Biological monitoring of occupational exposure to dichloromethane by means of urinalysis for un-metabolized dichloromethane.

The objective of the study is to establish exposure-excretion relationship between dichlorometane (DCM) in air (DCM-A) and in urine (DCM-U) in workplace to confirm a previous report. Male workers in a screen-printing plant participated in the study. Time-weighted average DCM-A was measured by diffusive sampling followed by gas-chromatography (GC), and DCM in end-of-shift urine samples was by head-space GC. The data were subjected to regression and other statistical analyses. In practice, 30 sets of DCM-A and DCM-U values were available. The geometric mean DCM-A was 8.4 ppm and that of DCM-U (as observed) was 41.1 µg/l. The correlation coefficients (0.70-0.85) were statistically significant across the correction for urine density. Thus, the analysis for un-metabolized DCM in end-of-shift urine samples is applicable for biological monitoring of occupational exposure to DCM, in support of and in agreement with the previous report. In conclusion, biological monitoring of occupational DCM exposure is possible by use of analysis for un-metabolized DCM in end-of-shift urine.

Simplified procedures for estimation of biological occupational exposure limits.

OBJECTIVES: To simplify the procedures to estimate biological occupational exposure limits (BOELs) by use of the ratio of geometric mean (GM) concentration of un-metabolized organic solvent in urine (U-GM) over GM organic solvent concentration in air (A-GM) (the [U-GM/A-GM] ratio). METHODS: Occupational Exposure Limits (OELs) and BOELs were cited from publications from the Japan Society of Occupational Health (JSOH) and the American Conference of Governmental Industrial Hygienists (ACGIH). Data on [U-GM/A-GM] and the SLOPE of exposure-excretion regression line were collected from published articles (men and women were treated separately). Correlation analysis and paired t test were employed as the method to examine statistical significances. RESULTS: Significant linear correlation was established between the SLOPE and the [U-GM/A-GM]. Thus, it was considered to be possible to calculate the SLOPE value from the [U-GM/A-GM]. Previously established equation of BOEL = SLOPE × OEL allowed to estimate BOEL values in 22 cases of data sets. The comparison of the estimated BOELs with the existing BOELs (JSOH's BOELs and ACGIH's BEIs) in terms of the ratio of [(estimated BOEL)/(existing BOEL)] showed that the ratios for the 22 cases probably distributed log-normally with a GM of 0.85, and the maximum was 5. Therefore, the estimated BOEL may be generally applicable in occupational health when BOEL remains yet to be established. In the worst case, the estimated BOEL may be five times greater than it should be. The recommended procedures for application of estimated BOEL values were described. CONCLUSION: Simplified procedures for estimation of BOEL values are proposed.

Evaluation of personal exposure of workers to indium concentrations in total dust and its respirable fraction at three Japanese indium plants.

This study aimed to evaluate personal exposures of 27 workers to indium compounds as "total" dust and its "respirable" fraction in their breathing zones at 3 Japanese indium plants. Eight-hour time-weighted average (TWA) indium concentrations of personal exposure to dust collected in sampling periods of 6 h or longer were determined by ICP-MS. The arithmetic means of exposure concentrations were 0.095 mg indium (In)/m3, when sampled as total dust, and 0.059 mg In/m3, as respirable fraction. ACGIH's TLV-TWA of 0.1 mg In/m3 for total particulate matter and Acceptable Exposure Concentration Limit (AECL) of 3×10-4 mg In/m3 for the respirable fraction notified by the Japanese Ministry of Health, Labour and Welfare were used to evaluate the exposure concentrations. Twenty-five out of 27 workers were exposed to indium concentrations lower than TLV-TWA, while all of the workers were exposed to the indium concentrations higher than AECL. We noted that there was a large discrepancy between the two occupational exposure limits referred to in this report, and these differences were attributed to the sampling strategies and health effects used as the prevention targets. Carcinogenicity of the respirable fraction of indium-containing particulates was considered in setting AECL, whereas it was not in ACGIH's TLV.

Biological monitoring of occupational ethylbenzene exposure by means of urinalysis for un-metabolized ethylbenzene.

This study aimed to examine quantitative relation between ethylbenzene (EB) in air (EB-A) and un-metabolized EB in urine (EB-U) for biological monitoring of occupational EB exposure by urinalysis for EB. In total, 49 men in furniture production factories participated in the study. Time-weighted average EB-A was monitored by diffusive sampling. Urinalysis for EB was conducted by head-space gas-chromatography with end-of-shift samples. Data were subjected to regression analysis for statistical evaluation. A geometric mean (GM) and the maximum (Max) EB-A levels were 2.1 and 45.5 ppm, respectively. A GM and the Max for EB-U (observed values) were 4.6 and 38.7 µg/l. A significant linear correlation was observed. The regression equation was Y=3.1+0.73X where X is EB-A (ppm) and Y is EB-U (µg/l) (r=0.91, p<0.01). The significant correlation between EB-A and EB-U coupled with a small intercept suggests that biological monitoring of occupational EB exposure is possible by analysis for un-metabolized EB in end-of-shift urine samples. Further validation studies (including those on applicability to women) are envisaged. The feasibility should be examined for biological monitoring and the applicability of the equation among the workers exposed to EB at low levels.

Further examination of log Pow-based procedures to estimate biological occupational exposure limits.

OBJECTIVES: To test the reliability of the procedures (described in a previous article) for estimation of biological occupational exposure limits (BOELs). METHODS: Data on four organic solvents (styrene, ethyl benzene, isopropyl alcohol and tetrachloroethylene) were obtained from recent publications and added to previously cited data for 10 organic solvents. Regression analysis was used for statistical evaluation. RESULTS AND DISCUSSION: The previously reported results obtained using 10 solvents were reproduced by the analysis with 14 solvents. Repeated randomized division of the 14 sets into two subgroups of equal size followed by statistical comparisons did not show a significant difference between two regression lines. This reproducibility suggests that the procedures used to estimate BOELs may be applicable across many solvents, and this may be of particular benefit for protecting the health of workers who work with skin-penetrating solvents.

Quantitative assessment of occupational exposure to total indium dust in Japanese indium plants.

This study quantitatively assessed personal exposure of 86 workers to indium compounds as total dust at 11 Japanese indium plants. The personal exposures to indium concentrations in the breathing zone during an 8 h work-shift were determined by ICP-MS. The arithmetic mean indium concentration of all the workers was 0.098 mg Indium (In)/m3, with individual values ranging from 0.0001 to 1.421 mg In/m3. There were 11 workers whose exposure to indium concentrations exceeded the American Conference of Governmental Industrial Hygienists' Threshold Limit Value-Time Weighted Average (TLV-TWA) of 0.1 mg In/m3. Based on the condition TLV-TWA

Control banding assessment of workers' exposure to indium and its compounds in 13 Japanese indium plants.

OBJECTIVES: This study aimed to assess workers' exposure to indium and its compounds in 55 indium-handling operations among 13 Japanese plants. The surveyed plants were selected from indium-manufacturing plants whose annual indium production exceeded 500 kg. METHODS: The Control of Substances Hazardous to Health (COSHH) Essentials control banding toolkit, which contains simple scales for hazard levels, quantities in daily use, and "dustiness" characteristics, was used to assess generic risks of indium-handling operations. The operations were then classified into one of four Control Approaches (CAs). RESULTS: There were 35 indium-handling operations classified into CA4 (requires expert advice) and 16 grouped into CA3 (requires containment). There were three operations classified into CA2 (requires engineering controls) and only one into CA1 (requires good general ventilation (GV) and working practices). Of the 51 operations classified as CA4 and CA3, 36 were found to be improperly equipped with local exhaust ventilation, and the remaining 15 operations solely relied on GV practices. Respiratory protective equipment (RPE) used in the 13 indium plants was examined with reference to the recommendations of the COSHH Essentials and Japan's Technical Guidelines. CONCLUSIONS: Our findings suggest that stringent engineering control measures and respiratory protection from indium dust are needed to improve indium-handling operations. Our results show that the most common control approach for Japanese indium-handling operations is to require expert advice, including worker health checks for respiratory diseases and exposure measurement by air sampling.

Changes of median nerve conduction velocity in rayon manufacturing workers: A 6-year cohort study.

OBJECTIVES: We conducted a 6-year cohort study to evaluate the relationship between carbon disulfide (CS2) exposure and reductions in the motor and sensory nerve conduction velocity (MCV and SCV) of the median nerve. METHODS: Study subjects at baseline included 432 exposed workers and 402 unexposed workers. Among the exposed workers, 145 workers terminated CS2 exposure during the follow-up period (ex-exposed workers). MCV and SCV were measured at baseline and followed up. CS2 personal exposure concentration was measured two times a year during a 6-year follow-up period and mean (range) CS2 exposure concentrations (ppm) were 5.96 (0.8-16.0) and 3.93 (0.6-9.9) in the exposed and ex-exposed workers, respectively. RESULTS: Reductions in MCV during the follow-up period did not differ among the exposed, ex-exposed, and unexposed workers. Reduction in SCV (m/s) of the exposed workers (-4.47±3.94) was significantly larger than that of the unexposed (-3.38±3.97) and ex-exposed workers (-3.26±3.79). For SCV reduction, a partial multiple regression coefficient of (ex-exposed workers) / (unexposed workers) was significantly positive (+0.915, p < 0.01) after adjustment for confounding variables. CONCLUSIONS: This cohort study showed that 6-year CS2 exposure around a mean level of 6 ppm did not affect MCV reduction but induced significant SCV reduction beyond the influence of aging. The effect of CS2 on SCV around a mean exposure level of 4 ppm may be reversible, since it disappeared in the ex-exposed workers after CS2 exposure cessation for a mean period of 4.1 years.

Assessment of workplace air concentrations of formaldehyde during and before working hours in medical facilities.

Workplace air concentrations of formaldehyde (FA) in medical facilities where FA and FA-treated organs were stored and handled were measured before and during working hours and assessed by the official method specified by Work Environment Measurement Law. Sixty-percent of the total facilities examined were judged as inappropriately controlled work environment. The concentrations of FA before working hours by spot sampling were found to exceed 0.1 ppm in some facilities, and tended to increase with increasing volume of containers storing FA and FA-treated materials. Regression analysis revealed that logarithmic concentrations of FA during working hours by the Law-specified analytical method were highly correlated with those before working hours by spot sampling, suggesting the importance for appropriate storing methods of FA and FA-treated materials. The concentrations of FA during working hours are considered to be lowered by effective ventilation of FA-contaminated workplace air and appropriate storage of FA and FA-treated materials in plastic containers in the medical facilities. In particular, such improvement by a local exhaust ventilation system and tightly-sealed containment of FA-treated material were urgently needed for the dissecting room where FA-treated cadavers were prepared and handled for a gross anatomy course in a medical school.

Estimation of biological occupational exposure limit values for selected organic solvents from logartihm of octarol water partition coefficient.

OBJECTIVES: For several organic solvents (solvents in short), biological occupational exposure limits (BOELs) have been established for un-metabolized solvents in urine, based on the solvent exposure-urinary excretion relationship. This study was initiated to investigate the possibiliy of estimating a BOEL from the Pow (the partition coefficient between n-octyl alcohol and water), a physico-chemical parameter. METHODS: Data were available in the literatures for exposure-excretion relationship with regard to 10 solvents for men and 7 solvents for women. RESULTS: Statistical analysis revealed that the slopes (after correction for molecular weights and logarithmic conversion) of the exposure-excretion regression lines linearly correlated (p<0.01) with the log Pow values the respective solvents. No significant difference (p>0.05) was observed between men and women, and it was acceptable to combine the data for the two sexes. Thus the log Pow-log slope relation was represented by a single equation for both sexes. Based on the observations, procedures were established to estimate BOEL values from Pow. Successful estimations of BOELs for styrene, tetrahydrofuran and m-xylene (a representative of xylene isomers) were calculated as examples. CONCLUSIONS: The present study proposed promising procedures for estimation of a BOEL from the Pow.

Applicability of concentrations obtained by working environment measurement to assessment of personal exposure concentrations of chemicals.

OBJECTIVE: This study determined the applicability of Japanese working environment measurements to assessment of personal exposure concentrations of chemicals by comparing both levels of concentrations. METHODS: The chemicals measured in this study comprised eight kinds of vaporous chemicals as well as two kinds of chemicals in dust. Personal exposure measurements, Japanese working environment measurements and spot sampling measurements were undertaken in 70 companies. RESULTS: Personal exposure concentrations and the arithmetic mean value (EA2) of the working environment measurement concentrations obtained according to the Japanese working environment control system had statistically positive correlations (r=0.732-0.893, p<0.01) after logarithmic transformation. The 5th to 95th percentile values of personal exposure concentrations divided by EA2 ranged from 0.17 to 7.69 for vaporous chemicals and from 0.27 to 18.06 for dust. There was a relatively large difference between the personal exposure concentrations and the EA2 obtained in weighing, forming and bonding use-processes. In such cases, the B-value measured in ten minutes in the Japanese working environment control system, which is almost the same as the spot measurement concentration in this study, is supposed to be substituted for the EA2 value. CONCLUSIONS: Ten times the EA2 of the working environment measurement concentrations, or ten times the B-value, obtained according to the Japanese working environment control system can be used to conservatively estimate the personal exposure concentrations in EU workplaces as well as in occupational exposure scenarios of the Regulation on Registration, Evaluation, Authorisation and Restriction of Chemicals.

Occupational safety and health in Japan: current situations and the future.

The Industrial Safety and Health Law enacted in 1972 has contributed much to the progress of occupational safety and health (OSH) activities. Many indicators including death and illness statistics show continued improvement up to date. The establishment of OSH organization within enterprises and 5-yr administrative programs formulated by the Ministry of Health, Labour, and Welfare (MHLW) were important factors for satisfactory management. The past programs indicate that the weight of self regulation in comparison to legal control gradually increased since late 1990s. In spite of the past achievement, many hazards such as overwork, mental stress, chemical agents and others still remain to be prevented. The systematic risk assessment of unregulated chemicals by the MHLW proved to be an effective scheme for risk-based management and to deserve continued implementation. The size of human resources for OSH was estimated at 1.5 million. In view of the adverse effect on OSH by economic, social and political environment in the future, the importance of the efficiency of OSH management was indicated. Since the efficiency depends on the competence of OSH personnel and the level of scientific basis, it was concluded that the fundamental policy for the future should give high priority to education and research.

Validation of urine density correction in cases of hippuric acid and un-metabolized toluene in urine of workers exposed to toluene.

To investigate if it is appropriate to apply urine density correction when a urine sample is dense or dilute. Data on hippuric acid (HA-U), toluene (Tol-U), creatinine (CR) and specific gravity (SG) in end-of-shift urine samples and exposure to air-borne toluene were cited from previous publications. In practice, 837 cases were available, and they were classified into dense, intermediate and dilute groups taking 0.3 and 3.0 g/l of CR and 1.010 and 1.030 of SG as cut-off points. Lines of regression of HA-U and Tol-U (as observed, CR-corrected or SG-corrected) with air-borne toluene were calculated for each density groups, and correlation coefficients (CCs) were compared. The dense groups gave CCs similar to those of the intermediate groups. Dilute versus intermediate group comparison also gave promising results. These conclusions were however based primarily on the findings with observed values, because the numbers of cases in the dilute or dense group were limited when CR- or SG-correction was applied. Literature survey showed that urine density correction does not always improve the correlation between solvents in air and exposure makers in urine. It was concluded that no correction for urine density may be necessary in evaluating HA-U and Tol-U in dense (and probably also dilute) urine samples as markers of occupational toluene exposure. Just in case when correction for urine density is desired for any reason, SG-correction may be recommended.

Limited validity of o-cresol and benzylmercapturic acid in urine as biomarkers of occupational exposure to toluene at low levels.

This study was initiated to evaluate o-cresol and benzylmercapturic acid in urine in comparison with other biomarkers, as tools to estimate the intensity of occupational exposure to toluene at low levels. In total, 108 solvent exposed workers (engaged in tape production) and 17 non-exposed controls (all men) participated in the study. The surveys were conducted in the second half of working weeks. Diffusive sampling was conducted to measure 8-h time-weighted average intensity of occupational exposure to toluene. Blood and urine samples were collected at the end of a working shift. Blood samples were subjected to analysis for toluene (Tol-B), and urine samples were analyzed for benzyl alcohol (BeOH-U), benzylmercapturic acid (BMA-U), o-cresol (o-CR-U), hippuric acid (HA-U) and toluene (Tol-U) by the methods previously described. The toluene concentrations in workplaces were low in general, with a geometric mean (GM) and the maximum concentration of 1.9 ppm and 8.8 ppm, respectively. The statistical analyses of the six biomarkers for correlation with air-borne toluene showed that both Tol-B and Tol-U gave a high correlation coefficient of 0.58 to 0.61 (p<0.01), whereas the coefficients for BeOH-U and BMA-U together with HA-U were all low (up to 0.22, depending on the correction for urine density) and statistically insignificant (p>0.10) in most cases. o-CR-U had an intermediary coefficient of 0.20 (p<0.05). Comparison with previous publications disclosed that BeOH-U, BMA-U and HA-U correlate with toluene in air when the exposure is intense (e.g., 50 ppm or above), but no longer proportional to air-borne toluene when the exposure is low, e.g., 2 ppm. Such appeared to be also the case for o-CR-U. In over-all evaluation, the validity of o-CR-U in monitoring occupational exposure to toluene at low levels (e.g., 2 ppm) appear to be limited, and BMA-U is not an appropriate biomarker. BeOH-U and HA-U are also inappropriate for this purpose. Only Tol-B and Tol-U may be employed to estimate toluene exposure at low levels.

Changes in correlation coefficients of exposure markers as a function of intensity of occupational exposure to toluene.

This study was initiated to identify a marker of choice to monitor occupational exposure to toluene through quantitative evaluation of changes in correlation coefficients (CCs), taking advantage of a large database. Six known or proposed exposure markers in end-of-shift blood (B) and urine (U) were studied, i.e., toluene in blood (Tol-B) and benzyl alcohol, benzylmercapturic acid, o-cresol, hippuric acid and toluene in urine (BeOH-U, BMA-U, o-CR-U, HA-U, and Tol-U, respectively). To construct a database, data on 8-h time-weighted average intensity of occupational exposure to toluene and resulting levels of the six exposure markers in blood or urine were cited for 901 cases from previous four publications of this study group and combined with 146 new cases. In practice, 874 cases (all men) were available when extremely dilute or dense urine samples were excluded. The 874 cases were classified taking the upper limit (from 120 ppm to 1 ppm) of the toluene exposure concentration, and the CCs for the six markers with TWA toluene exposure intensity were calculated. For further evaluation, the 874 cases were divided into 10 per thousand in terms of TWA toluene exposures, and several 10 per thousand were combined so that sufficient numbers of cases were available for calculation of the CCs at various levels of toluene exposure. Perusal was made to know whether or not and which one of the six makers gave significant CC even at low level of toluene exposure. The CCs for BMA-U, o-CR-U and HA-U with TWA toluene exposure were well >0.7 when toluene exposure was intense (e.g., up to 60-100 ppm as the upper limit of the exposure range), but were reduced when the upper limit of toluene exposure was less than 50 ppm, and the CCs were as small as <==0.2 when the upper limit was about 10 ppm or less. In contrast, Tol-U and Tol-B were correlated with exposure to toluene down to the 0.4 when the cases in the 60th-100th per thousand were examined. The CCs for Tol-U and Tol-B were >0.3 also for cases in the 0th-60th or 30th-70th per thousand, whereas the CCs for other four markers were <0.3. In over-all evaluation, it was concluded that HA and o-CR are among the markers of choice to monitor occupational toluene exposure at high levels, and that only un-metabolized toluene in urine or in blood is recommended when toluene exposure level is low (e.g., 10 ppm or less). Toluene in urine may be preferred rather than that in blood due to practical reasons, such as non-invasiveness.

Stability in urine of authentic phenylglyoxylic and mandelic acids as urinary markers of occupational exposure to styrene.

Phenylglyoxylic acid (PhGA) and mandelic acid (MA) are two popular urinary markers of occupational exposure to styrene, but PhGA has been considered to be relatively unstable when urine samples are stored. This study was initiated to examine the stability of PhGA in urine under two storage conditions, i.e., at room temperature (at 25 degrees C) and in refrigeration (at 4 degrees C) for up to 14 days. The experiments showed that no substantial decrease was observed in either PhGA or MA even at room temperature within one day, but, depending on urine samples, a gradual decrease in PhGA took place both at 4 degrees C and more markedly at 25 degrees C when kept for a week. Further reduction was observed in two weeks even at 4 degrees C. No reduction was observed in MA up to two weeks both at 4 degrees C and at 25 degrees C. The observation on stability of MA and limited stability of PhGA (i.e., no significant decrease for 4 days when stored as refrigerated) was confirmed by a repeated experiment. Further analyses disclosed that PhGA when stored at 4 degrees C tended to be more unstable when urine samples were alkaline (e.g., at pH 8) rather than acidic (e.g., at pH 6 or below), but the trend varied subject to individual samples. Thus, the practical recommendation is that urine samples should be analyzed on the day of collection if all possible, or kept at 4 degrees C, or more preferably at -20 degrees C. Refrigeration will allow storage of up to 4 days without substantial decrease in either PhGA or MA.