Recent reports on the mechanism of the development of contact sensitivity and on the method of assessing allergencity both in vivo and in vitro are reviewed. Various cell types and two processes, afferenet and efferent limbs, involved in the contact sensitivity are discussed. Conditions for applying contact sensitizers which induce specific unresponsiveness, desensitization and antigenic competition are also discussed. Diagnostic methods for identifying contact sensitizers in vivo, patch testing, and in vitro, migration inhibition test and blastoid transformation are repoeted. Moreover, methods of assessing the allergenicity of contact sensitizers are reported centering on the guinea pig maximization testing.

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It is presumed that a part of mechanisms in the occurrence of ventricular arrhythmia or fibrillation in cases of 1, 1, 1-trichloroethane (1, 1, 1-TCE) intoxication is related to cardiac sensitization to epinephrine. Experiment was performed 1) to determine the threshold concentration of 1, 1, 1-TCE to produce cardiac sensitization, and 2) to clarify the pattern of this reaction. Mongrel dogs were anesthetized with intravenous administration of sodium pentobarbital at 25-30 mg/kg, and tracheal intubation was performed. Experiments were carried out under positive pressure ventilation. Epinephrine (5 μg/ml) was injected intravenously using drip method until bigeminy occurred on the electrocardiogram, and dose of epinephrine was measured by a drop counter. A constant concentration of 1, 1, 1-TCE was made by inside circuit vaporizer, and this was inhaled during a constant period, then epinephrine was injected until bigeminy occurred. Dose of epinephrine was compared before and after inhalation of 1, 1, 1-TCE. Appearance of cardiac sensitization by epinephrine was shown when bigeminy was induced by lesser dose of epinephrine compared to the dose before inhalation. The concentration of 1, 1, 1-TCE in inspired air was measured with gas chromatography. Inhalation of the fresh air was performed (control), the ratio of epinephrine after to before the injection of epinephrine being 1.11±0.037(Mean±S.E.). After inhalation of 1, 1, 1-TCE of which concentration was less than 4, 900 ppm during 10 minutes, dose of epinephrine was not decreased compared that before inhalation. However, dose of epinephrine decreased when insprired concentration levels was more than 8, 500 ppm. It is suggested that threshold of the cardiac sensitization may be 4, 900 to 8, 500 ppm during 10 minutes' inhalation. Significant correlation was observed between the concentration of 1, 1, 1-TCE in inspired air and the ratio of epinephrine after to before the inhalation. Increase in the product of concentration (6, 900 to 69, 000 ppm) and inhalation period (0.5 to 20 minutes) was accompanied with the gradually decreased ratio of epinephrine. This result suggests that cardiac sensitization to epinephrine is understood by a dose response relationship. In addition, ventricular fibrillation was induced by 4.73 μg/kg of epinephrine after inhalation of very high concentration (6.5%) lasting 1 minute.

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A survey of medical examinations has been made on occupational maladjustment syndrome (O.M.A.S.). We have examined and treated on 358 patients with O.M.A.S. during the past 10-15 years at two clinics; one was a company's clinic (this company has 15, 000 employees) and the other was the clinic at the Dept. of Mental Health, Osaka Prefectural Institute of Public Health during the past 15 years. Discussions have been made on 150 patients whom we directly treated. Our 358 subjects having O.M.A.S. do not include those with secondary O.M.A. resulting from psychosis, depression, neurosis and physical impairment. From that reason, our subjects are categorized in a narrow sense, in a category which may be called as "adjustment disorder." The results are summarized as follows. 1. The patients with O.M.A.S. were found almost in males and most commonly found among patients in the twenties. 2. The average rate of patients with O.M.A.S. among all the patients who visited two clinics, was 4.1% at our clinic and 16.7% at the compahy's clinic. 3. At our clinic, the number of patients with O.M.A.S. was followed by the number of those with neurosis, schizophrenia and manic-depressive psychotic zone. This trend was also the same at the company's clinic. 4. As the cause of O.M.A.S., we found the following occupational factors; fistly, transposition by selective promotion, secondly, complication of job-quality, and thirdly, promotion to middle management position. As to personal factors, i.e. as to characteristic individual personality we found mostly rigid and serious trait, next immaturity and egotism, and timidity and nervouness. 5. The relation between the occupational and individual factors was examined from the psychodynamic point of view. From the result, O.M.A.S. was classified into 5 groups which conisisted of the core group, dropout group, special job maladjustment group, transient reaction group and others. 6. In conclusion of the above mentioned data, the authors emphasize that it is important to explain and advise by the therapists not only for patients and their families, but also for their colleagues or superiors in their working place.

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An epidemiological survey of pollenosis was carried out on 96 farmers engaged in a pear orchard in Toyama prefecture. All subjects were asked about the complaint of clinical manifestations from pollens and examined by the intradermal skin test with pollen extracts. Airborne pollens were collected in the pear orchard using a gravity sampler. The results are as follows. 1. Many pollen grains of annual bluegrass (Poa annua L.) and other grasses were observed in the atmosphere of the pear orchard throughout the late April to May. Almost all pollen grains of Japanese pear (Pyrus pyrifolia Nakai) were found in the late April, although a few of them were detected during May. 2. The prevalence rate of nasal symptoms and ocular symptom of the farmers was about 20%. The peak of incidence of nasal symptoms and ocular symptom was observed in April to June. During these months, artificial pollinations of Japanese pears are carried out and the annual bluegrass pollens were wafting in the air. 3. Positive skin reactions to Japanese pear pollens were observed in 5.4% of the farmers and positive skin reactions to annual bluegrass pollens in 31.5% of them. All the positive skin reactors to Japanese pear pollens also showed the positive skin reaction to annual bluegrass pollens. The positive reaction to annual bluegrass pollens was more common among the farmers who worked more than 11 years than those worked less than 10 years. 4. Nasal symptoms such as sneeze were more common among the positive skin reactors to annual bluegrass pollens compared with the negative skin reactors. The seasonal peak of nasal and ocular symptoms was observed only among the positive skin reactors. These results suggest that the pear farmers were exposed to the pollen grains of Japanese pear and annual bluegrass, and the pollen allergens sensitized them inducing nasal and/or ocular symptoms.

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Male mice of ICR-strain (four weeks old) were divided into seven groups, of each five animals. Sodium nitrite (NaNo₂), dissolved in the physiological saline solution, was administered orally at doses of 250, 220, 110, 80, 50 and 5 mg per kg, everyday during successive seven days to each group. The forced running distance was monitored by means of the treadmill (Eiken-model) during the period of the administration and recovery. All the mice which received 250 mg/kg dose died after the single shot. The capability of muscular exercise was found decreased particularly in the groups which received 110 and 80 mg/kg of NaNO₂. Mean methemoglobin level (Met-Hb) in the blood of male mice was about 1.0%. Mean Met-Hb levels were increased to about 1.2% and 3.8% after the oral administration of NaNO₂ at the dose of 110 mg/kg everyday for successive 7 and 21 days, respectively. Met-Hb levels were measured by means of modified Evelyn-Malloy's method. In the groups which received 110 mg/kg or less, no significant changes in the body weight as well as the other physical functions were observed, as compared with those received only physiological saline solutions.

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An electrophysiological study of the neurotoxicity of 2-octanone (an analogue of methyl n-butyl ketone) and 2-hexanol (a metabolite of n-hexane) was conducted on rats as a part of the study to determine the specific molecular arrangement required for the development of peripheral neuropathy. The compound 2-octanone or 2-hexanol was administered subcutaneously in the daily dose of 400 mg/kg of each compound into the back of seven rats, weighing 290 g, 5 days per week for a period of 21 weeks. Animals treated with 2-octanone for 21 weeks failed to exhibit apparent clinical and neurophysiological evidence except a slight inhibition of weight gain and narcotic effects after treatment with the compound. The same doses of 2-hexanol for 21 weeks caused hyersalivation, gait disturbances, crossing phenomena of hind limbs and a failure of normal growth. Retardation of the conduction velocity in the motor and sensory nerve fibers and the prolonged motor latencies of the tail nerves (distal part) began to appear at the 14th week of the experiment when 9.6g in the total dose had been given to each animal. These changes were intensified in the subsequent course of the experiment. Our previous experiments and the present results showed that n-hexane barely produced peripheral neuropathy in doses over 10.5g, and that 2-hexanone (MBK), 2, 5-hexanediol or 2, 5-haxanedione never failed to prouduce a neuropathy even in doses less than 9.6g of each compound. The above results suggest that the neurotoxic potency of 2-hexanol is greater than that of n-hexane but less than that of MBK, 2, 5-hexanediol or 2, 5-hexanedione.

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Tetrahydrofuran (THF) is known to show high volatility as a physico-chemical characteristic. Therefore, workers in the plants using THF may be exposed to THF vapor at high concentrations in some cases. On the other hand, some disturbances and hazards of the respiratory system by exposure to THF have been reported. We have, therefore, performed a model experiment by using rats in order to prove the respiratory toxicity of THF. Rats were exposed to THF of about 100 and 5, 000 ppm, and observations were made on the morphological changes and ciliary functions. As follows are the results. 1. Observation of ciliary beatings 1) In the case of exposure to THF of about 100 ppm for one day, number of ciliary beats of the tracheal mucous membrane was observed to be about 760 per minute, and that of the nasal mucous membrane was about 710. These values were nearly the same as in the control group. 2) In the case of exposure to THF of about 100 ppm for one week, the mean number of ciliary beats per minute of tracheal mucous membrane was about 720, which corresponded to about 5% decrease as compared with the control. Similarly, that of the nasal mocous membrane was about 640, being about 11% decrease as compared with the control. 3) The mean number of ciliary beats per minute of the tracheal mucous membrane exposed to THF of aout 100 ppm for 3 weeks was about 680, which was about 11% decrease as compared with the control. That of the nasal mucous membrane was about 460, being about 39% decrease as compared with the control. 4) The number of ciliary beats of the tracheal mucous membrane exposed to THF of about 5, 000 ppm for one day was about 750, which showed hardly any decrease as compared with the control. The number of ciliary beats per minute of the nasal mucous membrane was about 700, which showed also hardly any decrease as compared with the control. 5) In the case of exposure to THF of about 5, 000 ppm for one week, the number of the ciliary beats per minute of the tracheal mucous membrane was about 620, being about 18% decrease as compared with the control. Also, that of the nasal mucous membrane was about 520, being about 28% decrease as compared with the control. 6) The numbers of ciliary beats per minute of the tracheal mucous membrane exposed to THF of about 5, 000 ppm for 3 weeks was about 580, being about 24% decrease as compared with the control. On the other hand, the ciliary actions of the nasal mucous membrane was mostly absent. 2. Morphological observation 1) Any morphological changes was not noted in the tracheal mucosal epithelium exposed to THF of about 100 ppm. On the other hand, vacuolation of cytoplasm, formation of compound cilla and ballooning of the cell membrane were observed in the nasal mucosal epithelium. 2) In the tracheal mucosal epithelium exposed to THF of about 100 ppm for 3 weeks, sthenia of mucous secretion and slight expansion of intercellular space were noted. In nasal mucosal epithelium, remarkable vacuolation of ciliated cells, increase of high-electron density granules, absence of cilia, and partial destruction of the cell membrane were found. 3) In the tracheal mucosal epithelium exposed to THF of about 500 ppm for one week, increased large granules of high-electron density of cytoplasm, and the decrease of cilia were observed. Defect of cellular wall and loss of cellular organella were noted in the nasal mucosal cells. 4) In the tracheal mucosal epithelium exposed to THF of about 5, OOO ppm for 3 weeks, increased large granules of high-electron density and remarkable ballooning of the cytoplasm were noted. Absence of ciliated cells or goblet cells were found at the portion damaged most severly in the nasal mucosal epithelium.

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Mutagenicity of the following nine (A-I) aromatic amino derivatives used as epoxy resin hardners was examined by Ames method. (A) 4, 4'-methylene-bis-(2-chloroaniline), (B) 1, 4-phenylene-di-4-aminophenylether, (C) 4, 4'-diaminodiphenylmethane, (D) 4, 4'-diaminodiphenylether, (E) 4-aminodiphenylether, (F) 1, 3-phenylene-di-4-aminophenylether, (G) 3, 3'-dichloro-4, 4'-diaminodiphenylether, (H) 3, 4, 4'-triaminodiphenylether, (I) 4, 4'-diaminodiphenylsulfone. Eight compounds (A-H) showed mutagenic activity to Salmonella typhimurium TA 98 and TA-100 by metabolic activation with S-9 Mix. 4, 4'-Diaminodiphenylsulfone (compound I), which has been used for the chemotherapy of leprosy and now is being used as an epoxy resin hardner, did not show any mutagenic activity not only to Salmonella typhimurium TA 98 and TA 100 but also to E. coli WP2uvrA and WP2uvrA/pKM.

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