Kenzaburo Tsuchiya

Biological response and subjective symptoms in low level lead exposure.

Workers occupationally exposed to lead in the air of up to 60μg/cu m were examined for blood lead (Pb-B), urinary δ-aminolevulinic acid (ALA), erythrocyte ALA dehydrase (ALAD), hemoglobin, hematocrit, red blood cell count, and subjective symptoms. The Pb-B and ALAD showed consistent increases and decreases, respectively, corresponding with the levels of Pb exposure, while other tests revealed no association with Pb. The range of Pb exposure as expressed by Pb-B was up to 50μg/100 gm. Subjective symptoms and urinary ALA are not likely to be increased at the Pb-B level of about 50μg/100 gm and less.

Increased urinary beta 2-microglobulin in cadmium exposure: dose-effect relationship and biological significance of beta 2-microglobulin.

A study on the general population from both cadmium-polluted and control areas and on cadmium alloy workers indicates that beta 2-MG in urine is very closely correlated with aging, but it indicates an association with cadmium exposure. However, the age factor is stronger than cadmium exposre in both polluted and control areas among persons without clinical proteinuria. On the other hand, cadmium exposure is most likely correlated with beta 2-MG even in nonpolluted areas. Thus it seems that there is no noneffect level of cadmium dose in affecting the elevation of beta 2-MG in urine. beta 2-MG in serum indicated a very close correlation with cadmium in blood among cadmium alloy workers. This may suggest that an increase of beta 2-MG in both blood and urine in an early stage of cadmium exposure is caused by the increased level of beta 2-MG in blood, which may be a result of stimulation due to cadmium, but not necessarily by the clinical dysfunction of reabsorption of beta 2-MG in the renal.

Variation of Cadmium Accumulation among Japanese

Human liver, renal cortex, and heart muscle from 394 autopsied Japanese who had lived in eight districts of Japan were sampled. Subjects included 200 males between 0 to 89 yr of age and 194 females between 0 to 94 yr of age. Cadmium, copper, and zinc in both liver and renal cortex, as well as cadmium in heart muscle were compared by district, sex, age, and smoking habits. Statistical results revealed that the difference of each heavy metal distribution by eight districts is significant and that cadmium and zinc levels in liver and renal cortex sampled from north-central Japan were the highest. This probably results from the larger intake of dietary cadmium and zinc via rice since this area is known as one of the better rice growing regions in Japan. Although there is a lack of precise information on smoking habit, cadmium in liver and zinc in liver and renal cortex of males smoking eight or more cigarettes per day were statistically higher than that of nonsmokers and those who smoked less than seven cigarettes per day. However, cadmium in renal cortex was not significant between the two smoking groups. Further studies should be performed to determine the health significance of an increased intake of cadmium by populations from the viewpoint of global biogeochemistry.

An epidemiological study of occupational bladder tumours in the dye industry of Japan.

This report studies 100 cases of occupational bladder cancer which were reported between 1949 and 1970 by large companies producing dye. It is estimated that in fact a great many more than 100 cases may have developed during the 56 years from 1914 to 1970, as this period corresponds with the beginning of dye production to the termination of benzidine and beta-naphthylamine manufacture in Japan. New cases of occupational bladder tumour should diminish significantly in the future in Japan on account of the prohibition of the production of beta-naphthylamine and benzidine. However, it is important to follow-up continuously workers who have been exposed to these amines. In Japan no cases of occupational bladder tumours from the rubber industry have been reported. It is emphasized that prospective epidemiological studies are required not only in the rubber industry but also in other industries where amines may constitute an occupational hazard.

Pulmonary deposition and clearance of a nickel oxide aerosol by inhalation

Wistar male rats were exposed to nickel oxide (NiO) aerosols (mass median aerodynamic diameter, 1.2 μm). The average exposure concentration was controlled from low level (0.6 mg/m3) to high level (8.0 mg/m3) and total exposure time ranged from 140 to 216 h. Some rats were sacrificed just after the exposure, whereas others were exposed for 1 mo and kept for a 1-yr clearance period before sacrifice.There were no differences in body weight gain between NiO exposure groups and controls.Nickel concentrations in lungs of exposure groups were much higher than those of controls. No apparent deposition of nickel was observed in liver, kidney, spleen, heart, brain, and blood, but lung burdens of up to about 2.35 mg of NiO were found. The apparent deposition fractions were 19.8 and 14.5% after the exposure to average concentrations of 1.4 and 6.5–7.0 mg/m3, respectively.The clearance rate of NiO deposited in lungs may be small.

LUNG CANCER AMONG COKE OVEN WORKERS

In the largest iron and steel works in Japan, six cases of lung cancer had been found among coke oven workers from 1947 to 1971. Labour Standard Bureau of the Ministry of Labour organized a task group of specialists to conduct an investiga-tion whether these cases should be considered as occupational. This paper is an English version of the report submitted to Labour Standard Bureau from the task group.An epidemiological survey conducted by the Ministry of Labour indicated that lung cancer incidence among retired blast furnace coke oven workers in the iron and steel works exceeded that of the expected number calculated from the general Japanese male polulation and the relative frequency of lung cancer cases to malign-ant neoplasia of all sites also exceeded that of the expected number. The task group was not able to conduct research on coke manufacturing chemical companies and manufacturing (specialized) companies because the number of lung cancer cases was too small.

Biological half-time and body burden of cadmium in dogs after a long-term oral administration of cadmium

To investigate the kinetic behavior of cadmium, we conducted a long-term oral administration experiment, using beagle dogs. The experimental animals were given a commercial diet and pelleted food containing 1, 3, 10, 50, and 100 mg of cadmium per day in the form of cadmium chloride for 8 yr. A single injection of cadmium (as CdCl2) into dogs was also performed in order to obtain fundamental kinetic information for a dog.The kinetic behavior of cadmium in chronic experiment is described theoretically, using a two-compartment model. The model was selected based on the elimination pattern of cadmium from the blood in the single injection experiment. The parameters of the model were estimated from the acute and chronic experimental data. The theoretical value of the cumulative amount of cadmium excreted in urine agreed with the experimental one. This result suggests that the two-compartment model used in this study is useful to elucidate the kinetic behavior of cadmium after a long-term exposure to cadmium.The terminal biological half-time in the two-compartment model was estimated at about 1 to 2 yr for both male and female dogs given 1, 3, 10, and 50 mg of cadmium, and for the male dog given 100 mg of cadmium, but only 0.3 to 0.5 yr for the female dog given 100 mg of cadmium. The amount of cadmium in the central compartment and tissue compartment increased continuously and then gradually reached a steady state. The amount of tissue compartment was much higher than that of the central compartment for each beagle dog.

Retention of nickel oxide (green) aerosol in rat lungs by long-term inhalation

Wistar male rats were exposed to green nickel oxide [NiO(G)] aerosols (mass median aerodynamic diameter, 0.6 μm) for 7 h/d, 5 d/wk for up to 12 mo. The average exposure concentration was controlled at 0.3 mg/m3 and 1.2 mg/m3 during the exposure period. Some rats were sacrificed just after the 3- and 6-mo exposures, and others were sacrificed after the termination of the 12-mo exposure.There were no differences in body weight gain between NiO(G) exposure groups and controls. The lung weights in the exposed rats were heavier than those in the control ones.Nickel concentrations in lungs of exposure groups were much higher than those of controls. The nickel concentrations in liver, kidney, spleen, and blood slightly increased with the passing of the exposure time.The nickel content in rat lungs during the 12-mo exposure was estimated theoretically. The estimated values agreed with the experimental data. This result shows that the clearance rate increases with the decreasing of the particle diameter.

LEAD EXPOSURE AND THE DERIVATION OF MAXIMUM ALLOWABLE CONCENTRATIONS AND THRESHOLD LIMIT VALUES

The terms maximum allowable concentration (M.A.C.) and threshold limit value (T.L.V.) differ in their respective meanings. The M.A.C. is a ceiling concentration whereas the T.L.V. is a time-weighted average of the concentration of the hazardous agent in the atmosphere. The value attributed to M.A.C. or T.L.V. will vary with the criteria decided upon for the response selected. This response may be a clinical or biochemical change in human subjects resulting from the hazardous agent. An investigation of lead workers is reported, and from the data obtained from them and from their working environment recommendations have been made. The survey was carried out in printing works and storage battery factories; the order of development of abnormal biochemical findings was reconfirmed. The T.L.V. was determined for each stage of lead absorption by a graphic method. T.L.V.s for an eight to 10-hour working day were determined as 0·10 mg./m.3 to produce a urinary lead of 0·15 mg./l., 0·12 mg./m.3 for a coproporphyrinuria of about 50 μg./l., 0·14 mg./m.3 for basophilic stippling at the 0·3 per thousand level, and most likely 0·14 to 0·15 mg./m.3 for lead anaemia. The biochemical function chosen was an increased excretion of coproporphyrin, and to keep this below 50 μg./l. we would suggest that the T.L.V. should be about 0·12 mg./m.3 or a little more in the case of a 40-hour week.

Cadmium distribution in blood and urine of dogs after long-term oral administration of cadmium.

Fourteen beagle dogs, six‐ or eight‐months old, were divided into five experimental groups. The experimental animals were given a commercial diet and pelleted food containing 1, 3, 10, 50, 100 mg Cd per day over a period of 8 years. In the groups exposed to 1, 3, 10 mg Cd per day, no biological alterations, such as GOT, GPT, ALP etc., were observed during the period of 400 weeks, although Cd concentration in blood and Cd excretion in urine had increased continuously and reached slowly to steady state. In the groups highly exposed to Cd of 50 and 100 mg per day, Cd levels in blood and urine were much higher than those of the lower exposure groups.