Kazunori Seiji

Mutual metabolic suppression between benzene and toluene in man

SummaryThe exposure intensity during a shift and the metabolite levels in the shift-end urine were examined in male workers exposed to either benzene (65 subjects; the benzene group), toluene (35 subjects; the toluene group), or a mixture of both (55 subjects; the mixture group). In addition, 35 non-exposed male workers (the control group) were similarly examined for urinary metabolites to define background levels. A linear relationship was established between the intensity of solvent exposure and the corresponding urinary metabolite levels (i.e. phenol, catechol and quinol from benzene, and hippuric acid and o-cresol from toluene) in each case when one of the three exposed groups was combined with the control group for calculation. Comparison of regression lines in combination with regression analysis disclosed that urinary levels of phenol and quinol (but not catechol) were lower in the mixture group than in the benzene group when the intensities of exposure to benzene were comparable, indicating that the biotransformation of benzene to phenolic compounds (excluding catechol) in man is suppressed by co-exposure to toluene. Conversely, metabolism of toluene to hippuric acid was suppressed by benzene co-exposure. Conversion of toluene to o-cresol was also reduced by benzene, but to a lesser extent. The significance of the present findings on the mutual suppression of metabolism between benzene and toluene is discussed in relation to solvent toxicology and biological monitoring of exposure to the solvents.

Sister chromatid exchanges in peripheral lymphocytes of workers exposed to benzene, trichloroethylene, or tetrachloroethylene, with reference to smoking habits

SummaryThe frequencies of sister chromatid exchanges (SCE) were studied in peripheral lymphocytes from four groups of solvent workers, i.e. 36 nonsmoking women exposed to benzene at about 50 ppm on the average, 38 men and women (male smokers and nonsmokers, and female nonsmokers) exposed to trichloroethylene (TRI) at 7 ppm, 27 men and women (both smokers and nonsmokers) with tetrachloroethylene (TETRA) exposure, and 19 workers (both smokers and nonsmokers in men, and nonsmokers in women) exposed to a mixture of TRI (at 8 ppm) and TETRA (at 17 ppm) (TRI + TETRA). The results were compared with the findings in control subjects matched by age, sex, smoking habits and place of residence. No significant increase in SCE frequencies was observed in association with exposure to benzene, TRI, TETRA or TRI + TETRA. The SCE frequency was, however, significantly higher in the TRI-, TETRA-or TRI + TETRA-exposed smoking men than in the concurrent nonsmoking controls of the same sex. Possible synergism between solvent exposure and smoking is discussed.

Effects of smoking and drinking on excretion of hippuric acid among toluene-exposed workers

SummaryIn order to investigate possible effects of smoking and drinking on the metabolism of toluence in occupational settings, 206 toluene-exposed men (mean age: 31.4 years) in shoemaking, painting, or surface-coating workshops together with 246 nonexposed control men (36.8 years) were studied for the time-weighted average intensities of exposure to toluene, hippuric acid concentration in shift-end urine samples, and the two social habits of smoking and drinking. The mean daily consumptions of cigarettes and ethanol were about 20 pieces and 10 g among smokers and drinkers, respectively. The geometric mean toluene concentration among the exposed subjects was about 20 ppm, with a maximum of 521 ppm. Regression analysis after classification of the subjects by smoking and drinking clearly demonstrated that the two social habits, when combined, markedly reduce the hippuric acid level in the urine of workers exposed to was a significant association between smoking and drinking habits, which hindered separate evaluation of the effects of the two habits on toluene metabolism. Comparison of the present results with the findings reported in the literature, however, suggested that the observed effects may be attributable to smoking rather than to drinking habits.

Excretion of methylhippuric acids in urine of workers exposed to a xylene mixture: comparison among three xylene isomers and toluene

SummaryThe correlation between exposure to three xylene isomers and resulting urinary excretion of corresponding methylhippuric acid (MHA) isomers was studied among 175 Chinese workers of both sexes who had been predominantly exposed to xylenes (exposure to xylenes accounting for 70% or more of the total exposure on a ppm basis). Nonexposed controls (281 men and women) were also studied to define the background level of MHAs in urine. The solvent exposure of xylene-exposed workers during their workshift was monitored by diffusive sampling of breathing zone air, and MHAs in shift-end urine were determined by high-performance liquid chromatography. Regression analysis showed that the concentration of each MHA isomer correlated significantly with the time-weighted average intensity of exposure to the corresponding xylene isomer, and therefore the correlation between the sum of three xylene isomers in air and that of three MHA isomers in urine was also significant; the slope of the regression line was essentially the same among the three isomers. The calculated regression line suggested that the urinary MHA level after hypothetical exposure to xylenes at 100 ppm will be somewhat less than the proposed biological exposure index and biological tolerance value. Two social habits of smoking and drinking in combination suppressed the conversion of xylenes to MHAs in male workers.

Exposure monitoring and health effect studies of workers occupationally exposed to cyclohexane vapor.

SummaryA survey was conducted in the second half of a working week on 33 women who either applied glue (with cyclohexane as an almost exclusive solvent component) or worked in the vicinity of glue application. Carbon cloth-equipped diffusive samplers were used for personal measurement of time-weighted average intensity of exposure to the solvent. The geometric mean and the highest cyclohexane concentration observed in air were 27 ppm and 274 ppm, respectively. Concentrations of cyclohexanol in urine samples and cyclohexane in whole blood and serum collected at the end of a shift showed significant correlations with the solvent exposure levels. Urinary cyclohexanone also correlated, but with a smaller correlation coefficient. The observation suggests that cyclohexanol in urine and cyclohexane in blood or serum collected at the end of a shift are useful indicators of occupational exposure to cyclohexane vapor. Quantitative estimation of balance at the end of the shift suggested that only a minute portion (< 1%) of cyclohexane absorbed is excreted in the urine as cyclohexanol, almost exclusively as a glucuronide. A survey of subjective symptoms revealed an increase in the prevalence of “dimmed vision” and “unusual smell”, but hematology and serum biochemistry testing did not indicate any specific signs.

Possible ethnic difference in toluene metabolism: A com- parative study among chinese, turkish and japanese sol- vent workers

Toluene metabolism was studied in 192 Chinese workers in comparison with that in 130 Japanese and 17 Turks. Time-weighted average concentrations of toluene in the breathing zone of workers were measured utilizing passive dosimeters, and hippuric acid (HA) and omicron-cresol (omicron C) concentrations in shift-end spot urine samples by high-performance liquid chromatography (HPLC) and gas chromatography (GC), respectively. Under similar exposure conditions, male Japanese excreted almost twice as much HA as male Chinese, although such difference was less marked between female Chinese and Japanese. In contrast, the excretion of oC did not differ between the two ethnic groups. The ratio of oC over HA was highest among Turkish workers followed by Chinese, and lowest among Japanese. Possible roles of differences in toxicogenetics as well as in life patterns were discussed.

Simultaneous Determination of Hippuric Acid, o-, m-, and p-Methylhippuric Acid, Phenylglyoxylic Acid, and Mandelic Acid by HPLC

Xylene is the most widely used solvent only second to toluene (Kumai et al., 1983; Inoue et al., 1983). In practical application, 3 xylene isomers are present together with toluene and ethylbenzene especially when technical grade xylenes are in use. Because toluene and 3 isomers of xylenes are known to be metabolized primarily to hippuric acid (HA) and corresponding isomers of methylhippuric acids (MHA), respectively (Williams, 1959; Lauwerys, 1984) whereas ethylbenzene is biotransformed to 2 metabolites of phenylglyoxylic (PhGA) and mandelic acids (MA), simultaneous determination of the 6 metabolites is requested when comprehensive biological monitoring of exposure to the solvent mixture is attempted by means of urinalysis (Hasegawa et al., 1983; Inoue et al., 1986).

Blood lead levels of the general populations of three chinese cities

Blood samples were obtained from 537 adults (age greater than or equal to 16 years) living in three cities in China; in Hefei in 1985, and in Shenyang and Jinxi in 1987. The samples were subjected to blood lead (Pb-B) analyses. The subjects were factory workers either in solvent-synthesizing or solvent application plants with no known exposure to metals (including lead). Their smoking and drinking habits were confirmed in medical interviews. Blood lead was significantly higher in smokers than in non-smokers, although no dose-dependency was observed. The Pb-B values in non-smokers were log-normally distributed. The Pb-B among non-smokers was significantly higher in men [104.0 micrograms l-1 (1.428) 87] [geometric mean (geometric standard deviation) number of determinations] than in women [75.5 micrograms l-1 (1.358) 225] when the data from the three cities were combined. There was a significant difference in the Pb-B levels of non-smoking men in the three cities studied, suggesting that regional food habits should be considered as a possible contributory factor of a non-occupational nature. The present findings are compared with observations from Korea and Japan from the viewpoint of environmental health.

Subtle increase in leukocyte counts in association with drinking and smoking habits

Peripheral leukocyte counts were examined in venous blood of more than 800 male workers exposed to toluene, xylenes, a combination of the two, or neither. Information on the social habits of smoking and drinking was obtained in an occupational health interview. The analysis showed that smoking (15 cigarettes/day on average) induced a significant increase (by 7%) in leukocyte counts, and that an additional increase was induced when the drinking habit was coupled with smoking. Drinking alone tended to increase the leukocyte counts but the effect was statistically nonsignificant, possibly because the number of nondrinking smokers was limited. The study stresses the importance of paying attention to smoking and drinking habits when evaluating hematological parameters such as peripheral leukocyte counts in solvent-exposed workers.

Urinary vanadium as a biological indicator of exposure to vanadium

SummaryVanadium was determined in urine and blood of two workers (Worker Nos. 1 and 2 with direct exposure to vanadium pentoxide) and 13 fellow workers (with indirect or no vanadium exposure), and the results were compared by means of personal and stationary sampling of vanadium in air. Worker No. 1, a foreman with the heaviest exposure to vanadium, had a green tongue, complained of frequent productive coughing, and excreted 47 to 124 ng/ml vanadium in his late morning and mid-afternoon urine. Worker No. 2, a helper to the foreman with less exposure, had no green tongue or subjective complaints, and excreted no vanadium at a measurable level even in his mid-shift urine. No vanadium was detected in urine samples from other workers, nor in blood from all workers including Worker Nos. 1 and 2. Application of inductively coupled plasma emission spectrometry to measurement of vanadium in biological materials is discussed.