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 acrylonitrile exposure

A study was made of the excretion pattern of acrylonitrile (AN) in urine of 15 AN-exposed workers. During a 7-day working period with the following 2 days off, the workers delivered all their urines separately. Exposure data, collected by personal monitoring, showed a mean 8-hour TWA value of 0.13 ppm. The excretion of AN in urine (AN(U)) showed a typical pattern; concentrations peaked at the end or shortly after the end of the workday and decreased rapidly until the beginning of the next workday. A control group of 41 nonexposed workers of the same company showed a significant increase of AN(U) with increasing number of cigarettes smoked. The AN(U) concentrations of the exposed workers however were, despite the low exposure, much higher than those of the controls, both during the workdays and during the days off. Biological monitoring of AN-exposed workers by assessing AN(U) therefore seems a very sensitive exposure evaluation method, especially because it accounts for inhalation as well as skin penetration as routes for entering the body.     

Biological monitoring of workers exposed to dimethylformamide in a textile polyurethane unit

Dimethylformamide (DMF) is a universal solvent noted for its solubility in both aqueous and lipid media. It is hepatotoxic, and there are concerns about its carcinogenicity. Our objective was to determine the correlation between air monitoring measurements and biological measurements of a suitable metabolite of DMF in a cohort of operatives in a polyurethane production unit. This was done with a view to assessing how much the inhalation route contributed to total DMF exposure, mainly for control purposes. We investigated the relationship between personal air sample measurements of DMF and biological measurements of N-methylformamide (NMF) in nine adult subjects, recruited across the shifts, with varying levels of exposure to DMF. Personal exposure monitoring was carried out with a low-flow-rate Model 222-4 SKC pump, while post-shift urine samples were obtained for further analysis. Operatives were asked to abstain from consuming alcohol for 24 h before the designated shift, as advised by the laboratory responsible for the analysis of urine samples. We found a very strong statistical association between air sample measurements of DMF and NMF in the urine of the sample population (R(2) = 0.95, P < 0.0001). This study suggests that airborne exposure contributes significantly to elevated levels of NMF and, therefore, indicates that efforts should be concentrated on engineering controls in reducing workplace DMF exposure.     

Biological monitoring of cobalt exposure,based on cobalt concentrations in blood and urine

Summary Cobalt exposure level and its concentrations in blood and urine were determined for 175 hard metal workers. For control data, the cobalt concentrations in blood and urine were measured for 20 office workers. The exposed workers had significantly higher cobalt concentrations in both blood and urine. The relationships between exposure level and cobalt concentrations in blood and urine were linear and positive. The results clearly showed that the cobalt concentration in the blood or urine can be used as an exposure indicator. With cobalt exposure of 100 g/m³, the cobalt concentration was 0.57 to 0.79 g/dl in blood and 59 to 78 g/l in urine with 95% confidence limits. In workers using respirators, the cobalt concentrations in the blood and urine decreased to 2/5 and 1/8, respectively, of those not using respirators.     

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     

Biological monitoring of TDI-derived amines in polyurethane foam production

BACKGROUND: Toluene diisocyanate (TDI) is used in industry in the production of flexible polyurethane foam, commonly a mixture of the 2,4- and 2,6- isomers. The production process may lead to exposure to diisocyanates which are associated with respiratory disease. A method has been available for the determination of TDI biomarkers in urine for some years. AIMS: To explore the usefulness of urinary toluenediamine (uTDA) in assessing whether dermal absorption of diisocyanates makes a significant contribution to a worker's total exposure. METHODS: Twenty-six workers took part in the study. Thirteen workers whose duties brought them into physical contact with uncured polyurethane foam during their shift (handlers) were compared to a control group of 13 workers in the same block plant environment had no physical contact with uncured foam on the day that sampling took place (non-handlers). Creatinine-adjusted uTDA levels in the two groups were compared across a work shift. RESULTS: Both groups of workers were exposed to similar levels of airborne TDI. Ten handlers were found to have TDA in post-shift urine samples above detection limits compared with two non-handlers (P < 0.05). No clear relationship was found between the level of airborne TDI exposure and post-shift uTDA. CONCLUSIONS: uTDA provides a useful indication of the contribution which skin absorption makes to total TDI exposure. The results suggest that skin protection when handling uncured polyurethane foam may not receive sufficient consideration.     

Dehydroabietic acid as a biomarker for exposure to colophony

BACKGROUND: Colophony (rosin) is a natural product derived from the resin of coniferous trees with many industrial applications including soldering fluxes. Exposure to colophony fume through soldering is one of the leading causes of occupational asthma in the UK. AIMS: To assess occupational exposure to colophony from solder fume at selected workplaces in the UK and to investigate the use of dehydroabietic acid (DHA) as a biomarker of exposure. METHODS: Six companies in the UK electronics industry were visited and occupational hygiene assessments of extent and control of exposure to rosin-based solder flux fume were undertaken. Urine samples were analysed for one of the main constituents of rosin, DHA. RESULTS: There was a positive linear relationship between airborne exposure to solder fume and urinary DHA level. The levels of urinary DHA measured in UK workers were significantly lower than those previously measured in African workers because of the use of appropriate exposure control measures, for example, local exhaust ventilation with fixed ducting and flexible hose, tip extraction, etc. It is suggested that good occupational hygiene practice would result in urinary DHA levels of <3 micromol/mol creatinine in a post-shift urine sample. CONCLUSIONS: Urinary DHA is a valid biomarker of exposure to colophony in solder fume. Further work on the excretion kinetics of urinary DHA, the possibility of skin absorption and further occupational hygiene surveys would be beneficial.     

Determination of mercury in blood,urine and saliva for the biological monitoring of an exposure from amalgam fillings in a group with self-reported adverse health effects

It has been argued that the release of mercury from amalgam fillings is of toxicological relevance. The aim of the study was to determine the internal mercury exposure of two groups differing in their attitude towards possible health hazards by mercury from amalgam fillings. It was to be examined if the two groups differ with regard to the mercury concentration in different biological matrices and to compare the results with current reference values. Blood, urine and saliva samples were analyzed from 40 female subjects who claimed to suffer from serious health damage due to amalgam fillings ("amalgam sensitive subjects"). 43 female control subjects did not claim any association ("amalgam non-sensitive controls"). Mercury was determined by means of cold vapour atomic absorption spectrometry. Number and surfaces of amalgam fillings were determined by dentists for each subject. Median (range) mercury levels in blood were 2.35 (0.25-13.40) micrograms/l for "amalgam sensitive subjects" and 2.40 (0.25-10.50) micrograms/l for "amalgam non-sensitive controls". In urine, the median mercury concentrations were 1.55 (0.06-14.70) micrograms/l and 1.88 (0.20-8.43) micrograms/g creatinine respectively. No significant differences could be found between the two groups. Mercury levels in blood and urine of the examined subjects were within the range of background levels in the general population including persons with amalgam fillings. Stimulated saliva contained 76.4 (6.7-406.0) micrograms mercury/l in "amalgam sensitive subjects" and 57.0 (2.8-559.0) micrograms mercury/l in controls (not significant). Mercury levels in saliva did not correlate with the concentrations in blood and urine, but merely with the number of amalgam fillings or of the filling surfaces. Mercury in saliva is therefore not recommended for a biological monitoring.     

Biological monitoring standards for industrial toluene exposure recommended for South Africa

Coal combustion is used in many industrial processes in SouthAfrica. The exposure of workers and the absence of internationalbiological monitoring standards for toluene created a problem.A cross-sectional study on 100 workers indicated that the biologicalthreshold for ortho-cresol:creatinine ratio reference valueof <1 mg/g could presently be used as a reference for non-industrialhuman exposure while the <2 mg/g rate is for worker exposurein an industrial environment at a coal combustion plant.     

Occupational exposure to inorganic mercury vapour and reproductive outcomes

The effect of exposure to inorganic mercury on the pregnantwoman and her foetus has received little attention. Transportof elemental inorganic mercury into foetal tissues has beenreported, and prior studies indicate a higher incidence of adversepregnancy outcome. The effects of occupational exposure to inorganicmercury on pregnancy were investigated among 46 exposed womenworkers; controls were 19 women working in non-production areasof the same factory. There were 104 recorded total pregnanciesduring the period 1948–77. The study revealed a higherfrequency of adverse reproductive outcomes, especially congenitalanomalies, among the women exposed to inorganic mercury levelsat or substantially lower than 0.6 mg/m³; no significant differencesin the stillbirth or miscarriage rates were noted between thetwo groups of women. The overall foetal death rate in this studywas similar to New York state (USA) and national levels forthe same period.     

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。     

Identification of a possible biomarker for colophony exposure.

Colophony is known to cause occupational asthma and dermatitis. Biological monitoring may be useful in assessing exposure. This paper describes a method for the analysis of dehydroabietic acid in urine and its potential use as a marker of colophony exposure. The method involves hydrolysis, solvent extraction, derivatization and analysis by gas chromatography-mass spectrometry. Twenty-eight workers from a soldering factory in South Africa were monitored. Results showed that levels of dehydroabietic acid in urine may be correlated with a subjective assessment of 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     

Occupational styrene exposure: Environmental and biological monitoring

Occupational exposure to styrene was studied by environmental and biological monitoring in 22 workers employed in a fiberglass reinforced plastic factory. The mean environmental styrene concentration in individual workplaces ranged from 120 to 684 μl/l. Blood styrene, which was tested at the end of the work shift, ranged from 450 to 3700 μg/l. Urinary mandelic and phenylglyoxylic acid, which were determined at the end of the work shift, ranged from 133 to 2100 and from 107 to 685 mg/l, respectively. Environmental styrene exposure was better correlated with styrenemia than with mandelicuria and phenylglyoxylicuria considered either individually or together. The ratio between environmental and blood styrene showed that styrenemia was, on average, 3.3–4.9 times higher than environmental styrene concentration.     

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 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     

Biological monitoring of styrene exposure and possible interference of acetone co-exposure

 The object of this study is the evaluation of some of the toxicokinetic effects of exposure to low concentrations of styrene, and the possible influence of simultaneous exposure to acetone. To this end we studied 19 workmen simultaneously exposed to both solvents. During a week of 4-h work shifts, the workmen underwent daily personal environmental monitoring and the collection of urine samples, at both the beginning and the end of the work period, for the determination of mandelic acid (MA) and phenylglyoxylic acid (PGA). The presence of the solvents in the atmosphere was evaluated using passive personal monitoring and gas chromatography. Average exposure to styrene and acetone were respectively 72.2 mg/m³ and 225.7 mg/m³. MA and PGA were quantified by high-performance liquid chromatography (HPLC). The daily urinary concentration averages, both at commencement and at the end of work shifts, of both the metabolites studied and of the sum of the two, were in statistically significant linear correlation with the average daily styrene exposure. Concentrations of MA and PGA in urine samples collected at the start of the work shift averaged 61.5 mg/g creatinine and 45.2 mg/g creatinine respectively, representing 41% and 72% of those at the end of the work shift which were 148.3 and 62.6 mg/g creatinine, respectively. With equal exposure to styrene, the average urinary concentrations of MA and PGA at both the beginning and end of the work shift increased significantly (P<0.001) during the working week. Moreover, we found that with equal exposure to styrene, urinary excretion of MA, PGA and MA+PGA at the end of the shift was inversely correlated with the intensity of acetone exposure (r=0.4659, 0.3410 and 0.4542 respectively, P<0.001). In conclusion, these results express slower urinary kinetics of styrene metabolites than is usually described in the literature, and favor a tendency to accumulate MA and PGA in the organism as a consequence of the retardation of urinary excretion kinetics. Acetone apparently represents one of the determining factors in this interference. Received: 3 July 1996/Accepted: 20 September 1996     

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     

Dermal exposure assessment in occupational medicine

The importance of dermal exposure has increased during the last few years, mainly because of the reduction of respiratory exposure to toxicants. Pesticides, aromatic amines and polycyclic aromatic hydrocarbons are considered to be the chemicals at highest dermal risk. In the occupational exposure limit lists of the American Conference of Governmental Industrial Hygienists (ACGIH) and of many countries, compounds that can be absorbed through the skin are identified by a skin notation. However, a generally accepted criterion for assigning skin notation does not exist. The recent attempts to develop health-based dermal occupational exposure limits (DOELs) have not been accepted, thus in practice their use has remained limited. To predict the systemic risk associated with dermal exposure and to enable agencies to set safety standards, penetration data are needed. Moreover, there is a need for a practical risk assessment model, particularly for small and medium-sized enterprises.