1. Met-hemoglobin formation with the aminoderivative (p-chloraniline). As reported in Reports 1 and 2, amino-derivative of pCNB showed remarkable met-hemoglobin. When liver homogenate or slices were added in the system consisted of incubation medinm, p-CL-aniline and human blood, remarkable formation was observed as shown in Figure 1. According to this result, I think that the amino derivate itself cannot form the met-hemoglobin, but that it can be a met-former through being metabolized by liver cells to an active metabolite. In this case, it is easily considered that, turned into aminophenol. the amino-derivate forms met-hemoglobin but that the conjugating aminophenol derivate (5-Cl-2-aminophenol) can form only an amount of a half or one fifth or less of the met-hemoglobin as compared with the case of amino (as shown by the in vivo experiment, cf. Fig. 3 of Report 1), so the met-hemoglobin formation with the amino-detivate could not be considered to be performed only by way of its aminophenol. 2. Mechanisms of each metabolite. Summarized results of the experiments till now are showed in the Table 1. According to the results, the mechanisms of each metabolite were considered as follows: 1) The nitroso-derivate (p-Cl-nitrosobenzene) has a function of direct oxidation of hem-Fe, 2) the hydroxylamino-derivate (p-Cl-phenylhydroxylamine) may act as a perturbator to globin-protein and it or its oxydized compound oxydized hem-Fe, 3) the amino-derivate, obviously, is converted into an active substance by liver or other organs, and affects hemoglobin, and 4) the aminophenol affects as a perturbator to globin, and its oxidized compound (iminoquinone) oxidizes hem-Fe. 3. Specific inhibition of aminophenol-derivative on aerobic glycolysis. Formerly, Onishi, a member of our laboratory, investigating the influences of various derivatives of anthranilic acid manometrically on respiration and glycolysis of Ehrlich ascites tumor cells, observed that the anthranilic acid and its aminophenol-derivatives (ortho and para) remarkably inhibited only aerobic glycosis of the tumor cells specifically at low concentrations in which respiration and anaerobic glycolysis were not inhibited (10^-4 or 10^-5 mol). I, with collaboration of Fukui and Takatsuka, examining the inhibition by these derivatives and by 2-carboxy, 5-aminophenol by means of chemical estimation of lactate, noticed the same results. So supposing that the action observed was caused by the aminophenol structure of these compounds, I also tested p-aminophenol, a simple and typical aminophenolic compound. Results showed specific inhibition in aerobic glycolysis at low concentrations in which oxygen-uptake and anaerobic lactate-formation were not inhibited (cf. Table 2). The action of specific inhibition on lactate-formation is probably caused by a decrease of NAPH (reduced form) that results from over-oxidation of NAPH cattalyzing the lactate-formation, or inhibition on reduction of NAP (oxidized form), by oxidized aminophenol. Since the inhibiting does not occur at anaerobic conditions, it is presumed that compounds of amino or aminophenol oxidize NAPH in aerobic conditions by their oxidized forms and deprived of its activity. Reduction of met-hemoglobin to hemoglobin is catalyzed by NAPH, so decrease of NAPH by amino or aminophenol may probably be one of the mechanisms of met-hemoglobin formation.

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In order to clarify (1) the most suitable sound level for hearing BGM and (2) suppression of noise by BGM, I studied the influences of background music (BGM) on EEG and pulse and respiration rates. Subjects were seven health men ranging in age from 20 to 26 years. They attended to 3 experimental sessions on 3 different days. On the first day they were exposed for 1 hour to (1) BGM 50∼60 db, (2) BGM 60∼70db, and (3) BGM 70∼80db respectively. On the second day to (1) white noise 90 db, (2) white noise 90 db+BGM 70∼80 db, and (3) white noise 90 db+BGM 80∼90 db. And on the third day to (1) white noise 65 db, (2) white noise 65 db+ BGM 50∼60db, (3) white noise 60 db+BGM 60∼70 db, and (4) white noise 65 db+BGM 70∼80 db, for 30 minutes respectively. The subjects sat in an electrically shielded and sound-proof chamber which was kept at a constant temperature and humidity. EEG from left and right frontal, temporal, parietal and occipital areas were recorded monopolarly by a 12-channel electroencephalograph. The EEG was visually evaluated except that the alpha wave from the occipital area was measured. At the same time pulse and respiration rates were recorded. The results obtained are as follows: 1) The alpha wave more increased with BGM 50∼70 db than without BGM, but it decreased with BGM70∼80 db significantly. 2) In comparison between white noise 90 db and white noise 90 db+BGM 70∼80 db, the alpha wave of the examinees increased significantly in the latter. 3) In comparison between white noise 65 db and white noise 65 db+BGM 70∼80 db, the latter produced a significant increase of the alpha wave. 4) Pulse and respiration rates increased with stimuli of either white noise or BGM, but the pulse rate tended to decrease more with white noise+BGM stimuli than with mere white noise. 5) BGM seems to be effective on the human body with its proper use.

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A study was made on the test for the selective complex reaction time, which, regarded as one of the tests for the ability to dispose of informations, has been developed by our Department, as to its applicability to the aptitude for automobile drivers. The subjects were 208 healthy male employees, of whom 76 P.C. are in their twenties, of a vehicle manufacturing factory. Inquiries were made whether car accidents occurred within 10 to 24 months after this test, and the relationship between the test results of those who caused an accident and of those who did not was studied. The following are the conclusions: 1. The drivers having an accident showed a shorter reaction time, a lower overlooking rate, but a higher erring rate than those who had no accident. 2. Those who had an erring rate of over 22‰ were more inclined to cause automobile accidents. Therefore, it may be a reasonable attempt to screen out drivers with 22‰ or more as a tentative criterion. 3. The higher the frequency of automobile accidents, the shorter was the reaction time, the lower the overlooking rate, and the higher the erring rate. The difference was not significant, but there were tendencies among them. 4. Those who had as accident other than a rearend collision had a higher erring rate than those who had this. 5. The younger a driver, the higher the accident rate. The lower the driving frequency, the higher the accident rate as the first party. The first party means persons who caused accidents by themselves, and the second party means people who were involved in the accidents caused by the first party.

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The concentration of dusts in the air has been assessed by measuring only fallout particles on the roofs or on the open places. No one, however, has measured the suspended dusts which are drifting in the air around the inhabitants. The suspended dusts are so liable to variation by wind or rain that it is difficult to catch them in their whole aspects. I tried to measure the dusts being suspended indoors, outdoors and above the streets in the factory district in Kawasaki City. As a result of these measurements the concentrations were found to be 200-700 particles per cubic centimeter of air. These figures well compare with the values found in the mills or throwing plants of pottery works in Aichi, Gifu, and Mie districts. I suspected that the inhabitants in Kawasaki City were not free from respiratory impairments, for I had ever found some pneumoconiosis-patients among workers in those pottery works. And, I carried out lung X-ray examinations of those who had lived more than ten years in the factory district but had never worked in the dusty environments. I examined 498 people between 1958 and 1966, and found 132 abnormal cases out of them. In brief, these 132 cases had radiological opacities in the lung, which were similar to the appearance of pneumoconiosis. Most of them showed granular opacities (p according to the international classification) and a part of them linear opacities (L according to the international classification). This appearance is not necessarily due solely to the air pollution, but since I have never found such strong opacities in other districts, I think the air pollution as a potent factor.

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