Guidance values for the biomonitoring of occupational exposure. State of the art.

Biomonitoring was developed for the assessment of the health risks from exposure to chemicals at work, and the approaches and concepts of biomonitoring are derived from such exposures. At present, biomonitoring is increasingly used also to assess exposure from the environment. Biomonitoring and assessment of external exposure are complementing activities, where the exposure assessments are much more widely applied, especially when the number of chemicals concerned is considered; environmental analysis also offers the distinct advantage of speciation analysis--which is very poorly developed for biomonitoring. Biomonitoring on the other hand provides information on exposure from all sources, and via all absorption routes, and considers also accumulation of the chemical in the body. Bio monitoring using exposure biomarkers thus consider interindividual differences in the absorption, while use of effec biomarkers ideally also considers interindividual differences in sensitivity. Few effect biomarkers, however, have been validated. The major challenges of biomonitoring are the development of monitoring methods, which are inexpensive enough to be applied at a frequency that makes possible meaningful biomonitoring of chemicals with a short half-time; development of exposure biomarker guidance values specific to individual species of different metals; ex pansion of the repertoire of validated effect biomarkers; and validation and application to effect monitoring of the omic technologies. Another major challenge is a reconsideration of the basis of biomonitoring action limits to reflec the change in the work place: Biomonitoring should be adapted to assist in the generation of a healthy workplace which is capable of attracting workers, and assist them to perform their work effectively--rather than just to guarantee absence of serious health effects.

Vinyl chloride: still a cause for concern.

Vinyl chloride (VC) is both a known carcinogen and a regulated chemical, and its production capacity has almost doubled over the last 20 years, currently 27 million tons/year worldwide. According to recent reports it is still a cause for concern. VC has been found as a degradation product of chloroethylene solvents (perchloroethylene and trichloroethylene) and in landfill gas and groundwater at concentrations up to 200 mg/m(3) and 10 mg/L, respectively. Worldwide occupational exposure to VC still seems to be high in some countries (e.g., averages of approximately 1,300 mg/m(3) until 1987 in one factory), and exposure may also be high in others where VC is not regulated. By combining the most relevant epidemiologic studies from several countries, we observed a 5-fold excess of liver cancer, primarily because of a 45-fold excess risk from angiosarcoma of the liver (ASL). The number of ASL cases reported up to the end of 1998 was 197 worldwide. The average latency for ASL is 22 years. Some studies show a small excess risk for hepatocellular carcinoma, and others suggest a possible risk of brain tumors among highly exposed workers. Lung cancer, lymphomas, or leukemia do not seem to be related to VC exposure according to recent results. The mutation spectra observed in rat and human liver tumors (ASL and/or hepatocellular carcinoma) that are associated with exposure to VC are clearly distinct from those observed in sporadic liver tumors or hepatic tumors that are associated with other exposures. In rats, the substitution mutations found at A:T base pairs in the ras and p53 genes are consistent with the promutagenic properties of the DNA adduct 1,N(6)-ethenoadenine formed from VC metabolites. Risk assessments derived from animal studies seem to overestimate the actual risk of cancer when comparing estimated and reported cases of ASL.

IPCS guidelines for the monitoring of genotoxic effects of carcinogens in humans. International Programme on Chemical Safety.

The purpose of these guidelines is to provide concise guidance on the planning, performing and interpretation of studies to monitor groups or individuals exposed to genotoxic agents. Most human carcinogens are genotoxic but not all genotoxic agents have been shown to be carcinogenic in humans. Although the main interest in these studies is due to the association of genotoxicity with carcinogenicity, there is also an inherent interest in monitoring human genotoxicity independently of cancer as an endpoint. The most often studied genotoxicity endpoints have been selected for inclusion in this document and they are structural and numerical chromosomal aberrations assessed using cytogenetic methods (classical chromosomal aberration analysis (CA), fluorescence in situ hybridisation (FISH), micronuclei (MN)); DNA damage (adducts, strand breaks, crosslinking, alkali-labile sites) assessed using bio-chemical/electrophoretic assays or sister chromatid exchanges (SCE); protein adducts; and hypoxanthine-guanine phosphoribosyltransferase (HPRT) mutations. The document does not consider germ cells or gene mutation assays other than HPRT or markers of oxidative stress, which have been applied on a more limited scale.

Safety of pyrethroid-treated mosquito nets.

The use of insecticide treated nets (ITNs) for personal protection against malaria vector Anopheles mosquitoes (Diptera: Culicidae) has become popular during the past decade. With the precautions outlined in this paper, field use of pyrethroids--at concentrations recommended for treatment of mosquito nets--poses little or no hazard to people treating the nets or to users of the treated nets. With frequent exposure to low concentrations of pyrethroids, the risk of toxicity of any kind is remote. Pyrethroids entering the systemic circulation are rapidly metabolized to much less toxic metabolites. Toxicologically, pyrethroids have a useful characteristic--the production of skin paraesthesia--which gives an early indication of exposure. This reversible symptom of exposure is due to transient stimulation of peripheral sensory nerves and not a toxic effect. In the retail market, for home use, the provision of proper packaging and labelling, with clear instructions on safe and effective use of the product are most important. Because many domestic users of pyrethroid 'home treatment kits' for ITNs may not be fully literate, it is essential that 'instructions for use' should be portrayed via pictograms with supporting text in appropriate local language(s).

Exposure and effect monitoring: a critical appraisal of their practical application.

The prerequisite for the use of biomarkers of exposure as indicators of health risk is that the relationship between the biomarker and the health effects and the representation in time of the biomarker level are known. Some exposure biomarkers may be applied for the quantitative assessment of the amount of exposure. In this task, the half-time of the parameter measured is crucial, since it determines what length of time of exposure the result reflects. For reliable assessment of the exposure the species (e.g. metal, oxide or salt) has to be known. For some chemicals the estimation of exposure from biomonitoring is based on several studies with uniform results and is quite reliable, while for others the uncertainty is wide. Exposure biomarkers have been successfully used in the identification of exposed individuals and follow-up of exposure. For example, macromolecule adducts and mutagenicity in urine have been successfully applied to the identification of workers exposed to carcinogens and as indicators of changes of exposure. Biomarkers of renal effects of cadmium, lead effects on haemoglobin synthesis and organophosphate effects on cholinesterase activities have been well validated and are widely used in routine monitoring activities. However, effect markers for lead and cadmium offer little advantage over the analysis of the chemical itself and where accurate metal analysis is readily available, they have a limited use today. For the analysis of chromosomal aberrations, limited data are available suggesting that elevated frequencies may indicate a carcinogenic risk. In several instances, genotoxic effect monitoring has been used to identify groups of people exposed to hazardous chemicals and in the follow-up of improvements in industrial hygiene.

Biomarkers and their use in occupational medicine.

Biomarkers of exposure, parent chemicals, metabolites, and also hemoglobin and DNA (deoxyribonucleic acid) adducts, even urinary mutagenicity, have been used successfully to identify exposed persons, follow-up exposure, and quantitatively assess exposure. Some have been validated as indicators of health risk. The avenues for future biomarkers of exposure are in the development of robust, simple, and inexpensive semiquantitative methods for daily use on every worker for assuring that no (excessive) exposure takes place. Some biomarkers of effect have also been well validated and are widely used in routine monitoring activities. However, with the exception of cholinesterase inhibitors, biomarkers of effect offer little advantage over the analysis of the chemical itself. Their use will be limited to carefully planned ad hoc studies. Biomarkers of susceptibility currently have no practical application in worker health protection. Biomarker research should concentrate on validating methods, in terms of the prediction of health effects, and on elucidating exposure-biomarker concentration relationships.

Exposure to methyl tert-butyl ether and tert-amyl methyl ether from gasoline during tank lorry loading and its measurement using biological monitoring.

OBJECTIVE AND METHODS: The exposure of Finnish tank lorry drivers to methyl tert-butyl ether (MTBE) and tert-amyl methyl ether (TAME) during loading of gasoline was studied using biological and breathing-zone sampling. During the field measurements in October 1994 and August 1995 the gasolines (95, 98, 99 RON) contained MTBE to 5.2-11.8% and TAME to 0-6%. RESULTS: The geometric mean (GM) breathing-zone concentration of MTBE was 4.3 mg/m3 (n = 15) in October and 6.4 mg/m3 (n = 20) in August. The GM concentration of TAME, measured only in August, was 0.98 mg/m3. The mean loading/sampling times were 37 and 35 min, the mean wind speeds were 0.8 and 0.6 m/s, and the mean air temperatures were -4.9 degrees and + 14.1 degrees C, respectively. Blood samples collected on average at 20 min after gasoline loading/exposure showed an MTBE concentration of 143 nmol/l (GM, n = 14) in October and 213 nmol/l (GM, n = 20) in August. Pearson's coefficient of correlation (r) between the MTBE breathing-zone concentrations and MTBE in blood was 0.86 (P = 0.0001) in October and 0.81 (P = 0.00001) in August. No correlation was found between MTBE in air and the metabolite tert-butanol (TBA) in blood. MTBE, but not TBA, in urine samples collected on average at 2.5 h after exposure showed a correlation with MTBE in air. The concentrations of TAME and its metabolite tert-amyl alcohol were below the quantitation limits ( < 7 and < 100 nmol/l, respectively) in most blood and urine samples. CONCLUSIONS: The breathing-zone measurements showed low levels of exposure to the two oxygenates, the concentrations being well below the current hygienic standards for MTBE (250-360 mg/m3 for 15 min and 90-180 mg/m3 for 8 h). The linear correlations obtained for MTBE suggest that MTBE in blood or urine can be adopted as a valid biological exposure index.

Occupational exposure to lead and neuropsychological dysfunction.

OBJECTIVE: To evaluate the neuropsychological effects of current low level and previous higher levels of exposure to lead and evaluate the relation between effects of lead and bone lead. METHODS: A neuropsychological test battery was given to 54 storage battery workers with well documented long term exposure to lead. The effect was studied in two subgroups: those whose blood lead had never exceeded 2.4 mmol/l (the low BPbmax group, n = 26), and those with higher exposure about 10 years earlier (the high BPbmax group, n = 28). In both groups, the recent exposure had been low. Correlations between the test scores and the indices of both long term and recent exposure--including the content of lead in the tibial and calcaneal bone--and covariance analyses were used to assess the exposure-effect relation. Age, sex, and education were controlled in these analyses. RESULTS: Analyses within the low BPbmax group showed a decrement in visuospatial and visuomotor function (block design, memory for design, Santa Ana dexterity), attention (digit symbol, digit span), and verbal comprehension (similarities) associated with exposure to lead and also an increased reporting of subjective symptoms. The performance of the high BPbmax group was worse than that of the low BPbmax group for digit symbol, memory for design, and embedded figures, but there was no reporting of symptoms related to exposure, probably due to selection in this group. No relation was found between the output variables and the tibial lead concentration. The calcaneal lead concentrations were related to the symptoms in the low BPbmax group. CONCLUSIONS: Neuropsychological decrements found in subjects with high past and low present exposure indicate that blood lead concentrations rising to 2.5-4.9 mmol/l cause a risk of long lasting or even permanent impairment of central nervous system function. Milder and narrower effects are associated with lower exposures; their reversibility and time course remain to be investigated. History of blood lead gives a more accurate prediction of the neuropsychological effects of lead than do measurements of bone lead.

Update of cancer incidence among workers at a copper/nickel smelter and nickel refinery.

OBJECTIVES: To assess cancer risk among nickel-exposed workers. METHODS: We updated cancer incidence among 1388 workers employed for at least 3 months at a copper/nickel smelter and nickel refinery in Harjavalta, Finland. There were 1155 workers exposed to nickel during the period 1960-1985 in the smelter (566 workers), repair shop (239 workers), or refinery (418 workers). Cancer incidence was followed through the files of the Finnish Cancer Registry up to 31 December 1995. For overall cancer and for a priori selected specific cancer types the ratio of observed to expected numbers of cases was computed as a standardized incidence ratio (SIR), controlled for age, gender, and calendar period and using the region-specific rates as a reference. RESULTS: The overall cancer incidence among both nickel-exposed and unexposed subcohorts was at the expected level. A small increase in lung cancer incidence, which reached statistical significance among workers with a latency exceeding 20 years, was observed among the smelter workers exposed to insoluble nickel compounds. Among workers in the refinery, who were exposed primarily to nickel sulfate at levels below 0.5 mg/m3 as well as to low concentrations of other nickel compounds, there was an increased risk for nasal cancer (SIR 41.1, 95% CI 4.97-148), positively associated with latency and duration of employment, and an excess risk for stomach (SIR 4.98, 95% CI 1.62-11.6) and lung (SIR 2.61, 95% CI 0.96-5.67) cancers. CONCLUSIONS: Since elevated nasal and lung cancer risks were confined to the refinery, where the primary exposure was to nickel sulfate, it is likely that nickel sulfate is mainly responsible for the elevated respiratory cancer risk. We cannot rule out whether the excess stomach cancer risk is a chance finding, or related to the working environment.

Exposure of gasoline road-tanker drivers to methyl tert-butyl ether and methyl tert-amyl ether.

Organic oxygenates, namely, methyl tert-butyl ether (MTBE) and methyl tert-amyl ether (MTAE), are added to gasoline to reduce carbon monoxide in exhausts and to enhance the octane number. The aim of this study was to investigate road-tanker drivers' exposure to oxygenate vapors during road-tanker loading and unloading as well as to evaluate the measurements of these ethers and their metabolites in the urine as a means of assessing the uptake of the ethers. A total of 11 drivers in different parts of Finland were trained to monitor their exposure with personal samplers, to report their working conditions, and to collect their whole-day urine samples. Charcoal tubes of the air samples were analyzed for MTBE, MTAE, benzene, toluene, and aliphatic hydrocarbons. For biological monitoring purposes the two main oxygenates, tertiary ethers MTBE and MTAE, as well as their main metabolites, tertiary alcohols tert-butanol (TBA) and tert-amyl alcohol (TAA), were determined in urine specimens. On average the drivers were exposed to vapors for short periods (21 +/- 14 min) three times during a work shift. The mean concentrations of MTBE and MTAE (mean +/- SD) were 8.1 +/- 8.4 and 0.3 +/- 0.4 mg/m3. The total MTBE uptake during the shift was calculated to be an average of 106 +/- 65 mumol. The mean concentrations of MTBE, TBA, MTAE and TAA detected in the first urine after the work shift were 113 +/- 76, 461 +/- 337, 16 +/- 21, and 40 +/- 38 nmol/l, and those found the next morning, 16 h later, were 18 +/- 12, 322 +/- 213, 9 +/- 10, and 20 +/- 27 nmol/l. The good relationship (r = 0.84) found between MTBE exposure and postshift excretion suggests that urinary MTBE can be used for biological monitoring of exposure, but at the present low level of exposure the corresponding metabolite TBA is not equally reliable. The determination of MTAE and its metabolite TAA in urine is sensitive enough to detect the low degree of exposure to MTAE, but in this study the data were too scarce to allow calculation of the correlations due to very low levels of MTAE exposure.

Effects of low level exposure to lead on neurophysiological functions among lead battery workers.

OBJECTIVES: Assessment of neurophysiological functions in workers with low level exposure to lead and evaluation of the efficacy of bone lead measurements in the prediction of effects of lead. METHODS: Exposure to lead of 60 workers from a lead battery battery factory was estimated from historical blood lead measurements and analysis of lead in the tibial and calcaneal bones with x ray fluorescence. Peripheral and central nervous system functions were assessed by measuring conduction velocities, sensory distal latencies, sensory amplitudes, and vibration thresholds as well as by quantitative measurement of the absolute and relative powers and mean frequencies of different electroencephalograph (EEG) channels. RESULTS: Sensory amplitudes, and to a smaller degree sensory or motor conduction velocities, showed a negative correlation with long term exposure to lead, most clearly with integrated blood lead concentration and exposure time. Vibration thresholds measured in the arm were related to recent exposure to lead, those measured in the leg to long term exposure. The alpha and beta activities of the EEG were more abundant in subjects with higher long term exposure to lead. Calcaneal lead content reflected short term exposure, tibial lead content reflected long term exposure. Blood lead history showed a closer relation with effects of lead than the tibial or calcaneal lead concentrations. CONCLUSIONS: Vibratory thresholds, quantitative EEG, and to a smaller extent the sensory amplitude, provide sensitive measures of effects of lead in occupationally exposed adults. Most accurate estimates of health risks induced by lead can be obtained from a good history of blood lead measurements. If such a history of blood lead concentrations is not available, analysis of bone lead may be used for the assessment of health risks.

Biological monitoring of exposure to benzene in the production of benzene and in a cokery.

The purpose of this study was to compare different biological methods in current use to assess benzene exposure. The methods involved in the study were: benzene in blood, urine and exhaled air, and the urinary metabolites t,t-muconic acid (MA) and S-phenylmercapturic acid (S-PMA). Blood, urine and exhaled air samples were collected from workers in a benzene plant (pure benzene exposure) and cokery (mixed exposure, e.g. polycyclic aromatic hydrocarbons--PAHs) in an Estonian shale oil petrochemical plant. The benzene in these samples was analysed with a head-space gas chromatograph, and the metabolites MA and S-PMA with a liquid chromatograph using methods developed from published procedures. Some of the values measured in the Estonian shale oil area were high in comparison with those published during the last few years, whereas the values measured in the control group did not show any exposure to benzene except in the smokers group. The highest median exposure was in the benzene factory, 0.9 cm3/m3 TWA (2.9 mg/m3) and the highest individual value was 15 cm3/m3 TWA (49 mg/m3). All biological measurements in this study gave the same assessment about exposure to benzene and correlated highly significantly with each other and with the air measurements (r = 0.8 or more). In the benzene factory the correlation was good even when calculated from samples with air concentration < 1 cm3/m3 (3.2 mg/m3) in the case of blood benzene and urinary MA. However, for S-PMA it was weak (r = 0.4) and for benzene in urine and exhaled air it did not exist any more. In the cokery, with mixed exposure, the correlation at low levels was weaker even for blood benzene and urinary MA (r = 0.6). According to the results in the benzene factory the exposure to pure benzene at the level 1 cm3/m3 (3.25 mg/m3) TWA gave: the blood benzene value about 110 nmol/l (8.6 micrograms/l), MA 23 mumol/l (3.3 micrograms/l) or 2.0 mg/g creatinine, S-PMA 58 micrograms/g creatinine or 0.4 mumol/l (95.7 micrograms/l), benzene in urine 499 nmol/l (39 micrograms/l), and benzene in the exhaled air 2.8 nmol/l (0.2 microgram/l). In general, the measurement of benzene in blood and in exhaled air, as well as benzene and its metabolites MA and S-PMA in urine, all gave similar results. However, at low exposure level (< 1 cm3/m3) the most reliable analyses were MA in urine and benzene in blood.

Analysis of aluminium in serum and urine for the biomonitoring of occupational exposure.

A reliable and sensitive graphite furnace atomic absorption spectrometry (GFAAS) method with Zeeman background correction was developed for the analysis of aluminium in serum and urine in the biological monitoring of aluminium exposure. The method is based on platform atomisation in pyrolytically coated graphite tubes after fourfold dilution with nitric acid. For serum analysis, a matrix matched standard curve is prepared and for urine the method of standard additions is used. The within-run imprecision (C.V.) for serum and urine was 3% and 5%, and the between-day imprecision, 6% and 7.2%, at a concentration level of 4.0 mumol/l. The between-day imprecision for urinary aluminium was 15.7% at a concentration level of 0.24 mumol/l. The detection limits were 0.02 mumol/l for serum and 0.07 mumol/l for urine. During 1 year of participation in TEQAS external quality assessment scheme of the Robens Institute for Health and Safety (Guildford, UK) for serum aluminium the maximum cumulative performance score was achieved. For urinary aluminium a certificate in the external quality control scheme of the German Society of Occupational Medicine was obtained. The mean concentration of aluminium in a non-exposed population, who did not use antacid drugs, was 0.06 mumol/l (S.D. 0.03, range 0.02-0.13, n = 21) in serum, and 0.33 mumol/l (S.D. 0.18, range 0.07-0.82, n = 44) in urine. The upper reference limit for aluminium in a healthy, non-exposed population was estimated to be 0.1 mumol/l in serum and 0.6 mumol/l in urine.

Exposure to soluble nickel in electrolytic nickel refining.

Past and present exposure to nickel was studied in an electrolytic nickel refinery, where an increased incidence of nasal cancer had been reported, using nickel analyses in air, blood and urine. Genotoxic effects were studied using analysis of micronuclei from acridine orange-stained smears from the buccal mucosa of the workers. Workers used respirators or masks in tasks where the exposure was expected to be high. Inside the mask, nickel concentrations were 0.9-2.4 micrograms m-3 in such tasks. In those tasks where masks were not used, nickel concentrations in the breathing zone were 1.3-21 micrograms m-3. Air-borne nickel concentrations (stationary sampling) varied between 230 and 800 micrograms m-3 in 1966-1988 with no systematic change; thereafter lower concentrations (170-460 micrograms m-3) have been observed. After-shift urinary concentrations of nickel were 0.1-2 mumol l-1; they showed no correlation with nickel concentrations in the air. Concentrations of nickel in the urine were still elevated after a 2-4 week vacation. The frequency of micronucleated epithelial cells in the buccal mucosa of nickel refinery workers was not significantly elevated by comparison with referents. No relationship was observed between micronucleus frequencies and levels of nickel in air, urine or blood.

Occupational exposure to nickel salts in electrolytic plating.

An occupational hygiene survey was made in 38 nickel plating shops in Finland and exposure to nickel was studied by means of biological measurements and, in three shops, by using air measurements. The average after-shift urinary nickel concentration of 163 workers was 0.16 mumol l.-1 (range 0.001-4.99 mumol l.-1). After the 1-5 week vacation the urinary nickel concentration was higher than the upper reference limit of non-exposed Finns indicating that a part of water-soluble nickel salts is accumulated in the body. Urinary nickel concentrations in the shops considered clean in the industrial hygiene walk-through were not different from those observed in the shops considered dirty. The correlation between the concentrations of nickel in the air and in the urine was low, and the amount of nickel excreted in the urine exceeded the calculated inhaled amounts, indicating exposure by other routes such as ingestion.

Hand dermatitis and allergic patch test reactions caused by nickel in electroplaters.

A worksite survey was conducted in all 38 Finnish electroplating plants. All workers (n = 163) who worked with nickel plating (bath workers, hangers and solution makers) were interviewed with a questionnaire about symptoms of nickel dermatitis, hand dermatitis, and about protective measures, atopy, etc. Patch testing with nickel sulfate was done with the TRUE TestTM method. All the workers, 94 men and 69 women, answered the questionnaire. The mean age of women was 41.1 years, and of men 43.1 years, respectively. Men had longer occupational exposure to nickel (14 years) than women (10 years). Most workers used protective gloves. 35% of women and 30% of men reported present or past hand dermatosis. 19% reported a history of atopic dermatitis. 15% of women (n = 8) and 4% (n = 2) of men had an allergic patch test reaction to nickel sulfate. 70% of those with an allergic patch test reaction to nickel reported past or present hand eczema. The prevalence of nickel allergy among the electroplaters was similar to that of patients in patch test clinics in Finland. An allergic patch test reaction to nickel sulfate does not necessarily oblige an electroplater to change jobs.

Respiratory health of workers exposed to low levels of chromium in stainless steel production.

OBJECTIVES: To determine whether occupational exposure to chromite, trivalent chromium, or hexavalent chromium causes respiratory diseases, an excess of respiratory symptoms, a decrease in pulmonary function, or signs of pneumoconiosis among workers in an integrated chain of stainless steel production. METHODS: This cross sectional study was carried out in 1993 and the inclusion criterion was a minimum of eight years of employment in the same production department. A self administered questionnaire was collected, and spirometry, measurement of diffusing capacity, chest radiography, and laboratory tests were carried out by a mobile research unit. RESULTS: There were 221 workers in the exposure groups and 95 in the control group. The average duration of employment was 18 years. No significant differences in the odds ratios (ORs) of the symptoms were found between the exposure and the control groups. In a logistic regression analysis age and smoking significantly explained the occurrence of most of the respiratory symptoms. The smokers in the chromite group had significantly lower forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and diffusing capacity than the corresponding values of the control group. The analysis of variance between study groups, smoking, and exposure time, without modelling for interactions, showed that the chromite group had lower values for FVC, FEV1, and diffusing capacity than the other groups. The occurrence of small opacities was more frequent on the chest radiographs of the workers in the chromite group. CONCLUSIONS: An average exposure time of 18 years in ferrochromium and stainless steel production and exposure to dusts containing low concentrations of hexavalent or trivalent chromium do not lead to any respiratory changes detectable by lung function tests or radiography nor to any increase in symptoms of respiratory diseases. The lung function values were lower and the occurrence of radiological findings was more frequent among the workers from the chromite mine than among the controls. The difference was partly caused by differences in age and smoking habits, but evidently also partly by higher exposures more than two decades ago or by the fibrous components of the dust.

Quality assurance in occupational and environmental laboratory medicine.

In a medical laboratory service, quality assurance (QA) concerns all those actions necessary to provide confidence that the results of laboratory tests will satisfy defined standards for quality. Taking into account the type of testing concerned and the techniques involved, quality assurance will encompass all steps taken to ensure that laboratory results are reliable. It covers the use of scientifically and technically sound practices for laboratory investigations, including selection, collection, transport, identification, storage, preparation and manipulation of specimens and recording, reporting and interpretation of the results. QA refers also to other activities designed to improve the reliability of investigations such as staff training and management, evaluation of the adequacy of the laboratory environment, maintenance and calibration of instruments and the use of technically validated and properly documented methods. All these activities should be described in a quality manual. This document is a prerequisite to obtain certification of the quality system or laboratory accreditation, according to the International Standard ISO 29000 series or the European Standard EN 45001, respectively.