Tomojiro Yasugi

Comparative evaluation of urinalysis and blood analysis as means of detecting exposure to organic solvents at low concentrations.

SummaryOne hundred and forty-three workers exposed to one or more of toluene, xylene, ethylbenzene, styrene, n-hexane, and methanol at sub-occupational exposure limits were examined for the time-weighted average intensity of exposure by diffusive sampling, and for biological exposure indicators by means of analysis of shift-end blood for the solvent and analysis of shift-end urine for the corresponding metabolite(s). Urinalysis was also performed in 20 nonexposed control men to establish the “background level.” Both solvent concentrations in blood and metabolite concentrations in urine correlated significantly with solvent concentrations in air. Comparison of blood analysis and urinalysis as regards sensitivity in identifying low solvent exposure showed that blood analysis is generally superior to urinalysis. It was also noted that estimation of exposure intensity on an individual basis is scarcely possible even with blood analysis. Solvent concentration in whole blood was the same as that in serum in the case of the aromatics, except for styrene. It was higher in blood than in serum in the case of n-hexane, and lower in the cases of styrene and methanol.

The method of choice for the determination of 2,5-hexanedione as an indicator of occupational exposure to n-hexane

SummaryTo identify the method of choice for analysis of urine for 2,5-hexanedione (2,5-HD) as an indicator of occupational exposure to n-hexane, the end-of-shift urine samples of 36 n-hexane exposed male workers and 30 non-exposed male workers were analyzed for 2,5-HD under three conditions of hydrolysis, i.e. enzymic hydrolysis at pH 4.8, acid hydrolysis at pH 0.5, and without hydrolysis. The 2,5-HD concentrations thus determined were examined for correlation with 8-h, time-weighted average exposure concentrations of n-hexane measured by diffusive sampling. The regression analysis showed that the 2,5-HD concentrations without any hydrolysis correlated best with the intensity of exposure to n-hexane. No 2,5-HD was detected in the urine of the non-exposed subjects under the analytical conditions with no hydrolysis. Thus, the analysis without hydrolysis was considered to be the method of choice from the viewpoint of simplicity in analytical procedures, sensitive separation of the exposed from the non-exposed, and quantitative increase in the amount of 2,5-HD after n-hexane exposure.

Monitoring of workers exposed to a mixture of toluene, styrene and methanol vapours by means of diffusive air sampling, blood analysis and urinalysis

SummaryExposure of 34 male workers to combined toluene, styrene and methanol was monitored by personal diffusive sampling of solvent vapours in breathing zone air, analysis of shift-end blood for the 3 solvents and analysis of shift-end urine for hippuric, mandelic and phenylglyoxylic acids and methanol. The exposure of most of the workers was below current occupational exposure limits. Regression analysis showed that a linear correlation exists for each of the 3 solvents between any pairs of the concentrations in air, blood and urine. Namely, toluene, styrene and methanol concentrations in blood obtained at the end of a shift are linearly related to the time-weighted average intensity of exposure to corresponding solvents, and also hippuric, mandelic and phenylglyoxylic acids as well as methanol in shift-end urine. The concentrations of hippuric, mandelic and phenylglyoxylic acids as well as methanol in urine correlated with the respiratory exposure intensity. Comparison of the present results with the exposure — excretion relationship after occupational exposure to the individual solvent showed that no modification in metabolism is induced by the combined exposure when exposure is low, as in the present case.

Urinary methylhippuric acid isomer levels after occupational exposure to a xylene mixture

SummaryThe quantitative relationship between exposure to xylene vapor and urinary excretion of methylhippuric acid (MHA) isomers were studied in the second half of a working week. The participants in the study were 121 male workers engaged in dip-coating of metal parts who were predominantly exposed to three xylene isomers. The intensity of exposure measured by diffusive sampling during an 8-h shift was such that the geometric mean vapor concentration was 3.8 ppm for xylenes (0.8 ppm for o-xylene, 2.1 ppm for m-xylene, and 0.9 ppm for p-xylene), 0.8 ppm for toluene, and 0.9 ppm for ethylbenzene. Urine samples were collected at the end of the shift and analyzed for metabolities by HPLC. The statistical analysis showed that there is a linear relationship between the intensity of exposure to xylenes and the concentration of MHA in urine, that the regression line passes very close to the origin, and that the increment in observed (i.e., noncorrected) MHA concentrations as a function of increasing xylene concentration was 17.8 mg × 1−1 ppm−1. Further examination on the basis on individual xylene isomers showed that the slopes of the regression lines for o- and m-isomers were similar (i.e., 17.1 and 16.6 mg l−1 ppm−1, respectively), whereas that for p-xylene was larger (21.3 mg l−1 ppm−1).

Urinalysis vs. blood analysis, as a tool for biological monitoring of solvent exposure

Blood and urine samples were collected at the end of an 8-h workshift from 30 male workers exposed to a mixture of n-hexane, ethyl acetate and toluene (each being about 2 ppm as geometric means) and also from 20 nonexposed male workers. Blood samples were analyzed for n-hexane and toluene, and urine samples were analyzed for n-hexane, toluene, 2,5-hexanedione (both with and without hydrolysis) and hippuric acid. Based on the correlation between biological exposure indicators and solvent concentrations in air, sensitivity as an exposure indicator was compared between solvents in blood and solvents or metabolites in urine in terms of the lowest solvent concentration at which the exposed subjects can be statistically separated from the nonexposed. Both n-hexane and toluene in blood were sensitive enough to detect the exposure at 6.1 ppm and 1.4 ppm, respectively. n-Hexane exposure below 2 ppm was detectable also by urinalysis for 2,5-hexadione without hydrolysis. Urinary hippuric acid, however, failed to detect low toluene exposure under the conditions studied. Of additional interest is the fact that toluene in urine correlated significantly with toluene in air, which apparently deserves further study for confirmation.

Methanol in urine as a biological indicator of occupational exposure to methanol vapor

SummaryThe exposure-excretion relationship and possible health effects of exposure to methanol vapor were studied in 33 exposed workers during the second half of 2 working weeks. Urinary methanol concentrations were also determined in 91 nonexposed subjects. The geometric mean value for methanol in urine samples from the latter was < 2 mg/1 (95% upper limit of normal, < 5 mg/l) when log-normal distribution was assumed. Among the exposed workers, the methanol level in urine samples collected prior to the work shift exceeded the 95% upper limit of normal. The time-weighted average intensity of exposure to methanol vapor was measured using personal sampling devices (in which water severed as an absorbent) in 48 cases of methanol exposure (i.e., 2 of the 33 exposed workers failed to provide urine samples, whereas 17 subjects were examined twice). Methanol concentrations in urine were determined in samples collected at the end of the shift from the 48 exposed cases as well as from 30 nonexposed controls. There was a significant correlation between the exposure to methanol vapor at concentrations of up to 5,500 ppm and the levels of methanol measured in the shift-end urine samples. The calculation indicated that a mean level of 42 mg methanol/l urine (95% confidence range, 26–60 mg/kg) was excreted in the shift-end urine sample following 8 h exposure to methanol at 200 ppm (the current occupational exposure limit). Dimmed vision and nasal irritation were among the most frequent symptoms complained during work. Three cases showing clinical signs of borderline significance were identified.

Toluene in blood as a marker of choice for low-level exposure to toluene

The validity of two new biological exposure markers of toluene in blood (TOL-B) and toluene in urine (TOL-U) was examined in comparison with that of the traditional marker of hippuric acid in urine (HA-U) in 294 male workers exposed to toluene in workroom air (TOL-A), mostly at low levels. The exposure was such that the geometric mean for toluene was 2.3 ppm with a maximum of 132 ppm; the workers were also exposed to other solvents such as hexane, ethyl acetate, styrene, and methanol, but at lower levels. The chance of cutaneous absorption was remote. Higher correlation with TOL-A and better sensitivity in separating the exposed workers from the nonexposed subjects were taken as selection criteria. When workers exposed to TOL-A at lower concentrations (< 50 ppm, < 10 ppm, < 2 ppm, etc.) were selected and correlation with TOL-A was examined, TOL-B showed the largest correlation coefficient which was significant even at TOL-A of < 1 ppm, whereas correlation of HA-U was no longer significant when TOL-A was < 10 ppm. TOL-U was between the two extremes. The sensitivities of TOL-B and TOL-U were comparable; HA-U showed the lowest sensitivity. Thus, it was concluded that TOL-B is the indicator of choice for detecting toluene exposure at low levels.

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.

Dose-dependent increase in 2,5-hexanedione in the urine of workers exposed to n-hexane

SummaryThe concentrations of 2,5-hexanedione (2,5-HD), an n-hexane metabolite, and 2-acetylfuran (2-AF) were measured in urine samples from 123 workers who had predominantly been exposed to n-hexane vapor and 53 workers who had experienced no exposure to solvents. The time-weighted average intensity of exposure to n-hexane vapor was determined by a diffusive sampling method. For biological monitoring of exposure, urine samples were collected late in the afternoon during the second half of a working week and were analyzed in the presence and absence of acid hydrolysis (at pH < 0.5) for 2,5-HD and 2-AF by gas chromatography on a non-polar capillary DB-1 column. The urinary 2,5-HD concentration increased as a linear function of the intensity of exposure to n-hexane, showing a correlation coefficient of 0.64–0.77 after acid hydrolysis and that of 0.730–0.83 in the absence of hydrolysis, depending on the correction for urinary density (P < 0.01 in all cases, with no improvement in the coefficient occurring after the corrections). In contrast, 2-AF levels were independent of n-hexane exposure. The geometric mean 2,5-HD concentration in urine samples from 53 nonexposed men was 0.26 mg/l as observed (i.e., with no correction), 0.19 mg/l after correction for a urinary specific gravity of 1.016, and 0.23 mg/g creatinine after correction for creatinine concentration, and the geometric standard deviation was approximately 2.

Exposure-excretion relationship of styrene and acetone in factory workers : a comparison of a lipophilic solvent and a hydrophilic solvent

A factory survey was conducted in the second half of a working week on 41 exposed male workers, who were engaged in fiber-reinforced plastics work and exposed to the mixed vapors of styrene and acetone. Nonexposed workers, 20 men, were recruited from the same factory. Styrene and acetone in respiratory zone air were monitored for a 8-h shift with carbon cloth- and water-equipped personal diffusive samplers, respectively. Blood and urine samples were collected at the shift-end. Acetone and styrene concentrations in whole blood, serum and urine were measured by head-space gas chromatography, and phenylglyoxylic acid in urine by high-performance liquid chromatography. All biological exposure indicators analyzed correlated significantly with the intensity of exposure to the corresponding solvent during the shift. The slopes of the regression lines indicate that a very small fraction of styrene absorbed will be excreted into urine as styrene per se, and that styrene is quite effectively excreted into urine after metabolic conversion. In contrast, the slopes of regression lines for acetone suggest that acetone distributes both in the blood and urine quite evenly. When the distribution of the solvent in serum was compared with that in the whole blood, it was found that almost all of styrene in blood is present in the serum, whereas acetone distributed very evenly in the cellular and noncellular fractions of the blood.