Biomonitoring of manganese in blood, urine and axillary hair following low-dose exposure during the manufacture of dry cell batteries

Objectives: A cross-sectional study was carried out on 100 workers from three different workplace areas in a dry cell battery manufacturing plant and on 17 currently nonexposed referents, to examine the relationship between the external exposure to manganese dioxide (MnO₂) and the body burden of manganese in blood, urine and hair. Methods: Inhalable dust was measured gravimetrically after stationary active sampling. Manganese was analyzed in dust samples, blood, urine and axillary hair by atomic absorption spectro- metry. Results: The average air concentrations of manganese in the three workplace areas were 4 μg/m³ (range: 1–12 μg/m³), 40 μg/m³ (12–64 μg/m³) and 400 μg/m³ (137–794 μg/m³). Manganese in blood and axillary hair correlated with airborne manganese in group-based calculations but not on an individual level. The manganese concentrations varied between 3.2 μg/l and 25.8 μg/l in the blood (mean: 12.2 ± 4.8 μg/l) and between 0.4 μg/g and 49.6 μg/g in hair (mean: 6.2 ± 6.2 μg/g in the proximal sequence), respectively. The results for the nonexposed referents were 7.5 ± 2.7 μg/l (mean) in the blood (range: 2.6–15.1 μg/l) and 2.2 ± 1.8 μg/g (mean) in axillary hair (range: 0.4–6.2 μg/g). In these matrices, manganese differed significantly between the highly exposed workers and both the reference and the low-exposure group. Manganese in blood revealed the lowest background variance. No differences for manganese in urine were observed between workers (mean: 0.36 ± 0.42 μg/l, range: 0.1–2.2 μg/l) and referents (mean: 0.46 ± 0.47 μg/l, range: 0.1–1.7 μg/l). Conclusions: Manganese in blood is a specific and suitable parameter for the biomonitoring of MnO₂ exposure, although its validity is limited to group-based calculations. Urinary manganese failed to allow a differentiation between exposed workers and referents. The suitability of manganese analysis in hair for biomonitoring purposes suffers from a relatively great background variation as well as from analytical problems. Received: 11 December 1998 / Accepted: 17 July 1999     

Normal liver function in women in the general Japanese population subjected to environmental exposure to cadmium at various levels

Objectives: Whereas it is well established that environmental exposure to cadmium (Cd) may induce kidney dysfunction, less attention has been paid to the possible disturbance of liver function by Cd exposure. The possibility that liver function is adversely affected by current levels of environmental exposure to Cd as investigated in women in the general population in Japan, where the background level of exposure to Cd is known to be high. Methods: From 1991 to 1997, 24-h food duplicate, peripheral blood and morning spot urine samples were collected from 607 non-smoking and non-habitually drinking women (age range 19–78 years) at 30 survey sites (with no known environmental pollution from heavy metals) throughout Japan. Liver function parameters in serum were examined by conventional methods. After wet-ashing, the food duplicate, blood and urine samples were analyzed for Cd intake via food (Cd-F), Cd in blood (Cd-B), and Cd in urine (Cd-U) by inductively-coupled plasma mass spectrometry. Results: The geometric mean values for Cd-F, Cd-B, and Cd-U were 24.7 (27.1) μg/day, 1.76 (2.07) μg/l, and 3.94 (4.61) μg/g creatinine (values in parentheses for 41- to 60 year-old women), respectively. It as found that the three parameters of ALP, ALT, and AST activity were positively and significantly related to the age of the subjects (whereas no association as detected in cases of γ-GTP, LAP, and albumin). Accordingly, a further analysis as made with 367 women selected by age (41–60 years; about 60% of the total population). Essentially, no Cd dose-dependent changes in liver function parameters were observed in the selected population of this narrower age range. Conclusions: Overall, it seemed prudent to conclude that liver function as not disturbed by the current environmental exposure to Cd in Japan. Received: 16 March 1999 / Accepted: 17 July 1999     

Further reduction in lead exposure in women in general populations in Japan in the 1990s, and comparison with levels in east and south-east Asia

Objective: The objective of the study was to elucidate the current level of environmental lead (Pb) exposure of women in general population in Japan, where the use of organic Pb in automobile gasoline was phased out from 1973 to reach a zero level early in the 1980s. Methods: A survey was conducted in 27 sites throughout Japan from 1991 to 1997. Five hundred and eighty-eight non-smoking women from the sites offered 24-h food duplicate, peripheral blood, and spot urine samples. Pb in food duplicates (Pb-F), blood (Pb-B), and urine (Pb-U) were analyzed by inductively-coupled plasma mass spectrometry. The results of Pb-F and Pb-B were compared with observations from a study conducted from 1977 to 1981 on 339 women at the same sites. Log-normal distribution was assumed for the evaluation of the results. Results: Geometric means (GMs) of Pb-F, Pb-B, and Pb-U in the 1991–1997 study were 9.0 μg/day, 20.2 μg/l, and 2.18 μg/g creatinine, respectively. The values for Pb-F and Pb-B were substantially lower than the values (32.8 μg/day for Pb-F and 31.7 μg/l for Pb-B) obtained in the 1977–1981 study, which were already low when compared internationally. Cd-U values in the period from 1991 to 1997 also appeared to be among the lowest in the world. Analysis for time-dependent changes in Pb-U was, however, not possible at the time of this study because no values were available for the period from 1977 to 1981. Conclusions: Substantial reductions from 1977–1981 levels in environmental Pb exposure were observed among the study populations in Japan. Current exposure levels appear to be lower than those in other parts of Asia, the USA, and Europe. Received: 16 March 1999 / Accepted: 27 August 1999     

Cadmium exposure of women in general populations in Japan during 1991–1997 compared with 1977–1981

Objectives: The Japanese people are known to have high environmental exposure to cadmium (Cd). The present survey was initiated to elucidate possible changes in the intensity of Cd exposure to the population by comparison of the present exposure level with the situation some 15 years ago. Methods: During 1991–1997, 24-h food-duplicate samples, peripheral blood specimens and morning spot urine samples were collected from 588 non smoking women from 27 survey sites in six regions, where food-duplicate and blood samples had also been obtained during 1977–1981 from 399 women. The samples were wet-ashed (after homogenization in the case of food-duplicates), and Cd in the wet-ashed samples was analyzed by inductively-coupled plasma mass spectrometry for Cd intake via foods (Cd-F), Cd concentration in blood (Cd-B) and Cd concentration in urine (Cd-U). The Cd-F and Cd-B were compared with the Cd-F and Cd-B obtained at the same sites in the 1977–1981 survey. Results: The exposure levels during 1991–1997 were such that Cd-F, Cd-B and Cd-Ucr (Cd–U after correction for creatinine concentration) were 25.5 μg/day, 1.90 μg/l and 4.39 μg/g creatinine. Comparison with the 1977–1981 survey results (i.e., 37.5 μg/day for Cd-F and 3.47 μg/l for Cd-B) showed that there were significant reductions (by 32 and 45%) in both parameters respectively during the last 15 years. The dietary route was an almost exclusive (i.e., 99% of the sum of dietary and respiratory uptake) route of Cd uptake, of which Cd in rice (11.7 μg/day) contributed about 40% of the total dietary intake. When compared among survey sites, inter-site variation in dietary Cd intake was primarily due to differences in the intake through boiled rice. Despite the recent reduction in Cd exposure, the current exposure level for Japanese people is still higher than the levels among other rice-dependent populations in Asia as well as in other parts of the world. Comparison was made between the present findings in general populations and observations among known Cd-pollution cases in Japan. Conclusions: Dietary uptake is an almost exclusive route of Cd exposure in the general Japanese population. Boiled rice is a strong determinant of variation in dietary Cd intake. Whereas there was a substantial reduction in Cd exposure among Japanese populations in the last 15 years, the current level is still high when compared internationally. Received: 1 March 1999 / Accepted: 17 July 1999     

Aluminium dust-induced lung disease in the pyro-powder-producing industry: detection by high-resolution computed tomography

Objective: The aim of this case study was to investigate the suitability of high-resolution computed tomography (HRCT) for detecting early stages of lung fibrosis induced by aluminium (Al) dust. Methods: A 40-year-old worker was studied who had worked as a stamper for 14 years in a plant producing aluminium powder and had been exposed to high levels of aluminium dust during this time. The investigation included the collection of general data on health and details on occupational history, immunological tests, a physical examination, lung function analysis, biological monitoring of Al in plasma and urine, chest X-rays and HRCT. Results: For many years the man has suffered from an exercise-induced shortness of breath. Lung function analysis revealed a reduction of the vital capacity to 57.5% of the predicted value. The Al concentration in plasma was 41.0 μg/l (upper reference value 10 μg/l) and in urine 407.4 μg/l [upper reference value 15 μg/l, biological tolerance (BAT) value 200 μg/l] at the time of diagnosis. Chest X-ray showed unspecific changes. HRCT findings were characterised by small, centrilobular, nodular opacities and slightly thickened interlobular septae. Exposure to other fibrotic agents could be excluded. Conclusions: HRCT was more sensitive than chest X-rays for detecting this early stage of Al-dust-induced lung disease. The suitability of HRCT in the surveillance of workers highly exposed to aluminium powder should be evaluated in further studies. Biological monitoring can be used to define workers at high risk. Received: 29 March 1999 / Accepted: 26 August 1999     

Determination of N-nitrosodiethanolamine in urine by gas chromatography thermal energy analysis: application in workers exposed to aqueous metalworking fluids

 Objective: The aim of this study was to describe a detailed and validated methodology designed for the analysis of carcinogenic N-nitrosodiethanolamine (NDELA) down to sub-μg/l levels in urine and its application to a number of workers exposed to NDELA-contaminated aqueous metalworking fluids (MWF). Methods: Following a work-up procedure based on solid-phase extraction of NDELA, the urinary extracts were analysed without derivatization by gas chromatography on a polar wide-bore column with chemiluminescent detection using a thermal energy analyser (TEA). N-Nitroso-(2-hydroxypropyl)amine was used as an internal standard. The method was applied to 12 workers using “nitrite-free” or “nitrite-formulated” MWF and to 15 unexposed subjects. The NDELA content of the MWF was also determined using a similar, but simpler method able to easily quantify NDELA down to at least 0.1 mg/l. Results: Contamination by NDELA traces of some chemicals used for the sample preparation, particularly ethyl formate, must be carefully checked since it can give rise to false-positive results of up to 1 or 2 μg/l. The response was linear in the range of 0–500 μg/l. Between 0.5 and 10 μg/l, the recovery rate was close to 95%, while repeatability ranged from 12.5 to 6.4% (n = 5). The detection limit was 0.3 μg/l (Signal/noise = 3). No detectable NDELA could be observed in the control workers. There was no significant increase in NDELA levels at the end of shift spot samples from an exposed worker over 1 week. Higher NDELA concentrations were found in two workers (4.3 and 10.7 μg/l) exposed to “nitrite-formulated” fluids (contaminated with 65 and 18 mg NDELA per l, respectively) than in nine workers (range, 0.4–1.3 μg/l exposed to “nitrite-free” fluids with lower levels of NDELA (range, 0.5–6.6 mg/l). Conclusion: The detailed methodology described in this work and applied to a limited industrial situation was found to be suitable for monitoring NDELA in the urine of workers exposed to aqueous MWF. A much larger screening has been undertaken with the aim of obtaining better information on the real exposure of workers sometimes exposed to “nitrite-formulated” fluids that are still used. Received: 8 December 1998 / Accepted: 3 April 1999     

Possible effects of environmental cadmium exposure on kidney function in the Japanese general population

Objectives: To examine whether the current level of environmental exposure to cadmium (Cd) is associated with kidney dysfunction among general populations in Japan. Methods: A nationwide survey was conducted in Japan from 1991 to 1997 at 30 survey sites (with no known environmental heavy metal pollution), by the collection of 24-h food-duplicate samples, peripheral blood specimens and morning spot urine samples. In practice, 607 non-smoking adult women provided these samples. After being wet-ashed, the samples were analyzed for Cd in food duplicates (Cd-F), in blood (Cd-B) and urine (Cd-U) by inductively-coupled plasma mass spectrometry (ICP-MS). Urine samples were also analyzed for α₁-microglobulin (α₁-MG), β₂-microglobulin (β₂-MG) and retinol-binding protein (RBP), creatinine (cr) and specific gravity. Possible tubular dysfunction in association with Cd exposure was examined by simple, multiple and logistic regression analyses, and comparison among three different Cd-dose groups. To minimize the confounding effects of aging, 367 women from 41 to 60 years old were selected and subjected to the same statistical analyses. Results: The analysis of a whole population of 607 women showed that α₁-MG and possibly β₂-MG increased as a function of Cd-F, Cd-B and Cd-U. When the analysis was repeated with the selected population of 367 women aged 41–60, the Cd dose-dependent changes in α₁-MG and β₂-MG became less evident. The distribution of the selected population with α₁-MG above two low cut-off values of >4.9 and >8.4 mg/g cr or with β₂-MG above the lowest cut-off value of >400 μg/g cr, was biased toward the group with higher Cd-Ucr, but such bias was not significant for both α₁-MG and β₂-MG when higher cut-off values were employed. No bias was detected with RBP. Logistic regression analysis with α₁-MG, β₂-MG and RBP (with cut-off values given above) in combination with age, Cd-F, Cd-B and Cd-Ucr gave essentially the same results. Conclusions: The evidence for kidney dysfunction was of borderline significance in the present study population for which geometric mean Cd-F, Cd-B and Cd-U were 24.7 μg/day, 1.76 μg/l, and 3.94 μg/g cr, respectively. The findings might suggest at the same time that the safety margin is small for the Japanese general population regarding environmental Cd exposure. Received: 26 February 1999 / Accepted: 24 July 1999     

Urinary lead as a possible surrogate of blood lead among workers occupationally exposed to lead

Objectives: The aim of the present study is to investigate whether lead (Pb) in urine (Pb-U) can be a valid surrogate of lead in blood (Pb-B), the traditional biomarker of exposure to lead in occupational health. Methods: Blood and spot urine samples were collected from 258 workers of both sexes occupationally exposed to lead. The samples were analyzed for lead by graphite furnace atomic absorption spectrometry, and the correlation between Pb-B and Pb-U was examined by linear regression analysis before and after logarithmic conversion. Results: The correlation coefficient (0.824; P < 0.01) was largest when the relationship between Pb-B and Pb-U was examined with 214 cases of one sex (i.e., men) after Pb-U was corrected for a specific gravity (1.016) of urine (Pb-Usg) and both Pb-B and Pb-Usg were converted to logarithms. The geometric means (GMs) of Pb-B and Pb-Usg for the 214 men were 489 μg/l and 81 μg/l, respectively. When Pb-Usg was assumed to be 100 μg/l in this set of correlations, the 95% confidence range of Pb-B for the group mean was narrow, i.e., 543–575 μg/l (with GM of 559 μg/l), whereas that for individual Pb-B values was as wide as 355–881 μg/l. Conclusions: The correlation of Pb-U with Pb-B among workers occupationally exposed to Pb was close enough to suggest that Pb-U may be a good alternative to Pb-B on a group basis, but not close enough to allow Pb-U to predict Pb-B on an individual basis. Received: 6 April 1999 / Accepted: 17 July 1999     

Biological monitoring of workers exposed to 4,4′-methylene-bis-(2-orthochloroaniline) (MOCA)

Objective: The objective of the study was to validate a new and simple method to determine MOCA in the urine of exposed workers. Methods: The separation, identification and quantification of urinary MOCA were performed in spiked urines by a sensitive and practical high-performance liquid chromatography (HPLC) method and applied to urine samples of 11 workers occupationally exposed to MOCA; the postshift urinary levels of MOCA in their urine samples with and without hydrolysis, “total” and “free” MOCA respectively, were determined. In addition, we investigated the use of citric or sulfamic acid as preservatives of urine samples. Results: The “total” and “free” MOCA were extracted with isooctane from hydrolysed and nonhydrolysed 20-ml urine samples respectively. After evaporation, the residue was dissolved in 4 ml of 2 · 10⁻² M aqueous hydrochloric acid and analysed by an isocratic HPLC system using both ultraviolet (UV) detection at 244 nm and electrochemical detection working in oxidation mode (0.9 V) with an Ag/AgCl reference electrode. Mobile phase (50% acetonitrile in water containing 0.4% acetate buffer solution pH = 4.6) was used to complete the 20-min analysis. “Free” and “total” MOCA were chromatographed on a reversed-phase C8 column (5 μm; 250 mm × 4 mm). The standard curve of MOCA was linear over the range 5–500 μg/l in human urine. The detection limit was 1 μg/l for a 20-μl injection volume; the repeatability ranged from 5.6 to 1.3% (n = 6) for spiked urines at 5 and 500 μg/l, with a percentage recovery of 94 ± 3%. The reproducibility of the method was 7.3% (n = 4) for spiked urine at 10 μg/l. The use of sulfamic acid as a preservative of urine samples is important to improve the precision and accuracy of the analysis. Conclusion: The results indicate that these analytical procedures using conventional apparatus may be used routinely and reliably with large numbers of urine samples for biological monitoring of the exposure to MOCA. The occupational exposure to MOCA in some factories in France is studied in the second part of this work. Received: 10 November 1998 / Accepted: 25 March 1999     

Urinary cotinine concentration in flight attendants, in relation to exposure to environmental tobacco smoke during intercontinental flights

Objectives: To measure and compare the urinary cotinine concentration (U-cotinine) in non-smoking cabin attendants (C/A) working with the Scandinavian Airlines System, before and after work on intercontinental flights with exposure to environmental tobacco smoke (ETS). Methods: The study material consisted of 24 cabin attendants and one pilot, all volunteers and all without exposure to ETS in the home, working on 15 intercontinental flights. Information on age, gender and occupation was gathered, as well as possible sources of ETS exposure in other places, outside work and during previous flights, during a 3-day period prior to the investigation. Urine samples were taken before departure and after landing, on board, and were kept frozen (−20 °C) until analysis. Cotinine was analyzed by a previously developed gas chromatographic method, using mass spectrometry (MS) with selected-ion monitoring (SIM). The difference in U-cotinine before and after the flight was compared. Moreover, the change in U-cotinine during the flight was related to occupation (work in the forward or aft galley) and observed degree of smoking during each flight. Results: The median U-cotinine was 3.71 μg/g crea; 2.4 μg/l (unadjusted) (interquartile range 2.08–8.67 μg/g crea) before departure, and 6.37 μg/g crea; 7.1 μg/l (interquartile range 3.98–19 μg/g crea) after landing, a significant difference (P < 0.003). C/A in the aft galley had a significantly higher concentration of U-cotinine after landing than subjects working in the front of the aircraft (P=0.01). In C/A working in the aft galley, the median increase of U-cotinine was 3.67 μg/g crea; 3.2 μg/l (interquartile range 0.04–13.8 μg/g crea) during flight. In contrast, those seven subjects working in the forward part of the aircraft had no increase in U-cotinine during the flight (median increase 0.97 μg/g crea; 0.5 μg/l interquartile range 0.27–2.65 μg/g crea). Conclusion: Tobacco smoking in commercial aircraft may cause significant exposure to environmental tobacco smoke among C/A working in the aft galley, despite high air exchange rates and spatial separation between smokers and non-smokers. This agrees with earlier studies, as well as measurements on the aircraft, showing a higher degree of ETS-related air pollution in the aft galley than in the forward galley. The average cotinine concentration in urine was similar to that in other groups with occupational exposure to ETS, e.g., restaurant staff, police interrogators and office workers. Since smoking in commercial aircraft may result in an involuntary exposure to ETS among non-smokers, it should be avoided. Received: 1 February 1999 / Accepted: 29 May 1999     

A comparison of different lead biomarkers in their associations with lead-related symptoms

Objectives: To evaluate whether dimercaptosuccinic acid (DMSA) -chelatable lead, an estimate of current bioavailable lead stores, is a better predictor of lead-related symptoms than are other commonly used lead biomarkers. Methods: A total of 95 male lead workers from three lead industries (one secondary lead smelting facility, one polyvinyl chloride-stabilizer manufacturing plant, and one lead-acid storage battery factory), and 13 workers without occupational lead exposure recruited from an occupational health institute, were studied. Blood lead, blood zinc protoporphyrin (ZPP), 4 h DMSA-chelatable lead (after oral administration of 10 mg/kg DMSA), urine lead, and urinary δ-aminolevulinic acid levels were evaluated as predictors of 15 lead-related symptoms, assessed by self-administered questionnaire, with linear and logistic regression controlling for covariates. Total symptoms and symptoms in three categories (gastrointestinal, neuromuscular, and general) were evaluated. Results: The mean (SD) 4 h DMSA-chelatable lead level was 288.7 (167.7) μg, with a range from 32.4 to 789 μg in the 95 lead workers. The mean (SD) in the non-exposed subjects was 23.7 (11.5) μg with a range from 10.5 to 43.5 μg. Blood lead, blood ZPP, and spot urine lead levels ranged from 21.4 to 78.4 μg/dl, 40 to 331 μg/l, and 7.5 to 153.0 μg/l, respectively, in the lead workers, and from 4.0 to 7.2 μg/dl, 27 to 52 μg/l, and 2.9 to 15.5 μg/l in the non-exposed controls, respectively. The overall mean symptom score (SD), derived as the sum of 0 or 1 point for absence or presence of 15 symptoms, of the lead workers was 3.7 (2.0), compared to 1.2 (1.5) for the non-exposed workers. DMSA-chelatable lead was the best predictor of symptom scores in both crude and adjusted analyses, compared with the other biomarkers. Lead workers with DMSA-chelatable lead values greater than the median (260.5 μg) were 6.2 times more likely to have frequent tingling or numbness of the arms or legs and 3.3 times more likely to have muscle pain than subjects with lower chelatable lead values. Three symptoms (tingling or numbness of arm or leg, muscle pain, and feeling irritation at the slightest disturbance) evidenced a dose-dependent relationship with DMSA-chelatable lead levels. Conclusions: DMSA-chelatable lead was found to be the best predictor of lead-related symptoms, particularly of both total symptom scores and neuromuscular symptoms, than were the other other lead biomarkers. Received: 27 January 1999 / Accepted: 29 January 2000     

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

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 μg/l and from 49 to 308 μg/l, with average values being 380 and 130 μg/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 μg/l) and methylhippuric acids in urine (2000 mg/l). Received: 27 May 1998 / Accepted: 3 September 1998     

Assessment of biological chromium among stainless steel and mild steel welders in relation to welding processes

Air and biological monitoring were used for assessing external and internal chromium exposure among 116 stainless steel welders (SS welders) using manual metal arc (MMA), metal inert gas (MIG) and tungsten inert gas (TIG) welding processes (MMA: n = 57; MIG: n = 37; TIG: n = 22) and 30 mild steel welders (MS welders) using MMA and MIG welding processes (MMA: n = 14; MIG: n = 16). The levels of atmospheric total chromium were evaluated after personal air monitoring. The mean values for the different groups of SS welders were 201 μg/m³ (MMA) and 185 μg/m³ (MIG), 52 μg/m³ (TIG) and for MS welders 8.1 μg/m³ (MMA) and 7.3 μg/m³ (MIG). The curve of cumulative frequency distribution from biological monitoring among SS welders showed chromium geometric mean concentrations in whole blood of 3.6 μg/l (95th percentile = 19.9), in plasma of 3.3 μg/l (95th percentile = 21.0) and in urine samples of 6.2 μg/l (95th percentile = 58.0). Among MS welders, mean values in whole blood and plasma were rather more scattered (1.8 μg/l, 95th percentile = 9.3 and 1.3 μg/l, 95th percentile = 8.4, respectively) and in urine the value was 2.4 μg/l (95th percentile = 13.3). The analysis of variance of chromium concentrations in plasma previously showed a metal effect (F = 29.7, P < 0.001), a process effect (F = 22.2, P < 0.0001) but no metal–process interaction (F = 1.3, P = 0.25). Concerning urinary chromium concentration, the analysis of variance also showed a metal effect (F = 30, P < 0.0001), a process effect (F = 72, P < 0.0001) as well as a metal–process interaction (F = 13.2, P = 0.0004). Throughout the study we noted any significant differences between smokers and non-smokers among welders. Taking in account the relationships between chromium concentrations in whole, plasma or urine and the different welding processes, MMA-SS is definitely different from other processes because the biological values are clearly higher. These higher levels are due to the very significant concentrations of total soluble chromium, mainly hexa- valent chromium, in welding fumes. Received: 9 May 1996 / Accepted: 14 March 1997     

Dust exposure in Munich public transportation: a comprehensive 4-year survey in buses and trams

Objectives: Published data obtained from outdoor stationary sampling stations cannot be applied directly to the exposure situation in vehicles. The aim of this study, therefore, was to assess the dust exposure relevant to passengers and drivers in public buses and trams. Method: In the years 1993 to 1996, PM₁₀ samples were taken during 201 journeys of typically 4 h duration on 14 routes (nine bus routes, five tramways) which were representative for the overall Munich transportation system with respect to area characteristics and traffic density. The concentrations of the samples were compared with those collected at the same time at sampling stations of the Bavarian State Office for Environmental Protection (OEP). Dust exposure was continuously and synchronously recorded by means of a tyndallometric device. Traffic and passenger density, weather conditions, special events, etc. were noted by our personnel, travelling on every journey. Results: The average PM₁₀ dust concentration for all rides was 155 μg/m³ (single journey max. 686 μg/m³, min. 13 μg/m³). Interior concentrations were 1.7 to 4.0 times above those collected at the static outdoor stations. We found only minor associations between dust concentrations and traffic density or time of day. During several journeys continuous recording disclosed anomalies, dependence on weather conditions and cyclic track characteristics. Conclusions: Interior PM₁₀ particulate concentrations were comparable to those found elsewhere in truck drivers' cabs and are in the region of German regulative limits established for the general population's long term outdoor exposure. Indoor concentrations were well above the values found at stationary outdoor stations. Additional continuous recording of dust concentrations proved to be helpful in unveiling anomalies and dependencies on external effectors. Received: 10 August 1999 / Accepted: 20 November 1999     

Benzene in environmental air and human blood

To study the blood benzene levels resulting from environmental and occupational benzene exposure. Methods: Benzene in venous blood was measured in 243 nonoccupationally exposed subjects (“normal” people) and in 167 workers occupationally exposed to benzene. All exposed workers gave blood samples at the end of the work shift and on the following morning before resuming work. Blood benzene was assayed by gas chromatography (GC)-mass spectrometry. Occupational benzene exposure was monitored by environmental personal samplers and measured by GC analysis. Results: The mean occupational benzene exposure for all 167 workers studied was 186 ng/l (58 ppb; range 5–1535 ng/l, 2–500 ppb). Overall, the mean blood benzene level of all workers was 420 ng/l at the end of the shift and 287 ng/l on the morning thereafter. The blood benzene levels measured the morning after turned out to be significantly lower (t = 3.6; P < 0.0001) than those measured at the end of the shift. The mean blood benzene level of the 243 “normal” subjects was 165 ng/l, which was significantly lower than that measured in the workers on the morning thereafter (t=5.8; P < 0.0000001). The mean blood benzene concentration was significantly higher in smokers than in nonsmokers in both the general population (264 versus 123 ng/l) and in the exposed workers. In the group of nonsmoking workers, whose workplace exposure to benzene was lower than 100 ng/l, blood benzene levels were similar (210–202 ng/l) to those measured in the nonsmoking general population (165 ng/l). End-of-shift blood benzene correlated significantly with environmental exposure (y=0.91x + 251; r=0.581; n=162; P < 0.00001). Finally, there was also a significant correlation between blood benzene measured at the end of the shift and that determined on the morning thereafter (y=0.45x + 109; r=0.572; n=156; P < 0.00001). Conclusion: Nonsmoking workers occupationally exposed to benzene at environmental levels lower than 100 ng/l (mean 35 ng/l) and the nonsmoking general population exposed to ubiquitous benzene pollution have similar blood benzene concentrations. This suggests that it is impossible to distinguish between occupational and environmental exposure when the benzene level in the workplace is less than 100 ng/l. Received: 31 December 1997 / Accepted: 4 August 1998     

Urinary nickel as bioindicator of workers' Ni exposure in a galvanizing plant in Brazil

Objectives: We measured urinary nickel (U-Ni) in ten workers (97 samples) from a galvanizing plant that uses nickel sulfate, and in ten control subjects (55 samples) to examine the association between occupational exposure to airborne Ni and Ni absorption. Methods: Samples from the exposed group were taken before and after the work shift on 5 successive workdays. At the same time airborne Ni (A-Ni) was measured using personal samplers. Ni levels in biological material and in the airborne were determined by a graphite furnace atomic absorption spectrometry validated method. In the control group the urine samples were collected twice a day, in the before and after the work shift, on 3 successive days. Results: Ni exposure low to moderate was detected in all the examined places in the plant, the airborne levels varying between 2.8 and 116.7 μg/m³ and the urine levels, from samples taken postshift, between 4.5 and 43.2 μg/g creatinine (mean 14.7 μg/g creatinine). Significant differences in U-Ni creatinine were seen between the exposed and control groups (Student's t test, P ≤ 0.01). A significant correlation between U-Ni and A-Ni (r = 0.96; P ≤ 0.001) was detected. No statistical difference was observed in U-Ni collected from exposed workers in the 5 successive days, but significant difference was observed between pre- and postshift samples. Conclusions: Urinary nickel may be used as a reliable internal dose bioindicator in biological monitoring of workers exposed to Ni sulfate in galvanizing plants regardless of the day of the workweek on which the samples are collected. Received: 28 January 1999 / Accepted: 10 July 1999     

Thyroid function in lead smelter workers: absence of subacute or cumulative effects with moderate lead burdens

Objective: To evaluate the effect of low to moderate occupational lead exposure on thyroid function we conducted a cross-sectional study of 151 male lead smelter workers. Methods: Parameters of thyroid function were assessed in relation to both subacute and cumulative lead exposure over a 10-year employment period. Blood lead levels, obtained from plant surveillance records, were used to establish four ordinal levels of current and cumulative exposure (<15, 15–24, 25–39, and ≥40 μ g/dl). Results: Mean values for the lowest as compared with the highest current exposure group were similar for thyroxine (T₄: 6.8 versus 6.1 μ g/dl), estimated free thyroxine (EFT₄: 1.6 ng/dl in both groups), and thyroid-stimulating hormone (TSH: 1.8 versus 1.7 mIU/l); there was no evidence of a significant trend for diminished thyroid function associated with increasing current lead exposure. Similarly, no significant difference was observed for T₄, EFT₄, or TSH in relation to the 10-year cumulative exposure or for adjusted analyses controlling for potential confounders, including age and alcohol use. Conclusion: In contrast to studies observing thyroid dysfunction in the setting of high lead exposure and related clinical poisoning, our findings weigh against a significant physiologic effect on thyroid function at lower levels (<60 μ g/dl) of occupational lead exposure. Received: 3 August 1997 / Accepted: 8 July 1998     

Manganese exposure in foundry furnacemen and scrap recycling workers

Objectives: Cast iron products are alloyed with small quantities of manganese, and foundry furnacemen are potentially exposed to manganese during tapping and handling of smelts. Manganese is a neurotoxic substance that accumulates in the central nervous system, where it may cause a neurological disorder that bears many similarities to Parkinson's disease. The aim of the study was to investigate the sources and levels of manganese exposure in foundry furnacemen by a combined measuring of blood-manganese (B-Mn) and manganese in ambient air (air-Mn). Methods: During a period of 16 months, Air-Mn and B-Mn (denoted `exposure values') were measured involving 24 furnacemen employed in three small size foundries and 21 scrap recycling workers from one plant. In the study period, 18 furnacemen had B-Mn measured 3–4 weeks after decreasing or stopping exposure (denoted `post-exposure values'). The reference group for the B-Mn measurements consisted of 90 Danish male subjects. Results: Furnacemen who work in insufficiently ventilated smelting departments inhale, absorb, and retain significant amounts of manganese in their blood (approx. 2.5–5 μg/l above reference values) despite a generally low measured airborne level of manganese fumes (0.002–0.064 mg/m³). The `exposure values' compared with `post-exposure values' revealed a significant decrease in the B-Mn (on average 3.7 μg/l) level of the most exposed furnacemen. Two persons in our study were suspected of suffering clinically subacute manganese intoxication as both had B-Mn levels beyond the normal limit (25 and 29 μg/l, respectively). The potential problem disappeared completely after cessation of exposure, and the B-Mn levels decreased to 9.4 and 14.1 μg/l, respectively. Conclusions: Risk assessment based on combined measurements of B-Mn and air-Mn seems to be valid in the interpretation of workers' hazard. Our study indicates that B-Mn may be a valuable parameter for estimating recent exposure (within 1–2 weeks). However, more knowledge is needed about the B-Mn level and its relation to neurological symptoms. Received: 20 January 1999 / Accepted: 14 June 1999     

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 μg/m³ in the furnace area and 0.31 μg/m³ in the casting area. Median values of 0.03 to 0.12 μg/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 μg/l with observation of the recommended TLV-TWA for inhalable dust of 0.2 μg/m³ (0.2 μg/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. Received: 15 May 2000 / Accepted: 8 September 2000     

Albumin, transferrin and α2-macroglobulin in bronchoalveolar lavage fluid following exposure to organic dust in healthy subjects

Objectives: The purpose of the present study was to investigate leakage of plasma proteins in connection with the inflammatory airway reaction following exposure to dust in a pig house. Inhalation of swine-house dust causes intense inflammation with influx of inflammatory cells, predominantly neutrophils, into the airways. The aim of the study was to compare the concentration of three different proteins in bronchoalveolar lavage (BAL) fluid as markers for the inflammation. Methods: In twenty healthy, non-allergic, non-smokers, not previously exposed to farm dust, BAL was performed ≈2 weeks before and 24 h after 3 h of exposure to swine dust in a swine-confinement building. Differential cell count and protein concentration were assessed in BAL fluid. Albumin (66.5 kDa) and α₂-macroglobulin (720 kDa) were quantified by the use of enzyme-linked immunosorbent assay (ELISA) techniques, and transferrin (80 kDa) by zone immunoelectrophoresis assay. The coefficient of variation for repeated protein measurements was <9%. Results: α₂-Macroglobulin concentration increased six-fold, from 68.0 (36.1–99.9) μg/l, mean (95% CI) before exposure to 411.2 (254.0–568.4) μg/l after exposure (P < 0.001). Transferrin and albumin increased from 19.7 (16.2–23.1) mg/l and 1.8 (1.4–2.2) mg/l, 2.6 and 1.9 times, respectively (P < 0.001). There was significant correlation between the exposure-induced increased protein levels in BAL fluid, although α₂-macroglobulin was a better discriminator of pre- and post-exposure concentrations than were albumin and transferrin. There was a significant correlation between the exposure-induced BAL-fluid neutrophilia and the increase in α₂-macroglobulin and transferrin, but not for albumin. This correlation was found only when pre- and post- differences, but not ratios, of plasma proteins were compared. Conclusions: The levels of plasma proteins increased in BAL fluid following exposure to swine-house dust. α₂-Macroglobulin was a better marker of this plasma leakage than were albumin and transferrin. Received: 25 July 2000 / Accepted: 10 November 2000