Effect of physical exertion on the biological monitoring of exposure of various solvents following exposure by inhalation in human volunteers: I. Toluene

Physical exertion (work load) has been recognized as one of several factors that can influence the kinetics of xenobiotics within the human body. This study was undertaken to evaluate the impact of physical exertion on two exposure indicators of toluene (TOL) in human volunteers exposed under controlled conditions in an inhalation chamber. A group of four volunteers (one woman, three men) were exposed to TOL (50 ppm) according to the following scenarios involving several periods during which volunteers were asked to perform either aerobic (AERO), muscular (MUSC), or both (AERO/MUSC) types of physical exercise (exercise bicycle, treadmills, pulleys). The target intensities (W) for each exercising period of 30 min--interspaced with 15 min at rest--were the following: REST, 50 W AERO (time-weighted average intensity [TWAI]: 46 watts); 50 W AERO/MUSC (TWAI: 38 watts) and 100 W AERO (TWAI: 71 watts) for 7 hours and 50 W MUSC for 3 hours (TWAI: 29 watts). Alveolar air and urine samples were collected at different time intervals before, during, and after exposure for the measurement of unchanged TOL in expired air (TOL-A) and urinary o-cresol (o-CR). Overall, the results showed that TOL-A measured during and after all scenarios involving physical activities were higher (approximately 1.4-2.0 fold) compared with exposures at rest. All scenarios involving physical exertion also resulted in increased end-of-exposure urinary o-CR (mean +/- SD): 0.9 +/- 0.1 mg/L (REST) vs. 2.0 +/- 0.1 mg/L (TWAI 46 watts). However, exposure at a TWAI of 71 watts did not further increase o-CR excretion (1.7 +/- 0.2 mg/L). This study confirms the significant effect of work load on TOL kinetics and showed that o-CR excretion increased proportionally with work load expressed as TWAI or with the estimated mean pulmonary ventilation during the period of exposure. This study also shows that exposure to TOL (50 ppm) involving a work load of around 50 W (light intensity) or lower is likely to produce urinary o-CR values that clearly exceed the current biological exposure index value for TOL.     

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.     

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.     

Biological monitoring of occupational exposure to tetrahydrofuran

Occupational exposure to tetrahydrofuran (THF) was studied by analysis of environmental air, blood, alveolar air, and urine from 58 workers in a video tape manufacturing plant. Head space gas chromatography (GC) with an FID detector was used for determination of THF concentration in alveolar air, urine, and blood. Environmental exposure to THF was measured by personal sampling with a carbon felt passive dosimeter. When the end of shift urinary THF concentrations were compared with environmental time weighted average (TWA) values, urinary THF concentration corrected for specific gravity correlated well with THF concentration in air (r = 0.88), and uncorrected urinary THF concentration gave a similar result (r = 0.86). Correction for creatinine in urine weakened the correlation (r = 0.56). For exposure at the TWA concentration of 200 ppm the extrapolated concentration of THF was 33 mumol/l in blood and 111.9 mumol/l (61 mumol/g creatinine) or 109 mumol/l at a specific gravity of 1.018 in urine. The correlation between exposure to THF and its concentration in exhaled breath and blood was low (r = 0.61 and 0.68 respectively). Laboratory methodological considerations together with the good correlation between urinary THF concentration and the environmental concentration suggest that THF concentration in urine is a useful biological indicator of occupational exposure to THF.     

Biological monitoring of occupational exposure to tetrahydrofuran.

Occupational exposure to tetrahydrofuran (THF) was studied by analysis of environmental air, blood, alveolar air, and urine from 58 workers in a video tape manufacturing plant. Head space gas chromatography (GC) with an FID detector was used for determination of THF concentration in alveolar air, urine, and blood. Environmental exposure to THF was measured by personal sampling with a carbon felt passive dosimeter. When the end of shift urinary THF concentrations were compared with environmental time weighted average (TWA) values, urinary THF concentration corrected for specific gravity correlated well with THF concentration in air (r = 0.88), and uncorrected urinary THF concentration gave a similar result (r = 0.86). Correction for creatinine in urine weakened the correlation (r = 0.56). For exposure at the TWA concentration of 200 ppm the extrapolated concentration of THF was 33 mumol/l in blood and 111.9 mumol/l (61 mumol/g creatinine) or 109 mumol/l at a specific gravity of 1.018 in urine. The correlation between exposure to THF and its concentration in exhaled breath and blood was low (r = 0.61 and 0.68 respectively). Laboratory methodological considerations together with the good correlation between urinary THF concentration and the environmental concentration suggest that THF concentration in urine is a useful biological indicator of occupational exposure to THF.     

Monitoring of exposure to cyclohexanone through the analysis of breath and urine.

Occupational exposure to cyclohexanone was studied for 59 workers through the analysis of environmental air, alveolar air, and urinary cyclohexanol. Environmental cyclohexanone exposure was measured by personal sampling with a carbon-felt passive dosimeter. Cyclohexanone in alveolar air and cyclohexanol in urine were determined with gas chromatography with a flame ionization detector. The end-of-shift urinary cyclohexanol levels correlated well with the time-weighted average environmental cyclohexanone values (r = 0.66). Urinary cyclohexanol corrected for creatinine correlated best with cyclohexanone in air (r = 0.77); when corrected for specific gravity, it gave a similar correlation coefficient (r = 0.73). When the time-weighted average of the exposure was 25 ppm, the corresponding calculated concentration for urinary cyclohexanol was 54.5 mg/1, 23.3 mg/g of creatinine, or 43.5 mg/l at a specific gravity of 1.018. The relationship between cyclohexanone exposure and its concentration in exhaled breath was found to be poorer than that for cyclohexanone exposure and the urinary metabolite (r = 0.51).     

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.     

Urinary benzylmercapturic acid as a marker of occupational exposure to toluene

OBJECTIVE: To examine if benzylmercapturic acid (or N-acetyl- S-benzyl cysteine) in urine can be used as a marker of occupational exposure to toluene. METHODS: A factory survey was conducted in the latter half of a working week. A group of 46 men, who volunteered for the study, was engaged in ink preparation, surface coating or printing work. Diffusive samplers were used to measure average solvent exposure in an 8-h shift. End-of-shift urine samples were analyzed for benzylmercapturic acid (BMA) by a modification of an HPLC method originally developed for phenylmercapturic acid determination. RESULTS: The workers were exposed primarily to toluene [TOL; 13 ppm as the geometric mean (GM) and 86 ppm at the maximum] together with isopropyl alcohol (<1 and 4 ppm), ethyl acetate (2 and 127 ppm) and methyl ethyl ketone (2 and 142 ppm). BMA in urine correlated closely [correlation coefficient ( r) =0.7] with TOL in air, irrespective of correction for urine density. The lowest TOL concentration at which urinary BMA increased to a measurable level was approximately 10 ppm, and urinary BMA could separate the exposed from the non-exposed when TOL exposure was 15 ppm or higher. CONCLUSIONS: BMA in end-of-shift urine samples is a good marker of occupational TOL exposure. Urinalysis for BMA is sensitive enough to detect TOL exposure at 15 ppm, and therefore BMA appears to be more sensitive than hippuric acid and possibly o-cresol as a urinary marker of TOL exposure.     

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.     

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.     

Occupational chronic exposure to organic solvents XVI. Ambient and biological monitoring of workers exposed to toluene

Object Ambient air and biological monitoring of an occupational toluene exposure was carried out on a group of 33 workers. Method The biological monitoring of the workers was based on determination of the concentration of toluene in blood and on quantification of the urinary metabolites o-cresol and hippuric acid. All blood and urine samples were collected post-shift. Results The average toluene concentration in the workplace air was 65?ppm, ranging from 13 to 151?ppm. An average concentration of toluene in blood of 911?μg/l was found, corresponding to an average urinary concentration of 2.9?mg/l (2.3?mg/g creatinine) o-cresol and 2.4?g/l (1.9?g/g creatinine) hippuric acid. Both urinary metabolites can be correlated with the concentration of toluene in ambient air and blood, respectively. Conclusions The results of our study indicate that the determination of the urinary o-cresol excretion represents a diagnostically specific and sensitive parameter for the estimation of an individual toluene uptake. In contrast, monitoring of the concentration of hippuric acid in urine cannot be recommended for assessment of individual exposure. To set up a biological tolerance value (BAT) for o-cresol, a urinary concentration of 3?mg/l o-cresol should be in accordance with the current MAK value of 50?ppm toluene.     

Biological monitoring of workers exposed to ethylbenzene and co-exposed to xylene

OBJECTIVE: Ethylbenzene is an important constituent of widely used solvent mixtures in industry. The objective of the present study was to provide information about biological monitoring of occupational exposure to ethylbenzene, and to review the biological limit values corresponding to the threshold limit value of ethylbenzene. METHODS: A total of 20 male workers who had been exposed to a mixture of ethylbenzene and xylene, through painting and solvent mixing with commercial xylene in a metal industry, were recruited into this study. Environmental and biological monitoring were performed during an entire week. The urinary metabolites monitored were mandelic acid for ethylbenzene and methylhippuric acid for xylene. Correlations were analyzed between urinary metabolites and environmental exposure for ethylbenzene and xylene. The interaction effects of a binary exposure to ethylbenzene and xylene were also investigated using a physiologically based pharmacokinetic (PBPK) model. RESULTS: The average environmental concentration of organic solvents was 12.77 ppm for xylene, and 3.42 ppm for ethylbenzene. A significant correlation (R2 = 0.503) was found between environmental xylene and urinary methylhippuric acid. Urinary level of methylhippuric acid corresponding to 100 ppm of xylene was 1.96 g/g creatinine in the worker study, whereas it was calculated as 1.55 g/g creatinine by the PBPK model. Urinary level of mandelic acid corresponding to 100 ppm of ethylbenzene was found to be 0.7 g/g creatinine. PBPK results showed that the metabolism of ethylbenzene was highly depressed by co-exposure to high concentrations of xylene leading to a non-linear behavior. CONCLUSIONS: At low exposures, both methylhippuric acid and mandelic acid can be used as indicators of commercial xylene exposures. However at higher concentrations mandelic acid cannot be recommended as a biological indicator due to the saturation of mandelic acid produced by the co-exposure to xylene.     

Toluene metabolism during exposure to varying concentrations combined with exercise

Summary The urinary excretion of hippuric acid (HA) and ortho-cresol (O-cr) in man was measured in two studies of 7-h exposure to toluene in a climate chamber, either constant concentration of 100 ppm or varying concentrations containing peaks of 300 ppm but with a time-weighted average of 100 ppm. In Study A, four males were exposed to clean air and to constant and varying concentrations of toluene in combination with rest and with 100 W exercise in 140 min. Exercise increased end exposure excretion rate of HA and O-cr by 47 and 114%, respectively. After exposure, all excess HA was excreted within 4 h, while O-cr was eliminated with a half life of about 3 h. Alveolar air concentration of toluene varied between 21 and 31 ppm during constant exposure and between 13 and 57 ppm during varying exposure, but no difference in mean alveolar toluene concentration or in metabolite excretion was seen between the exposure schedules. In Study B, 32 males and 39 females aged between 31 and 50 years were exposed once to either clean air, constant or varying concentrations of toluene. Background excretion rate of HA was 0.97 ± 0.75 mg/min (1.25 ± 1.05 g/g creatinine) and rose to 3.74 ± 1.40 mg/min (3.90 ± 1.85 g/g cr) during the last 3 h of exposure to 100 ppm toluene. The corresponding figures for O-cr were 0.05 ± 0.05 g/min (0.08 ± 0.14 mg/g cr), and 2.04 ± 0.84 g/min (2.05 ± 1.18 mg/g cr). The individual creatinine excretion rate was considerably influenced by sex, body weight and smoking habits, thus influencing the metabolite concentration standardised in relation to creatinine. It is concluded that both metabolites are estimates of toluene exposure. O-cr is more specific than HA, but the individual variation in excretion of both metabolites is large, and when implementing either of them as biological exposure indices, the influence of sex, body size, age as well as consumption of tobacco and alcohol has to be considered.     

Biological monitoring of occupational exposure to methyl ethyl ketone

Summary This study was conducted to evaluate the usefulness of three commonly used methods of biological monitoring for worker exposed to methyl ethyl ketone (MEK) under field conditions using blood, breath and urine. Environmental MEK exposures were measured by personal sampling with carbon-felt dosimeters. The correlation coefficient (r) between the time-weighted average (TWA) MEK concentration in air and the MEK concentration in blood collected at the end of the work shift was 0.85. The correlation coefficient between the TWA MEK level in air and the concentration exhaled in the breath of workers at the end of the work shift was 0.71. The end-of-shift urinary MEK excretion correlated best with the environmental concentration (r = 0.89). Correlations became lower after urine samples had been corrected for urinary creatinine (r = 0.83) or specific gravity (r = 0.73). After 8 h exposure to 200 ppm MEK, the corresponding end-of-shift urinary excretion was 5.11ol/l or 4.11 mg/g creatinine. This value is higher than that previously found in some studies, the difference probably being due to the physical acitivites of the present workers and their extensive skin contact with the solvent. The kinetics of inhaled MEK was also studied in eight subjects. Breath and urine samples were collected during the 8-h work shift on 2 consecutive Mondays. The results showed that urinary MEK excretion rose steadily until the end of exposure, whereas the MEK concentration in exhaled air varied markedly throughout the day. These findings suggest that the determination of MEK levels in end-of-shift urine samples appears to be the most reliable biological indicator of occupational exposure.     

Benzyl alcohol as a marker of occupational exposure to toluene

Benzyl alcohol (BeOH) is a urinary metabolite of toluene, which has been seldom evaluated for biological monitoring of exposure to this popular solvent. The present study was initiated to develop a practical method for determination of BeOH in urine and to examine if this metabolite can be applied as a marker of occupational exposure to toluene. A practical gas-liquid chromatographic method was successfully developed in the present study with sensitivity low enough for the application (the limit of detection; 5 microg BeOH /l urine with CV=2.7%). Linearity was confirmed up to 10 mg BeOH/l, the highest concentration tested, and the reproducibility was also satisfactory with a coefficient of variation of 2.7% (n=10). A tentative application of the method in a small scale study with 45 male workers [exposed to toluene up to 130 ppm as an 8-h time-weighted average (8-h TWA)] showed that BeOH in the end-of-shift urine samples was proportional to the intensity of exposure to toluene. The calculated regression equation was Y=50+1.7X (r=0.80, p<0.01), where X was toluene in air (in ppm as 8-h TWA) and Y was BeOH in urine (in microg/l of end-of-shift urine). The levels of BeOH in the urine of the non-exposed was about 50 microg/l, and ingestion of benzoate as a preservative in soft drinks did not affect the BeOH level in urine. The findings as a whole suggest that BeOH is a promising candidate for biological monitoring of occupational exposure to toluene.     

职业性砷暴露工人尿有机砷和8-羟基脱氧鸟苷水平的相关性

目的评价云南省某砒霜厂工人体内砷的代谢转化与DNA氧化损伤关系。方法选择云南省某砒霜厂一线工人37例（高暴露组）、管理和后勤人员16例（低暴露组）和当地近期无毒物接触史人员28例（对照组）为研究对象,检测尿中有机砷和8-羟基脱氧鸟苷水平,评价砷的代谢转化和DNA氧化损伤相关性。结果高、低暴露组男性尿有机砷分别为（0、48±0．37）mg／L、（0．08±0．05）mg／L,高、低暴露组女性尿有机砷分别为0．11mg／L、（0．30±0．24）mg／L,对照组均低于检出值下限（0．02mg／L）;高、低暴露组和对照组男性尿8-羟基脱氧鸟苷分别为（18．07±11．68）μmol／mol肌酐、（11．79±8．25）μmol／mol肌酐和（10．07±3．04）μmol／mol肌酐,高暴露组高于对照组（P〈0．05）;高、低暴露组和对照组女性尿8-羟基脱氧鸟苷浓度分别为84．35μmol／mol肌酐、（21．27±5．89）μmol／mol肌酐和（14．43±2．58）μmol／mol肌酐,暴露组女性尿8-羟基脱氧鸟苷浓度高于暴露组男性（P〈0．05）。尿中8-羟基脱氧鸟苷浓度随尿中有机砷浓度升高有上升趋势（rs=0．279,P=0．019）。结论砷职业暴露人群存在明显的DNA氧化损伤,对女性损伤更为明显,砷的代谢转化差异可能起关键作用。     

Evaluation of current biological exposure index for occupational N, N-dimethylformamide exposure from synthetic leather workers

The aim of this study was (1) to investigate the correlation between external exposure to N, N-dimethylformamide (DMF) and urinary excretion of DMF and N-methylformamide; (2) to assess whether the correspondence between the current occupational exposure limit setting and recommended urinary biological exposure index is substantial; and (3) to evaluate whether coexposure to toluene, methyl ethyl ketone, and ethyl acetate has an effect on urinary excretion of DMF and N-methylformamide (NMF). Urinary DMF and NMF were significantly correlated (P < 0.01) with one another and also significantly correlated with airborne DMF (P < 0.01) over the range of 1.55 to 152.8 mg/m. Urinary DMF can be considered a complementary marker for short-term exposure. Urinary concentration of NMF and DMF, corresponding to the 8-hour exposure to airborne DMF at 30 mg/m, was estimated to 38.4 mg/L or 39.4 mg/g creatinine for NMF and to 0.92 mg/L or 0.96 mg/g creatinine for DMF.     

Quantitative analysis of urinary glycine conjugates by high performance liquid chromatography: excretion of hippuric acid and methylhippuric acids in the urine of subjects exposed to vapours of toluene and xylenes

Summary A new method for the direct determination of hippuric acid (HA) and o-, m- and p-methylhippuric acids (MHAs) in the urine, metabolites of toluene and o-, m- and p-xylenes by high performance liquid chromatography (HPLC) is described. A stainless-steel column packed with silica gel having dinitrophenyl residue and a mixed solution of methanol/water/acetic acid (80/20/0.2) containing tetra-n-butylammonium bromide (0.2% w/v) as mobile phase was used. Concentrations of HA and MHAs were estimated from their peak height at a wave length of 225 nm. Urine can be analyzed directly without solvent extraction or pretreatment to obtain complete separation of HA and o-, m- and p-MHAs. Urine samples from male workers exposed to toluene or xylenes were analyzed for HA or MHAs. The urinary levels of HA and MHAs increased by exposure to toluene and xylenes in proportion to the environmental concentrations of the solvents, although there is a considerable variation in metabolite concentrations. The slope of regression line between toluene and HA and that between m-xylene and m-MHA were similar. The urinary concentrations of HA and MHAs corresponding to 100 ppm (TLV) of toluene was 2.35 g/g creatinine and that of m-MHA corresponding to 100 ppm (TLV) of m-xylene was 2.05 g/g creatinine. The warning levels of the urinary metabolite concentrations of a group of workers and that of an individual worker corresponding to TLV of organic solvent concentration is discussed.     

Biological monitoring of occupational exposure to isopropyl alcohol vapor by urinalysis for acetone

Summary The relationship of the intensity of occupational vapor exposure to isopropyl alcohol (IPA) with urinary excretion of acetone and unmetabolized IPA was studied in 99 printers of both sexes, who were exposed to up to 66 ppm IPA (as time-weighted average), together with toluene, xylenes, methyl ethyl ketone and/or ethyl acetate. Acetone and IPA concentrations in urine were studied also in 34 non-exposed subjects. Acetone was detectable in the urine of most of the non-exposed, and the urinary acetone concentration increased in proportion to the IPA exposure intensity (r = 0.84 for observed, non-corrected values), whereas the correction for creatinine concentration or specific gravity of urine did not give a larger correlation coefficient. IPA itself was not found in the urine of the non-exposed, and was detectable in urine of only those who were exposed to IPA above a certain level, e.g. 5 ppm. The present study results suggest that urinary acetone is a valuable index for biological monitoring of occupational exposure to IPA as low as 70 ppm.A part of this work was presented at 62nd Annual Meeting of Japan Association of Industrial Health, held in Hirosaki, Japan, on 27th–30th, April, 1989     

Correlation between urinary 2-methoxy acetic acid and exposure of 2-methoxy ethanol

OBJECTIVES: To examine the correlation between airborne 2-methoxy ethanol (ME) exposures and the urinary 2-methoxy acetic acid (MAA) and to recommend a biological exposure index (BEI) for ME. METHODS: 8 Hour time weighted average (TWA) personal breathing zone samples and urine samples before and after the shift were collected from Monday to Saturday for 27 workers exposed to ME and on Friday for 30 control workers. RESULTS: No correlation was found between airborne exposure to ME and urinary MAA for nine special operation workers due to the use of personal protective equipment. For 18 regular operation workers, a significant correlation (r = 0.702, p = 0.001) was found between urinary MAA (mg/g creatinine) on Friday at the end of the shift and the weekly mean exposures of ME in a 5 day working week. The proposed BEI, which corresponds to exposure for 5 days and 8 hours a day to 5 ppm, extrapolated from the regression equation is 40 mg MAA/g creatinine. A significant correlation was also found between the weekly increase of urinary MAA (Friday after the shift minus Monday before the shift) and the weekly mean exposures of ME (r = 0.741). The recommended value of the weekly increase of urinary MAA for 5 days repeated exposures of 5 ppm ME is 20 mg/g creatinine. No urinary MAA was detected in workers in the non-exposed control group. CONCLUSIONS: The Friday urinary MAA after the shift or the weekly increase of urinary MAA is a specific and a good biomarker of weekly exposure to ME.