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.

Simultaneous detection of the tetrachloroethylene metabolites S-(1,2,2-trichlorovinyl) glutathione, S-(1,2,2-trichlorovinyl)-L-cysteine, and N-acetyl-S-(1,2,2-trichlorovinyl)-L-cysteine in multiple mouse tissues via ultra-high performance liquid chromatography electrospray ionization tandem mass spectrometry.

Tetrachloroethylene (perchloroethylene; PERC) is a high-production volume chemical and ubiquitous environmental contaminant that is hazardous to human health. Toxicity attributed to PERC is mediated through oxidative and glutathione (GSH) conjugation metabolites. The conjugation of PERC by glutathione-s-transferase to generate S-(1,2,2-trichlorovinyl) glutathione (TCVG), which is subsequently metabolized to form S-(1,2,2-trichlorovinyl)-L-cysteine (TCVC) is of special importance to human health. Specifically, TCVC may be metabolized to N-acetyl-S-(1,2,2-trichlorovinyl)-L-cysteine (NAcTCVC) which is excreted through urine, or to electrophilic metabolites that are nephrotoxic and mutagenic. Little is known regarding toxicokinetics of TCVG, TCVC, and NAcTCVC as analytical methods for simultaneous determination of these metabolites in tissues have not yet been reported. Hence, an ultra-high-performance liquid chromatography electrospray ionization tandem mass spectrometry-based method was developed for analysis of TCVG, TCVC, and NAcTCVC in liver, kidneys, serum, and urine. The method is rapid, sensitive, robust, and selective for detection all three analytes in every tissue examined, with limits of detection (LOD) ranging from 1.8 to 68.2 femtomoles on column, depending on the analyte and tissue matrix. This method was applied to quantify levels of TCVG, TCVC, and NAcTCVC in tissues from mice treated with PERC (10 to 1000 mg/kg, orally) with limits of quantitation (LOQ) of 1-2.5 pmol/g in liver, 1-10 pmol/g in kidney, 1-2.5 pmol/ml in serum, and 2.5-5 pmol/ml in urine. This method is useful for further characterization of the GSH conjugative pathway of PERC in vivo and improved understanding of PERC toxicity.

Biological monitoring of exposure to perchloroethylene in dry cleaning workers.

BACKGROUND: Perchloroethylene (PCE) is the most widely used solvent in dry cleaning. OBJECTIVES: The aim was to evaluate PCE pollution and to identify the most reliable biological indicators for the assessment of workers' exposure. METHODS: The study was performed in 40 dry cleaning shops covering a total of 71 subjects. Environmental monitoring was carried out with personal diffusive samplers (Radiello) for the entire work shift; biological monitoring was performed by measuring PCE in urine and blood and trichloroacetic acid (TCA) in urine on Thursday evening at end-of shift and on Friday morning pre-shift. RESULTS: The mean concentration of PCE in air was 52.32 mg/m3, about 30% of the TLV-TWA and the mean value of the PCE inpre-shift blood samples was 0.304 mg/l, slightly more than 50% of the BEI. In dry cleaning shops employing less than 3 persons PCE in air exceeded the TLV-TWA in 7.8% of cases; the size of the shops was inversely related to pollution. Statistically significant correlations were found between PCE exposure and PCE in blood end-of-shift (r = 0.67) and pre-shift (r = 0.70), and PCE in urine end-of-shift (r = 0.68); no correlation was found between exposure and PCE in urine pre-shift and urinary TCA. CONCLUSIONS: Dry cleaning shops still register conditions of exposure and pollution by PCE, although to a lesser extent than in the past. The most reliable indicators for biological monitoring are CE in end-of-shift urine and PCE in blood both at end-of-shift and pre-shift at the end of the workweek.

Exposure assessment to trichloroethylene and perchloroethylene for workers in the dry cleaning industry.

Perchloroethylene and trichloroethylene are two particular organochloro compounds, are often used for dry-cleaning. In the present study the excretion of urinary Perchloroethylene and trichloroethylene were evaluated as biomarkers of exposure to these compounds. The mean value of Perchloroethylene in breathing zone and the total Perchloroethylene uptake during the work shift of the three groups of dry-cleaning workers according to the capacity of the dry-cleaning machine (8, 12 and 18 kg) were 31.04, 50.87 and 120.99 mg m(-3) and 11.46, 22.6 and 41.6 µg L(-1), respectively, which were significantly greater than the occupationally nonexposed groups. A good correlation (r = 0.907) between the mean values of Perchloroethylene in breathing zone and the urinary concentrations was observed.

Optimization of a novel procedure for determination of VOCs in water and human urine samples based on SBSE coupled with TD-GC-HRMS.

In this study, stir-bar sorptive extraction and thermal desorption followed by gas chromatography coupled with high resolution mass spectrometry was applied for determination of halo-organic compounds (bromodichloromethane, dibromochloromethane, bromoform, and tetrachloroethylene) in water and human urine samples. Time of extraction and stirring speed were optimized. The results show that the optimum extraction time is 30 min with 600 rpm of stirring speed with Twister of 20 mm in length and 1.0-mm film thickness of PDMS (126 microL). The calibration curves, limits of detection and quantification for all compounds were calculated. This procedure is characterized by very low limits of detection and quantitation: lower than 0.0017 microg/L and good repeatability for all four volatile compounds. This new analytical procedure was identified to be easy, reliable, sensitive, and requires only small amounts of sample. It can constitute a good alternative to well-known procedures based on application of head space and gas chromatography coupled with electron capture detection.

Biological exposure assessment to tetrachloroethylene for workers in the dry cleaning industry.

BACKGROUND: The purpose of this study was to assess the feasibility of conducting biological tetrachloroethylene (perchloroethylene, PCE) exposure assessments of dry cleaning employees in conjunction with evaluation of possible PCE health effects. METHODS: Eighteen women from four dry cleaning facilities in southwestern Ohio were monitored in a pilot study of workers with PCE exposure. Personal breathing zone samples were collected from each employee on two consecutive work days. Biological monitoring included a single measurement of PCE in blood and multiple measurements of pre- and post-shift PCE in exhaled breath and trichloroacetic acid (TCA) in urine. RESULTS: Post-shift PCE in exhaled breath gradually increased throughout the work week. Statistically significant correlations were observed among the exposure indices. Decreases in PCE in exhaled breath and TCA in urine were observed after two days without exposure to PCE. A mixed-effects model identified statistically significant associations between PCE in exhaled breath and airborne PCE time weighted average (TWA) after adjusting for a random participant effect and fixed effects of time and body mass index. CONCLUSION: Although comprehensive, our sampling strategy was challenging to implement due to fluctuating work schedules and the number (pre- and post-shift on three consecutive days) and multiplicity (air, blood, exhaled breath, and urine) of samples collected. PCE in blood is the preferred biological index to monitor exposures, but may make recruitment difficult. PCE TWA sampling is an appropriate surrogate, although more field intensive. Repeated measures of exposure and mixed-effects modeling may be required for future studies due to high within-subject variability. Workers should be monitored over a long enough period of time to allow the use of a lag term.

Toxicokinetics of inhaled trichloroethylene and tetrachloroethylene in humans at 1 ppm: empirical results and comparisons with previous studies.

Trichloroethylene (TRI) and tetrachloroethylene (TETRA) are solvents that have been widely used in a variety of industries, and both are widespread environmental contaminants. In order to provide a better basis for understanding their toxicokinetics at environmental exposures, seven human volunteers were exposed by inhalation to 1 ppm of TRI or TETRA for 6 h, with biological samples collected for analysis during exposure and up to 6-days postexposure. Concentrations of TRI, TETRA, free trichloroethanol (TCOH), total TCOH (free TCOH plus glucuronidated TCOH), and trichloroacetic acid (TCA) were determined in blood and urine; TRI and TETRA concentrations were measured in alveolar breath. Toxicokinetic time courses and empirical analyses of classical toxicokinetic parameters were compared with those reported in previous human volunteer studies, most of which involved exposures that were at least 10-fold higher. Qualitatively, TRI and TETRA toxicokinetics were consistent with previous human studies. Quantitatively, alveolar retention and clearance by exhalation were similar to those found previously but blood and urine data suggest a number of possible toxicokinetic differences. For TRI, data from the current study support lower apparent blood-air partition coefficients, greater apparent metabolic clearance, less TCA production, and greater glucuronidation of TCOH as compared to previous studies. For TETRA, the current data suggest TCA formation that is similar or slightly lower than that of previous studies. Variability and uncertainty in empirical estimates of total TETRA metabolism are substantial, with confidence intervals among different studies substantially overlapping. Relative contributions to observed differences from concentration-dependent toxicokinetics and interindividual and interoccasion variability remain to be determined.

Determination of dichloromethane, trichloroethylene and perchloroethylene in urine samples by headspace solid phase microextraction gas chromatography-mass spectrometry.

A method for the determination of volatile chlorinated hydrocarbons, namely dichloromethane (DCM), trichloroethylene (TCE), and perchloroethylene (PCE), in urine samples was developed using headspace solid phase microextraction (HS-SPME) gas chromatography-mass spectrometry (GC-MS). HS-SPME was performed using a 75 microm Carboxen-polydimethylsiloxane fiber. Factors, which affect the HS-SPME process, such as adsorption and desorption times, stirring, salting-out effect, and temperature of sampling have been evaluated and optimized. The highest extraction efficiency was obtained when sampling was performed at room temperature (22 degrees C), from samples saturated with salt and under agitation. Linearity of the HS-SPME-GC-MS method was established over four orders of magnitude and the limit of detection was 0.005 microg/l for all the compounds. Precision, calculated as %R.S.D. at three different concentration levels, was within 1-8% for all intra- and inter-day determinations. The method was applied to the quantitative determination of TCE and PCE in human urine samples from exposed (TCE, n=5; median, 9.32 microg/l and PCE, n=39; median, 0.58 microg/l) and non-exposed individuals (n=120; median concentrations, 0.64, 0.22 and 0.11 microg/l for DCM, TCE and PCE, respectively. In addition, two cases of acute accidental exposure to DCM are reported, and the elimination kinetics in blood and urine was followed up. The calculated half-lives of urinary and blood DCM were, respectively, 7.5 and 8.1 h for one subject and 3.8 and 4.3 h for the other.

Perchloroethylene in alveolar air, blood, and urine as biologic indices of low-level exposure.

We studied the reliability of biologic indices for monitoring perchlorethylene (PCE) exposure at low environmental solvent concentrations. Environmental monitoring was performed by personal sampling, biologic monitoring by measuring PCE in alveolar air (PCE-Alv), blood (PCE-B), and urine (PCE-U) in 26 low-exposed dry-cleaners. Correlation coefficients (r) between environmental PCE and PCE-B, PCE-Alv, and PCE-U were 0.94, 0.81, and 0.67 respectively. A high correlation was also found among biologic indices: r value was 0.96 between PCE-B and PCE-Alv, 0.95 between PCE-B and PCE-U, and 0.87 between alveolar PCE-Alv and PCE-U. The examined biologic indices proved sensitive enough for biologic monitoring of low exposure to PCE and can give substantially similar information in terms of exposure evaluation. PCE-Alv offers some advantages because it correlated better with exposure and is analytically simpler.

Tetrachloroethylene and trichloroethylene fatality: case report and simple headspace SPME-capillary gas chromatographic determination in tissues.

We describe a simple, precise, and sensitive assay of tetrachloroethylene and trichloroethylene in tissues, suitable both for emergency cases and forensic medicine. The method employs headspace solid phase microextraction-capillary gas chromatography and electron capture detection. The case is relative to a 45-year-old woman discovered unconscious in a laundry area. The concentrations of the solvents in tissues were determined and compared to other previously published fatalities.

[Environmental and biological monitoring of occupational exposure to perchloroethylene in dry cleaning shops]. / Il monitoraggio ambientale e biologico dell'esposizione occupazionale a percloroetilene nelle lavanderie a secco.

Occupational exposure to perchloroethylene (PCE) was studied in a total of 106 workers in 78 dry cleaning shops in the province of Pavia, Northern, Italy. Environmental monitoring was performed by personal passive sampling. The median time weighted average (TWA) level of PCE was 57 mg/m3, i.e., about 30% of the current Threshold Limit Value (TLV) proposed by the American Conference of Governmental Industrial Hygienists (ACGIH). However, in 12 workers exposure exceeded this limit. Biological monitoring was performed via measurement of urinary trichloroacetic acid (TCA), i.e. the exposure index currently used in Italy, and urinary excretion of unmodified perchloroethylene (PCE-U) in samples collected at the end of the half-shift. Median levels of TCA and PCE were 1.03 mg/l and 17.7 micrograms/l respectively. The correlation coefficient between environmental TWA concentrations of perchloroethylene and PCE-U was 0.755 (0.809 after logarithmic transformation), compared to 0.660 for TCA values. The subjects were then classified as "low exposed" and "heavily exposed" according to whether personal exposure was lower or higher than 57 mg/m3, the median TWA value of the whole group. PCE-U levels were significantly correlated to exposure in both subgroups whereas TCA was correlated only in the "heavily exposed subjects", but not in those with lower exposure. The results of the study show that in the majority of dry cleaning shops exposure to PCE was well below the current occupational limits. Nevertheless surveillance of dry cleaners is recommended as nearly 10% of the workers exceeded the environmental and biological limits. Urinary excretion of unmodified PCE appears to be a very reliable indicator for biological monitoring of PCE exposure in dry cleaning and is also significantly correlated to exposure at low levels. The estimated biological equivalent exposure level (BEEL) for PCE-U, corresponding to the current TLV-TWA proposed by the ACGIH, is 55 micrograms/l. Urinary TCA seems to be less suitable for assessment of individual exposure to perchloroethylene in dry cleaners as it is poorly representative of exposure to low levels of the solvent, which is a very common occurrence in this occupational group nowadays.

Blood and urine concentrations of chemical pollutants in the general population.

The concentration of 9 environmental chemical pollutants in the general population was measured in blood and urine. For the 9 different pollutants, the blood samples tested varied from 88 for acetone to 431 for benzene. Urine samples varied from 48 for styrene to 213 for n-hexane. Six of these agents (benzene, toluene, styrene, n-hexane, acetone and carbon disulphide) were present in all or almost all (100-94%) blood samples. The three chlorides (chloroform, trichloroethylene and tetrachloroethylene) were present only in 60-85% of samples. After acetone, with blood concentrations in microgram/1 (mean 840 microgram/l), the highest mean blood levels were those of toluene (1097 ng/l), chloroform (955 ng/l) and n-hexane (642 ng/l). Trichloroethylene and free carbon disulphide showed similar values (458 and 438 ng/l, respectively). Finally, benzene, styrene and tetrachloroethylene showed the lowest values (262, 217 and 149 ng/l, respectively). There was generally a significant difference between rural and urban workers in terms of blood benzene (200 ng/l vs 264 ng/l), trichloroethylene (180 ng/l vs 763 ng/l) and tetrachloroethylene (62 ng/l vs 263 ng/l). In a group of subjects potentially exposed to industrial solvents, classed as chemical workers, blood benzene, toluene, chloroform and n-hexane were significantly higher than in rural and urban workers. Smokers showed a significantly higher blood concentration than non-smokers for benzene (381 ng/l vs 205 ng/1), toluene (1431 ng/l vs 977 ng/l), and n-hexane (838 ng/l vs 532 ng/l). All or almost all urine samples (100-92%) contained all the compounds except trichloroethylene and tetrachloroethylene, present in 79% and 76% of samples, respectively (table 2). Urinary concentrations of all compounds did not differ significantly between rural and urban workers. Benzene and toluene were significantly higher in in urine of smokers than of non-smokers. Chloroform and n-hexane showed significantly higher urinary than blood values. Excluding acetone, with urinary and blood concentrations in pg/l, chloroform, toluene and n-hexane showed the highest mean concentrations both in blood and in urine.

Dermal absorption of dilute aqueous chloroform, trichloroethylene, and tetrachloroethylene in hairless guinea pigs.

Percutaneous absorption was measured in female hairless guinea pigs dermally exposed for 70 min to very dilute (approximately 10 to 100 ppb) aqueous solutions of 14C-labeled chloroform (CF), trichloroethylene (TCE), or tetrachloroethylene (PCE) in an airtight glass chamber containing no headspace. Similar experiments were conducted using aqueous solutions of TCE at 100,000 ppb. Dermal uptake was estimated by comparing the rate of radiolabel loss from chamber water in systems with and without experimental animals. After each low-concentration dermal-uptake experiment, radiolabel in total urine and feces excreted postexposure was measured and expressed as a fraction of corresponding estimated dermal uptake. For each of the compounds studied, the mean value of these fractions did not differ significantly from that obtained using animals injected with a known dose of that compound, indicating that our experimental system yielded accurate dermal-uptake estimates. The mean permeability coefficients obtained range from 0.13 cm/hr (CF) to 0.37 cm/hr (PCE); those obtained using low- vs high-concentration TCE are not significantly different. The value for CF is very close to one we calculate here from recently published data on CF uptake in human volunteers dermally exposed to aqueous CF while showering with normal tap water. Our results suggest that dermal absorption may be an important route of human exposure to chlorinated volatile organic compounds in domestic water supplies.

A comparative study of human levels of trichloroethylene and tetrachloroethylene after occupational exposure.

The rate of trichloroethylene (TRI) and perchloroethylene (PER) absorption was investigated in workers who were (1) occupationally exposed to TRI in four dry-cleaning shops (Group 1, n = 10) and (2) occupationally exposed to PER in one dry-cleaning shop (Group 2, n = 18). Concentrations of TRI and PER in blood were analyzed, and concentrations of trichloroethanol (TCE) and trichloroacetic acid (TCA) in blood and urine were analyzed. Results varied widely: PER was found in the blood of workers in group 1, but TRI was not detected in blood from any worker in group 2; most blood samples from group 2 workers did not contain a detectable quantity of TCE, and urine TCE concentrations in this group were very low. During the work week, a significant difference was found in group 1 for TRI in blood and TCE in blood and urine. In group 2, however, the only significant difference during the work week was for PER in blood. Therefore, the most reliable biological indicators for TRI and PER exposure are TCE in blood and PER in blood, respectively.

Dose-excretion relationship in tetrachloroethylene-exposed workers and the effect of tetrachloroethylene co-exposure on trichloroethylene metabolism.

Personal monitoring of 8-hour time-weighted average intensity of exposure with diffuse samplers and analysis of shift-end urine for total trichloro-compounds (TTC) and other metabolites were conducted in two groups of workers in China, one (121 subjects) exposed to tetrachloroethylene (TETRA) alone, and the other (38 subjects) exposed to a mixture of TETRA and trichloroethylene (TRI). Urinalysis was also performed on samples from 103 non-exposed controls. A linear exposure-excretion relationship could be observed in both groups of workers. Comparison of these results with those of Japanese TETRA-workers suggested the presence of ethnic difference in TETRA metabolism. Urinary metabolite levels were markedly lower in the mixed (TETRA + TRI) exposure group as compared to previous findings in a group exposed to TRI alone. The observation indicates that metabolism of TRI is suppressed by the co-exposure to TETRA in humans.

Urinary excretion of tetrachloroethylene (perchloroethylene) in experimental and occupational exposure.

Fifteen human volunteers were exposed to tetrachloroethylene (perchloroethylene, tetrachloroethene) vapor at 3.6-316 mg/m3 for 2-4 hr at rest (10 cases) and during light physical exercise (5 cases). Subsequently, 55 workers who were occupationally exposed to tetrachloroethylene in eight commercial dry cleaning facilities were studied (median value, 66 mg/m3; geometric standard deviation, 3.15 mg/m3). In both the experimentally exposed subjects and occupationally exposed workers the urinary concentration of tetrachloroethylene showed a linear relationship to the corresponding environmental time-weighted average concentration. The findings indicate that the urinary concentration of tetrachloroethylene can be used as an appropriate biological exposure indicator. In occupationally exposed subjects performing moderate work, the urinary tetrachloroethylene concentration corresponding to the time-weighted average of the threshold limit value proved to be 120 mcg/L and its 95% lower confidence limit (biological threshold) 100 mcg/L. The effects of workload on the tetrachloroethylene urinary elimination are also accounted for.

[Use of gas chromatography with flame ionization (GC-FID) in the measurement of solvents in the urine]. / Impiego della gas cromatografia a ionizzazione di fiamma (GC-FID) per la misura dei solventi tal quali nelle urine.

The urinary concentration of some solvents (acetone, cyclohexane, 1,2 dichloropropane, n-hexane, methyl ethyl ketone, perchloroethylene, styrene, toluene, 1,1,1, trichloroethane) was measured by means of a gas chromatography Hewlett-Packard 5890 supplied with a flame ionization detector (GC-FID, DANI HS 3950). The coefficient of variation of the method was lower than 5%. The sensitivity of the GC-FID was very similar to what of mass spectrometer detector (GC-MSD, HP 5970 A).

Metabolites of chlorinated solvents in blood and urine of subjects exposed at environmental level.

After a two-level selection, 141 blood donors living in Milan, Italy, were analyzed for their content of plasma and urinary trichloroacetic acid (TCA) and trichloroethanol (TCE). Environmental levels of exposure to trichloroethylene (TRI) and tetrachloroethylene (PER) through drinking water and air were also measured. The plasma TCA levels were in the range of previously found concentrations. Relationships among plasma and urinary metabolites were found and discussed.