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PubMed2000

Biological monitoring of workers exposed to N,N-dimethylformamide in the synthetic fibre industry.

OBJECTIVES: Monitoring of workplace air and biological monitoring of 23 workers exposed to N,N-dimethylformamide (DMF) in the polyacrylic fibre industry was carried out on 4 consecutive days. The main focus of the investigation was to study the relationship between external and internal exposure, the suitability of the metabolites of DMF for biological monitoring and their toxicokinetic behaviour in humans. METHODS: Air samples were collected using personal air samplers. The limit of detection (LOD) for DMF using an analytical method recommended by the Deutsche Forschungsgemeinschaft (DFG) was 0.1 ppm. The urinary metabolites, N-hydroxymethyl-N-methylformamide (HMMF), N-methylformamide (NMF), and N-acetyl-S-(N-methylcarbamoyl)-cysteine (AMCC), were determined in one analytical run by gas chromatography with thermionic sensitive detection (GC/TSD). The total sum of HMMF and NMF was determined in the form of NMF. The LOD was 1.0 mg/l for NMF and 0.5 mg/l for AMCC. RESULTS AND CONCLUSIONS: The external exposure to DMF vapour varied greatly depending on the workplace (median 1.74 ppm, range < 0.1-159.77 ppm). Urinary NMF concentrations were highest in post-shift samples. They also covered a wide range (< 1.0-108.7 mg/l). This variation was probably the result of different concentrations of DMF in the air at different workplaces, dermal absorption and differences in the protective measures implemented by each individual (gloves, gas masks etc.). The urinary NMF concentrations had decreased almost to zero by the beginning of the next shift. The median half-time for NMF was determined to be 5.1 h. The concentrations of AMCC in urine were determined to be in the range from < 0.5 to 204.9 mg/l. Unlike the concentrations of NMF, the AMCC concentrations did not decrease during the intervals between the shifts. For the exposure situation investigated in our study, a steady state was found between the external exposure to DMF and the levels of AMCC excreted in urine about 2 days after the beginning of exposure. AMCC is therefore excreted more slowly than NMF. The half-time for AMCC is more than 16 h. Linear regression analysis for external exposure and urinary excretion of metabolites was carried out for a sub-group of 12 workers. External exposure to 10 ppm DMF in air (the current German MAK value) corresponds to an average NMF concentration of about 27.9 mg/l in post-shift urine from the same day and an average AMCC concentration of 69.2 mg/l in pre-shift urine from the following day. NMF in urine samples therefore represents an index of daily exposure to DMF, while AMCC represents an index of the average exposure over the preceding working days. AMCC is considered to be better suited for biomonitoring purposes because (1) it has a longer half-time than NMF and (2) its formation in humans is more closely related to DMF toxicity.

Acetylcysteine↗

PubMed1999

Occupational chronic exposure to organic solvents XVII. Ambient and biological monitoring of workers exposed to xylenes.

OBJECTIVE: Ambient-air and biological monitoring of occupational xylene exposure were carried out on 2 groups of workers (13 and 10 men, respectively) exposed to a mixture of xylenes during the production of paints or during spraying. METHODS: Personal ambient-air monitoring was performed for one complete work shift. Blood and urine samples were collected directly at the end of the shift. Biological monitoring was based on the determination of the concentration of xylenes in blood and on the quantification of the sum of the three methylhippuric acids in urine. RESULTS: Average xylene ambient-air concentrations were 29 ppm (production) and 8 ppm (spraying), ranging from 5 to 58 ppm and from 3 to 21 ppm, respectively. The concentrations of xylenes in blood ranged from 63 to 715 microg/l and from 49 to 308 microg/l, with average values being 380 and 130 microg/l, respectively. Accordingly, the workers engaged in paint production also excreted more methylhippuric acids in their urine (average 1221 mg/l, range 194 2333 mg/l) than did the sprayers (average 485 mg/l, range 65-1633 mg/l). DISCUSSION: Our results as well as a literature review indicate that occupational xylene exposure on average barely exceeds the threshold limit value of 100 ppm as proposed by both American and German institutions. Biological monitoring based on the determination of xylenes in blood and of methylhippuric acids in urine provides sufficient sensitivity and specificity for occupational health surveillance. The results also confirm the current limit values (BAT values) proposed by the Deutsche Forschungsgemeinschaft for xylenes in blood (1500 microg/l) and methylhippuric acids in urine (2000 mg/l).

Adult↗

PubMed1993

Biological monitoring of nickel in humans.

The literature since 1985 on the biological monitoring of occupational, environmental, or iatrogenic exposures of humans to nickel is surveyed from the author's perspective. Urine and serum are the body fluids commonly analyzed for nickel. Nickel concentrations in urine specimens from unexposed persons usually exceed the current analytical detection limits, while nickel concentrations in their serum specimens are close to the detection limits. For this reason, and because urine collection is painless, noninvasive, and convenient, urine is more practical than serum for the biological monitoring of nickel-exposed workers. Electrothermal atomic absorption spectrometry with Zeeman background correction is currently the method of choice for the analysis of nickel in biological materials. Procedures for quality assurance and strategies for biological monitoring are summarized, as performed in the author's laboratory, and current reference values are listed for nickel concentrations in urine and serum specimens from healthy unexposed persons.

Environmental Monitoring↗

PubMed1997

Ethnic differences in biological monitoring of several organic solvents. I. Human exposure experiment.

OBJECTIVES: In order to improve the reliability of biological monitoring and the development of biological limit values, ethnic differences for several organic solvents were studied in Orientals and Caucasians. METHODS: Six Caucasian and six Oriental volunteers were exposed to each organic solvent in an exposure chamber for 6 h. Exposure concentration to each organic solvent studied was 50 ppm for perchloroethylene, 50 ppm for styrene and 100 ppm for m-xylene, respectively. Biological monitoring was carried out for the parent organic solvents in exhaled air and in blood, and for the metabolites in urine during and after exposure. RESULTS: Caucasians showed higher concentrations of perchloroethylene in exhaled air than Orientals after exposure. But Caucasians showed lower concentrations of styrene in the exhaled air than Orientals during the second half of exposure and after it. Orientals showed lower concentrations of urinary metabolites than Caucasians except for mandelic acid. There were no statistically significant differences in the concentrations of solvent in blood for all three solvents. CONCLUSIONS: Implications of these differences in biological levels, under identical exposure conditions, are discussed in the context of biological monitoring.

Adult↗

PubMed1997

Ethnic differences in biological monitoring of several organic solvents. II. A simulation study with a physiologically based pharmacokinetic model.

To improve the reliability of biological monitoring and the development of biological limit values, ethnic differences in the biological monitoring of several organic solvents were studied in Orientals and Caucasians. Six Caucasian and six Oriental volunteers were exposed to each organic solvent in an exposure chamber for 6 h at rest. The exposure concentrations were 50 ppm for perchloroethylene, 50 ppm for styrene, and 100 ppm for m-xylene, respectively. Experimental results were compared with simulation results of a physiologically based pharmacokinetic (PB-PK) model. Differences between Orientals and Caucasians under occupational exposure were also estimated by extrapolation. The simulation results obtained for the Caucasian group showed good agreement with the experimental results. However, the Oriental group did not show good agreement when the same metabolic parameters values applied to Caucasians were used in the PB-PK model. By modification of the metabolic parameters it was possible to get a good fit between the model and the results of the Oriental group. The simulation results obtained for occupational exposure also showed differences in biological levels between the two ethnic groups. Implications of these differences between experimental and simulation results are discussed in the context of the application of biological monitoring and in the development of biological limit values.

Adult↗

PubMed2001

Biological monitoring and exposure to mercury.

Occupational health professionals' interest in controlling mercury (Hg) exposure, and the use of biological monitoring in this context, has been ongoing for a number of years. Evidence from urinary Hg results in a number of UK firms who have undertaken some form of biological monitoring or occupational health surveillance suggest that exposure has decreased over the last 10-15 years. This decrease precedes the establishment in the UK of an advisory biological monitoring guidance value (HGV) for urinary Hg and the production of updated medical guidance from the Health & Safety Executive on Hg exposure (MS12 1996). This latter document recommends a urinary sampling interval for urinary Hg of between 1 and 3 months, which is consistent with the reported toxicokinetics of Hg excretion, but we highlight that urinary Hg represents integrated exposure over many previous months. Mercury is a recognized nephrotoxin and MS12 1996 mentions the use of regular dipstick protein estimations. We review our experience of investigating proteinuria and enzymuria in a large-scale cross-sectional occupational study. The incidence of Hg-induced renal disease is probably very rare at current exposure levels. Therefore acceptance of a high false-positive rate of proteinuria not related to Hg exposure needs to be considered in any urinary protein testing regime of Hg workers. The establishment of an HGV for urinary Hg has raised questions about the uncertainty associated with a urinary Hg result, including factors such as diurnal variation, whether urine correction by creatinine or specific gravity is preferable and the possibility of non-occupational sources of Hg contributing significantly towards breaching the HGV. Correction of urinary Hg results by creatinine or specific gravity and the use of a fixed sampling time, such as the beginning or end of the day, substantially reduce the uncertainty in a urinary Hg measurement. But even with good laboratory precision, an individual with a true urinary Hg excretion of 20 nmol/mmol creatinine could supply urine samples of between 14 and 26 nmol/mmol creatinine. The influence of dietary sources in the UK contributing to urinary Hg values approaching or exceeding the HGV is unlikely. The use of tribal or ethnic cosmetics and remedies needs to be considered if a urinary Hg result looks inappropriately high, as some such preparations have been found to contain Hg and can be absorbed through the skin. The ability of excessive chewers or teeth grinders who have a large number of dental amalgam fillings to breach the urinary HGV in the absence of substantial occupational Hg exposure has been reported in a few Scandanavian studies. We report here a likely case of this phenomenon. Since the establishment of the HGV, our biological monitoring Hg data from a number of industry sectors using inorganic or metallic Hg have suggested that a minority of samples (13%) are still greater than the HGV.

Cross-Sectional Studies↗

PubMed2004

Comparison of unchanged n-hexane in alveolar air and 2,5-hexanedione in urine for the biological monitoring of n-hexane exposure in human volunteers.

INTRODUCTION AND AIM: Biological monitoring of n-hexane (HEX) is based on the measurement of urinary 2,5-hexanedione (2,5-HD). In 2001, the American Conference of Governmental Industrial Hygienists modified the biological exposure index (BEI) for HEX and suggested measuring free urinary 2,5-HD (without hydrolysis) (3.5 micromol/l) instead of total 2,5-HD (acid hydrolysis). This BEI value was derived from four field studies that involved worker exposures to variable concentrations of HEX and other solvents. This study was undertaken to characterize, for 5 consecutive days, the relationship between HEX exposure (25 ppm and 50 ppm) and (1). 2,5-HD urinary excretion and (2). HEX in alveolar air. METHODS: Five volunteers (three women, two men) were exposed to HEX in an exposure chamber for 2 non-consecutive weeks (7 h/day). They were exposed to 50 ppm HEX, during the first week and to 25 ppm during the second week. Alveolar air and urine samples were collected at different intervals before, during and after the exposures. The concentration of unchanged HEX in alveolar air and the concentration of urinary 2,5-HD under three analytical conditions (with acid, or enzymatic hydrolysis and without hydrolysis) were measured. RESULTS: The results show that the mean concentrations of HEX in alveolar air were 18 ppm (25 ppm) and 37 ppm (50 ppm), which indicates that approximately 73% of inspired HEX was expired unchanged in alveolar air by the volunteers. The mean (+/- SD) concentrations of urinary 2,5-HD for the last 4 h of exposure at the end of the week (day 5) following exposure to 50 ppm HEX were 30.4 micromol/l (+/-7.8 micromol/l) (acid hydrolysis); 5.8 micromol/l (+/-1.0 micromol/l) (enzymatic hydrolysis); 6.2 micromol/l (+/-0.9 micro mol/l) (without hydrolysis). Following the volunteers' exposure to 25 ppm HEX, the urinary excretion concentrations were 15.2 micromol/l +/- 1.9 micromol/l, 3.1 micromol/l +/- 0.7 micromol/l and 3.7 micromol/l +/- 0.5 micromol/l, respectively. CONCLUSION: Both free urinary 2,5-HD and HEX in alveolar air measurements could be used for the biological monitoring of HEX. Between these two indicators, HEX in alveolar air is less variable than 2,5-HD in urine, but the sampling time is more critical. Therefore, biological monitoring of HEX based on the measurement of free urinary 2,5-HD is preferable to HEX in alveolar air. Additionally, we believe that the 2,5-HD values reported in this study better reflect the actual levels of exposure to HEX alone than what has been previously reported in studies that involved co-exposure to other solvents, and that the current BEI value for HEX is most likely more protective than what has been believed up until now.

Adult↗

PubMedDate not supplied

[Role of biological monitoring in health and epidemiological surveillance: a proposal].

Biological markers can be used at an individual level for medical surveillance or at group level within the context of epidemiological surveillance. However, the use of biological monitoring for medical and epidemiological surveillance is heavily conditioned by the critical issue of biomarker validation. One effective means for combining biological monitoring with medical and epidemiological surveillance is the mandatory annual report on anonymous and collective data; this will be made possible after providing adequate training schemes for the occupational physicians involved and the definition of appropriate guidelines, aimed at improving the quality of occupational health services. It will then be possible to design multicentric surveys to assess the quality of occupational health services using validated indicators.

Environmental Monitoring↗

PubMed1993

Application of thermal desorption to the biological monitoring of organic compounds in exhaled breath.

We have developed a thermal desorption-gas chromatographic method for the analysis of organic compounds in exhaled breath air, to be used in the biological monitoring of environmental exposure. The exhaled breath sampler is based on the concentration of compounds present in alveolar air in a solid sorbent material. Isoflurane (1-chloro-2,2,2-trifluoroethyl-difluoromethyl-ether), an inhaled anaesthetic used widely in surgery, and styrene, used in boat construction and the manufacture of fibreglass-reinforced plastics, are partially eliminated from the body in exhaled breath, samples of which can therefore be used to monitor biological exposure to these two organic compounds. Recoveries were tested in controlled atmospheres of isoflurane or styrene, with Chromosorb 106 or Tenax, respectively, as the adsorbent. We also investigated the influence of relative humidity, an important factor in breath sampling, on adsorption.

Air↗

PubMed1996

Biological monitoring of deltamethrin exposure in greenhouses.

This study examined the possibility of using biological monitoring to assess deltamethrin exposure among greenhouse workers. The synthetic pyrethroid deltamethrin was sprayed in five greenhouses by cold for generators, and the exposure was biologically monitored by analysing the concentration of its metabolite, 3-phenoxybenzoic acid, by a gas chromato-graphic method after derivatization with pentafluorobenzyl bromide. 3-Phenoxybenzoic acid was found in the urine of two of the ten workers studied. The urine concentration of the metabolite varied from 2.4 to 51.7 micrograms/l. These results show that 3-phenoxybenzoic acid is suitable for biological monitoring for the assessment of exposure to deltamethrin.

Adult↗

PubMed1993

On the need of a sampling strategy in biological monitoring: the example of hexane exposure.

Ambient and biological monitoring of hexane exposure were repeatedly carried out in 14 female shoe makers. Airborne hexane (Ci-H) was measured in 4-h samples collected by a diffusive method. Urinary spot samples were collected before, during (at noon), and at the end of a work shift. 2,5-Hexanedione (2,5HD) in urine collected at noon was poorly related to morning Ci-H. End-of-shift 2,5HD were also poorly related to afternoon air samples. The correlation was still relatively low when end-of-shift 2,5HD was related to 8-h TWA Ci-H (r = 0.44; P < 0.01 on a linear scale, and r = 0.58, P < 0.01 on a log-log scale). End-of-shift 2,5HD levels estimated on the basis of pre-shift values using a mathematical model were much higher (2.3 times on average) than those experimentally measured during the study period. Owing to its relatively long half-time, 2,5HD seems to be influenced not only by current exposure, but also by hexane absorbed during the day(s) preceding sampling. The lack of a sampling strategy may account not only for inconsistencies between environmental and biological data, but also for a possible misuse of biological monitoring when utilized for risk assessment. Despite sometimes poor correlations with Ci-H, 2,5HD may still be preferred to other indicators as a marker of effective internal dose. A sampling strategy should ensure that measured values are representative of the individual risk for adverse effects.

Adult↗

PubMedDate not supplied

The biological monitoring of inhalation anaesthetics.

The biological monitoring of inhalation anaesthetics. Occupational exposure to inhalation anaesthetics is an undesired consequence of the work in the operating theatre. Anaesthesia is currently practised using nitrous oxide associated with one or more potent anaesthetics (halothane, enflurane, isoflurane). In the present study we evaluated the occupational exposure to inhalation anaesthetics during anaesthesia in 190 operating theatres of 41 hospitals in Italy. Nitrous oxide, halothane, enflurane, isoflurane were detected in the urine of 1521 exposed subjects (anaesthetists, surgeons and nurses). Significant correlations were found between the anaesthetic concentrations in urine produced during the shift (Cu) and anaesthetic environmental concentrations (CI). The results show that the urinary anaesthetic concentration can be used as an appropriate biological exposure index. The biological threshold values (urinary concentration values) proposed are the following: nitrous oxide, 15, 28 and 57 micrograms/L for an environmental exposure of 25, 50 and 100 ppm respectively; halothane, 97 micrograms/L (for an environmental exposure of 50 ppm), 6.1 micrograms/L (for an environmental exposure of 2 ppm) and 3.3 micrograms/L (for an environmental exposure of 0.5 ppm); enflurane, 145 micrograms/L (for an environmental exposure of 50 ppm), 22.7 micrograms/L (for an environmental exposure of 10 ppm), 3.7 micrograms/L (for an environmental exposure of 1 ppm); isoflurane, 5.3 micrograms/L (for an environmental exposure of 2 ppm) and 1.8 micrograms/L (for an environmental exposure of 0.5 ppm). These values apply to urine samples collected at the end of 4-hours' exposure to the anaesthetics.

Anesthetics, Inhalation↗

PubMed1984

Biological monitoring of lead effects in a smelter community before and after emission control.

Biological monitoring of lead effects in specific population groups living in the vicinity of a lead smelter has been followed up after effective emission control, in order to estimate the length of time necessary before the characteristic indicators of increased lead absorption normalize. The period established could be a realistic basis for predicting the time necessary to elapse before a lead contaminated area can be proclaimed as safe for normal living. Three groups of subjects were examined: preschool children, school children and mothers. The biological monitoring included the measurement of delta-aminolevulinic acid dehydratase activity (ALAD) and the concentration of zinc-protoporphyrin (ZPP), blood lead (Pb-B) and hemoglobin (Hb). The results obtained demonstrated a gradual normalization of the characteristic indicators of lead absorption, although they were still outside corresponding values in the control group even four years after the installation of effective emission control. These findings emphasize the advantages of biological monitoring over environmental for objective assessment of internal and external lead exposure following effective engineering control of the emission source.

Adolescent↗

PubMed1993

Biological monitoring of exposure to mercury vapor.

Biological monitoring of mercury in whole blood (B-Hg) or urine (U-Hg) can be used to assess exposure to mercury vapor if the kinetics and other sources of variation are taken into account. Its rapid rise postexposure makes B-Hg a good indicator of recent exposure peaks, while U-Hg (corrected for urinary flow rate) reflects average long-term exposure. However, high intraindividual variation sometimes requires the average of several U-Hg determinations. In the general population, methylmercury from fish and mercury from dental amalgam influence B-Hg and U-Hg, respectively, and must be considered if other exposures are being monitored. The quantitative relations between mercury in biological fluids and critical organs are poorly understood. Monitoring U-Hg is useful for assessing the risk of adverse effects and the need for preventive measures. At average U-Hg levels of about 50 micrograms.g creatinine-1 (28 nmol.mmol creatinine-1) the prevalence of symptoms and slight objective changes in the central nervous system and the excretion of certain urinary proteins are increased.

Air Pollutants↗

PubMed1989

Biological monitoring and our water resources.

Biological monitoring is a means of assessing water quality, or the toxicity of chemicals, employing living organisms as the sensors. Relatively recent environmental regulations have led to the application of biomonitoring techniques by wastewater discharges and chemical manufacturers. Classical approaches to biomonitoring have included the acute bioassay which takes death as the end-point of the test. Recent developments include automated and real time biomonitors which utilize computer technologies for assessing changes in physiological or behavioural parameters to indicate the presence of toxics.

Animals↗

PubMed1995

Medical screening and biological monitoring. A guide to the literature for physicians.

The use of medical screening and biological monitoring has seen substantial changes in the past two decades specifically in the provision of occupational medical services. For example, national surveys of workplaces conducted by the National Institute for Occupational Safety and Health (NIOSH) showed that the provision of off-site medical care to workers increased from 19.6% in 1972-1974 to 57.8% in 1981-1983, although the percent of workers receiving on-site services remained stable during the same period. After a recent survey in 1990-1991, the Occupational Safety and Health Administration (OSHA) estimated that 6.3% of US industries have a medical surveillance program at their individual establishment. We reviewed NIOSH documents, OSHA's Code of Federal Regulations, and texts on biological monitoring and medical screening for recommendations on medical surveillance of workers. This report summarizes the medical tests (including biologic monitoring) recommended or used by independent investigators and by the government for OSHA-regulated substances to provide guidance to physicians and occupational health professionals in accessing the pertinent literature; the utility of the recommendations is not evaluated.

Environmental Monitoring↗

PubMed1997

Korean analytical quality assurance (KAQUA) program for biological monitoring.

The Korean analytical quality assurance (KAQUA) program on biological monitoring was performed by the Industrial Health Research Institute in Korea in spring, 1995. The object of the KAQUA program is to improve the analysis capability for the biological monitoring of hazardous chemicals and to confirm the reliability of data from each laboratory. The items chosen for the first round were analyses of lead in blood (PbB) and of hippuric acid in urine (HAU). Eighty-eight laboratories in Korea participated in this program. Two levels of samples, randomly chosen among six levels for each item, were sent to the participants. The consensus value from participants and reference laboratories was determined by statistical analysis and used as a reference value. The tolerance range was +/-15% (+/-6 micrograms/dl for PbB below 40 micrograms/dl) of the reference value. The mean proficiency rate of analytical data increased dramatically in the first round compared with a pre-round that was provided as part of a training course for participants before performing the first round. The mean proficiency rate of PbB was 69% at pre-round and increased at 91% at the first round; for HAU the increase was from 58% to 88%. Not only the analytical results but also raw data were reviewed to find problems which might have arisen during the analytical process. Re-education courses provided after final evaluation of each participant by means of telephone discussion, correspondence course, and experimental practice, were helpful in achieving the purpose of the analytical quality assurance program.

Chemistry, Clinical↗

PubMed1997

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

OBJECT: Ambient air and biological monitoring of an occupational toluene exposure was carried out on a group of 33 workers. METHOD: The biological monitoring of the workers was based on determination of the concentration of toluene in blood and on quantification of the urinary metabolites o-cresol and hippuric acid. All blood and urine samples were collected post-shift. RESULTS: The average toluene concentration in the workplace air was 65 ppm, ranging from 13 to 151 ppm. AN average concentration of toluene in the blood of 911 microns/1 was found, corresponding to an average urinary concentration of 2.9 mg/1 (2.3 mg/g creatinine) o-cresol and 2.4 g/l (1.9 g/g creatinine) hippuric acid. Both urinary metabolites can be correlated with the concentration of toluene in ambient air and blood, respectively. CONCLUSIONS: The results of our study indicate that the determination of the urinary o-cresol excretion represents a diagnostically specific and sensitive parameter for the estimation of an individual toluene uptake. In contrast, monitoring of the concentration of hippuric acid in urine cannot be recommended for assessment of individual exposure. To set up a biological tolerance value (BAT) for o-cresol, a urinary concentration of 3 mg/l o-cresol should be in accordance with the current MAK value of 50 ppm toluene.

Air Pollutants, Occupational↗