Biological monitoring of exposure and effects in workers employed in a selenium-processing plant.

PURPOSE: The aim of the study was to assess external and internal selenium exposure and potential biological effects in employees working in a selenium-processing plant. METHODS: Twenty male employees of a selenium-processing plant (exposed) and 20 age-matched male individuals without occupational selenium exposure (controls) participated in the study. Exposure to selenium at the workplace was determined by personal air sampling. Internal exposure was assessed by measuring total selenium concentration in plasma after a workshift and after holidays as well as by measuring the selenium concentration in urine before and after shift and after holidays. The activity of glutathione peroxidase (GPx) in blood and the prothrombin time were determined as biological effect parameters. RESULTS: The exposure to selenium in the workplace air ranged from 8 to 950 µg/m(3) and exceeded in a large part current occupational exposure limits. The selenium levels in plasma samples of the exposed ranged from 49 to 182 µg/L during exposure and were significantly higher than the plasma levels observed after holidays as well as in the control group. The selenium concentration in pre- and post-shift urine samples did not differ significantly, and the average urinary selenium levels of the employees (18-1,104 µg/g creatinine) were significantly higher than those measured after holidays or determined in controls. Both the concentration of selenium in plasma and in urine did not correlate with the current external exposure of the employees at the workplace. However, we found a strong and significant association between the two biomonitoring parameters. In spite of the considerable high external exposure to elemental selenium, we did not find any effect on the GPx activity in blood as well as on the prothrombin time. CONCLUSIONS: Both the selenium levels in plasma and urine may be used as biological monitoring parameters for the assessment of chronic occupational exposure to selenium. Nevertheless, the toxicokinetics of the urinary excretion of selenium remain still unclear and require further investigations. Moreover, our findings emphasise the necessity of a re-evaluation of occupational exposure limits for elemental selenium and inorganic selenium compounds.

[Nickel levels in female dermatological patients]. / Innere Nickelbelastung von dermatologischen Patientinnen.

Nickel levels in urine were determined among 163 female dermatological patients aged 18 to 46 years. Data on life-style factors were collected in parallel via a questionnaire. Urinary nickel excretion was in the normal range of the German female population (0.2-46.1 microg Ni/g creatinine). The 95th percentile (3.9 microg Ni/l urine) exceeded the German reference value (3.0 microg Ni/l urine). In the multivariate regression analyses we found a statistically significant increase of ln-transformed nickel levels with increase in age and in women using dietary supplements. The following variables were not associated with Nickel urine levels: suffering from nickel eczema, smoking, drinking stagnated water, eating foods with high nickel contents and using nickel-containing kitchen utensils as, for example, an electric kettle with an open heater coil. We conclude that personal urinary levels should be assessed with simultaneous consideration of habits and life-style factors. A German national survery would be useful. Those patients who experience the exacerbation of their eczema in cases of oral provocation, for example, by a high nickel diet should be aware of potential sources of nickel, such as supplements.

Longitudinal study on potential neurotoxic effects of aluminium: II. Assessment of exposure and neurobehavioral performance of Al welders in the automobile industry over 4 years.

OBJECTIVES: This is the second of two parallel longitudinal studies investigating Al exposure and neurobehavioral health of Al welders over 4 years. While the first published study in the trail and truck construction industry examined the neurobehavioral development of Al welders from age 41-45 in the group mean (Kiesswetter et al. in Int Arch Occup Environ Health 81:41-67, 2007), the present study in the automobile industry followed the development from 35 to 39. Although no conspicuous neurobehavioral developments were detected in the first study, which furthermore exhibited the higher exposure, it cannot be excluded that exposure effects appear in earlier life and exposure stages. METHODS: The longitudinal study is based on a repeated measurement design comprising 4 years with three measurements in 2 years intervals. 92 male Al welders in the automobile industry were compared with 50 non-exposed construction workers of the same industry and of similar age. The repeated measurements included total dust in air, and Al pre- and post-shift plasma and urine samples. Neurobehavioral methods comprised symptoms, verbal intelligence, logic thinking, psychomotor behavior, memory, and attention. The computer aided tests came from the Motor Performance Series and the European Neurobehavioral Evaluation System. The courses of neurobehavioral changes were analyzed with multivariate covariance-analytical methods considering the covariates age, indicators of 'a priori' intelligence differences (education or markers of 'premorbid' intelligence), and alcohol consumption (carbohydrate-deficient transferrin in plasma). Additionally, the interrelationship, reliability and validity of biomonitoring measures were examined. RESULTS: The mean environmental dust load during welding, 0.5-0.8 mg/m(3), and the mean internal load of the welders (pre-shift: 23-43 microg Al/g creatinine in urine; 5-9 microg Al/l plasma) were significantly lower than in the parallel study. Under low exposure, the stability of biomonitoring measures was reduced, but the Al load differed significantly between Al welders and referents. It could not be shown that the development of neurobehavioral performances over the 4-year period differed between both groups. Mainly, markers of premorbid intelligence and age were related to neurobehavioral performance differences but not Al exposure. CONCLUSIONS: The biomonitoring and neurobehavioral results are in line with the results of the first published study. The repeated measurement models of both studies showed no adverse neurobehavioral effects of Al welding. A modular lifetime-oriented research concept is outlined aiming at the investigation of sequential periods of exposure life with special focus on the biologically most sensitive phases like first exposure and old age.

Percutaneous absorption of aromatic amines - a contribution for human health risk assessment.

Several aromatic amines (AA) are human carcinogens. AA are widely-used, e.g., in the rubber industry. The uptake of AA at the workplace occurs by inhalation and percutaneous absorption. At present there are no risk assessment studies for percutaneous AA absorption using occupationally relevant concentrations. We conducted diffusion cell experiments for aniline (ANI), o-toluidine (OT), 4,4'-methylenedianiline (MDA) and N-phenyl-2-naphthylamine (PBNA). Excised human skin was exposed to different AA concentrations in vehicles containing water and solvents. Recovery for ANI in receptor fluid was about 20-38% and for MDA 15% over 24h. PBNA could not be detected in the receptor fluid. Further data for OT and beta-naphthylamine (BNA) were considered from our recent study. A semi-quantitative percutaneous absorption ranking for AA was derived: BNA>OT>ANI>MDA>PBNA. For aqueous ANI solutions up to saturation a linear relationship of exposed dose and penetrated amount was observed. However, a linear extrapolation of the flux of neat compounds, as often recommended for risk assessment policies, underestimates considerably the percutaneous uptake. The in vitro data support our recent findings in rubber industry workers that the percutaneous absorption may significantly contribute to overall exposure of AA.

Indicadores biológicos para la valoración de la exposición humana a compuestos químicos industriales : Aluminio

Traducción de la obra en inglés \"Biological indicators for the assessment of human exposure to industrial chemicals\" (EUR 8903 EN) publicada por la Oficina para las Publicaciones Oficiales de las Comunidades Europeas. Contiene: propiedades químicas y físicas del aluminio, efectos en los humanos, metabolismo, indicadores biológicos...

Longitudinal study on potential neurotoxic effects of aluminium: I. Assessment of exposure and neurobehavioural performance of Al welders in the train and truck construction industry over 4 years.

OBJECTIVES: Previous cross sectional studies on potential neurotoxic effects of long-term aluminium exposures by aluminium welders lack clear interpretable results for methodological reasons. The present longitudinal study examined on the one hand the reliability and representativity of Al-biomonitoring as indicator of individual long-term exposure and on the other hand the long-term changes of neurobehavioural performance in Al welders in relation to Al exposure and neurobehavioural performance changes of a non-exposed control group. METHODS: The longitudinal study compared repeatedly measured exposure data and neurobehavioural data of 20, initially 44, male Al welders in the train and truck construction industry with data of a control group of similar age on the basis of three investigations over a period of 4 years. The repeated measurements of exposure included total dust in air as well as Al in pre- and post-shift plasma and urine samples. Neurobehavioural methods comprised symptoms, verbal intelligence, logic thinking, psychomotor behaviour, memory, and attention. Computer-aided tests from the Motor Performance Series (MLS) and the European Neurobehavioural Evaluation System (EURO-NES) were used. The characteristics of the biomonitoring data and the relationship to neurobehavioural data were examined with methods of correlation and regression analysis. The courses of neurobehavioural changes were analysed with multivariate covariance-analytical methods (MANCOVA) considering the covariates age, indicators of 'a priori' intelligence differences (education or 'premorbid' intelligence), and alcohol consumption (carbohydrate-deficient transferrin in plasma, CDT). RESULTS: The mean total dust load during welding, near to the routinely worn ventilated helmets, was in the range of 5-8 mg/m(3). The biomonitoring data of the welders (pre-shift: 88-140 microg Al/g creatinine in urine; 13-16 microg Al/l plasma) showed a high long-term stability but also sensitivity to acute shift dependent exposure changes. The Al welders who had been working in this profession at an average of 15 years showed no significantly increased symptom levels compared with the control group. Explorative regression and covariance analyses revealed neither a correlation between biomonitoring and performance variables nor a significant difference between Al-exposed and controls in the performance courses during the 4 years period. Explorative modelling indicated that the structure of neurobehavioural outcomes could be determined by possible indicators of intellectual 'a priori' (premorbid) differences between subjects but not by their exposure information. CONCLUSIONS: Compared to studies in the literature this study is characterized by relatively high and non-confounded Al exposure of the welders, a repeated-measurement design, and multivariate analyses. However, the long-term stable interindividual differences of internal Al exposure were not related to interindividual differences in neurobehavioural performances. Additionally, the lack of processual changes of neurobehavioural performances during the observation phase and the insignificant group differences do not make it very probable that degenerative processes caused by Al had happened before study onset or stopped just at this time point.

Percutaneous absorption of aromatic amines in rubber industry workers: impact of impaired skin and skin barrier creams.

BACKGROUND: Several aromatic amines (AA) could cause bladder cancer and are an occupational hygiene problem in the workplace. However, little is known about the percutaneous absorption of chemicals via impaired skin and about the efficacy of skin protection measures to reduce internal exposure. AIMS: To determine the impact of skin status and of skin protection measures on the internal exposure to AA in workers manufacturing rubber products. METHODS: 51 workers occupationally exposed to aniline and o-toluidine were examined. The workplace conditions, risk factors for skin and the use of personal protective equipment were assessed by means of a self-administered questionnaire. The skin of hands and forearms was clinically examined. Exposure to aniline and o-toluidine was assessed by ambient air and biological monitoring (analyses of urine samples and of haemoglobin adducts). RESULTS: Haemoglobin-AA-adduct levels in workers with erythema (73%) were significantly higher (p<0.04) than in workers with healthy skin (mean values: aniline 1150.4 ng/l vs 951.7 ng/l, o-toluidine 417.9 ng/l vs 118.3 ng/l). The multiple linear regression analysis showed that wearing gloves significantly reduced the internal exposure. A frequent use of skin barrier creams leads to a higher internal exposure of AA (p<0.03). However, the use of skincare creams at the workplace was associated with a reduced internal exposure (p<0.03). From these findings we assume that internal exposure of the workers resulted primarily from the percutaneous uptake. CONCLUSIONS: The study demonstrates a significantly higher internal exposure to AA in workers with impaired skin compared with workers with healthy skin. Daily wearing of gloves efficiently reduced internal exposure. However, an increased use of skin barrier creams enhances the percutaneous uptake of AA. Skincare creams seem to support skin regeneration and lead to reduced percutaneous uptake.

Indicadores biológicos para la valoración de la exposición humana a compuestos químicos industriales : cobre

Traducción de la obra en inglés \"Biological indicators for the assessment of human exposure to industrial chemicals\" (EUR 8903 EN) publicada por la Oficina para las Publicaciones Oficiales de las Comunidades Europeas. Contiene: propiedades químicas y físicas del cobre, efectos en los humanos, metabolismo, métodos analíticos, indicadores biológicos, etc.

Indicadores biológicos para la valoración de la exposición humana a compuestos químicos industriales : Vanadio

Traducción de la obra en inglés \"Biological indicators for the assessment of human exposure to industrial chemicals\" (EUR 11135 EN) publicada por la Oficina para las Publicaciones Oficiales de las Comunidades Europeas. Contiene: propiedades químicas y físicas del vanadio, exposiciones laborales principales, efectos en los humanos, metabolismo, indicadores biológicos y de efectos.

[Lactational transfer of presumed carcinogenic and teratogenic organochlorine compounds within the first six months of life]. / Ubertragung potenziell schädlicher Organochlorverbindungen durch mütterliches Stillen im Verlauf der ersten 6 Lebensmonate.

BACKGROUND: Despite a decline of 70 to 90 % during the past 20 years, many presumed carcinogenic and teratogenic organochlorine compounds (OC) are still present in our biosphere and accumulate in our food-chain. They are prenatally transmitted from mother to fetus, and mother's milk due to its high lipid content is an elimination pathway of special importance in all mammals. It was the aim of the present study to investigate whether breast-feeding increases the body pollution of human infants with OC during the first six months of life. METHODS: The study was approved by the committee on Biomedical Research of the Heinrich Heine University Düsseldorf, Germany. With written informed consent of the parents, blood samples were taken from 10 breast-fed and bottle-fed infants at the age of six weeks and six months, respectively. Three higher chlorinated PCB (polychlorinated biphenyls) congeners (IUPAC nos. 138, 153, and 180), HCB, and DDE, the main metabolite of DDT in mammals, were analyzed with capillary gas chromatography with electron capture detection. Reliability was tested with gas chromatography-mass spectrometry. Furthermore, the sum of the three higher chlorinated biphenyls (SigmaPCB) was calculated. RESULTS: There were no differences between the study groups of breast-fed and bottle-fed infants with regard to sex distribution, gestational age, birth weight, age of the mothers, and smoking behavior of the parents. However, serum concentrations of all OC were significantly higher (p < 0.0001) in breast-fed than in bottle-fed infants as early as at six weeks of age, and their concentrations nearly doubled until the age of six months (median [microg/L]; A = six weeks; B = six months): PCB 138, A: 0.40 vs. 0.09; B: 0.72 vs. 0.07; PCB 153, A: 0.57 vs. 0.11; B: 0.99 vs. 0.09; PCB 180, A: 0.33 vs. 0.04; B: 0.58 vs. 0.02; Sigma PCB, A: 1.19 vs. 0.29; B: 2.28 vs. 0.18; HCB, A: 0.13 vs. 0.04; B: 0.43 vs. 0.07; DDE, A: 1.05 vs. 0.18 ; B: 1.90 vs. 0.19. DISCUSSION: Breast-feeding significantly increases the serum concentration of our infants with different OC within the first six months of life, which leads to a body burden with OC, in this amount last measured in the mid-1980 s in Germany. In face of these results, common recommendations for breast-feeding should be reconsidered, taken into account the availability of infants formula (industrial vs. Third World countries).

Organochlorine compounds in breast-fed vs. bottle-fed infants: preliminary results at six weeks of age.

BACKGROUND: Polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) are ubiquitous compounds with carcinogenic and teratogenic properties. They are chemically very stable and lipophilic and, therefore, accumulate in our food-chain. They are prenatally transmitted from mother to foetus, and mother's milk due to its high lipid content is an elimination pathway of special importance. Therefore, breast-feeding has been held responsible for elevated concentrations of these organochlorine compounds as well as for harmful effects in children later in life. METHODS: Blood samples (2.5 ml) were taken from each 10 breast-fed and bottle-fed infants at 6 weeks of age. Blood specimens were immediately centrifuged, and serum was stored in glass tubes at -20 degrees C until analysis. Three higher chlorinated PCB congeners (IUPAC nos. 138, 153 and 180), HCB, and the organic metabolite of DDT, p,p << -DDE, were analysed with capillary gas chromatography with electron capture detection. Reliability was tested with gas chromatography-mass spectrometry. RESULTS: There were no differences between the study groups of breast-fed and bottle-fed infants with regard to sex distribution, gestational age, birth-weight, age of the mothers, and smoking behaviour of the parents. In contrast, serum concentrations of all organochlorine compounds were significantly higher (P < 0.0001) in breast-fed than in bottle-fed infants (mean): PCB 138, 0.38 vs. 0.10 microg/l; PCB 153, 0.49 vs. 0.1 microg/l; PCB 180, 0.31 vs. 0.04 microg/l; SigmaPCB, 1.19 vs. 0.29 microg/l; HCB, 0.13 vs. 0.04 microg/l; p,p << -DDE, 1.05 vs. 0.18 microg/l. CONCLUSIONS: Breast-feeding significantly increases the pollution of our infants with different organochlorine compounds as early as at 6 weeks of age. The progress of the present study will show whether this pollution will further increase with longer duration of breast-feeding, and whether breast-feeding bears any health risks for our offspring.

In vitro predictions of skin absorption of caffeine, testosterone, and benzoic acid: a multi-centre comparison study.

To obtain better insight into the robustness of in vitro percutaneous absorption methodology, the intra- and inter-laboratory variation in this type of study was investigated in 10 European laboratories. To this purpose, the in vitro absorption of three compounds through human skin (9 laboratories) and rat skin (1 laboratory) was determined. The test materials were benzoic acid, caffeine, and testosterone, representing a range of different physico-chemical properties. All laboratories performed their studies according to a detailed protocol in which all experimental details were described and each laboratory performed at least three independent experiments for each test chemical. All laboratories assigned the absorption of benzoic acid through human skin, the highest ranking of the three compounds (overall mean flux of 16.54+/-11.87 microg/cm(2)/h). The absorption of caffeine and testosterone through human skin was similar, having overall mean maximum absorption rates of 2.24+/-1.43 microg/cm(2)/h and 1.63+/-1.94 microg/cm(2)/h, respectively. In 7 out of 9 laboratories, the maximum absorption rates of caffeine were ranked higher than testosterone. No differences were observed between the mean absorption through human skin and the one rat study for benzoic acid and testosterone. For caffeine the maximum absorption rate and the total penetration through rat skin were clearly higher than the mean value for human skin. When evaluating all data, it appeared that no consistent relation existed between the diffusion cell type and the absorption of the test compounds. Skin thickness only slightly influenced the absorption of benzoic acid and caffeine. In contrast, the maximum absorption rate of testosterone was clearly higher in the laboratories using thin, dermatomed skin membranes. Testosterone is the most lipophilic compound and showed also a higher presence in the skin membrane after 24 h than the two other compounds. The results of this study indicate that the in vitro methodology for assessing skin absorption is relatively robust. A major effort was made to standardize the study performance, but, unlike in a formal validation study, not all variables were controlled. The variation observed may be largely attributed to human variability in dermal absorption and the skin source. For the most lipophilic compound, testosterone, skin thickness proved to be a critical variable.

Longitudinal study examining the neurotoxicity of occupational exposure to aluminium-containing welding fumes.

OBJECTIVES: The neurotoxicity of occupational exposure to aluminium (Al)-containing welding fumes has been discussed with controversial results. The aim of the longitudinal study was to examine a group of Al welders for significant central nervous changes in comparison with a non-exposed cohort. METHODS: A group of 98 Al welders (mean age 37 years) in the car-body construction industry, with a median of 6 years of occupational exposure to Al welding fumes, and an education-matched, gender-matched, age-matched control group of 50 car-production workers (mean age 36 years) at the same plant, were included in this longitudinal study. Two cross-sectional studies were done in 1999 and 2001. In the second cross-sectional study 97 welders and 50 controls could be examined. The examination programme consisted, for example, of a standardised anamnesis, focussing on occupational history, education, illnesses, medication, accidents and current alcohol consumption, a physical examination that included neurological status, and the assessment of Al concentration in plasma and urine. The neurobehavioral methods included a symptom questionnaire, modified Q16, and computerised and non-computerised tests: psychomotor performance (steadiness, line tracing, aiming, tapping), verbal intelligence (WST), simple reaction time, digit span, block design (HAWIE), symbol-digit substitution, digit span, switching attention (European neurobehavioral evaluation system, EURO-NES), and standard progressive matrices. The data were analysed by multivariate analysis of covariance (MANCOVA) for repeated measurements with covariates age, education, and carbohydrate-deficient transferrin in plasma (CDT). RESULTS. The median Al urine concentration (mean preshift/postshift) was 52.4 microg/g creatinine (2001) and 57.6 microg/g creatinine (1999). Median respirable air dust was 0.67 mg/m(3) (2001) and 0.47 mg/m(3) (1999). Welders and controls did not report significantly more symptoms in the modified Q16. Furthermore, no significant differences in psychomotor performance and other neurobehavioral tasks, except for reaction time, were seen between welders and non-welders. Regression analyses reveal a significant relationship between reaction time and Al excretion in urine that was confounded by other factors. CONCLUSIONS: At present the outcome for reaction time has to be interpreted as a single result. However, as the modified Q16 questionnaire and the rest of the psychomotor performance showed no significant changes, the next cross-sectional study, in 2003, will provide further information on which a final conclusion can be based.

In vitro evaluation of the efficacy of skin barrier creams and protective gloves on percutaneous absorption of industrial solvents.

OBJECTIVES: The aim of the experiments was to evaluate the efficacy of skin barrier creams (SBCs) and protective gloves and its potential for reduction of percutaneous absorption of industrial solvents. METHODS: We assessed percutaneous absorption of ethylene glycol (EG), isopropyl alcohol (IA) and 1,2,4-trimethylbenzene (TMB), using static diffusion cells. These solvents were applied neat (EG, TMB) as well as in 10% and 50% aqueous solution (EG, IA) or in 10% and 50% ethanol-diluted solution (TMB). Furthermore, we tested the percutaneous absorption of IA mixed in one cleaning agent (CA), used in newspaper printing shops to clean the rollers of printing machines. Additionally, the penetration behaviour of 10% and 50% solutions of EG, IA and TMB was tested. The experiments were carried out on untreated and on SBC-treated excised human skin from one donor, and on protective gloves. Saline was used as receptor fluid for EG and IA, and neat ethanol for TMB. RESULTS: The penetration of 50% EG, IA and TMB solutions through SBC-treated skin was higher than in untreated skin (factor 3.9 for EG, 0.32 for IA and 0.06 for TMB). The penetration of IA in the IA-CA mixture was five-times higher through untreated skin as for the single compound in 10% aqueous solution. In skin, treated with SBC, we found a 17-fold penetration enhancement of IA in the IA-CA mixture. No appreciable penetration of EG and IA was observed through nitrile rubber gloves. CONCLUSIONS: Our in vitro experiments could not demonstrate an efficacy of SBC to protect skin penetration for the tested solvents. The percutaneous absorption of all solvents in 50% solution was increased through skin treated with SBCs. Furthermore, SBCs enhance the penetration rates of solvents from complex mixtures compared with the single solvents. The tested gloves showed sufficient protection for the hydrophilic solvents, but not for TMB.

Quality assurance of biological monitoring in occupational and environmental medicine.

Biological monitoring of chemical exposure in the workplace has become increasingly important in the assessment of health risk as an integral part of the overall occupational health and safety strategy. In environmental medicine biological monitoring plays also an important role in the assessment of excessive, acute or chronic exposure to chemical agents. To guarantee that the results obtained in biological monitoring are comparable with threshold limit values and results from other laboratories, the analysis must be carried out with tested and reliable analytical methods and accompanied by a quality assurance scheme. Confounding influences and interferences during the pre-analytical phase can be minimised by recommendations from experienced laboratories. For internal quality control commercially available control samples with an assigned concentration are used. External quality control programs for biological monitoring are offered by several institutions. The external quality control program of the German Society of Occupational and Environmental Medicine has been organised since 1982. In the meantime the 27th program has been carried out offering 96 analytes in urine, blood and plasma for 47 substances. This program covers most of the parameters relevant to occupational and environmental medicine. About 350 laboratories take part in these intercomparison programs. At present, ten German and 14 international laboratories are commissioned to determine the assigned values. The data evaluated from the results of the intercomparison programs give a good overview of the current quality of the determination of analytes assessed in occupational and environmental toxicological laboratories. For the analysis of inorganic substances in blood and urine the tolerable variation ranges from 7.5 to 43.5%. For organic substances in urine the tolerable variation ranges from 12 to 48%. The highest variations (36-60%) were found for the analysis of organochlorine compounds in plasma. The tolerable variations for the determination of solvents in blood by head space gas chromatography range from 26 to 57%. If the recommendations for the pre-analytical phase, the selection of reliable analytical methods by the laboratory and the carrying out of adequate quality control are observed, the pre-requisites for reliable findings during biological monitoring are fulfilled

Exposure assessment in the hard metal manufacturing industry with special regard to tungsten and its compounds.

OBJECTIVES: To assess the exposure to tungsten, cobalt, and nickel in a plant producing hard metals. The main components of hard metals are tungsten carbide and cobalt metal. According to recent studies, these two components may be responsible for both fibrogenic and carcinogenic effects. METHODS: 87 workers were investigated (86 male, one female) with a median age of 42 (range 22-58) and a mean duration of exposure of 13 years (range 1-27 years). Stationary and personal air sampling, and biological monitoring were carried out. RESULTS: Ambient monitoring yielded maximum tungsten concentrations of 417 microg/m3 in the production of heavy alloys. A maximum cobalt concentration of 343 microg/m3 and a maximum nickel concentration of 30 microg/m3 were found at the sintering workshop. The highest urinary cobalt concentrations were found in the powder processing department. The mean concentration was 28.5 microg/g creatinine and the maximum value was 228 microg/g creatinine. The maximum nickel concentration in urine of 6.3 microg/g creatinine was detected in the department producing heavy alloys. The highest tungsten concentrations excreted in urine were found in grinders and had a mean value of 94.4 microg/g creatinine and a maximum of 169 microg/g creatinine. Due to the different solubility and bioavailability of the substance, there was no correlation between the tungsten concentrations in air and urine on a group basis. CONCLUSIONS: Despite its low solubility, tungsten carbide is bioavailable. The different bioavailability of tungsten metal and tungsten compounds has to be considered in the interpretation of ambient and biological monitoring data in the hard metal producing industry. The bioavailability increases in the order: tungsten metal, tungsten carbide, tungstenate. Only if both monitoring strategies are considered in combination can a valid and effective definition of high risk groups be derived.

Urinary beryllium--a suitable tool for assessing occupational and environmental beryllium exposure?

OBJECTIVES: The reasons for the slow progress and lack of new knowledge in the biological monitoring of beryllium (Be) are to be found in the presumed small number of working activities involving exposure to the metal, and the lack of adequate analytical methods. The reference values for urinary Be reported earlier in the literature appear to be too high, due to the poor specificity and sensitivity of the adopted methods. The aim of this study was to correlate Be air concentrations and Be urinary levels to ascertain whether the biological indicator was suitable for assessing occupational exposure to the metal. METHODS: To investigate the relationship between the Be concentrations in air and those excreted in urine, we examined 65 metallurgical workers exposed to very low levels of the metal, and 30 control subjects. The exposed workers were employed in two electric steel plants and two copper alloy foundries. The alloys were produced in electric furnaces, starting with scrap containing Be as an impurity. The Be concentrations in the air were monitored by area samplers and the levels of Be in the urine of the workers were determined in samples taken at the end of the shift. Both determinations were carried out by ICP-MS. RESULTS: The median airborne Be concentrations in the copper alloy plants were 0.27 microgram/m3 in the furnace area and 0.31 microgram/m3 in the casting area. Median values of 0.03 to 0.12 microgram/m3 were determined in the steel plants, the relatively wide range probably due to differing amounts of Be in the scrap. Regression analysis was performed on the median values from four work areas and the corresponding urinary samples. A significant correlation was found for the relationship between external and internal exposure. The urinary Be levels were in the range between 0.12 and 0.15 microgram/l with observation of the recommended TLV-TWA for inhalable dust of 0.2 microgram/m3 (0.2 microgram/l at the upper 95th percentile). CONCLUSIONS: Sufficient data are not currently available to be able to propose a BEI for urinary Be. Our results show that new investigations are necessary to improve the evaluation of dose indicators and the relationship between external and internal exposure to Be.

External quality assurance program for biological monitoring in occupational and environmental medicine.

Biological monitoring of chemical exposure in the workplace and in the environment has become increasingly important in assessing health risk. The analysis must be carried out under a quality assurance scheme to guarantee that the results obtained in biological monitoring are comparable with the threshold limit values and results from other laboratories. Since 1982, the German Society for Occupational and Environmental Medicine has offered 28 intercomparison programs. These programs cover 96 analytes in urine, blood, and plasma for 47 substances and cover most parameters that are relevant in occupational and environmental medicine. The data obtained in these programs provide a good overview of the current quality of the determination of analytes that are assessed in occupational and environmental toxicological laboratories. For the analyses of inorganic substances in blood and urine, the tolerable variation ranges from 7.5% to 43.5%. For organic substances in urine, the tolerable variation ranges from 12% to 48%. For organic substances in urine, the tolerable variation ranges from 12% to 48%. The highest variations (36% to 60%) were found for the analysis of organochlorine compounds in plasma. The tolerable variations for determining solvents in blood by head space gas chromatography range from 26% to 57%. The overall average success rates for the participants of the external quality programs range from 65% to 75%.

Occupational exposure to polycyclic aromatic hydrocarbons in a fireproof stone producing plant: biological monitoring of 1-hydroxypyrene, 1-, 2-, 3- and 4-hydroxyphenanthrene, 3-hydroxybenz(a)anthracene and 3-hydroxybenzo(a)pyrene.

OBJECTIVES: Assessment of external and internal exposure to polycyclic aromatic hydrocarbons (PAH) in a fireproof stone producing plant. METHODS: Five personal and four stationary air measurements were performed to determine the concentrations of benz(a)anthracene, benzo(a)pyrene, benzo(b)fluoranthene, chrysene, dibenz(a,h)anthracene, fluoranthene, phenanthrene and pyrene, in air. To estimate internal exposure, we determined the urinary excretion of 1-hydroxypyrene, 1-, 2-, 3-, and 4-hydroxyphenanthrene, 3-hydroxybenz(a)anthracene and 3-hydroxybenzo(a)pyrene in 19 workers, using a sensitive and reliable high-performance liquid chromatographic method with fluorescence detection. RESULTS: During the production of fireproof stones, the German technical exposure limit (TRK) for benzo(a)pyrene of 2 microg/m3 was exceeded in two cases. The mean values of the sum of eight PAHs were 12.6 microg/m3 (stationary air measurement) and 22.2 microg/m3 (personal air measurement). Urinary 1-hydroxypyrene excretion predominated, with a median of 11.1 microg/g creatinine (creat.), followed by 3-hydroxyphenanthrene (median 2.2 microg/g creat.), 1-hydroxyphenanthrene (median 1.9 microg/g creat.) and 2-hydroxyphenanthrene (median 1.6 microg/g creat.). 4-Hydroxyphenanthrene (median 0.3 microg/g creat.) and 3-hydroxybenz(a)anthracene (median 0.17 microg/g creat.) were found in far lower concentrations, while 3-hydroxybenzo(a)pyrene was found only in very low concentrations (median 0.014 microg/g creat.). No correlations could be detected for a relationship between external and internal exposure. A significant correlation between urinary metabolite concentrations could be calculated only for 3-hydroxybenz(a)anthracene and 1-hydroxypyrene. CONCLUSIONS: In comparison with other industries, the internal PAH exposure at workplaces in a fireproof stone producing plant is high. This is probably caused by dermal PAH-absorption. Therefore, biological monitoring must be performed in the health surveillance of fireproof stone producing workers. The urinary PAH metabolites should be determined: 3-hydroxybenz(a)anthracene could probably be used as a biomarker representing the group of carcinogenic PAH.