Biological monitoring of occupational exposure to sevoflurane

Sevoflurane has been used in the last few years in brief surgical operations, either alone or in combination with nitrous oxide. Occupationally exposed groups include anesthesiologists, surgeons and operating room nurses. In 1977 the National Institute for Occupational Safety and Health (NIOSH) recommended that occupational exposure to halogenated anesthetic agents (halothane, enflurane, and isoflurane), when used as the sole anesthetic, should be controlled so that no worker would be exposed to time-weighted average concentrations greater than 2 ppm during anesthetic administration. When halogenated anesthetics are associated with nitrous oxide, NIOSH recommends that the limit value should not exceed 0.5 ppm. We think these recommendations can be extended to sevoflurane. Metabolism of sevoflurane is catalyzed by cytochrome P-450; this involves oxidation of the fluoromethyl side chain of the molecule, followed by glucuronidation. Two urinary metabolites of sevoflurane have been identified: inorganic fluoride (which, however, is not specific) and a non-volatile compound that yields hexafluoroisopropanol (HFIP) when digested with the enzyme beta-glucuronidase. In order to investigate the role of urinary HFIP as an indicator of occupational exposure to sevoflurane (CI, ppm), CI was measured in 145 members of 18 operating room staffs. The measurements of the time-weighted average of CI in the breathing zone were made by means of diffusive personal samplers. Each sampler was exposed during the whole working period. Sevoflurane was desorbed with CS2 from charcoal and the concentrations were measured on a gas chromatograph (GC) equipped with a mass selective detector (MSD). The GC was equipped with a 25 meter cross-linked phenylmethylsilicon column (internal diameter 0.2 mm). GC conditions were as follows: injector column temperature = 200 degrees C; column temperature = 30 degrees C; carrier gas = helium; injection technique of samples = splitless. The analytical conditions for the MSD were the following: ion mass monitored = 131 m/e; dwell time = 50 msec; selected ion monitoring window time = 0.1 amu; electromultiplier = 400 V. Urine samples were collected near the end of the shift and were analyzed for HFIP by head-space gas chromatography after glucuronide hydrolysis. 0.5 ml of urine and 1.5 ml of 10 M sulfuric acid were added to 21.8 ml headspace vials. The vials were immediately capped, vortexed, and loaded into the headspace autosampler. Samples were maintained at 100 degrees C for 30 min, after which glucuronide hydrolysis was 99% complete. Analyses were performed on a GC equipped with a MSD. The analytical conditions for urine analysis were as follows: cross-linked 5% phenylmethylsilicon column (internal diameter 0.2 mm, length 25 m); column temperature = 35 degrees C; carrier gas = helium. The analytical conditions for the MSD were: monitored ions = 51.05 and 99; dwell time = 100 ms; selected ion monitoring window time = 0.1 amu; electromultiplier voltage = 2000 Volt. With our analytical procedure, the detection limit of HFIP in urine was 20 micrograms/L. The variation coefficient (CV) for HFIP measurement in urine was 8.7% (on 10 determinations; mean value = 1000 micrograms/L). The median value of CI was 0.77 ppm (Geometric Standard Deviation = 4.08; range = 0.05-27.9 ppm). The correlation between CI and HFIP (Cu, microgram/L) was: Log Cu (microgram/L) = 0.813 x Log CI (ppm) + 2.517 (r = 0.79, n = 145, p < 0.0001). On the basis of the equation it was possible to establish tentatively the biological limit values corresponding to the respective occupational exposure limit values proposed for sevoflurane. According to our experimental results, HFIP values of 488 micrograms/L and 160 micrograms/L correspond to airborne sevoflurane concentrations of 2 and 0.5 ppm respectively.     

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 for occupational exposure to toluene

A study was undertaken to examine the relationship between exposure of workers to toluene in the work environment and biological indicators of toluene exposure. The biological indicators studied were toluene in expired air, toluene in blood obtained by the finger prick method, and urinary hippuric acid. The study was undertaken in a factory in Singapore that manufactures speakers for audio systems. A total of 86 female workers exposed to toluene at the workplace and a control group of workers not exposed to toluene were examined. All of them were teetotalers, were nonsmokers, and gave no history of chronic drug usage. The 8-hr time-weighted average exposure level of toluene ranged from 1.6 ppm to 263 ppm. The study showed the expected toluene levels in finger prick blood was 1.4 micrograms/mL after an 8-hr exposure to 100 ppm of toluene. Toluene concentration in expired air of 16 ppm after an 8-hr exposure to 100 ppm compared favorably with other studies. The toluene in blood/expired air ratio was observed to be lower than in other studies. In this study, the expected urinary hippuric acid level for a 100-ppm exposure to toluene was 2.7 g/g creatinine. This level is higher than that recorded in other studies. The results showed that at low levels of toluene, urinary hippuric acid is not a valuable indicator of exposure. Toluene in expired air is the most reliable biological indicator of exposure to toluene.     

Biological monitoring of exposure to low concentrations of styrene

A field study was conducted on 39 male workers exposed to styrene at concentrations below 40 ppm (time weighted average, TWA). Analyses were carried out on environmental air, exhaled air, blood, urine, and two major urinary metabolites of styrene: mandelic acid (MA) and phenylglycoxylic acid (PGA). Head space gas chromatography (GC) with a flame ionization detector (FID) was used for determination of styrene in blood and urine. Postexposure exhaled air was analyzed using capillary GC. Environmental styrene exposure was measured by personal sampling using carbon cloth personal samplers. Urinary metabolites of styrene were determined by high pressure liquid chromatograph (HPLC). When the end-of-shift breath, blood, and urine styrene levels were compared with environmental TWA values, blood styrene correlated best with styrene in air (r = 0.87), followed by breath styrene (r = 0.76). Poor correlation (r = 0.24) was observed between environmental styrene exposure and urine styrene. When styrene metabolites were compared with environmental styrene, the sum of urinary MA and PGA correlated better with styrene in air than MA or PGA alone. The correlations between urinary metabolites and environmental styrene improved when corrected for the specific gravity of urine. Even better correlations were observed when the urinary metabolites were corrected for creatinine. The correlation coefficients for environmental styrene and end-of-shift MA, PGA, and MA + PGA were 0.83, 0.84, and 0.86, respectively. The correlation coefficients between environmental styrene and next morning urinary metabolites fell to 0.47, 0.61, and 0.65 for MA, PGA, and MA + PGA, respectively. These results suggest that determination of the total MA and PGA in urine samples is preferred than separate measurements of MA or PGA. The good correlation between environmental exposure and styrene in the exhaled air also suggests that breath styrene level can be a useful indicator for low level styrene exposure, as the method is specific, noninvasive, and rapid. Urinary styrene seems to be a less reliable indicator for low level styrene exposure. © 1994 Wiley-Liss, Inc.     

Biological monitoring of occupational exposure to airborne pollutants

Biological monitoring of inert substances requires knowledge of the mechanisms regulating respiratory absorption. The authors examine the influence of parameters such as work load, exposure duration and biotransformation on the respiratory absorption of inert airborne pollutants in the workplace. Attention is also given to the possibility of using biological thresholds or Biological Equivalent Limits (BELs).     

Biological monitoring of occupational exposure to inorganic arsenic

OBJECTIVES: This study was undertaken to assess reliable biological indicators for monitoring the occupational exposure to inorganic arsenic (iAs), taking into account the possible confounding role of arsenicals present in food and of the element present in drinking water. METHODS: 51 Glass workers exposed to As trioxide were monitored by measuring dust in the breathing zone, with personal air samplers. Urine samples at the end of work shift were analysed for biological monitoring. A control group of 39 subjects not exposed to As, and eight volunteers who drank water containing about 45 micrograms/l iAs for a week were also considered. Plasma mass spectrometry (ICP-MS) was used for the analysis of total As in air and urine samples, whereas the urinary As species (trivalent, As3; pentavalent, As5; monomethyl arsonic acid, MMA; dimethyl arsinic acid, DMA; arsenobetaine, AsB) were measured by liquid chromatography coupled with plasma mass spectrometry (HPLC-MS) RESULTS: Environmental concentrations of As in air varied widely (mean 84 micrograms/m3, SD 61, median 40) and also the sum of urinary iAs MMA and DMA, varied among the groups of exposed subjects (mean 106 micrograms/l, SD 84, median 65). AsB was the most excreted species (34% of total As) followed by DMA (28%), MMA (26%), and As3 + As5 (12%). In the volunteers who drank As in the water the excretion of MMA and DMA increased (from a median of 0.5 to 5 micrograms/day for MMA and from 4 to 13 micrograms/day for DMA). The best correlations between As in air and its urinary species were found for total iAs and As3 + As5. CONCLUSIONS: To avoid the effect of As from sources other than occupation on urinary species of the element, in particular on DMA, it is proposed that urinary As3 + As5 may an indicator for monitoring the exposure to iAs. For concentrations of 10 micrograms/m3 the current environmental limit for iAs, the limit for urinary As3 + As5 was calculated to be around 5 micrograms/l, even if the wide variation of values needs critical evaluation and application of data. The choice of this indicator might be relevant also from a toxicological point of view. Trivalent arsenic is in fact the most active species and its measure in urine could be the best indicator of some critical effects of the element, such as cancer.

 

     

Biological monitoring of occupational exposure to aluminum]

The meaning and usefulness of biological indicators in the study of occupational exposure to aluminium (Al) was assessed on the basis of the most recently acquired knowledge on the toxicokinetics of aluminium absorbed by inhalation, results of environmental and biological investigations recently carried out in industrial sectors with low risk of aluminium absorption (refining, casting and pressure moulding covering a total of 8 plants and 119 workers) and the results of investigations on a group of welders exposed to Al concentrations between 5 and 10 mg/m3. It was confirmed that not only the environmental Al concentrations but also certain chemical and physical characteristics (particle size, allotropic state, solubility), simultaneous exposure to other dusts, and mode of exposure (existence of exposure peaks) play a significant role in lung absorption of Al. Urinary Al (AlU) may be considered as an indicator of "recent" exposure with biphase excretion kinetics influenced also by duration of exposure, whereas Al in serum (AlS) can probably furnish indications both on overall exposure and on body burden. In low-level Al exposure (below 0.5 mg/m3), these indicators (especially AlU) permit differentiation of the exposed groups from the general population without, however, any clear relationship with the various environmental Al concentrations. It was also seen that AlU increased with increasing work seniority and was more marked in certain processes, such as casting, and in the first few months or years of work.(ABSTRACT TRUNCATED AT 250 WORDS)     

砷的职业接触生物监测指标

砷是一种自然界中多以化合物形式存在的常见类金属元素,在生产中应用广泛。随着职业接触人群越来越多,砷中毒越来越受到人们的重视。环境中的砷主要通过消化道、呼吸道和皮肤黏膜等进入人体,长期暴露于无机砷环境中可引起人体多种脏器损伤及其功能障碍,严重时可引发癌前病变。本文将对职业接触人群有关砷的生物监测指标予以综述。     

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 toluene diisocyanate

Summary The study validated the use of urinary toluene diamine (TDA) in postshift samples as an indicator of preceding 8-h exposure to toluene diisocyanate (TDI). Nine workers exposed in TDI-based polyurethane foam production were studied. Their exposure levels varied in 8-h time-averaged samples from 9.5 to 94 g/m³. The urinary TDA concentrations varied from 6.5 to 31.7g/g creatinine and they were linearly related to the atmospheric TDI levels. Approximately 20% of TDI is metabolized to diamines but their specificity is remarkable to the extent that by analysis for the 2,4- and 2,6-diamino isomers an idea of the percutaneous absorption may be had.     

Biological monitoring of styrene: a review

Recent literature about the biological monitoring of styrene-exposed workers is reviewed. Styrene primarily exhibits its toxicity on the central and peripheral nervous systems, although its mutagenicity and chromosome damaging ability also may be relevant. Uptake, transformation and excretion of styrene show that beside the usual biological indicators, such as urinary mandelic and phenylglyoxylic acids (main metabolites), other indicators also may be of interest. These include styrene in expired air, in blood or in urine. Moreover, intermediate or final metabolites such as styrene glycol or mandelic acid in blood also have been proven to be useful in the interpretation of individual values. The most widely used analytical methods for these indicators are gas or high performance liquid chromatography. Correlations between exposure and the different biological indicators mentioned above show that the most reliable indicators are mandelic acid (MA) in urine sampled at the end of the work shift (but not the first day of the week) and the sum of mandelic and phenylglyoxylic acids (MA + PGA) in urine sampled 16 hr after exposure (before the next shift). The biological exposure limit values corresponding to the threshold limit value-time-weighted average (TLV-TWA) of 50 ppm of styrene are 850 mg MA/g creatinine in the end-of-shift sample and 330 mg MA + PGA/g creatinine in the next-morning sample. Other biological indexes, such as styrene glycol (phenyl ethylene glycol) in blood or styrene in urine, look promising but require further research in field situations.     

Biological monitoring of styrene metabolites in blood

Ten men occupationally exposed to styrene in two glass-fiber reinforced plastics factories were studied during three consecutive workdays. The mean external exposure level was 99 mg/m3. The total pulmonary uptake of styrene was estimated from measurements of the styrene concentration in inspired air, the pulmonary ventilation, and the relative uptake. A gas chromatographic method based on electron capture detection was used to quantify styrene glycol, as well as styrene-7,8-oxide, in blood. The concentration of styrene glycol appeared to be linearly related to the preceding uptake of styrene. When the uptake during 5 h immediately before the blood sampling was considered, the correlation coefficient (r) obtained the value of 0.90. The concentration of styrene-7,8-oxide was at the detection limit of 0.02 mumol/l in most samples. A weaker correlation between the concentration of styrene in blood and the uptake during the hour immediately preceding the blood sampling was obtained (r = 0.71).     

Biological monitoring of environmental and occupational exposure to mercury

Summary Biological monitoring was used to assess mercury exposure from occupational and environmental sources in a group of chloralkali workers (n = 89) and in a control group (n = 75). In the control group, the median value for blood mercury (B-Hg) was 15 nmol/l, that for serum mercury (S-Hg) was 4 nmol/l and that for urinary mercury (U-Hg) was 1.1 nmol/mmol creatinine. Corresponding levels in the chloralkali group were 55 nmol/l, 45 nmol/l and 14.3 nmol/mmol creatinine, respectively. In the control group, there were statistically significant relationships between fish consumption and both B-Hg and S-Hg values (P < 0.001), whereas U-Hg correlated best with the individual amalgam burden (P < 0.01). In the chloralkali group, the mercury levels in blood and urine were significantly related to the type of work (P < 0.001) but not to the length of employment, to fish consumption or to the quantity of dental amalgam fillings. In both groups there were poor correlations between smoking or alcohol intake and the mercury levels in blood and urine. The results strongly suggest that fish is an important source of methylmercury exposure and that amalgam fillings are probably the most important source of inorganic mercury exposure among occupationally unexposed individuals. In the chloralkali group, mercury exposure from fish and amalgam was overshadowed by occupational exposure to inorganic mercury.     

Biological monitoring of occupational exposure to benzene and toluene

This study was carried out to evaluate the biological monitoring of occupational exposure to benzene and toluene in a total number of 31 male exposed workers and 30 control subjects. The present study showed a statistically significant higher level of biological indices of exposure (p < 0.01) of phenol and hippuric acid in urine of workers exposed to benzene and toluene than control subjects. Significant changes (p < 0.05, 0.01) in the levels of hematological and biochemical findings have been observed among exposed workers and control group. In addition, statistically significant higher levels of Mg, Mn and Ca were found among workers exposed to benzene and toluene while statistically significant lower levels of serum iron (p < 0.05) have been observed. No significant variations could be detected in the level of Zn and Cu between exposed and control subjects.     

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.     

Multi-endpoint biological monitoring in combined,carcinogenic occupational exposures

We aimed to develop a relevant multi-endpoint biomonitoring system by studying different genotoxicity biomarkers in complex carcinogenic exposures under occupational situations. Altogether 109 workers were followed in five different workplaces. The combined carcinogenic exposures were monitored in the urine and peripheral blood samples using Ames mutagenicity test and cytogenetic analyzes. The different genotoxicity endpoints studied showed different results in the same carcinogenic exposure situations. The urinary mutagenicity tests provided more information and proved to be more sensitive compared to the cytogenetic tests in the majority of cases. In complex exposures multistep biomonitoring panel should be applied, because the exact mechanisms of the combination of single exposing agents are not known. Such a panel should involve monitoring different endpoints, e.g. point mutations, chromosomal mutations. A relatively affordable and rapid testing panel was developed using validated tests as Ames and cytogenetic assays, but its practical use should be confirmed by further investigations.     

Genetic susceptibility to occupational exposures

Because of their high prevalence in the general population, genetic variants that determine susceptibility to environmental exposures may contribute greatly to the development of occupational diseases in the setting of specific exposures occurring in the workplace. Studies investigating genetic susceptibilities in the workplace may: (1) provide mechanistic insight into the aetiology of disease, in particular the determination of environmentally responsive genes; (2) identify susceptible subpopulations with respect to exposure; and (3) provide valuable input in setting occupational exposure limits by taking genetic susceptibility into account. Polymorphisms in the NAT2 and the HLA-DPB1(G)(lu69) genes provide classic examples of how genetic susceptibility markers have a clear role in identifying disease risk in bladder cancer and chronic beryllium disease, respectively. For diseases with more complex and multifactorial aetiology such as occupational asthma and chronic airways disease, susceptibility studies for selected genetic polymorphisms provide additional insight into the biological mechanisms of disease. Even when polymorphisms for genetic susceptibility have a clear role in identifying disease risk, the value of wide scale genetic screening in occupational settings remains limited due to primarily ethical and social concerns. Thus, large scale genetic screening in the workplace is not currently recommended.     

The biological monitoring of occupational exposures to solvents by using their urinary concentrations

For many years biological monitoring of occupational exposure to solvents is achieved via their specific urinary metabolites. In the last 10 years many publications have shown that the urinary concentrations of unchanged solvents are well correlated with environmental exposure and could therefore be used for biological monitoring. For acetone, methanol, methyl ethyl ketone and methyl iso butyl ketone, the American Conference of Governmental Industrial Hygienists and the Deutsche Forschungsgemeinschaft have proposed urinary concentrations of substance itself as biological exposure indices. A critical revision of the literature on this matter reveals discrepancies between the results obtained by different authors. The correlations between environmental data and respective solvents give excellent indices of correlation. However, the differences observed when comparing the regression lines obtained from different research groups are very wide. For example, for an exposure to toluene corresponding to 50 ppm, some authors found urinary concentrations equal to 35 micrograms/l, others found urinary concentration higher than 100 micrograms/l. Similarly for benzene, styrene and methyl ethyl ketone the differences were also marked. We have not identified an explanation for such different results. Biological data variability could help to explain part of these disagreements. It should also be remembered that for benzene, the analytical methodology performed in different conditions can give rise to very different results. The mechanisms of excretion of organic solvents in urine are discussed considering biological variability and analytical method problems. The current hypotheses do not allow a satisfactory interpretation of the literature results. In conclusion further experience is needed that will more clearly show which results better express the relationship between occupational exposure to organic solvents and their specific urinary concentrations.     

Biological monitoring of occupational exposure to low levels of benzene.

To obtain reference values for the biological monitoring of benzene, the kinetics of benzene were studied in volunteers. Benzene in blood and expired air could easily be followed until the next morning after a 4-h exposure to a benzene concentration of 10 cm3.m-3. Even after exposure to 1.7 cm3.m-3 the benzene levels in the morning blood and expired air samples differed from those in unexposed subjects. One hour after exposure to 10 and 1.7 cm3.m-3 the mean levels of benzene were 238 and 25 nmol.l-1 in blood and 13.2 and 2.5 mumol.m-3 in exhaled air, respectively. It was concluded that, at high benzene levels (approximately 10 cm3.m-3), samples collected 16 h after exposure reflect the body burden of benzene, while at low exposure (< 1 cm3.m-3) samples collected 1 h after exposure may be used to estimate the exposure over the preceding few hours. Exposure to benzene from smoking is a potential confounder in estimating occupational exposure to low levels of benzene.