0.609logX₂+0.858logZ₂ We assumed that both equations are very fit and signficant.

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It has been known that CA change during physical exercises and associate with dynamic aspects of the coagulation fibrinolysis system of the blood. Therefore, we studied fibrin and fibrinogen degradation products (FDP) under physical exercises together with LDH, CPK, LA, CRE, Na, K and P.1) College students of Department of Education majoring in sciences of physical education significantly increased activities of CPK and LDH during the training for volleyball games compared with the pre-training values. This increment was remarkable for those who exercised hard, that is, who were loaded with large physical stress. 2) Changes in LA were included in the range of its normal values. Freshmen who had not been traind much and consequently whose adaptability for physical stress was insufficient increased the LA level sighificantly relative to the pre-training level. 3) Although changes in P were included in the range of its normal values, significant increase was observed by physical stress. Examinations by individual disclosed that a tendency of changes in P was similar to that in CPK and FDP. 4) The tendency of changes in FDP agreed with that in CPK and P and an increase was observed for those who were loaded with large physical stress. It was further observed that especially for those who were loaded with large mental stress together with physical stress the increase in FDP was evident. Therefore, it has been suggested that FDP can be used as an index of biotic effects of not only physical stress but also mental stress.

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We assumed the possibility of adopting FDP as an index of fatigue and carried out examinations upon various load conditions causing stress. For our observations other indices which are thought effective for fatigue evaluation, such as urine CA, flicker values, response time, Uchida's Kraepelin test, and examination of subjective symptoms recommended by the Japan Association of Industrial Health, were adopted at the same time. 1) Both mental and physical loads increased FDP values both in serum and in urine. 2) These changes in FDP values agreed comparatively well with the changes in CA by load. 3) The FDP value showed changes by load which was so light that it did not induce functional deterioration detectable by the response time or the flicker value which was considered to be one of effective physiological indices. 4) The extent or degree of subjective symptoms found by the survey agreed well with the changes in FDP values. Through above examinations, FDP values of serum and urine seem to be useful as an index of transient fatigue; especially they can well reflect mental fatigue which cannot be indicated well by other biochemical indices. Also FDP can well show individual characteristics, namely FDP indicates comparatively satisfactorily both individual sensitivity and specificity. Furthermore, this method does not require special techniques and examinations can be done simply.

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In order to study the effects of lead in the circulating peripheral blood on the erythrocyte membrane, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of protein in the erythrocyte membrane was performed in 28 men exposed to lead in a scrap lead refining factory and 18 men working in railway construction as the controls. Furthermore, in order to corroborate the effects in vitro experiments by SDS-PAGE of protein in the mixture of human erythrocyte membranes with added lead were performed. 1) In the lead workers compared with the controls, SDS-PAGE of protein in the erythrocyte membrane showed that relative concentrations of bands 1, 2, 3 and 4.1 were significantly decreased while those of bands 2.3, 6 and 7 were significantly increased. 2) SDS-PAGE of protein in the in vitro experiment showed that the relative concentrations of bands 1, 2, 3, 4.1 and 4.2 were decreased while those of bands 2.3, 4.5, 5, 6 and 7 were increased. Therefore, these results show the same trends as those of the in vivo experiments. 3) For the lead workers, the correlation coefficients between blood lead and bands 2, 2.3 and 3 were r=-0.414 (p<0.05) r=0.545 (p<0.01) and r=-0.509 (p<0.01), respectively. Also a higher coefficient of correlation (r=-0.777, p<0.001) was found between bands 2 and 2.3. 4) As the molecular weight of substances showing bands 2 and 2.3 were 220700 and 133800, respectively, according to PAGE using molecular weight markers, band 2.3 is considered to be due to a cleavage product from that of band 2. From these results, we summarized as follows. Lead combined with erythrocyte membrane decreases the band 3 penetrating lipid bilayer, and that causes the decrease of membrane transportation. On the other hand, the variation of band 2 and 4.1 influences the spectrin-actin network. This is considered to be one of the reasons that MCV is decreased.

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In Japan the extrinsic asthmatic bronchitis and the interstitial lung disease were legally recognized as occupational bronchopulmonary diseases due to the hard metal dust for the first time in February, 1981. But their pathogeneses are still unknown. In 1981, we examined clinically 247 workers employed in a hard metal factory (14 powder workers, 20 press operators, 40 shapers, 29 sintering workers, 119 grinders, and 25 others). The clinical evaluation was based on respiratory questionnaires, physical examinations, chest X-ray films and pulmonary function tests (VC, FEV, D_LCO). These thorough investigations for all workers exposed to hard metal dust was thought to be the first trial conducted in this country. As a result, 27 workers with chronic bronchitis were found, but the relation between the chronic bronchitis and the exposure to the hard metal dust could not be confirmed. Three workers complained of asthmatic attacks without any relation to such dusty work. Pulmonary function tests revealed seven workers with restrictive ventilatory impairment, two with obstructive impairment and one with mixed impairment. Out of the seven, one with restrictive disorder revealed micronodulations on the chest X-ray film, and four of them had old tuberculous scars and/or pleural adhesions. Two of them had neither respiratory symptoms nor abnormal chest X-ray findings. Two with obstructive impairment and one with mixed ventilatory impairment complained of persistent coughs and sputa and/or asthmatic attacks. Chest roentgenograms taken from three workers engaged in shaping, press operation and powder handing, respectively, showed diffuse micronodulations mainly in bilateral middle lung fields. The findings were nearly the same as those in chest X-ray films taken three years ago. Two of them had been exposed exclusively to the hard metal dust and had had the longest exposure history among the workers in this factory. These radiological changes may represent nuisance particle shadows which were due to accumulations of hard metal dust predominantly of tungsten carbide. Serial chest roentgenograms of one worker, who had been employed as a press operator for 5 years and then as a shaper for 4 years, revealed progressive reticulonodular opacities with confluent tendency in upper and middle zones bilaterally. Previously he had been exposed to iron and sand dusts for only one year. Lung specimens obtained by means of transbronchial lung biopsy showed peribronchiolar and perivascular fibrosis with black deposited particles and peribronchiolar cellular aggregation. Particles in speciments examined by X-ray microanalysis were identified as tungsten. This case is highly suspected to be related to hard metal dust inhalation and to his individual susceptibility. Japan Association of industrial Health has not yet proposed recommendations to the industry as to the threshold limit values for cobalt, tungsten etc. Therefore, all the hard metal industries have to undergo thorough medical and environmental evaluations by themselves to take preventive and precautionary actions without delay.

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It is reported that circulatory shock following inhalation of 1, 1, 1-trichloroethane (1, 1, 1-TCE) at high concentrations may be related to the cause of death. However, a mechanism of the fall in the blood pressure due to 1, 1, 1-TCE inhalation is still uncertain. The purpose of this experiment was to investigate the mechanism of systemic hypotension due to 1, 1, 1-TCE inhalation using hemodynamic and neuroelectrophysiologic technics. Adult fifty mongrel dogs were anesthetized with sodium pentobarbital, injected at 25-30 mg/kg intravenously. Tracheal intubation was performed, and experiment was carried out under positive pressure ventilation. Various concentrations of 1, 1, 1-TCE vapor were made by an inside circuit vaporizer to be inhaled during a period of thirty seconds to two minutes. Concentrations of 1, 1, 1-TCE in the inspired air were measured by gas chromatography. Aortic blood flow and pressure were measured by an electromagnetic flow meter (Nihon Kohden, MFV-1100) and a strain gauge transducer (Nihon Kohden, MPU-0.5), respectively, in thoracotomized dogs. Total peripheral vascular resistance (T.P.R.) was calculated from aortic blood pressure/aortic blood flow. After incision of the left flank, left kidney was exposed. Then the efferent renal sympathetic nerve activity was recorded using bipolar platinum electrodes. In acute inhalation experiment, the threshold concentration of 1, 1, 1-TCE to produce a fall in blood pressure was 0.4 to 0.5% in inspired air, and a dose-response relationship between the fall in the blood pressure and the concentration of 1, 1, 1-TCE which exceeded the threshold level was observed. T.P.R. obviously decreased during inhalation, and gradually returned to pre-inhalation level after termination of inhalation. Therefore, it is suggested that the fall in the blood pressure following 1, 1, 1-TCE inhalation may be related to the decrease in T.P.R. In addition, a doseresponse relationship between the change of T.P.R. and the concentration of 1, 1, 1-TCE was observed. Efferent renal sympathetic nerve activity increased, associated with a slight fall in the blood pressure, following inhalation of relative low concentrations of 1, 1, 1-TCE, whereas, renal sympathetic nerve activity decreased, accompanied with a marked decrease in the blood pressure, following inhalation of high 1, 1, 1-TCE concentrations. Such reversion as the effect of the renal sympathetic nerve activity was observed in the range of the lowered blood pressure level at 70-80 mmHg, following inhalation of intermediate concentration of 1, 1, 1-TCE. Reactions of the renal sympathetic nerve activity following inhalation were not affected by bilateral cervical vagotomy. On the other hand, the increase in the renal sympathetic nerve activity following inhalation of relatively low concentrations was disappeared by transection of both vagi and carotid sinus nerves. However, the decrease in the activity following inhalation of high concentrations was not affected by such transection. From these results, it is suggested that systemic hypotension due to 1, 1, 1-TCE inhalation at high concentrations may be related to the decrease in T.P.R., and may be induced by a mechanism which is not related to the sympathetic nervous system and other neurogenic mechanisms.

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There are many kinds of chromium compounds in nature, and most of them exist as Cr⁶⁺- and Cr³⁺-compounds. Generally, these two kinds of compounds are stable in normal circumstances. When the chromium in biomaterial or in atmospheric substances is analyzed, the samples are usually ashed with strong acids at high temperatures to destroy the organic components, and chromium compounds are changed to water soluble salts in this ashing process. And then chromium is determined in various methods. The relation between the used acids and the behavior of chromium were investigated, and the following facts have been cleared. Though the total amount of chromium in the samples remains constant, the valence of chromium is apt to change easily in the ashing process (Cr⁶⁺&lrhar;Cr³⁺). As Cr³⁺ is more stable than Cr⁶⁺ in acid solution, the reductive reaction proceeds mainly as (Cr⁶⁺→Cr³⁺). But each acid has the peculiar reductive action on Cr⁶⁺. Even if the same acid is used, its reductive power changes very sensitively as the used conditions are altered. The reductive action of mixed acid differs from that of original acid remarkably. Certain acid has the oxidizing action on Cr³⁺. Thus, the mechanisms and reactions between strong acids and chromium are very complicated. So, for the determination of the amounts of individual Cr⁶⁺ and Cr³⁺, the oxidizing or reductive action of the used acid must be considered causiously.

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Male mice were exposed to three levels of carbon monoxide, i, e. 500, 1, 000 and 3, 000 ppm for 60, 10 and 7 minutes per day respectively. Durations of the exposure were 1 and 5 days and 3, 6 and 9 weeks. As the effect of carbon monoxide exposure, induction of the drug metabolizing enzyme was observed, which was ascertained by the decrease of sleeping time by pentobarbital and by the increase of activities of liver microsomal p-nitroanisole demethylase and of aniline hydroxylase. These results should be due to an adaptive response to carbon monoxide exposure, but the mechanisms of the enzyme induction were not fully explained in this study. In 5 days' exposure to carbon monoxide, there was a dose-response relationship between the degree of carbon monoxide exposure and the extent of enzyme induction. But in the prolonged exposure to higher concentrations of carbon monoxide (1, 000 and 3, 000 ppm), the increase of drug metabolism became less pronounced and 9 week's exposure to 1, 000 ppm carbon monoxide, little induction of the drug metabolizing enzyme was observed. These results suggest that the induction of the drug metabolizing enzyme by carbon monoxide exposure has a certain limit.

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5°C-water 10-minute immersion test, generally used in Japan, is useful to diagnose vibration diseases. But severe pains during the immersion is troublesome. We strdied the availability of 10°C-water 10-minute immersion test to reduce the pain during the test. Subjects were forty-nine chainsaw operators, nineteen patients with vibration disease, and twelve controls. The same subject underwent both 5°C and 10°C immersion tests. The following results were obtained. 1) Skin temperatures in the highest score group after the immersion tests both at 5°C and 10°C was lower than that in the control group. Mean skin temperatures for the last five minutes during the immersion and the recovery activity in both the immersion tests showed a similar trend among subjects groups. Skin temperatures in patients under medical treatment (R'group) did not differ from those in the control group. 2) Hyperemia time by nail press test in the R'group and in the high score group after both immersion tests was longer than that in the control group. But this difference between chainsaw operators and the control group after 5°C immersion test was more marked than that after 10°C immersion test. 3) Vibratory sense as well as pain sense in the R'group and in the high score group after both immersion tests were less sharp than those in the control group. 4) Skin temperatures, nail press test, vibratory sense, and pain sense after 5°C immersion test and those after 10°C immersion test showed statistically significant positive correlation. 5) 10°C immersion test is as effective as 5°C immersion test in finding nervous disorders, but 5°C immersion test is more effective than 10°C immersion test in finding circulatory disorders. However patiens with Raynaud's phenomena or moderate circulatory disorders can also be found even by 10°C immersion test. 6) Cold water immersion test revealed disorders not only in skin temperature and by nail press test but revealed also disorders in vibratory sense and pain sense, therefore it is desiable that cold water immersion test should be done in the examination of vibration diseases.

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