Akio Koizumi

Cadmium levels in the blood of inhabitants in nonpolluted areas in Japan with special references to aging and smoking

Blood samples, 2259 in winter and 523 in other seasons of the year, were collected nationwide in Japan from inhabitants (primarily farmers) in areas with no known man-made pollution, and analyzed for cadmium. The levels were distributed log normally, and were lower among young adults and increased gradually to reach a plateau at the 40-59 age group, where the values in females (about 3.6 ng/ml as a geometric mean) were significantly higher than in males (3.0-3.4 ng/ml). The sex difference was positive (P less than 0.01) even when 77 pairs of levels were compared between husbands and their wives, both being nonsmokers in the age range of 40-59 years. Smoking habits gave an additional increase in the blood cadmium level. The increase was dose dependent up to 20-29 cigarettes/day and leveled off with further consumption. Effects of passive smoking could not be confirmed. Seasonal variation in blood cadmium level appeared negligible. Variation in the level by geographic location in the country was of doubtful significance. The estimated ratio of cadmium doses by two routes, i.e., via the gastrointestinal tract and via the lungs, was in agreement with the ratio of the blood cadmium level among nonsmokers and the additional increase in the level due to smoking.

Dietary cadmium intakes of farmers in nonpolluted areas in Japan, and the relation with blood cadmium levels

During a period of 1977 to 1981, 24-hr duplicates of daily diets were collected nationwide in 49 regions in 21 prefectures in Japan. More than 1000 samples were obtained in winter from the inhabitants (predominantly farmers) of areas with no known environmental pollution, together with more than 200 additional samples in the immediately preceding or succeeding summer. Cadmium contents (analyzed by wet digestion-flameless atomic absorption spectrophotometry) in the winter diet samples distributed log--normally with males and females giving results (geometric mean (geometric standard deviation] of 43.9 micrograms/day (1.86) and 37.0 micrograms/day (1.85) for 368 and 674 samples, respectively; the difference was statistically significant (P less than 0.01). A slight reduction (ca. 13% in males and 21% in females) in cadmium content was observed in summer diets as compared with winter ones. In winter samples, cadmium levels in diets correlated significantly (P less than 0.01) with the cadmium levels in blood when the results from the examinees of the same survey region were pooled and the two levels were compared in terms of geometric means. Correlation on the individual basis was not remarkable, probably due to day-by-day variation in diet constituents as well as cadmium contents. High cadmium intakes of over 150 micrograms/day were recorded in some cases but did not associate with high cadmium levels in blood.

Dietary intake of lead among Japanese farmers.

More than 1,000 24-h duplicates of food consumed were collected from farmers in 49 nonpolluted regions in Japan during the winter and summer seasons of 1977-1981. The samples were analyzed for lead to assess dietary intake. The dietary intake distributed log-normally in both winter and summer. The geometric mean (GM) (geometric standard deviation [GSD]) for winter samples was 38.2 micrograms/d (1.94) for males (N = 381) and 32.8 micrograms/d (1.91) for females (N = 711). A seasonal variation was detected in females but not in males. The findings on regional differences in dietary intake were inconclusive. The levels observed were lower than most values reported in the literature. The low dietary intake levels were in agreement with the low blood lead levels found among the subjects, which may reflect of Japans decision in 1975 to withdraw alkyl lead from automobile gasoline. No significant correlation could be established between dietary intake and blood lead levels when GMs for the study regions were compared, or when dietary intake and blood lead levels were compared in 555 nonsmoking and nondrinking females who were between 30 and 59 y of age. It is estimated that 2-4 micrograms of lead is absorbed daily from the diet (i.e., food and water), and 0.1-1 micrograms is absorbed via respiration, and that cigarette smoking and alcohol consumption may increase lead absorption.

Styrene exposure and biologic monitoring in FRP boat production plants

SummaryA survey on styrene exposure was conducted in five small to medium-sized fiber-reinforced plastic (FRP) boat plants utilizing carbon felt dosimeters as personal and stationary samplers to measure 4 h (TWA) exposure during workday afternoons. The heaviest exposure, up to 256 ppm by personal sampling and 174 ppm by stationary sampling, took place during the lamination on a mold to produce a boat shell, and the work inside narrow holds also resulted in exposures of a comparable degree. Styrene levels were much lower in other auxiliary works. The TWA of exposure in an entire boat production was estimated to be 40–50 ppm. Installation of several flexible hoses as an exhaust system was proved to be effective in decreasing the vapor concentration. Gas masks were also useful in reducing the exposure. Urine samples were collected from 96 male workers at the end of 8h work (4 h in the morning and 4 h in the afternoon) and also from 22 nonexposed male subjects, and analyzed for mandelic acid (MA), phenylglyoxylic acid (PhGA), and hippuric acid (HA). When the results of urinalyses were compared with 4-h styrene TWA as monitored by personal sampling, the best correlation was obtained with MA + PhGA/creatinine (the correlation coefficient, 0.88), followed by MA (0.84). For these two cases, regression lines and 95% confidence limits for the group means and for the individual values were calculated. The urinary levels of MA, PhGA, and HA in the 22 nonexposed male subjects were also tabulated.

A servomechanism for vapor concentration control in experimental exposure chambers

The servomechanism established consisted of 5 components: 4 vapor generators, 4 stainless steel chambers built in parallel, a GLC with FIDs as a vapor analyzer, a computer with a printer and a flow controller. Methane was employed as a calibration gas. Vapor concentration analyses were repeated automatically, of which the time frequency was dependent on the retention time(s) of the test material(s). Concentration at command levels could be produced under the control of the computer by regulating the rate of flow through each vapor generator. In continuous 34 hour vapor generation experiments in which trichloroethylene (TRI) was used, 4 graded series of concentrations using 4 chambers in parallel were produced. The frequency of unacceptable values (i.e., values out of the ±15% range of the command concentration) was zero in the total 512 (128×4) measurements. The connection of multiple generators to each chamber made possible the exposure to mixed vapors at the desired concentration for each vapor constitu...

Limited capacity of humans to metabolize tetrachloroethylene

SummaryPersonal monitoring of exposure to tetrachloroethylene (TETRA) with carbon felt dosimeters and analyses of urine for total trichloro-compounds (TTC) were carried out in two groups of workers (36 males and 25 females), one group (20 males and 19 females) in dry-cleaning workshops and the other (16 males and 6 females) engaged in the removal of glue from silk cloth. Comparison of the urinary TTC levels with TETRA in the environment revealed that, while the metabolite levels increased essentially linear to TETRA concentrations up to 100 ppm, leveling off was apparent in the metabolite excretion when the exposure to TETRA was more intense (e.g. more than 100 ppm), indicating that the capacity of humans to metabolize TETRA is rather limited, as previously discussed. From the set of the data thus obtained, screening levels of 30 and 61 mg TTC (as TCA)/l urine as the lower 95% confidence limits for a group mean were calculated for the biological monitoring, by means of urinalysis, of exposure to TETRA at 50 and 100 ppm (TWA), respectively. A tentative calculation with additional exhaled-air analyses indicated that, at the end of an 8-h shift with exposure to TETRA at 50 ppm (TWA), 38% of the TETRA absorbed through the lungs would be exhaled unchanged and less than 2% would be metabolized to be excreted into the urine, while the rest would remain in the body to be eliminated later.

Biological monitoring of occupational exposure to methyl ethyl ketone by means of urinalysis for methyl ethyl ketone itself.

SummaryHead space gas chromatography (GC) was applied to measure methyl ethyl ketone (MEK) in urine from 62 MEK-exposed male workers, whose individual intensity of exposure to MEK was monitored utilizing the carbon felt dosimeter. The urinary MEK level increased rapidly to reach a plateau in the first quarter of the daily 8-h work, while very little MEK was detected in the preshift urine. When the MEK levels in the urine at the end of the shift were compared with the afternoon MEK-TWA values, the uncorrected MEK in urine correlated best with MEK in air (r=0.774, n=62), while correction for creatinine gave a comparable result and the correlation was poorer when corrected for a specific gravity of urine or for the lapse of time after preceding passage of urine. Balance of MEK absorption via inhalation and MEK excretion into urine revealed that only 0.1% of MEK absorbed will be excreted unchanged into urine. Wider application of head space GC is discussed for the analysis of unmetabolized solvents in urine.

Cytogenetic and cytokinetic investigations on lymphocytes from workers occupationally exposed to tetrachloroethylene

Lymphocytes from 10 factory workers, who had been exposed to tetrachloroethylene for 3 months to 18 years, were examined for possible chromosome aberration, increased sister chromatid exchanges, and modified cell-cycle kinetics. The exposure intensity was such that the workroom air analyses disclosed 92 ppm as a geometric mean in the workshops for Group 1 (6 workers from decreasing workshops), but was in the range of 10 to 40 ppm for Group 2 (4 workers from a support department). Urinalyses for total trichloro-compounds showed 50.7 and 19.0 mg (as trichloroacetic acid)/l as a geometric mean in Group 1 and 2, respectively. cytogenetic and cytokinetic studies did not reveal any significant dose-related changes in chromosome aberrations (either numerical or structural), SCEs rate, the proportion of M2 + M3 metaphases or mitotic index, compared with concurrent controls. Mitomycin C treatment also failed to induce any difference between exposed workers and controls.

Inhibition of δ-aminolevulinate dehydratase in trichloroethylene-exposed rats, and the effects on heme regulation

A pronounced and irreversible depression of the erythroid and liver delta-aminolevulinate dehydratase (porphobilinogen synthase; 5-aminolevulinate hydro-lyase, EC 4.2.1.24) activity was observed in rats exposed to trichloroethylene, a widely used solvent. The depression could not be restored after the treatment with dithiothreitol and zinc; however, radioimmunoassay of delta-aminolevulinate dehydratase indicated that trichloroethylene exposure did not essentially decrease the amount of enzyme. The depression of the enzyme activity thus proved to be due not to a reduction in the enzyme amount but to enzyme inhibition. The purified holoenzyme (fully activated delta-aminolevulinate dehydratase with 1 atom zinc per subunit) and apoenzyme (fully activated enzyme with the remaining zinc less than 0.1 atom per subunit) were prepared to investigate the in vitro inhibition of the enzyme by trichloroethylene. Incubation with trichloroethylene did not inhibit the holoenzyme, but inhibited the apoenzyme dose-dependently. Trichloroethylene inhibited the holoenzyme when incubated with the mixed function oxidase system. The in vitro experiments reported here indicate two mechanisms of the enzyme inhibition by trichloroethylene. In the liver of rats exposed to trichloroethylene, cytochrome P-450 concentration and heme saturation of tryptophan pyrrolase (EC 1.13.11.11) are reduced; in addition, the activity of delta-aminolevulinate synthase (EC 2.3.1.37) increased. After exposure to trichloroethylene at 2.14 g/m3, urinary delta-aminolevulinic acid increased to 142% of the control, while the excretion of coproporphyrin was reduced to 19.6% of the control.

Correlation of cerebrovascular disease standardized mortality ratios with dietary sodium and the sodium/potassium ratio among the Japanese population.

One thousand seventy-two 24-hr diet duplicate samples were collected from inhabitants of 49 regions in various parts of Japan during the winters of 1977-1981. An additional 238 samples were collected in an adjacent summer. The samples were analyzed for sodium (Na) and potassium (K) by flame atomic absorption spectrometry and for chloride (Cl) with a chloride counter. The winter-summer differences in Na, Cl, and Na/K were essentially negligible. When the regional means of Na, K, Cl, and Na/K were compared with the 1969-1978 standardized mortality ratios of each region, positive and significant correlations were observed between winter Na and the standardized mortality ratios for cerebrovascular disease (P less than 0.01), cerebral infarction (P less than 0.01), and subarachnoid hemorrhage (P less than 0.05) in both males and females. The correlation (P less than 0.01) with the cerebrovascular disease standardized mortality ratio was further confirmed by the values for 1978-1982. In the case of the Na/K ratio, the correlation with the standardized mortality ratio for each of the three diseases was significant for men (P less than 0.01 or 0.05, depending on the disease) but not for women (P greater than 0.05). Both Na and Na/K showed significant associations with the ischemic heart disease standardized mortality ratio in men (P less than 0.05) but not in women (P greater than 0.05). In contrast, no positive association was found between Na, K, Cl, or Na/K and standardized mortality ratios for diabetes mellitus, liver cirrhosis, tuberculosis, or liver cancer (P greater than 0.05). Current blood pressure did not appear to correlate with any of the Na, K, Cl, or Na/K measurements. The validity of the present observation is discussed.