Miho Kumai

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.

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.

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.

An exposure system for organic solvent vapor.

A servomechanized system for the exposure of small laboratory animals to the vapor of organic solvents was previously described (Koizumi and Ikeda 1981); as a basic performance, the system was able to generate the organic solvent vapors at any constant concentrations in a range of i0 to i000 ppm with a coefficient of variation (CV) of less than 10%. Succeedingly, efforts were made to improve the function of the system to be able to generate the vapor at the concentration of below i0 ppm and also over i000 ppm so that the system can simulate the exposures of the inhabitants near the factory (Verbeck and Scheffers 1980) as well as the cases of thinner/glue sniffers (Knox and Nelson 1966; Suzuki et al. 1974). The achievements will be reported in the present communication.

Inhibition of δ-aminolevulinic acid dehydratase by trichloroethylene

Abstract Male Wistar rats (8 animals/group; 180–200 g) were exposed continuously to trichloroethylene (TRI) for 48 or 240 h or methylchloroform (1,1,1-trichloroethane: MC for 48 h at 50, 400 and 800 ppm. The inhibition of δ-aminolevulinic acid dehydratase (ALA-D) was examined in liver, blood and bone marrow of naive and phenobarbital pretreated animals exposed to TRI. A clear cut dose-effect relationship between the exposure concentration or duration of exposure and the inhibition of ALA-D activity was seen for rats exposed to TRI. In addition to this finding, significant interaction between TRI exposure and phenobarbital treatment was observed in the inhibition of ALA-D in liver and blood. MC did not produce inhibition. Trichloroacetic acid and trichloroethanol failed to inhibit the ALA-D activity in vitro. It seems that a metabolite(s) of TRI other than the above 2 substances may play a role in the inhibition of ALA-D. The inhibition of ALA-D (38% or 48% of the control in liver or in blood, respectively) observed after the 240 h exposure at 400 ppm to TRI was accompanied by the significant elevation of δ-aminolevulinic acid synthase (186% of the control) in liver and the increase in excretion of δ-aminolevulinic acid in urine (142% of the control). This occurred without an apparent weight loss, liver injury or hematological changes.

Nationwide survey of high-density lipoprotein cholesterol among farmers in Japan

A total of 2,134 blood samples (788 from men and 1,346 from women), were collected nationwide from adult farmers in Japan (44 regions in 21 prefectures) during the winters of 1978 through 1981. They were analyzed in a single laboratory for high-density lipoprotein cholesterol (HDL) by means of a precipitation method. The serum HDL level was 47.3 +/- 14.2 mg/100 ml (mean +/- SD; n = 788) in men and 47.4 +/- 12.8 mg/100 ml (n = 1,346) in women. Sex and age differences in HDL were not statistically significant (P greater than 0.10). Alcohol consumption was associated with elevated HDL levels in both sexes; the association was statistically significant only in men (P less than 0.05) and was positively correlated with daily alcohol consumption (P less than 0.05). Conversely, smoking habits were negatively (P less than 0.05) associated with HDL in men. The comparison of HDL in the nondrinking and nonsmoking population revealed that HDL in women (47.0 +/- 12.8 mg/100 ml; n = 900) did not differ significantly (P greater than 0.10) from the male values (45.3 +/- 12.5 mg/100 ml; n = 60). When 23 nondrinking and nonsmoking married couples were selected from 348 couples, for whom information on drinking and smoking habits was available, the HDL (+/- SD) was essentially the same in husbands (44.2 +/- 12.8 mg/100 ml) and in wives (43.7 +/- 9.5 mg/100 ml). In the blood samples collected from 535 subjects once in winter and once in summer, HDL concentration was significantly higher in summer than in winter (P less than 0.01 in both men and women); the HDL means (+/- SD) in winter and in summer were 48.1 +/- 14.3 and 50.9 +/- 11.3 mg/100 ml, respectively, for men, and 47.0 +/- 12.0 and 50.3 +/- 11.0 mg/100 ml, respectively, for women. The mean HDL distributed across a fairly wide range depending on the 44 regions studied. Maximum-minimum mean values were 58.3-33.1 mg/100 ml in men and 59.7-37.4 mg/100 ml in women, and the regional difference was statistically significant (P less than 0.01) both in men and women. Furthermore, a significant inverse relation (P less than 0.05) was observed in men between the mean regional HDL values and standardized regional ratios of mortality from coronary heart diseases.

The simultaneous determination of the products of estrogen 2- and 4-hydroxylase action; the use of high-performance liquid chromatography with electrochemical detection.

Abstract A new method for the simultaneous assay of estrogen 2- and 4- hydroxylases consists of determining the enzymatically produced catechol estrogens by means of high-performance liquid chromatography with electrochemical detection. Estradiol was incubated with the enzyme preparation in the presence of NADPH. 2-Hydroxyestrone, 2-hydroxyestradiol, 4-hydroxyestrone, and 4-hydroxyestradiol formed were purified by an extraction method with boric acid and then separated by high-performance liquid chromatography. The peaks on the chromatogram were characterized by gas chromatography-mass spectrometry together with microchemical reactions. The amounts of the four catechol estrogens could be determined using 2-hydroxy-16-ketoestradiol 17-acetate as an internal standard with satisfactory accuracy and precision. The assay method was found to be superior in simplicity, sensitivity, and versatility.

Increased o- and p-cresol/hippuric acid ratios in the urine of four strains of rat exposed to toluene at thousands-ppm levels

Rats (Fisher, Wistar, Donryu and Sprague-Dawley strains) were exposed to 5 approximately 3500 ppm toluene for 8 h, and urine samples were analyzed for hippuric acid and cresols. While hippuric acid increased in proportion to the exposure concentration, a sharp increase in o-cresol excretion was observed at high toluene concentrations so that the o-cresol/hippuric acid ratio was elevated after 500 approximately 3500 ppm exposures. Changes in the p-cresol: hippuric acid ratio were less marked. There were strain differences in toluene metabolism. Fisher rats were highest and Sprague-Dawley rats lowest in o-cresol excretion and in the o-cresol: hippuric acid ratio, whereas Wistar rats excreted p-cresol most abundantly.