Evaluation of occupational exposure to benzene by urinalysis

Urinary phenol determinations have traditionally been used to monitor high levels of occupational benzene exposure. However, urinary phenol cannot be used to monitor low-level exposures. New biological indexes for exposure to low levels of benzene are thus needed. The aim of this study was to investigate the relations between exposure to benzene (Abenzene, ppm), as measured by personal air sampling, and the excretion of benzene (U-benzene, ng/l),trans,trans-muconic acid (MA, mg/g creatinine), andS-phenylmercapturic acid (PMA, g/g creatinine) in urine. The subjects of the study were 145 workers exposed to benzene in a chemical plant. The geometric mean exposure level was 0.1 ppm (geometric standard deviation = 4.16). After logarithmic transformation of the data the following linear regressions were found: log (U-benzene, ng/l) = 0.681 log (A-benzene ppm) + 4.018; log (MA, mg/g creatinine) = 0.429 log (A-benzen ppm) – 0.304; and log (PMA, g/g creatinine) = 0.712 log (A-benzene ppm) + 1.664. The correlation coefficients were, respectively, 0.66, 0.58, and 0.74. On the basis of the equations it was possible to establish tentative biological limit values corresponding to the respective occupational exposure limit values. In conclusion, the concentrations of benzene, mercapturic acid, and muconic acid in urine proved to be good parameters for monitoring low benzene exposure at the workplace.     

Trans,trans-muconic acid, a biological indicator to low levels of environmental benzene: some aspects of its specificity

BACKGROUND: The specificity of trans,trans-muconic acid (MA) as a biomarker of exposure to low benzene levels and the role of sorbic acid (SA) as a confounding factor were evaluated. MA, a urinary ring-opened metabolite of benzene, has been recently proposed for the biological monitoring of populations exposed to low levels of this chemical. The usual presence of MA in urine of non-occupationally exposed people is generally attributed to benzene world-wide contamination (mainly by smoking habits, urban pollution, and maybe by food contamination). However, the scientific literature reveals that the common food preservative and fungistatic agent SA is converted into MA though in trace amounts. METHODS: Urinary benzene and MA before and after administration of SA were measured in smokers and non-smokers. Benzene dissolved in urine was analyzed injecting a headspace sample in a gas-chromatografic system. Urinary MA was measured by means of a HPLC apparatus. RESULTS: The mean background values of MA were about 60 mg/L (or 50 mg/g creat.); after experimental administration of SA (447 mg), the mean urinary MA concentration became more than 20 times higher. The biotransformation rates of SA into MA after ingestion of 447 mg of SA ranged from 0.05 to 0.51%. The ratio between unmetabolized benzene in the two groups of smokers and non-smokers was significantly different from the ratio between MA in the same two groups. DISCUSSION: Other sources of MA excretion, different from benzene, influence the urinary concentration of the metabolite: only 25% of MA background values can be attributed to benzene. The urinary MA induced by 100 mg of ingested MA is 77% of that expected after an 8-hour benzene exposure to 0.5 ppm (current threshold limit value according to ACGIH). In conclusion, MA is not a sufficiently specific biomarker of low benzene exposure; a significant effect of SA ingestion is predictable.     

Application of the urinary S-phenylmercapturic acid test as a biomarker for low levels of exposure to benzene in industry.

Recently, the determination of S-phenylmercapturic acid (S-PMA) in urine has been proposed as a suitable biomarker for the monitoring of low level exposures to benzene. In the study reported here, the test has been validated in 12 separate studies in chemical manufacturing plants, oil refineries, and natural gas production plants. Parameters studied were the urinary excretion characteristics of S-PMA, the specificity and the sensitivity of the assay, and the relations between exposures to airborne benzene and urinary S-PMA concentrations and between urinary phenol and S-PMA concentrations. The range of exposures to benzene was highest in workers in chemical manufacturing plants and in workers cleaning tanks or installations containing benzene as a component of natural gas condensate. Urinary S-PMA concentrations were measured up to 543 micrograms/g creatinine. Workers' exposures to benzene were lowest in oil refineries and S-PMA concentrations were comparable with those in smoking or nonsmoking control persons (most below the detection limit of 1 to 5 micrograms/g creatinine). In most workers S-PMA was excreted in a single phase and the highest S-PMA concentrations were at the end of an eight hour shift. The average half life of elimination was 9.0 (SD 4.5) hours (31 workers). Tentatively, in five workers a second phase of elimination was found with an average half life of 45 (SD 4) hours. A strong correlation was found between eight hour exposure to airborne benzene of 1 mg/m3 (0.3 ppm) and higher and urinary S-PMA concentrations in end of shift samples. It was calculated that an eight hour benzene exposure of 3.25 mg/m3 (1 ppm) corresponds to an average S-PMA concentration of 46 micrograms/g creatinine (95% confidence interval 41-50 micrograms/g creatinine). A strong correlation was also found between urinary phenol and S-PMA concentrations. At a urinary phenol concentration of 50 mg/g creatinine, corresponding to an eight hour benzene exposure of 32.5 mg/m3 (10 ppm), the average urinary S-PMA concentration was 383 micrograms/g creatinine. In conclusion, with the current sensitivity of the test, eight hour time weighted average benzene exposures of 1 mg/m3 (0.3 ppm) and higher can be measured.     

人尿中酚,粘糠酸,苯巯基尿酸的生物监测

为了探索接触低浓度苯的生物监测指标，在建立了灵敏、特异的尿中反，反－粘糠酸（ｔ，ｔ－ＭＡ）的高效液相色谱（ＨＰＬＣ）、苯巯基尿酸（Ｓ－ＰＭＡ）的色谱／质谱／质谱（ＬＣ／ＭＳ／ＭＳ）测定方法的基础上，对４９位接触低浓度苯的工人及２０位非职业接触者进行了生物监测。结果表明：在苯接触浓度低于３．２ｍｇ／ｍ３（１ｐｐｍ）的情况下，作业工人的尿ｔ，ｔ－ＭＡ和Ｓ－ＰＭＡ浓度与空气中苯的ＴＷＡ浓度显著相关；尿酚与空气中苯的ＴＷＡ浓度之间的相关性很差。吸烟能增加尿ｔ，ｔ－ＭＡ和Ｓ－ＰＭＡ的浓度。     

Biological monitoring of exposure to benzene: a comparison between S-phenylmercapturic acid, trans,trans-muconic acid, and phenol.

OBJECTIVES--Comparison of the suitability of two minor urinary metabolites of benzene, trans,trans-muconic acid (tt-MA) and S-phenylmercapturic acid (S-PMA), as biomarkers for low levels of benzene exposure. METHODS--The sensitivity of analytical methods of measuring tt-MA and S-PMA were improved and applied to 434 urine samples collected from 188 workers in 12 studies in different petrochemical industries and from 52 control workers with no occupational exposure to benzene. In nine studies airborne benzene concentrations were assessed by personal air monitoring. RESULTS--Strong correlations were found between tt-MA and S-PMA concentrations in samples from the end of the shift and between either of these variables and airborne benzene concentrations. It was calculated that exposure to 1 ppm (8 hour time weighted average (TWA)) benzene leads to an average concentration of 1.7 mg tt-MA and 47 micrograms S-PMA/g creatinine in samples from the end of the shift. It was estimated that, on average, 3.9% (range 1.9%-7.3%) of an inhaled dose of benzene was excreted as tt-MA with an apparent elimination half life of 5.0 (SD 2.3) hours and 0.11% (range 0.05%-0.26%) as S-PMA with a half life of 9.1 (SD 3.7) hours. The mean urinary S-PMA in 14 moderate smokers and 38 non-smokers was 3.61 and 1.99 micrograms/g creatinine, respectively and the mean urinary tt-MA was 0.058 and 0.037 mg/g creatinine, respectively. S-PMA proved to be more specific and more sensitive (P = 0.030, Fisher's exact test) than tt-MA. S-PMA, but not tt-MA, was always detectable in the urine of smokers who were not occupationally exposed. S-PMA was also detectable in 20 of the 38 non-smokers from the control group whereas tt-MA was detectable in only nine of these samples. The inferior specificity of tt-MA is due to relatively high background values (up to 0.71 mg/g creatinine in this study) that may be found in non-occupationally exposed people. CONCLUSIONS--Although both tt-MA and S-PMA are sensitive biomarkers, only S-PMA allows reliable determination of benzene exposures down to 0.3 ppm (8 h TWA) due to its superior specificity. Because it has a longer elimination half life S-PMA is also a more reliable biomarker than tt-MA for benzene exposures during 12 hour shifts. For biological monitoring of exposure to benzene concentrations higher than 1 ppm (8 h TWA) tt-MA is also suitable and may even be preferred due to its greater ease of measurement.     

Urinary t,t-muconic acid as an indicator of exposure to benzene

A method for rapidly determining t,t-muconic acid (MA) by high performance liquid chromatography was developed and successfully applied to urine samples from 152 workers exposed to benzene (64 men, 88 women) and 213 non-exposed controls (113 men, 100 women). The MA concentrations in urine correlated linearly with time weighted average benzene concentrations in the breath zone air of workers. A cross sectional balance study showed that about 2% of benzene inhaled is excreted into the urine as MA. The MA concentrations in the urine of the non-exposed was below the detection limit (less than 0.1 mg/l) in most cases, and the 95% lower confidence limit of MA for those exposed to benzene at 5 ppm (5.0 mg/l as a non-corrected value) was higher than the 97.5%-tile values for the non-exposed (1.4 mg/l). In practice, it was possible to separate those exposed to 6-7 ppm benzene from the non-exposed by means of urine analysis for MA. The urinary MA concentration was suppressed by coexposure to toluene.     

Urinary t,t-muconic acid as an indicator of exposure to benzene.

A method for rapidly determining t,t-muconic acid (MA) by high performance liquid chromatography was developed and successfully applied to urine samples from 152 workers exposed to benzene (64 men, 88 women) and 213 non-exposed controls (113 men, 100 women). The MA concentrations in urine correlated linearly with time weighted average benzene concentrations in the breath zone air of workers. A cross sectional balance study showed that about 2% of benzene inhaled is excreted into the urine as MA. The MA concentrations in the urine of the non-exposed was below the detection limit (less than 0.1 mg/l) in most cases, and the 95% lower confidence limit of MA for those exposed to benzene at 5 ppm (5.0 mg/l as a non-corrected value) was higher than the 97.5%-tile values for the non-exposed (1.4 mg/l). In practice, it was possible to separate those exposed to 6-7 ppm benzene from the non-exposed by means of urine analysis for MA. The urinary MA concentration was suppressed by coexposure to toluene.     

职业接触苯乙烯的生物限值研究

目的：研究职业接触苯乙烯的生物限值。方法：高效液相色谱法测定苯乙烯作业工人班前、班后尿中苯乙醛酸（PGA）和苯乙醇酸（MA）的含量，监测工人8h苯乙烯的接触水平，同时研究两者的相关性。结果：尿中的PGA和MA浓度与苯乙烯的接触量有明显的剂量－反应关系。根据作业场所空气中苯乙烯的国家卫生标准，按回归方程推导出职业接触苯乙烯的生物限值。结论：对职业接触苯乙烯的生物限值提出的推荐值：工作班末MA为220mmol/mol肌酐或300mg/g肌酐，下一班前为88mmol/mol肌酐或120mg/g肌酐；PGA班末为7mmol/mol肌酐或100mg/g肌酐，下一班前为30mmol/mol肌酐或40mg/g肌酐。     

Biological monitoring of styrene in the reinforced plastics industry in Emilia Romagna,Italy

Summary Biological monitoring of styrene exposure among workers in the reinforced plastics industry is widely implemented in the region of Emilia Romagna, Italy. More than 18000 urine samples measurements of the main metabolites of styrene, mandelic (MA) and phenylglyoxylic acid, were retrieved for the period 1978–1990, and 4689 values of MA in postshift urine samples were analyzed for various variables thought to influence styrene exposure. The job performed was found to be the most important predictor of styrene exposure. Hand laminators had the highest exposure (mean MA 682 mg/g creatinine); spray laminators showed lower values (404 mg/g), while levels in semiautomatic process operators(243 mg/g) were only slightly higher than in nonprocess workers (186 mg/g). The use of ventilation resulted in lower exposure, but differences in average values were not particularly wide. Exposure decreased weakly during the study period in all work categories, but the percentage of measurements exceeding the current biological limit value (900 mg/g creatinine, 1300 mg/1 corrected for density) is still very high (20% of measurements among hand laminators in 1990). These results indicate that the control measures implemented are only partially effective for the prevention of styrene exposure.The work was done at the International Agency for Research on Cancer (Lyon, France) and at the Documentation and Information Center on Occupational and Environmental Health and Safety (Bologna, Italy)     

Fluoride in workplace air and in urine of workers concentrating fluorspar

The urinary fluoride concentrations of workers exposed to calcium fluoride (CaF2) during fluorspar processing were measured. Personal dust measurement showed that the mean occupational exposure to fluoride for 12 workers in the most dusty environment was 24.3 mg/m3, which is 9.7 times the threshold limit value (TLV) of 2.5 mg/m3. Exposure was below the TLV for the remaining 23 workers. Urinary fluoride concentrations were measured pre- and postshift. The heavily exposed workers had a mean preshift concentration of 3.3 mg/liter (range 1.4-8.5 mg/liter), only slightly higher than the mean of 2.8 mg/liter (range 1.3-4.2 mg/liter) in the workers with fluoride exposure below the TLV. Four of the preshift concentrations exceeded the recommended upper limit of 4 mg/liter. The mean postshift concentration for workers exposed above the TLV was 4.4 mg/liter (range 2.4-7.1 mg/liter) and the difference between pre- and postshift concentrations was significant (p less than 0.05). Only one urinary concentration exceeded the recommended upper limit of 7 mg/liter. There was poor correlation between intensity of environmental exposure to fluorspar and postshift fluoride concentration in the urine. Eighteen workers provided a urine sample 7-14 hr after the end of a shift. The mean fluoride concentration was 4.7 mg/liter (range 2.4-11.7 mg/liter), which exceeded their postshift concentration by 0.2 mg/liter. These results indicate that the low aqueous solubility of fluorspar reduced the biologic availability of the fluoride ion but that this did not prevent excessive fluoride absorption in some workers.     

Kinetics of styrene urinary metabolites: a study in a low-level occupational exposure setting in Singapore

Summary Biological monitoring of styrene exposure commonly involves measurement of styrene metabolites, mainly mandelic acid (MA) and phenylglyoxylic acid (PGA), in the urine of exposed subjects. Previous studies on the kinetics of styrene metabolites in urine were mostly conducted in a controlled environment on subjects exposed to high concentrations of styrene. In this study, we examined subjects exposed to low levels of styrene in a fiber-reinforced plastics (FRP) plant to see whether the excretion kinetics of styrene metabolites are similar under field conditions. Eight healthy Chinese male volunteers were exposed to styrene for 4 h with a mean environmental concentration of 11 ppm. Urine samples were collected continuously for 20 h after termination of the exposure and concentrations of urinary MA and PCA were determined. The results showed that MA was rapidly excreted in urine after the exposure, with a half-life of 2.1 h or 1.9 h when corrected with urine creatinine. The excretion of PGA followed that of MA and the half-life was 8.1 h or 5.1 h after correction with creatinine. The half-lives are considerably shorter compared to those in previous reports, suggesting that environmental factors, exposure conditions, or ethnic differences may affect the excretion kinetics of styrene metabolites. The fast excretion of styrene metabolites is also consistent with the observation that urine MA and PGA levels correlated better with the half-day time-weighted average (TWA) concentration of environmental styrene than with the whole-day TWA concentration. Our findings thus underscore the need for information on excretion kinetics in order to develop an appropriate biological monitoring scheme for specific exposure settings and subjects.     

Carbon disulphide

The reported investigations on the uptake of carbon disulphide (CS₂) and the excretion of its metabolite 2-thiothiazolidine-4-carboxylic acid (TTCA) were based on results from 403 personal air samples (352 passive and 51 active samples) and 362 TTCA determinations in biological material measured during a field study on the adverse effects due to CS₂ exposure. The external exposure ranged from below the detection limit (0.2 ppm) to 66 ppm and the urinary TTCA excretion from below the detection limit (0.16 mg./1) to 33.4 mg/1. The excretion of TTCA in postshift urine related to creatinine and volume showed a linear correlation to the CS₂ air concentration. On the basis of these results the influence on the internal exposure of physical work load, dermal exposure and individual parameters (age, Brocaindex, disturbed skin barrier) was evaluated. Correlations between the TTCA values in the postshift urine and the individually measured CS₂ concentrations were carried out separately for individual departments and persons with and without indications of a disturbed skin barrier. In order to be able to judge the individual internal exposure related to external exposure, a personal quotient was formed from the TTCA level in the urine and the CS₂ air concentration measured on the same day (relative interal exposure RIE index = TTCA mg/g creatinine/CS₂ in ppm). On investigating interindividual differences, higher relative internal exposures were found in persons with a heavy physical work load and more intensive skin contact. It could be shown for a large group of persons exposed to CS₂ that a pathological skin condition leads to an increase in the dermal penetration rate of hazardous substances. By means of the RIE index it could be shown that the TTCA excretion related to the individual external exposure increases significantly with a decreasing Broca index, which must be taken into consideration with greatly overweight persons and exposures in the range of the currently valid threshold limit values. The interindividual differences in internal exposure found at the same ambient air concentration emphasize the importance of biological monitoring for individual health protection and the setting of biological threshold limit values.Dedicated to Professor G. Zehnert on the occassion of his 65th birthday     

Personal exposures of benzene treated workers and a simple biological monitoring

A simple method of biological monitoring has been developed for occupational benzene exposure. Personal benzene exposure monitoring using a passive sampler and GC/FID was carried out on 74 workers from a benzene-treated company. Their urines were collected before and after work-shift. After treatment of urine samples using solid phase extraction (SPE), trans, trans-muconic acid(t, t-MA) concentration in the elute was analysed by HPLC. Correlation between benzene exposure (X: ppm) and urinary t, t-MA concentration (Y: mg/g x creatinine) for non-smokers was Y = 0.948X + 0.586 (r = 0.798, P < 0.01) and Y = 0.885X + 0.894 (r = 0.871, P < 0.01) for smokers, respectively. The t, t-MA concentration on 1 ppm TLV exposure to benzene was estimated as 1.5 and 1.8 (mg/g creatinine) for non-smokers and smokers, respectively. These values are in agreement with some investigators. This indicates that our simple method for biological monitoring of benzene exposure can be of great service.     

Assessment of exposure to carbon disulfide in viscose production workers from urinary 2-thiothiazolidine-4-carboxylic acid determinations.

The follow-up of environmental carbon disulfide (CS2) exposure and urinary excretion of 2-thiothiazolidine-4-carboxylic acid (TTCA) among 20 operatives over a 4-day working week in two viscose producing factories confirmed earlier observations that TTCA is a sensitive and reliable indicator of exposure to CS2. Exposure to as low as 0.5-1.0 ppm (1.6-3.2 mg/m3) of CS2 (8-hour time-weighted average [TWA]) was associated with detectable amounts of TTCA in end-of-shift urine. Moreover, the excretion of TTCA, relative to estimated CS2 uptake, appeared surprisingly constant in the studied work force. Approximately 3% (range 2-6.5%) of absorbed CS2 was detected in urine as TTCA. The proportional TTCA excretion did not show dose dependency in the estimated CS2 dose range which varied by about 20-fold. TTCA elimination exhibited both a fast (T 1/2 6 hour) and a slow (T 1/2 68 hour) phase. The slow elimination is compatible with a high lipid solubility and reversible protein binding of CS2. Consequently, urinary excretion of TTCA, relative to CS2 exposure, increased by about a third during the workweek. Urinary TTCA concentration of 4.5 mmol/mol creatinine in a postshift sample corresponded to a TWA exposure to 10 ppm CS2 towards the end of the working week.     

Delayed and Competitively Inhibited Excretion of Urinary Hippuric Acid in Field Workers Coexposed to Toluene,Ethyl Benzene,and Xylene

The purpose of this study was to investigate whether the metabolic suppression of hippuric acid (HA) occurs in field workers coexposed to toluene, xylene and ethyl benzene. Eleven male spray painters were recruited into this study and monitored for 2 weeks using a repeated-measures study design. The sampling was conducted for 3 consecutive working days each week. Toluene, ethyl benzene, and xylene in the air were collected using 3M 3500 organic vapor monitors. Urine samples were collected before and after work shift, and urinary HA, methyl hippuric acid, mandelic acid, and phenylgloxylic acid concentrations were determined. In the first week, toluene concentrations were 2.66 ± 0.95 (mean ± SE) ppm, whereas ethyl benzene and xylene concentrations were 27.84 ± 3.61 and 72.63 ± 13.37 ppm, respectively, for all subjects. Pre–work shift HA concentrations were 230.23 ± 37.31 mg/g creatinine, whereas pre–work shift HA concentrations were 137.81 ± 14.15 mg/g creatinine. Mean urinary HA concentration was significantly greater in the pre–work shift samples than in the pre–work shift samples (p = 0.043). In the second week, toluene concentrations were much lower (0.28 ppm), whereas ethyl benzene and xylene were 47.12 ± 8.98 and 23.88 ± 4.09 ppm, respectively, for all subjects. Pre–work shift HA concentrations were 351.98 ± 116.23 mg/g creatinine, whereas pre–work shift HA concentrations were 951.82 ± 116.23 mg/g creatinine. Mean urinary HA concentration was significantly greater in the pre–work shift samples than in the pre–work shift samples (p <0.01); a significant correlation (r = 0.565; p = 0.002) was found between pre–work shift urinary HA levels and ethyl benzene exposure. This study showed that urinary HA peak was delayed to next morning for workers coexposed to toluene, ethyl benzene, and xylene; xylene and ethyl benzene probably played competitive inhibitors for metabolism of toluene. The study also presumed that urinary HA became the major metabolite of ethyl benzene at the end of work shift, when the exposure concentrations of ethyl benzene were 2.0 times those of xylene.     

Biological monitoring of vehicle mechanics and other workers exposed to low concentrations of benzene

 It has been suggested that the threshold limit value (TLV) for the time-weighted average (TWA), of benzene be lowered because of its possible leukemogenic effect at low exposure concentrations. This requires the development of new methods of biological monitoring. In this cross-sectional study the diagnostic power of blood and breath benzene and of urinary phenol, catechol, hydroquinone, S-phenylmercapturic acid, and muconic acid were compared in a population of 410 male workers exposed to benzene in garages, in two coke plants, and in a by-product plant. Benzene exposure was assessed by personal air sampling (charcoal tube and passive dosimeter). In all, 95% of the workers were exposed to less than 0.5 ppm benzene. According to the multiple regression equation, the muconic acid and S-phenylmercapturic acid concentrations detected in nonsmokers exposed to 0.5 ppm benzene were 0.3 mg/g and 6 μg/g, respectively (range 0.2–0.6 mg/g and 1.2–8.5 μg/g, respectively). With muconic acid very few false-positive test results were found, and this determination remained reliable even around a cutoff level of 0.1 ppm benzene. Moreover, the diagnostic power of this test proved to be good even when diluted or concentrated urine samples were not excluded. S-Phenylmercapturic acid (S-PMA) also performed fairly well. Blood and breath benzene as well as urinary phenol (PH) and hydroquinone (HQ) were clearly less suitable biomarkers than muconic acid (MA). Catechol (CA) was not associated with occupational benzene exposure. According to the results of biological monitoring, the skin resorption of benzene from gasoline or other fuels seems negligible. Correlation, multiple regression, and likelihood ratios consistently showed that MA and S-PMA concentrations were fairly good indicators of benzene exposure in the 0.1- to 1-ppm range, even in a population comprising both smokers and nonsmokers. PH, HQ, CA, and blood and breath benzene were less suitable, if at all, in the same exposure range. Received: 31 July 1996/Accepted: 29 November 1996     

Assessment of urinary trans, trans-muconic acid as a biomarker of exposure to benzene

OBJECTIVE: To assess the use of trans, trans-muconic acid as a biomarker of occupational exposure to benzene. METHODS: Trans, trans-muconic acid in urine samples of exposed (exposed group, n=36) and non-exposed (non-exposed group, n=116) workers to benzene. Urinary levels of trans, trans-muconic acid were quantified by high-performance liquid chromatography. The study sample consisted of subjects exposed to benzene in an oil refinery in Belo Horizonte, Brazil. Non-parametric statistical analysis was carried out using Kruskall-Wallis test, Mann-Whitney test and Spearman correlation at p<0.05. RESULTS: Workers were exposed on average to benzene levels of 0.15 +/- 0.05 mg/m3 (0.05 ppm) and they showed a urinary trans, trans-muconic acid mean value of 0.19 +/- 0.04 mg/g of creatinine. The reference value range of trans, trans-muconic acid in non-exposed subjects was 0.03 to 0.26 mg/g of creatinine (mean 0.10 +/- 0.08 mg/g of creatinine). There was seen a statistical difference between trans, trans-muconic acid levels in urine samples from exposed and non-exposed groups. There was no correlation between urinary trans, trans-muconic acid and air benzene levels. There was no correlation between urinary trans, trans-muconic acid levels in the exposed group and smoking. Alcohol consumption up to 48 hours before sampling procedure showed no effect on trans, trans-muconic acid levels in both exposed and non-exposed groups. There was however a correlation between age (range 18 to 25 years) and urinary metabolite levels in the latter group. CONCLUSIONS: The results show that it is important to evaluate the effect of age and smoking habits on urinary trans, trans-muconic acid levels.     

Biological monitoring of occupational exposure to methyl ethyl ketone in Japanese workers

The relationship between occupational exposure to methyl ethyl ketone (MEK) and its concentration in urine and blood was studied in a group of 72 workers in a printing factory. Personal exposure monitoring was carried out with passive samplers during the workshifts. The time weighted average (TWA) concentration of MEK ranged from 1.3 to 223.7 ppm, with a mean concentration of 47.6 ppm. In addition to MEK, toleuene, xylene, isopropyl alcohol, and ethyl acetate were detected as the main contaminants in all samples.At the end of the workshift, urine samples were collected to determine the urinary MEK, hippuric acid (HA), and creatinine, and blood samples were also collected at the same time for determination of MEK. The concentrations of urinary MEK ranged from 0.20 to 8.08 mg/L with a mean of 1.19 mg/L and significantly correlated with TWA concentrations of MEK in the air with a correlation coefficient of 0.889 for uncorrected urine samples. The concentration of MEK in the blood was also significantly correlated with the TWA concentration of MEK with a correlation coefficient of 0.820.From these relationships, MEK concentrations in urine and blood corresponding to the threshold limit value-TWA (200 ppm; ACGIH 1992) were calculated to be 5.1 mg/L and 3.8 mg/L as a biological exposure index (BEI), respectively. Although the BEI for urinary MEK obtained from the present study was higher than that of previous reports and ACGIH's recommendation (2.0 mg/L), the BEI agreed well with a previous study in Japan. On the other hand, the relationship between toluene exposure and urinary HA level, an index of toluene exposure, was also studied at the same time. The urinary concentration of HA corresponding to TWA at 100 ppm was 2.6 g/g creatinine as BEI. This value agreed well with both ACGIH's recommendation (2.5 g/g creatinine) and the values reported by Japanese researchers who have studied Japanese workers. Ethnic differences of MEK metabolism may affect the relationship between exposure and BEI.     

Evaluation of dermal absorption and protective effectiveness of respirators for xylene in spray painters

Objectives To determine the contribution of dermal absorption on the total exposure dose and the performance of respirators in the field for xylene in spray painters. Methods Eighteen male spray painters worked at shipyard were recruited for this study. The subjects were monitored during a 3-day-work period using a repeated-measures study design. Personal exposure to xylene outside and inside mask were collected using two 3 M model 3500 organic vapor monitors, respectively. Urine was collected before and after the work shift and urinary methyl hippuric acid (MHA) was determined. Total 98 of air and urine samples were obtained, respectively. Results Air sampling results showed that workers were primarily exposed to xylene and ethyl benzene. Xylene and ethyl benzene concentrations outside the mask were 52.6 ± 63.7 (mean ± SD) and 33.2 ± 32.4 ppm, and concentrations inside the mask were 2.09 ± 2.74 and 1.79 ± 2.16 ppm, respectively. The median workplace protection factors of respirators for xylene and ethyl benzene were 25.0 and 17.4, respectively. On average, workers could reduce xylene inhalation by 96% and ethyl benzene inhalation by 94% for wearing respirators. A significant correlation (R ² = 0.935; P < 0.001) was found between the WPFs for xylene and ethyl benzene. Total urinary MHA concentration was 240.2 ± 42.3 (mean ± SE) mg/g creatinine, whereas urinary MHA via skin absorption was estimated to be 202.1 ± 40.1 mg/g creatinine. The contribution of dermal absorption to the total exposure dose of xylene was 64 ± 4.3%. Conclusion The present study showed that inhalation of solvent vapors in workers decreased as a result of wearing respirators and dermal exposure became the main contributor to the total body burden of solvents. Because workers had different attitude and behavior to wear respirators, the measured workplace protection factors varied. It is therefore equally important to prevent from being exposed to solvents through skin for shipyard spray painters.     

Biological monitoring of the occupational exposure to halothane (fluothane) in operating room personnel

The concentration of halothane (fluothane) in the ambient atmosphere was determined in five operating theaters of two hospitals in Italy. The concentrations of halothane in the ambient air exceeded the NIOSH recommended time-weighted average exposure levels (median value: 10.38 mg/m3). Halothane was detected in the urine of 58 exposed subjects (anesthetists, surgeons, and nurses). A significant correlation was found between the halothane concentration in urine produced during the shift (Cu, micrograms/L) and halothane environmental concentration (CI, mg/m3) (Cu = 0.242 x CI + 3.51) (N = 58; r = 0.92; p less than 0.0001). The results show that the urinary halothane concentration can be used as an appropriate biological exposure index. The biological values proposed are: 92 micrograms/L, corresponding to a 50 ppm of environmental exposure; 6.5 micrograms/L, corresponding to 2 ppm of environmental exposure and 3.9 micrograms/L, corresponding to a 0.5 ppm of environmental exposure.