Commercial heterogeneous solvent products (e.g., paints, inks and ad-hesives) were collected nationwide in Japan in 1980. The vapor phase of the product containers were analyzed for volatile organic solvent constituents by means of FID-gas chromatography on two FS-WCOT (OV-101 and PEG-600) capillary columns. Of 657 products collected (358 paints, 62 inks, 165 abhesives and 72 others), 136 samples were not analyzable because 75 gave numerous peaks (presumably containing gasoline) and others had no volatile component. Among the remaining 521 samples (298 paints, 52 inks, 120 achesives and 51 others), 70 gave only one peak while others gave multiple peaks, indicating the mixture of solvents rather than single solvent was commonly used. Of the organic solvent components identified, toluene was the most popular solvent throughout paints (appearing in 80%), inks (62%), adhesives (51%) and others (65%), being detected in 70% of the total products analyzed. This popularity of toluene was followed by xylenes [predominantly m-(66%) and p-isomer (61%, )] in the case of paints, isopropyl alcohol (35%) in inks, and n-hexane (27%) and methyl ethyl ketone (23%) in adhesives, while benzene was not detected in any samples analyzed nor even in the gasoline-containing products. The concentrations of each solvent component in the vapor phases varied depending on the products, following a log-normal distribution. When the relative exposure risk of each of eight leading solvents of various chemical structures was calculated as the geometric mean concentration multiplied by the frequency of detection, n-hexane in adhesives was highest in the risk ranking while toluene and xylenes in paints scored much less because of low volatility.

The change of convulsion threshold in the rat exposed to toluene was studied in an attempt to experimentally confirm the clinical experience that paroxysm-like abnormal EEGs by injection of 50mg Bemegride and the attacks of syncope or con-vulsion occurred in some patients exposed mainly to toluene.Sprague-Dawley strain male rats had been exposed to 2, 000 ppm toluene vapor 8 hr a day for 8 weeks, and convulsion threshold and body weight were observed.he body weight of the exposed group did not increase during the first week of exposure to 2, 000 ppm toluene, but steadily increased afterward. The body weight of the exposed rats was constantly kept a little less than the control during the exposure, with no significant staistical difference.he convulsion threshold was determined by the peritoneal injection of Bemegride. The total sum of Bemegride injected in a rat till the beginning of convulsion was regarded as convulsion threshold. The convulsion threshold of the exposed group steadily became smaller than the control from 1 to 6 weeks after the beginning of exposure and there were significant statistical differences between the two groups, but after 8 weeks the convulsion threshold became larger a little and there was no significant difference.The decrease in the convulsion threshold by Bemegride suggests that some func-tional and/or organic changes should occur in the central nervous system owing to the exposure to toluene vapor.

Diencephalon-hypohysis-adrenal cortex system is one of the most sensitive systems to harmful evironmental factors and this system has an important role for the organism to exist in the harmful environment. Takeuchi, one of the authors, in the previous experiment, obtained the. results that toluene vapor might effect diencephalon-hypohysis-adrenal cortex system and that the function of this system might decrease in the chronic exposure to toluene.We think in order to make clear toxicity of organic solvents, it is very important to study the response of this system to organic solvents. And we performed the following animal experiments using male rats. As indices of the responce of diencephalon-hypohysis-adrenal cortex system, adrenal weight, 11-OHCS concentration in the blood, eosinophile count of the blood and thymus weight were determined.The results are as follows : 1) In 8 hr exposure to 2000 ppm toluene vapor, adrenal weight and 11-OHCS concentration in the blood of the exposed animal increased significantly and eosinophile count of the blood decreased significantly in comparison with the control. But, 16 hr after the end of exposure, these significant differences were not found.2) In 8 hr exposure to 1000 ppm toluene, adrenal weight and 11-OHCS concentration in the blood of the exposed animals significantly increased and eosinophile count of the blood was significantly smaller in comparison with the control as well. And in 8 hr exposure to 100 ppm toluene, the change of these indices was similar as in the case of 1000 ppm, except adrenal weight which did not significantly increase in comparison with the control. The changes of these indices in 8 hr exposure to 100 ppm toluene were larger than in the case of 100 ppm.3) In the exposure of 8 hr a day for 4 weeks to 1000 ppm toluene, adrenal weight of the exposed animals increased significantly in comparison with the control after 2 weeks and became still larger after 4 weeks. Eosinophile count increased and after 4 weeks it was significantly larger than the control. 11-OHCS concentration in the blood of the exposed animals decreased after 1 week but the difference between the exposed and the control was not found after 2 weeks.After 4 weeks, 11-OHCS concentration in the blood of the exposed animals increased but this increase was statistically not significant in comparison with the control. The reactivity of these indices against the exposure to 1000 ppm toluene chan gedbetween the exposed and the control remarkably after 4 weeks.From the results of these three animal experiments, it was found that the diencephalon-hypohysis-adrenal cortex system responses remarkably against the exposure to toluene vapor, and even in 8 hr exposure to 100 ppm toluene the changes of these indices are found, and in 4 weeks exposure to 1000 ppm toluene, the changes of these indices are cummulative.

In order to investigate the effects of toluene exposure on blood and organs of rats with respect to the concentration and the duration, the following experiments were made. Donryu strain male rats were used as the experimental animals. The exposure with low concentrations, i.e. 100 ppm or 200 ppm toluene vapour, was 8 hours a day, 6 days a week, for one year. Examinations were carried out with respect to peripheral blood, liver function, and testes. And the weight of various organs was measured. The exposure with high concentrations was carried out at 2000 ppm toluene vapour for 10, 18 or 43 weeks. And various organs were weighed and examined histopathologically after the exposure. The results of the examination of peripheral blood and liver function are: (1) In 100 ppm and 200 ppm groups appearance ratio of Mommsen's toxic granules tends to increase in linear proportion to the exposed concentration of toluene. (2) In 200 ppm group Leucoindex (N/L ratio) tends to decrease. (3) No change in erythrocyte counts and leucocyte counts and (4) No change in serum total protein and choline-esterase activity (Table 2). As to the weight of organs in 2000 ppm group, those of liver and kidneys increased each time after the exposure and those of adrenals increased only at the early stage. The weight of thymus and spleen tended decrease from the beginning and had decreased remarkably at the 43rd week of exposure (Fig.1). In 100 ppm and 200 ppm groups, the weight of testes decreased markedly, while that of liver tended to decrease anyhow, and that of heart increased (Fig.2). As to the histopathological findings, many hyaline droplets were found in the renal tubules in 2000 ppm group. The longer the duration, the more and the larger the hyaline droplets (Photo. 1 and 2). The histopathological findings of the testes in 100 ppm, 200 ppm and the control groups were: degeneration of germinal cells in four animals (33%) of 200 ppm group (Photo. 3, 4, 5 and 6).

Authors investigated the effect of toluene exposure on food and water consumption and the body weight gain in rats. Donryu strain male rats were used in the experiments. Fourty eight rats of nine weeks old were divided into two groups, 24 rats each: 2, 000 ppm group and the control group. Fourty eight rats of eight weeks old were divided into three groups, 16 rats each: 100 ppm group, 200 ppm group and the control group. All animals were maintained in gas chambers all day long. The animals of each exposed to the aimed concentration of pure toluene vapor for eight hours a day, six days a week, for four weeks, and those of the control group to only fresh air. Vapor concentrations of toluene in the chamber are shown in Table 1. Consumption of food was more in the 2, 000 ppm group, and less in 100 and 200 ppm groups than in the control group (Figs. 1 and 2). Consumption of water was more in the 2, 000 ppm group than in 100 and 200 ppm groups (Figs. 1 and 2). Increase of body weight was smaller in the 2, 000 ppm group, and lager in 100 and 200 ppm groups than in the control group (Figs, 1 and 3). Relative increase of body weight in each group correlated to that of the amount of food consumed.

In 1967 there occurred many polyneuropathy cases in household vinyl sandal manufacturers at F-disrict in Mie prefecture. In this district among 3, 210 people (788 families) most of them engaged in vinyl sandal manufacture (as of Oct, 1967). Ninety three patients suffering from polyneuropathy were found by our survey. Out of these 93 patients those suffering from sensory polyneuropathy were 53, from sensorimotor polyneuropathy 32 and from sensorimotor polyneuropathy with muscle atrophy 8 (cf. Tab. 1). The work conditions and the factors contributing to the intoxication's were investigated, and the method of prevention was suggested. The results are as follows. (1) The patients occurred in 1961 at first and the number of them increased rapidly from 1965 and showed a peak in 1967 (cf. Tab. 2). This increase was in parallel with the amount of adhesives containing "n-Hexane" used in this district (cf. Tab. 3, 4). Outbreak of many patients in winter and spring may due to poor ventilation in winter. (2) The causative substance was considered to be "n-Hexane". But "n-Hexane" on sale contains 2-methylpentane, 3-methylpentane, n-hexane, and methylcyclopentane, and the quantity of n-hexane in "n-Hexane" is about 60% (cf. Fig. 6). (3) The work conditions of the vinyl sandal manufacturers among whom many cases of "n-Hexane" intoxication occurred were as follows. 1) The work was primitive household manufacture and living rooms were used as the working place (cf. Fig. 1, 3). 2) As adhesives containing a large quantity of highly volatile "n-Hexane" were used in narrow rooms, the concentration of "n-Hexane" vapor became high and reached about 500-2500 ppm in the work room. The vapor concentrations were especially high in winter because of closed windows. (cf. Fig. 7, 8, 9). 3) Since the workers (subcontractors) were paid by the number of manufacturedgoods, their working period was unrestrictedly long and some worked for 14 hours per day (cf. Fig. 10). 4) The work intensity was high and some starched 3, 000 times per day. It seems that the more the times of starching, the heavier the degree of symptoms (cf. Fig. 11). 5) As the adhesives were used with hand brushes, the vapor concentrations were high at the site near the noses of the workers, so that they inhaled the organic solvent vapor at high concentrations. 6) As the organic solvents vapor ignite easily, the work rooms were not heated and they were working at quite low temperatures in winter (cf. Tab. 5). 7) The workers were not instructed as to the toxicity and the handling method of the organic solvents. 8) Usual health supervision was not performed at all. (4) The chief cause of the occurrence of intoxications was that a large amount of the organic solvents was used under very poor work conditions as above mentioned combined with neglected supervision. Moreover, that which gave impetus to the occurrence of the intoxication was that the easily drying adhesives containing a large quantity of "n-Hexane" were used in order to increase the number of the manufactured goods, because the pay per one of the goods was not increased for these several years in spite of the recent inflation. (5) As the urgent measure for the prevention, though instruction on the toxicity and the handling method of the organic solvents, improvement of the ventilation and the working methods, guidance by the health center and so on were made, these are only certain aspects of measures for the prevention. The danger of the intoxication may not be perfectly removed without the fundamental reform in the work conditions.

This study was carried out to make clear the chronic effect of toluene on the peripheral blood and adrenal gland. In this experiment, twenty four rats in growing period were used and divided into four groups. Rats of three groups were exposed to 200, 1000 and 2000 ppm toluene vapour for eight hours a day during 32 weeks respec-tively, and then exposed to 250 ppm benzene vapour for 39 days. Rats of the other one group were used as control and exposed to only 250 ppm benzene.During the exposure to toluene and benzene vapour, these rats were examined on body weight, erythrocyte counts, hemoglobin contents, hematocrit values, plasma total protein, leucocyte counts, eosinophiles and appearance-ratio of Mommsen's toxic granules. When the exposure to benzene finished, all rats were killed by decapitation, and the internal organs were weighed and examined patho-histologically. The results obtained were as follows.1. The hematopoietic system showed no remarkable change in this experiment. From this experiment, it seems inappropriate to estimate the toxicity of toluene by the results of blood examination.2. The values of eosinophile counts in the exposed groups decreased rapidly in the first three weeks, and then showed a gradual increase till the previous values, though the process differed by the concentration of toluene. The weight of adrenal gland per body weight were significantly lighter in the exposed groups than in the control. The patho-histological examination showed the build of the secondary hypofunction of the adrenal cortex. This fact may suggest that the function of diencephalon-hypophysis-adrenal cortex system are suppressed by the chronic toluene exposure.3. From these results, the author thinks that the present value of MAC of toluene (200 ppm) should be reconsidered in the near future.

To examine pituitary-adrenocortical functions of workers exposed to nitroglycol some investigations were made.1. Evaluating by the reaction to 25 units of ACTH-Z (ACTH-Gel), the decrease of the adrenocortical functions of dynamite workers were noted, in spite of rather healthful environmental conditions of the investigated shops. The decrease of eosinophil counts induced by ACTH injection was remarkably small.2. In case of 0.25 mg synthetic ACTH administration similar data were obtained con- cerning the decrease of circulating eosinophil counts.3. The increase of the circulating concentration of free plasma 11-hydroxycorticosteroids, which was induced by 0.25 mg synthetic ACTH administration, was obviously small in case of workers who had been exposed to nitroglycol so far.4. No significant correlation was acquired, however, between ACTH-induced eosinopenia and increment of the steroids.The general conclusions drawn from the above data are that the pituitary-adreno- cortical functions which were evaluated by Thorn's test and rapid ACTH test decreassed in the workers exposed to nitroglycol, and that the dysfunctions are connected with the outcome of sudden death in case of the serious nitroglycol poisoning.

Following the previous studies, similar biological reactions were checked on subjects exposed for longer days for the purpose of determining the MAC value of acetone. Male students 22 years old or thereabouts were exposed to acetone for 6 days, 6 hours a day, in the exposing chamber made by us for men, and were examined for 10 days since the beginning of the exposure. Acetone concentration in the air were set at 500 and 250 ppm respectively for different groups of six members each. On the 250 ppm and the control groups a working load of about 2 in the relative metabolic rate was imposed in separate experiments besides those without such load. The items and the methods of the experiments were selected according to the results of the previous studies. 1. Subjective symptoms were almost the same as those of the "one-day exposure". The complaints, e.g. objectionable odor and irritation on the mucous membrane during the exposure, and various physical disorders, which lasted until the next morning, were remarkable in the 500 ppm group but slight in the 250 ppm group irrespective of the working load. 2. Acetone concentration in the blood and the urine increased rapidly during the exposure. In the 250 ppm group it decreased to the ordinaty value in the next morning notwithstanding the working load, but in the 500 ppm group it remained fairly high at least 48 hours after the exposure. Moreover, in the 500 ppm group the course of the acetone concentrations revealed a characteristic trend with the lapse of days of the exposure. 3. Leucocyte counts of the peripheral circulating blood increased, phagocytic activity of neutrophils decreased, and eosinophil counts increased in the 500 ppm group. In the 250 ppm group almost the same results were obtained, though slight, irrespective of the working load. The difference between the 250 ppm groub and control was not statistically significant. 4. The simple reaction time showed a clear difference between the exposure groups and the control. In the 250 ppm group, the reaction time was found to delay as compared with that of the control at an early stage of the exposure, but it became nealy the same afterwards. In the 500 ppm group, though similarly the delay was noted during the exposure, the reaction time was even shorter than that of the contral during the recovery period. From the above results and those appearing in the literatures, we think that the present MAC value of 500 ppm, determined by the Japan Association of Industrial Health, is questionable, and that it is preferable to lower it tentatively to some 200 ppm.