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Systemic toxicity of p,p'-DDE (DDE) in aged male rats was investigated in Wistar rats by oral administration of DDE. About 10 mg/kg DDE had been daily administered for 28 days from 48 weeks to 52 weeks of age and its effects were observed subsequently. The administration of DDE did not give rise to any overt signs of toxicity. Male reproductive organs were not affected and serum biochemistry was not impaired at the dose of this experiment. Organ weights of the liver and spleen slightly increased and the thymus weight reduced with DDE administration. Serum total cholesterol and free T4 levels slightly decreased with DDE administration, albeit statistically insignificant. Our results indicated that even aged male rats were resistant to DDE exposure at the daily dose of ca. 10 mg/kg. However, metabolic and immunological changes still remained uncertain. Further investigation should be performed to reveal the entire effects of DDE on aged male rats.

Toxic effects of gallium arsenide (GaAs), indium arsenide (InAs) and arsenic trioxide (As2O3) were studied in male Syrian golden hamsters. GaAs (7.7 mg/kg) and As2O3 (1.3 mg/kg) particles were instilled intratracheally twice a week a total of 16 times, while InAs (7.7 mg/kg) was instilled a total of 14 times. As a control, hamsters were treated with the vehicle, phosphate buffer solution. During the instillation period, the cumulative body weight gain of the InAs-, but not the GaAs- or As2O3-treated hamsters was suppressed significantly, when compared with the control group. Slight to severe inflammatory responses were observed in the lung for all treatment groups. The most severe inflammatory change, characterized by an accumulation of neutrophils and macrophages, exudation, thickness of the pleura and fibrotic proliferation was found in the InAs-treated hamsters. Extensive alveolar or bronchiolar cell hyperplasia with or without keratinizing squamous cell metaplasia was observed in almost all the InAs-treated hamsters. Furthermore, squamous cell metaplasia or squamous cell hyperplasia developed in some of the InAs-treated hamsters, but not in the GaAs- or As2O3-treated hamsters. Slight to mild lesions were found in the convoluted tubules of the kidney in both the GaAs and InAs groups. From the present study, the toxic potency of these particles was provisionally estimated to be in the following order: InAs > GaAs > As2O3, at the dosage level used in this study. Furthermore, there was evidence that InAs particles could induce pulmonary, renal or systemic toxicity, and as such, InAs particles may produce pulmonary precancerous change when instilled intratracheally into hamsters.

We tried to use particle size distribution analyzer to count the number of sperm. The epididymis was removed from male Syrian golden hamsters intratracheally instilled with indium arsenide, indium phosphide or phosphate buffer only, and the homogenate of the cauda epididymidis was used as the sperm sample. The number of sperm counted with particle size distribution analyzer correlated well with the number of sperm counted with hemocytometer (r = 0.96) and the coefficient of the regression line was almost 1. When the same sperm sample was counted repetitively (n = 4), there was no difference in the coefficient of variation between the sperm number counted with particle size distribution analyzer and the sperm number counted with hemocytometer (6.4 +/- 5.8% vs. 7.8 +/- 4.0%). From these results, particle size distribution analyzer was thought to be useful for counting the number of sperm.

Chronic toxicity of indium arsenide (InAs) and indium phosphide (InP) was studied in male Syrian golden hamsters which received InAs or InP particles containing a total dose of 7.5 mg of arsenic or phosphorus by intratracheal instillations once a week for 15 weeks. As a control, hamsters were treated with the vehicle, phosphate buffer solution. During their total life span, the cumulative body weight gain of hamsters in the InAs group was suppressed significantly compared with that in the control group, but not in the InP group when compared with that in the control group. Concerning the histopathological findings of the lung, the incidence rates of proteinosis-like lesions, alveolar or bronchiolar cell hyperplasia, pneumonia, emphysema and metaplastic ossification observed in the InAs or InP group were significantly higher than those observed in the control group. From these results, it would seem that InAs and InP produced severe damage to the lungs of hamsters.

Chronic toxicity of tar from heavy-duty diesel exhaust (HD tar) was studied in male Syrian golden hamsters which received 15 mg, 7.5 mg or 1.5 mg of HD tar as the total dosages by intratracheal instillations once a week for 15 weeks. As a control group, hamsters were treated with the 0.1 ml of Tween 60: ethanol: phosphate buffer (pH 6.88, 0.25 M) solution (5.8: 8.7: 100 by volume) once a week in the same manner. The survival rate during the instillation period in the group given 15 mg of HD tar, the high-dose group of HD tar, was the lowest, and the effect was dose-dependent. However, the survival rates during the subsequent observation period showed no marked differences among HD tar treated groups. During their total life span, one papilloma in the larynx was seen in the 44 hamsters in the group given 1.5 mg of HD tar, one papilloma in the larynx was appeared in the 59 hamsters in the group given 1.5 mg of HD tar and one lung adenoma was developed in the 58 hamsters in the control group. There were no tumors in the respiratory tract in the group given 7.5 mg of HD tar. Concerning the histopathological findings of the lung, the incidence of alveolar cell or bronchiolar cell hyperplasia in the group given 1.5 mg of HD tar was significantly higher than that in the control group. From these results, although we could not observe any tumorigenicity or carcinogenic effect of HD tar, it would seem that HD tar caused weak but positive damage to the lungs of hamsters.

The dose-dependent testicular toxicity of propylene oxide (PO) was evaluated in male Wistar rats when administered by intraperitoneal injections. In 23 mg/kg, 47 mg/kg, and 93 mg/kg groups, PO was given three days a week for six weeks, while PO was given three days a week for two weeks plus once a week after the third week in a 186 mg/kg group. In the 186 mg/kg group, the epididymal weight and sperm count in the body plus tail of the epididymis decreased, while the rate of sperm with morphological abnormalities increased significantly. The number of sperm with an immature head increased slightly, although significantly, even in the 47 mg/kg group and a dose-dependent effect could be seen. The serum testosterone concentration did not change significantly and there were no apparent histopathological changes in Leydig cells in any of the treatment groups. This is the first detailed study concerning the dose-dependent testicular toxicity of PO.

Male ICR mice were administered allyl chloride at dose of 496 mg/kg, 600 mg/kg, 720 mg/kg, 864 mg/kg or 1037 mg/kg by a single subcutaneous injection. Sixteen of 25 mice died by the 7th day after the injection and LD50 was calculated 621 mg/kg body weight (95% C.I.: 522-739 mg/kg). A marked congestion with severe hemorrhage and edema were observed in the lung. Liver and kidney damages were also found, and these were characterized by the dilated sinusoids, degenerative change of hepatic cells, and focal necrosis in the liver; and necrosis of epithelium in convoluted tubules of the kidneys. Nine mice have survived by the 7th day after the injection and all of them showed a various degree of damages in the testes. The testicular lesions could be classified into two types. One type of the lesion was characterized by degeneration and exfoliation of germ cells, appearance of polynuclear giant cells in the seminiferous tubules, and mild proliferation of Leydig cells in the interstitium. In another type of the lesion, all type of cells in tubules, including Sertoli cells, and Leydig cells became necrotic. This is the first study reporting the testicular toxicity of allyl chloride.

In the present study, we tried to use the hemiorchiectomy method to examine a reversibility of the testicular damage induced by ethylene oxide (EtO). Wistar male rats were exposed to EtO at a concentration of 500 ppm, 6 hours a day, 3 days a week for 8 weeks. Thereafter we evaluated the reversibility after 13-week recovery period. From the result about a propriety of the hemiorchiecyomy method for recovery study, it was suggested that hemiorchiectomy did not affect remaining testis and epididymis after the recovery period and there was no laterality about the testicular damage just after the exposure period. Therefore we concluded that the hemiorchiectomy method could be used for recovery study for EtO-induced testicular damage. The reversibility was evaluated by comparing the damages of hemiorchiectomized testis just after the exposure period and those of remaining testis removed after the recovery period in the same rat. The result indicated that the reversibility of EtO-induced testicular damage may depend on a degree of damage just after the exposure.

Validity of five weight-height obesity indices, Broca-Katsura index, weight/height ratio, BMI, Rohrer index and Benn index were evaluated as an obesity index in male medical students of Kyushu University. Validity of them was evaluated using the following three criteria: (1) it should be highly correlated with body weight and its distribution should be independent of height; (2) it should be highly correlated with obese rate to the standard body weight of Japanese young men; (3) it can accurately classify individuals as overweight or not overweight. BMI met all three criteria in this population. Benn index proved to be not only independent of body height but also highly correlated with body weight and obese rate, though we could not evaluate this obesity index using criterion (3) because there is no generally-accepted cut-off point of overweight of it. Broca-Katsura index, weight/height ratio and Rohrer index were not independent of body height. From these results, it is concluded that BMI is the best weight-height obesity index in this population.