Biological monitoring values for occupational exposure: a United Kingdom perspective

Policy developments in the United Kingdom have been aimed at facilitating the appropriate use of biological monitoring. Recent initiatives have established clear criteria for the interpretation of biological monitoring results, and new guidance that deals with the ethical and practical issues involved in operating an effective biological monitoring programme has been promulgated. The United Kingdom now has a system of non-statutory biological monitoring guidance values. There are two types, the health guidance value and the benchmark guidance value. Over a number of years, biological monitoring programmes have shown that they help in reducing exposure by regular monitoring and demonstrating adequate control. Received: 2 March 1999 / Accepted: 25 March 1999     

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.     

Biologic monitoring of workers exposed to silver

Summary Air-lead levels (PbA) and biological indices were studied in three ceramic factories (185 workers altogether). A difference in the pattern of lead exposure was found in the largest factory (A) and the other two smaller factories (B and C). PbA never exceeded 67 g/m³ in factory A, but reached values as high as 378 g/m³ in factory B. 19% of PbB values were higher than 40 g/100 ml in factory A, 63% in factory B and 35% in factory C. As was expected, a closer analysis of the jobs confirmed a higher exposure level in people directly in contact with lead glazes (glazers and kiln operators). In factories B and C, however, there was also a significant lead uptake in selection and maintenance staff, who worked in areas at some distance from the glazing lines. This may be due in part to pollution spread over all departments, but also to the lack of hygiene and washing facilities whose importance is stressed for effective prevention. Biological monitoring is suggested as being useful for all workers, whatever the lead-air level, bearing in mind the possibility of lead intake orally through soiling.     

Di(2-ethylhexyl)phthalate (DEHP) exposure of voluntary plasma and platelet donors

Each year thousands of healthy volunteers undergo apheresis procedures to donate blood components and safe lives. However, many disposables used in apheresis contain di(2-ethylhexyl)phthalate (DEHP). This way, donors are exposed to DEHP, which is a reproductive and developmental toxicant in animals and a suspected endocrine modulator in humans. We quantified the DEHP exposure of six plasma donors, six discontinuous-flow platelet donors and six continuous-flow platelet donors by determining three specific metabolites in urine (5OH-MEHP: mono(2-ethyl-5-hydroxyhexyl)phthalate; 5oxo-MEHP: mono(2-ethyl-5-oxo-hexyl)phthalate and MEHP: mono(2-ethylhexyl)phthalate). We found maximum concentrations in urine samples after the discontinuous-flow plateletpheresis procedure with 826 microg/l for 5OH-MEHP, 774 microg/l for 5oxo-MEHP and 266 microg/l for MEHP (mean of the six volunteers). Metabolite excretions were found to be significantly (p<0.0001) higher for both plateletpheresis techniques compared to plasmapheresis and controls. Continuous-flow plateletpheresis led to significantly higher (p<0.0001) excretions than discontinuous-flow plateletpheresis. Mean absolute DEHP exposures were 1.2 mg for discontinuous- and 2.1 mg for continuous-flow plateletpheresis. Exposure for plasmapheresis (0.37 mg) was in the range of the controls (0.41 mg). Mean DEHP doses for both plateletpheresis techniques (18.1 and 32.3 microg/kg/day) were close to or exceeded the reference dose (RfD) of the US EPA and tolerable daily intake (TDI) value of the EU on the day of the apheresis. Therefore, margins of safety might be insufficient to protect especially young men and women in their reproductive age from effects on reproductivity. At present, discontinuous-flow devices should be preferred to avert conceivable health risks from plateletpheresis donors. Strategies to avoid DEHP exposure of donors during apheresis need to be developed.     

尿邻甲酚作为接触甲苯生物监测指标的探讨

目的探讨尿邻甲酚作为接触甲苯生物监测指标的可能性。方法建立柱前衍生高效液相色谱法测定人体尿中邻甲酚,且使用该方法测定非职业及职业接触甲苯人群尿中邻甲酚水平,并进行接触评定。结果甲苯接触者尿邻甲酚水平为(2.61±1.94)mg/L,明显高于对照组[(0.32±0.23)mg/L],差异有显著性(P<0.001),且接触甲苯工人班后尿邻甲酚水平比班前明显升高,最高可达29倍。接触甲苯者尿邻甲酚水平与个体接触甲苯浓度明显相关(r=0.6295,P<0.01)。结论尿邻甲酚可以作为接触甲苯的生物监测指标。     

Biological monitoring of controlled toluene exposure

Objectives: Widespread exposure to toluene occurs in the printing, painting, automotive, shoemaking, and speaker-manufacturing industries. The relationship between air concentrations and the absorbed dose is confounded by dermal exposure, personal protective devices, movement throughout the workplace, and interindividual differences in toluene uptake and elimination. Methods: To determine the best biological indicator of exposure we examined the blood and alveolar breath concentrations of toluene as well as the urinary excretion rates of hippuric acid and of o-, m-, and p-cresols from 33 controlled human inhalation exposures to 50 ppm for 2 h. Results: Among the metabolites, o-cresol was least influenced by background contributions, whereas the p-cresol and hippuric acid rates were obscured by endogenous and dietary sources. Toluene levels in alveolar breath proved to be the most accurate and noninvasive indicator of the absorbed dose. A physiologic model described blood and breath data using four measured anthropometric parameters and the fit values of extrahepatic metabolism and adipose-tissue blood flow. Conclusions: After breathing rate and extrahepatic metabolism had been set to conservative (protective) values (the 97.5th and 2.5th percentiles, respectively) the model predicted that pre-final-shift breath levels of ≤10 μmol/m³ and post-final-shift levels of ≤150 μmol/m³ corresponded to average workplace exposure levels of ≤50 ppm toluene. Alternately, we used the distributions and covariances of the measured and fit model parameters to yield conservative pre-final-shift levels of ≤7.3 μmol/m³ and post-final-shift breath levels of ≤120 μmol/m³ that were reflective of workplace exposure levels of ≤50 ppm toluene. Received: 30 December 1997 / Accepted: 12 June 1998     

Propylene glycol monomethyl ether (PGME) occupational exposure

An analytical method was developed for the determination of free and conjugated PGME-α in urine. The method involves a solid-phase extraction on LC-18 columns and a GC/FID analysis after derivatization with trimethysilylimidazole. The assay was linear (least-squares regression coefficient 0.996), specific, reproducible (intraassay variability 10%, interassay variability 10%), and allowed a high level of PGME recovery (more than 90%). The assay was applied to the analysis of urine samples from three workers who were occupationally exposed to PGME to estimate their exposure. The highest value of PGME concentration in urine was 7.78 mg/l. Air concentrations of PGME ranged between 20 and 40 ppm. A statistically significant correlation was found between measurements of external exposure and PGME in urine. An important fraction of PGME in urine was found to be conjugated. Received: 6 July 1999 / Accepted: 27 December 1999     

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.     

Concentration of di(2-ethylhexyl) phthalate (DEHP) in foods and its dietary exposure in China

Di(2-ethylhexyl) phthalate (DEHP) is a common plasticizer used in food contact materials that has been reported as an endocrine disruptor. In the present study, DEHP concentrations were analyzed in foods in order to determine dietary exposure among the Chinese population, including the general population (aged 2–100) and four age group, that is children aged 2–6, adolescent aged 7–12, young people aged 13–17 and adults aged 18 years old and above. 1704 food samples were collected during 2011–2012 and categorized into 12 food groups which covered major foods in China. Food consumption data were taken from China National Nutrient and Health Survey which was performed in 2002 and includes data from 68,959 subjects. Mean concentrations of DEHP were combined with individual food consumption data to estimate dietary exposure. It was found that DEHP levels in foods ranged from not detected to 3.41 mg/kg, with highest mean values in meat (0.23 mg/kg) and vegetable oils (0.21 mg/kg). Mean dietary intakes of DEHP in the general population, children, and adults were 2.34, 4.51, 2.03 μg/kg bw per day, respectively. The 97.5% intakes in these populations were 5.22, 8.43, 3.64 μg/kg bw per day, respectively. The main food sources of DEHP dietary intake were cereals (39.44%), drinking water (16.94%) and meat (15.81%) in children, and cereals (44.57%), meat (15.70%) and drinking water (12.28%) for adults. These findings suggested that dietary exposure to DEHP among Chinese population was lower than tolerable daily intake of DEHP and there are no health concerns based on generally accepted exposure limits.     

Biological monitoring of exposure to di(2-ethylhexyl) phthalate in six French factories: a field study

Objective  

The aim of this study was to assess, by biological monitoring, workers’ exposure to di(2-ethylhexyl) phthalate (DEHP) in the flexible-PVC industry in France to provide additional occupational exposure data, which are particularly scarce.     

龙岗区铬作业工人职业暴露情况调查

目的 通过开展铬职业暴露现状调查与铬职业暴露人群呼吸系统健康损害检查,有助于详细掌握辖区内铬职业暴露人群的铬暴露量、健康状况和职业危害现状,为开展铬职业暴露人群的健康效应评估、健康监护和基本职业卫生服务提供翔实的基础数据.方法 调查辖区全部五金电镀厂基本情况,对作业场所空气、作业工人血进行采样和检测,同时对铬作业工人进行职业健康检查.结果 作业场所空气铬时间加权平均浓度为0.012 mg/m3(浓度范围:0.01 ～0.24 mg/m3),低于国家容许卫生标准(0.15 mg/m3),未发现铬酸盐超标.对372名工人鼻部进行检查,发现鼻中隔黏膜糜烂2例、鼻中隔软骨部穿孔2例,总检出率为1.08％.工人工龄与血铬浓度两者间的相关分析结果无统计学意义(r=-0.04,P=0.445).作业场所空气铬浓度组间铬鼻部位征检出率之间的差异无统计学意义(x2 =2.18,P=0.140).结论 地方政府部门需要高度关注辖区五金电镀行业铬作业职业病危害的现状,积极采取综合整治措施,建立长效管理机制,控制铬职业病危害.     

出生前邻苯二甲酸二(2-乙基己基)酯暴露对子代大鼠血清皮质醇激素水平的影响

目的探讨出生前邻苯二甲酸二(2-乙基己基)酯(DEHP)暴露对大鼠肾上腺功能的潜在干扰作用。方法将32只健康SD孕鼠按体重随机分为溶剂对照组(玉米油)及2、10、50 mg/kg DEHP染毒组,每组8只。自孕14~19 d连续灌胃染毒,每日1次。子代大鼠于出生后第21天断乳,雌雄分笼饲养至70日龄,断头处死,取血及双侧肾上腺,计算肾上腺脏器系数,并采用Luminex液态芯片技术测定血清皮质醇水平。结果成年雌性仔鼠肾上腺脏器系数在各染毒组间有差异,与对照组相比,2 mg/kg染毒组的肾上腺重量及脏器系数较低,差异有统计学意义(P0.05);成年雄性仔鼠肾上腺脏器系数在各染毒组间差异均无统计学意义(P0.05)。与对照组相比,10、50 mg/kg染毒组的成年雌性仔鼠血清皮质醇水平较高,差异有统计学意义(P0.01);而2 mg/kg染毒组与对照组相比无明显差异(P0.05)。与对照组相比,10 mg/kg染毒组的成年雄性仔鼠血清皮质醇水平较高,差异有统计学意义(P0.01);而2、50 mg/kg染毒组与对照组相比无明显差异(P0.05)。结论出生前DEHP暴露可能干扰子代大鼠肾上腺功能。     

Enzymuria in workers exposed to inorganic mercury

Summary Urinary excretion of beta-hexosaminidase (NAG = N-acetyl-beta-glucosaminidase) and albumin was examined in 41 chlor-alkali workers exposed to inorganic mercury and 41 age-matched controls. Either U-HG or B-Hg levels for these workers were available dating from the 1960s to the present. Increased U-NAG was seen in workers with a U-Hg today of more than 4g/mmol creat (about 50g/l; 35 g/g creat). Multiple linear regression analysis showed that U-NAG was correlated to U-Hg and integrated dose but not to the present B-Hg level. No albuminuria (detection limit 12.5 mg/1) was found in any of the subjects. In a longitudinal study, no decrease in UNAG levels was seen in 15 chlor-alkali workers after their vacation (x = 20 d). In five workers followed for ten months after a short exposure period, no definite time trend could be seen. The results show that there is a slight effect on renal tubules even at rather low levels of exposure to mercury vapour. The clinical significance of the enzymuria levels found here is, however, debatable.     

Urine phthalate determinations as an index of occupational exposure to phthalic anhydride and di(2-ethylhexyl)phthalate

Although it has been estimated that over 600 000 workers in the United States are exposed to di(2-ethylhexyl)phthalate (DEHP), an animal carcinogen, and that over 100 000 are exposed to phthalic anhydride (PA), few data are available on levels of phthalates in biological fluids of these workers. For a determination of occupational exposure to PA and DEHP at a plant manufacturing DEHP from PA and 2-ethylhexanol, air samples were taken for PA and DEHP, and pre- and postshift urine samples were collected for the determination of total phthalates. Urine samples were obtained from 48 workers in jobs with high exposure to phthalates and from 47 workers in jobs with low exposure. The airborne concentrations of DEHP ranged from 20 to 4 110 micrograms/m3, and the concentrations of PA ranged from 4 to 203 micrograms/m3. The most heavily exposed workers had the highest mean postshift urine phthalate concentration (geometric mean 7.6 nmol/ml) (p = 0.015), and also the greatest mean increase (4.4 nmol/ml) in preshift to postshift urine phthalate levels. Twofold increases over the shift in urine phthalate concentration and postshift phthalate levels of greater than 10 nmol/ml were observed in 8 (25%) of 32 chemical operators, but in none of 52 other workers. These data suggest that measurement of urine phthalate levels may have utility for monitoring the exposure of workers manufacturing or using PA.     

Urinary sevoflurane and hexafluoro-isopropanol as biomarkers of low-level occupational exposure to sevoflurane

Objectives: Sevoflurane is an inhalation halogenated anaesthetic widely used in day and paediatric surgery. We were interested in evaluating biological markers of exposure to sevoflurane, which should improve the health surveillance of occupationally exposed personnel. Methods: A group of 36 subjects (13 male, 23 female) occupationally exposed to volatile anaesthetics in paediatric operating rooms was studied in a 2-week survey. Post-shift urine samples and specimens from passive samplers (for personal monitoring) were collected after 1.75–6 h morning exposure and analysed by headspace gas chromatography–mass spectrometry (GC–MS). Multiple determinations were assumed as independent values (in total, n=78: 24 from men, 54 from women; 25 from smokers, 53 from non-smokers). Results: Median sevoflurane external values were 0.13 parts per million (ppm) (range 0.03–18.82) (n=78), urinary sevoflurane 0.6 g/l_urine (ND–18.5)(n=76) and total urinary hexafluoro-isopropanol (HFIP) 0.49 mg/l_urine (ND–6833.4) (n=75). A lower limit of detection (LOD) was achieved for urinary sevoflurane (0.03 g/l_urine), allowing quantitation of all but one of the samples; >25% of urine samples were unquantifiable by HFIP and were assigned a value equal to half the LOD of 0.10 mg/l_urine. Urinary sevoflurane correlated well with breathing-zone data (r²=0.697 at log–log linear regression), whereas total urinary HFIP (r²=0.562 at log–log linear regression) seemed to be better described by a three-parameter logistic function and appeared to be influenced by smoking habits. Biological indices corresponding to National Institute for Occupational Safety and Health (NIOSH) exposure limits, calculated as means of linear regression slope and y intercept, were 3.9 g/l_urine and 1.4 g/l_urine for sevoflurane (corresponding to 2 ppm and 0.5 ppm, respectively), and 2.66 mg/l_urine and 0.82 mg/l_urine for HFIP. Conclusions: On the basis of our data, urinary unmodified, sevoflurane seems to be a more sensitive and reliable biomarker of short-term exposure to sevoflurane with respect to total urinary metabolite HFIP, which appears to be influenced by physiological and/or genetic individual traits, and seems to provide an estimate of integrated exposure.     

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. Received: 6 March 2000 / Accepted: 10 June 2000     

Internal exposure of nursery-school children and their parents and teachers to di(2-ethylhexyl)phthalate (DEHP)

Di(2-ethylhexyl)phthalate (DEHP) is the main plasticizer for polyvinyl chloride (PVC) products. It has become widely spread in our environment and among people. DEHP is suspected to be responsible for endocrine-disruptor-like effects in mankind. Children are probably most susceptible to these endocrine effects. In this study we determined the internal exposure of nursery school children (aged 2-6 years) to DEHP and compared it to their parents' and teachers' exposure. The DEHP-metabolites mono(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP), mono(2-ethyl-5-oxo-hexyl)phthalate (5oxo-MEHP) and mono(2-ethylhexyl)phthalate (MEHP) were determined in first morning urine. The sum of the three DEHP metabolites in children's and in adults' urine was 90.0 and 59.1 micrograms/l respectively (median values; p = 0.074). Concentrations of the secondary metabolites 5OH-MEHP (median: 49.6 vs. 32.1 micrograms/l; p = 0.038) and 5oxo-MEHP (median: 33.8 vs. 19.6 micrograms/l; p = 0.015) were significantly higher in children than in adults. MEHP concentrations were low both in adults and children (median: 6.6 micrograms/l vs. 9.0 micrograms/l). Creatinine adjusted values should more accurately reflect the dose taken up with respect to body weight when comparing children with adults. Total creatinine adjusted DEHP metabolites in urine were significantly higher in children than in adults (median values: 98.8 vs. 50.9 micrograms/g creatinine; p < 0.0001). This also applied to the concentrations of both secondary metabolites 5OH-MEHP (55.8 vs. 28.1 micrograms/g creatinine; p < 0.0001) and 5oxo-MEHP (38.3 vs. 17.2 micrograms/g creatinine; p < 0.0001). Creatinine corrected concentrations for the monoester MEHP in children and adults were very similar (8.7 vs. 8.6 micrograms/g creatinine; p = 0.908). Based on the sum of the three determined metabolites we estimated the DEHP dose (in microgram/kg body-weight) taken up by children to be about twice as high as the dose taken up by adults. Routes of the ubiquitous exposure to DEHP remain indistinct. In children's urine the mean relative ratios of MEHP to 5OH-MEHP to 5oxo-MEHP were 1 to 7.1 to 4.9, in adults they were 1 to 3.4 to 2.1. This might indicate an enhanced oxidative metabolism in children. To date no information on the biological activity and toxicity of oxidative metabolites of DEHP is available. Since these are the major metabolites of DEHP toxicological data on these metabolites is urgently needed.     

Biological monitoring of hexachloroethane

A small group (n=12) of military white smok munition workers provided blood plasma during a production break (S I) and after five weeks' production (S II) of a hexachloroethane (HCE)/titanium dioxide formula. Plasma was also obtained from a sex and age matched control group (n=12) and a group (n=13) of previously HCE-exposed workers, respectively. HCE in plasma (P-HCE) was determined with gas chromatography and electron capture detection. No HCE was found in the plasma samples from the two control groups. In the HCE exposed group the mean (± SD) P-HCE level increased almost two orders of magnitude from S I (0.08 t 0.14 g/l) to S 11(7.30 ± 6.04g/l) despite efforts to minimize the internal dose. Biological monitoring of HCE could be useful in occupational hygiene.     

某化工厂过氯酸铵粉尘作业工人健康状况调查

目的 了解过氯酸铵(AP)粉尘对作业工人健康的影响,为其预防措施提供依据.方法 选择该厂接触AP粉尘的36名作业工人为接触组,不接触AP粉尘的48名该厂工人为对照组.调查工厂的一般情况,监测作业场所的AP粉尘浓度,对两组人群进行职业健康体检,检测血常规、肝肾功能、甲状腺激素指标,进行肺通气功能和X线胸片检查.结果 AP总粉尘浓度以组批车间最高,为(51.63±43.27) mg/m3.接触组收缩压[(146.14±21.03)mmHg]明显高于对照组[(134.67±18.58)mmHg],差异有统计学意义(P＜0.05).接触组全身各系统症状(皮粗、皮痒、气短、咳嗽、咳痰、咽干、疲乏无力等)累计检出率、气短及皮痒的检出率分别为86.11％、30.56％、36.11％,均明显高于对照组(66.67％、12.50％、10.42％),差异均有统计学意义(P＜0.05).接触组的游离三碘甲状腺原氨酸(FT3)水平[(1.29±0.20) ng/ml]明显低于对照组[(1.41±0.23) ng/ml],差异有统计学意义(P＜0.01).接触组工人的1秒用力肺活量与用力肺活量百分比值(FEV1.0/FVC)低于对照组,但差异无统计学意义(P＞0.05).接触组检出1例肺部X线影像异常者,并诊断为尘肺,对照组检出1例左肺门区有1约1.0x1.0小结节影.结论 接触组工人的收缩压明显高于对照组,不排除与接触AP粉尘有关;接触组工人的FT3低于对照组,提示长期接触AP粉尘可能会对作业工人甲状腺功能造成影响.     

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.