An occupational disease in tobacco cultivating farmers has been reported in Florida, North Carolina, and India. This disease is termed "Green-tobacco sickness" with characterized symptomsdizziness, nausea, and generalized weakness. The symptoms develop after the exposure to wet and raw tobacco leaves, and are probably caused by absorption of nicotine through the skin from the leaves. No case of this disease has been reported in Japan until now. In the present study, two cases of the disease were detected in the southern part of Kumamoto Prefecture. These cases, who were tobacco harvesters, have exhibited the "green symptoms" after cropping wet tobacco leaves every year since 7-8 years ago. One was a man aged 55, the other a 42-year-old woman. They were non-smokers and non-drinkers. These cases were diagnosed as the Green-tobacco sickness by the following reasons: 1) They showed the characteristic symptoms of the disease after cropping tobacco leaves in rainy days. 2) Those symptoms have repeatedly observed since 7-8 years ago under the same circumstances; i.e., they handled wet and raw tobacco leaves without rain coats, and were exposed to dew on tobacco leaves. They had no evidence to handle any other toxic substances at that time. 3) The symptoms usually disappeared on the next morning. 4) Food poisoning was neglected. 5) Efforts to avoid the contact with wet tobacco leaves made them free from the disease. An additional experiment using animals revealed that minimum toxic dose of nicotine through the skin was less than 21 mg/kg of body weight in the rat. Furthermore, analysis of the literatures on the Green-tobacco sickness permitted the suggestion that the toxic dose of nicotine through the skin in humans might be less than 1.96 mg/kg of body weight.

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Male Japan white rabbits were given orally with two doses of tricyclohexyltin hydroxide (TCHT, 250 mg/kg body weight) at 48 hr intervals and their carbohydrate and lipid metabolisms were investigated 48 hr after the last administration. Elevated fasting blood glucose levels and a significant in hibition of insulin (IRI, immunoreactive insulin) release in response to the intravenous glucose infusion were observed. Microscopic examination of pancreatic islets did not reveal any histological alteration. Plasma triglyceride levels were elevated in the TCHT-treated rabbits. Ultracentrifugation of plasma lipoproteins revealed a marked increase in chylomicron+VLDL (very low density lipoprotein) fraction. Rates of triglyceride secretion into plasma were not different between the TCHT-treated and the control animals. These data suggest that TCHT induces hyperglycemia and hyperlipidemia in rabbits, and the disturbance of metabolism seems to be related to the inhibition of insulin release from the pancreatic islets by TCHT.

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Recent studies have demonstrated that triphenyltin fluoride (TPTF), widely used as an agricultural chemical and a marine antifoulant, inhibits collagen-induced platelet aggregation and ATP secretion in rabbits ex vivo. The aim of the present investigation was to elucidate the mechanism of the inhibitory action of TPTF by investigating platelet malondialdehyde (MDA) formation, aggregation and ATP secretion following the stimulation by various stimuli of rabbit platelets treated in vitro with TPTF, other triphenyl metals and aspirin. Although no inhibitory effect of TPTF was found on sodium arachidonate-induced platelet aggregation and ATP secretion, TPTF inhibited dose-dependently both platelet aggregation and ATP secretion induced by collagen. The antiaggregating (IC₅₀) concentration of TPTF was 6.O×10^-6 M against collagen. In addition, TPTF prevented the collagen-, and thrombin-induced formation of MDA, but had little inhibitory effect on the conversion of exogenous arachidonic acid to MDA in platelets. In contrast, aspirin (10^-3M) inhibited platelet aggregation, ATP secretion and MDA formation induced by all the stimuli tested. Other triphenyl metals did not any inhibitory effect on collagen-, and sodium arachidonate-induced platelet aggregation and ATP secretion even at a final concentration at 10^-3M. These results suggest that TPTF has a specific inhibitory effect on platelet aggregation and ATP secretion by acting at some step(s) of platelet membrane between the binding site of collagen and thrombin and the release of arachidonic acid.

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Natural history of cadmium health effects was studied on monkeys and rabbits given cadmium chloride orally or subcutaneously for a long period: 6 male monkeys were given pelleted food containing 100μg Cd/g over a period of 180 weeks, 15 male rabbits pelleted food containing 300μg Cd/g over a period of 24 weeks, 13 male rabbits daily subcutaneous injections at a dose level of 0.5 mg Cd/kg over a period of 44 week, and 23 rabbits subcutaneous injections at a dose level of 0.5 mg Cd/kg 6 times a week over a period of 21 weeks, respectively. Sodium dodecyl polyacrylamide gel electrophoresis and silver staining (detection limit of protein: 80μg/dl) revealed that urinary protein of molecular weight 12, 000 (probably β₂-microglobulin) increased slightly prior to the appearance of proteinuria, glycosuria or aminoaciduria. Remarkable increase in urinary protein of molecular weight 12, 000 was observed by Amidoblack 10 B staining (detection limit: 4 mg/dl) around the time when renal dysfuctions appeared. The above result might suggest that the remarkable increase in urinary β₂-microglobulin is associated with renal dysfunctions, while the slight increase is caused by other mechanisms than renal dysfunctions.

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