Urinary N -acetyl-β-glucosaminidase as an indicator of renal dysfunction in electroplating workers

Objectives: To investigate chromium-induced renal dysfunction in electroplating workers. Methods: A cross-sectional study was used to evaluate four biochemical markers of renal function. A total of 178 workers were divided into 3 comparable groups consisting of 34 hard-chrome plating workers, 98 nickel-chrome electroplating workers, and 46 aluminum anode-oxidation workers, who represented the reference group. Ambient and biological monitoring of urinary chromium were performed to measure exposure concentrations. Results: Overall, urinary chromium concentrations were highest among hard-chrome plating workers (geometric mean 2.44 μg/g creatinine), followed by nickel-chrome electroplating workers (0.31 μg/g creatinine) and aluminum workers (0.09 μg/g creatinine). Airborne chromium concentrations were also highest in the hard-chrome plating area (geometric mean 4.20 μg/m³), followed by the nickel-chrome electroplating area (0.58 μg/m³) and the aluminum area (0.43 μg/m³). A positive correlation was found between urinary chromium and airborne concentrations (r = 0.54, P < 0.01). Urinary concentrations of N-acetyl-β-d-glucosaminidase (NAG) were also highest among hard-chrome plating workers (geometric mean 4.9 IU/g creatinine), followed by nickel-chrome workers (3.4 IU/g creatinine) and aluminum workers (2.9 IU/g creatinine). The prevalence of “elevated” NAG (>7 IU/g creatinine) was significantly highest among hard-chrome plating workers (23.5%), then among nickel-chrome workers (7.1%) and aluminum workers (8.7%). Differences in β₂-microglobulin, total protein, and microalbumin were not significant. Conclusion: The author's evidence indicates that NAG is an early indicator of renal dysfunction in hard-chrome plating workers.     

Biological monitoring of occupational exposure to cyclohexane by urinary 1,2- and 1,4-cyclohexanediol determination

Objectives: This article reports the results obtained with the biological and environmental monitoring of occupational exposure to cyclohexane using 1,2-cyclohexanediol (1,2-DIOL) and 1,4-DIOL in urine. The kinetic profile of 1,2-DIOL in urine suggested by a physiologically based pharmacokinetic (PBPK) model was compared with the results obtained in workers. Methods: Individual exposure to cyclohexane was measured in 156 workers employed in shoe and leather factories. The biological monitoring of cyclohexane exposure was done by measurement of 1,2-DIOL and 1,4-DIOL in urine collected on different days of the working week. In all, 29 workers provided urine samples on Monday (before and after the work shift) and 47 workers provided biological samples on Thursday at the end of the shift and on Friday morning. Another 86 workers provided biological samples at the end of the work shift only on Monday or Thursday. Results: Individual exposure to cyclohexane ranged from 7 to 617 mg/m³ (geometric mean value 60 mg/m³). Urinary concentrations of 1,2-DIOL (geometric mean) were 3.1, 7.6, 13.2, and 6.3 mg/g creatinine on Monday (pre- and postshift), Thursday (postshift) and Friday (pre-shift), respectively. The corresponding values recorded for 1,4-DIOL were 2.8, 5.1, 7.8, and 3.7 mg/g creatinine. A fairly close, statistically significant correlation was found between environmental exposure to cyclohexane and postshift urinary 1,2-DIOL and 1,4-DIOL on Monday. Data collected on Thursday and Friday showed only a poor correlation to exposure with a wide scatter. Both metabolites have a urinary half-life of close to 18 h and accumulate during the working week. Conclusions: Comparison between data obtained from a PBPK model and those found in workers suggests that 1,2-DIOL and 1,4-DIOL are urinary metabolites suitable for the biological monitoring of industrial exposure to cyclohexane. Received: 17 June 1998 / Accepted: 23 September 1998     

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     

Exposure to cobalt and nickel in the hard-metal production industry

Objective The shortage of cobalt (Co) on the metal market forced the industry to add nickel (Ni) to Co as a binding agent for the sintering of hard metal. This change enabled us to study (1) the exposure to Ni powder and (2) the effect of Ni on Co uptake (and vice versa). Methods Equal amounts of Co and Ni were used in the mixture in a plant employing 50 workers. Both personal ambient-air samples and single-void urine samples were taken twice in the same week, i.e., on Monday and Thursday. Atomic absorption spectroscopy (AAS) was used for analyses. Results The airborne availability of Ni (mean value 41.65 ± 6.29 μg/m³) was 2-fold that of Co (mean value 21.85 ± 24.25 μg/m³), although the two series of data (n = 20) were significantly correlated. Even if the Co and Ni urinary concentration values (n = 45) recorded on Monday morning and Thursday evening were significantly correlated, at the end of the week there was a 3-fold increase, specifically, from 7.3 to 22.28 μg/l, in Co elimination (a significant difference) and a 30% increase in Ni elimination from 11.98 to 15.83 μg/l. Moreover, on Monday morning, 90% of Ni urinary concentration values were higher than those of Co as opposed to only 33% on Thursday evening. In the six cases in which both airborne and urine determinations were performed on the 2 days, no significant relationship was found between external exposure and biological monitoring data. Conclusions Although Ni uptake was variable, it was generally low, whereas Co uptake was substantial, as had previously been observed in the same plant when Co was the only binder under use. It was therefore possible to rule out any influence of Ni exposure on Co uptake and to suggest the contrary, as has been demonstrated in bacterial species and in rats using everted intestinal sacs. Received: 18 March 1997 / Accepted: 2 October 1997     

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     

Blood benzene concentrations in workers exposed to oxygenated fuel in Fairbanks,Alaska

 Objective: In November 1992 residents of Fairbanks, Alaska became concerned about the potential health effects of an oxygenated fuel program during which 15% (by volume) methyl tertiary butyl ether (MTBE) was added to gasoline. To address those concerns, we earlier completed a survey of occupational exposure to MTBE. We conducted a follow-up survey of workers’ exposure to benzene from gasoline in Fairbanks. Design: Cross-sectional exposure survey. Methods: We examined blood concentrations of benzene from a convenience sample of workers taken in December 1992 during the oxygenated fuel program and from another convenience sample of workers taken in February 1993 after the program was suspended. Results: In December, the median blood benzene concentration of samples taken from four mechanics after their workshift (postshift) was 1.32  μg/l (range, 0.84–2.61 μg/l), and seven nonmechanics (drivers and other garage workers) had a median postshift blood benzene concentration of 0.27 μg/l (range, 0.09– 0.45 μg/l). In February, nine mechanics had a median postshift blood benzene concentration of 1.99 μg/l (range, 0.92–3.23 μg/l), and nine nonmechanics had a median postshift blood benzene concentration of 0.26 μg/l (range, 0.2–0.46 μg/l). Conclusion: Mechanics had higher blood benzene concentrations than did nonmechanics, but further study is needed to determine the impact of the oxygenated fuel program on exposure to benzene. Received: 6 November 1995/Accepted: 2 April 1996     

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     

Distribution of nickel in lungs from former nickel workers

Objective: The purpose of this work was to study the distribution of nickel within lung tissue obtained from nickel-exposed people and to evaluate the␣use of only one single sample for determination of the nickel burden of the lung. Methods and materials: The material used was lung tissue obtained from 15 former nickel refinery workers who had been exposed to a variety of nickel compounds such as Ni₃S₂, NiO, Ni⁰, NiSO₄, and NiCl₂. Ten samples taken from different locations of the lung as well as from the right and left bronchus and from the right lower lobe (total 13 samples per individual) were analyzed for nickel by electrothermal atomic absorption spectrometry. Samples obtained from ten people not connected to the refinery served as a reference group. Results: The arithmetic mean value ± SD for nickel concentration was 50 ± 150 μg g⁻¹ dry wt. Biopsies collected on the center of the lower right lobe had an average nickel concentration of 82 ± 252 μg g⁻¹. The average nickel concentration detected in the right and left bronchus was 5.9 ± 11.6 and 3.8 ± 6.0 μg g⁻¹, respectively. Lung tissue obtained from ten people not connected to the refinery had an average nickel concentration of 0.74 ± 0.44 μg g⁻¹. Conclusions: The significant findings based on log-normal distribution of the nickel concentration were as follows: (1) samples obtained from the right lung showed no significant difference from samples taken from the left lung–a comparison of the nickel concentration detected in all the lung lobes showed that no single lobe differed from another; (2) the concentration of nickel found in the main bronchus of the refinery workers, although elevated, was significantly lower than the concentration detected in the remaining tissue; and (3) one single biopsy did not reflect the nickel burden of the lung. Received: 20 November 1997 / Accepted: 21 April 1998     

Biological monitoring of environmental exposure to polycyclic aromatic hydrocarbons in subjects living in the vicinity of a creosote impregnation plant

Objective: This study was undertaken to evaluate the environmental exposure to polycyclic aromatic hydrocarbons (PAHs) in nonsmoking adult subjects living in the vicinity of a creosote impregnation plant in Delson, Canada. Urinary metabolites of naphthalene, α- and β-naphthol, and pyrene metabolite 1-hydroxypyrene (1-OHP), were used as biomarkers of exposure. Methods: Morning and evening urine samples were collected in mid-August from 30 exposed individuals living at a distance of 50–360 m downwind of the plant and from a control group in the adjoining municipality residing at a distance of 1.9–2.7 km upwind of the plant. Metabolites were measured by gas chromatography/mass spectrometry. Results: Excretion values of α- and β-naphthol were significantly higher in the exposed group than in controls (P < 0.04), after accounting for possible confounding variables by multivariate analyses. The respective geometric mean concentrations (5th and 95th percentiles) of α-naphthol for the exposed and nonexposed groups were 2.04 (0.55–6.00) and 1.37 (0.39–7.02) μmol/mol creatinine for evening samples, and 2.49 (0.77–8.43) and 1.17 (0.37–6.88) μmol/mol creatinine for morning samples. Corresponding values for β-naphthol were 1.78 (0.82–3.67) and 1.36 (0.63–5.07) μmol/mol creatinine for evening samples, and 1.94 (1.03–4.96) and 1.08 (0.49–5.05) μmol/mol creatinine for morning samples. On the other hand, no significant difference in 1-OHP excretion was observed between the exposed and the control group (P>0.5). The respective geometric mean concentrations (5th and 95th percentiles) of 1-OHP for these groups were 0.05 (0.01–0.17) and 0.06 (0.01–0.48) μmol/mol creatinine for evening samples, and 0.05 (0.02–0.12) and 0.05 (0.01–0.42) μmol/mol creatinine for morning samples. Conclusions: The measurement of α- and β-naphthol urinary concentrations appears to be an approach sufficiently sensitive to reveal differences in low exposure levels of volatile PAHs due to creosote impregnation plant emissions. However, uptake of pyrene due to the plant was too small to contribute significantly to 1-OHP excretion. Received: 13 June 2000 / Accepted: 21 April 2001     

Human toxicokinetics of inhaled monochlorobenzene: latest experimental findings regarding re-evaluation of the biological tolerance value

Objective: The aim of this study was to obtain toxicokinetic data on the absorption and elimination of monochlorobenzene (MCB) in blood and its main metabolite 4-chlorocatechol (4-ClCat) as well as on the isomeric chlorophenols (o-ClPh, m-ClPh, and especially p-ClPh as the main ClPh metabolite) in urine for re-evaluation of the biological tolerance (BAT) value of MCB. Methods: Eight subjects performed 8-h inhalation tests daily over five successive days in an exposure chamber, at a maximum allowable concentration at the workplace (MAK) value of 10 ppm MCB. Five and two probands carried out the test series during physical activity levels of 75 and 50 W, respectively, for 10 min/h on a bicycle ergometer, and one subject was exposed continuously while at rest. MCB and its metabolites were analyzed by gas chromatography in combination with mass spectrometry. Results: The mean MCB blood concentration of the five subjects exposed during physical activity of 75 W was 217 ± 42 μg/l. The relationship of the mean blood concentration measured under the conditions of rest or 50 and 75 W activity levels was in a ratio of about 1:1.7:2.8. The half-life values in the first hour after ending the exposures were 53 min and 150 min for the ensuing period, with steady-state being reached after 45 min. The mean 4-ClCat concentration in urine at the end of the five days was 150 ± 13 mg/g creatinine in the case of the subjects exposed at 75 W, which decreased to 25 mg/g creatinine at the beginning of the next exposure. The analogous p-ClPh concentrations were 25 ± 2 and 9 ± 2 mg/g creatinine. The elimination half-life values of the ClPh isomers ranged from 12.4 to 16.5 h, and the half-life of 4-ClCat was 6.4 h. There was no apparent tendency for MCB and its metabolites to accumulate in blood or urine. Conclusions: The results are in accordance with relevant field and laboratory studies. Taken into consideration with the 95th percentile, the evaluated BAT values should be set at levels of 300 μg MCB/l blood, 175 mg 4-ClCat/g creatinine or alternatively at 30 mg p-ClPh/g creatinine in urine after the end of a shift. At the beginning of the next shift, the BAT values of the metabolites should be 35 and 15 mg/g creatinine, respectively. Received: 20 December 1999 / Accepted: 25 April 2000     

Biological monitoring of triethylamine among cold-box core makers in foundries

Objectives: The objectives of the study were to assess triethylamine (TEA) exposure in cold-box core making and to study the applicability of urinary TEA measurement in exposure evaluation. Methods: Air samples were collected by pumping of air through activated-charcoal-filled glass tubes, and pre- and postshift urine samples were collected. The TEA concentrations were determined by gas chromatography. Design: Tea was measured in air and urine samples from the same shift. Breathing-zone measurements of 19 workers in 3 foundries were included in the study, and stationary and continuous air measurements were also made in the same foundries. Pre- and postshift urine samples were analyzed for their TEA and triethylamine-N-oxide (TEAO) concentrations. Results: The TEA concentration range was 0.3–23 mg/m³ in the breathing zone of the core makers. The mean 8-h time-weighted average exposure levels were 1.3, 4.0, and 13 mg/m³ for the three foundries. Most of the preshift urinary TEA concentrations were under the detection limit, whereas the postshift urinary TEA concentrations ranged between 5.6 and 171 mmol/mol creatinine. The TEAO concentrations were 4–34% (mean 19%) of the summed TEA+TEAO concentrations. The correlation between air and urine measurements was high (r = 0.96, P < 0.001). A TEA air concentration of 4.1 mg/m³ (the current ACGIH 8-h time-weighted average threshold limit value) corresponded to a urinary concentration of 36 mmol/mol creatinine. Conclusions: The TEA exposure levels of foundries and their core makers vary greatly. Stationary air measurements in factories are not sufficient to assess TEA exposure; instead, personal sampling is needed. The biological monitoring of TEA in postshift urine samples provides a practical and accurate method for assessing exposure. Received: 9 May 1997 / Accepted: 27 August 1997     

Indoor exposure to polycyclic aromatic hydrocarbons and carbon monoxide in traditional houses in Burundi

Objectives: Wood combustion is used as a major energy source in African countries and could result in indoor, pollution-related health problems. This exploratory study was undertaken to estimate polycyclic aromatic hydrocarbon (PAH) and carbon monoxide exposure in individuals living in traditional rural houses in Burundi. Methods: Standard methods were used to determine indoor air concentrations of 12 PAHs, and carbon monoxide. The urinary excretion of 1-hydroxypyrene (1-OHP) was measured in occupants of traditional houses, and compared with that of individuals living in the town of Bujumbura, the capital of Burundi. Results: Mean airborne concentration of four volatile PAHs, naphthalene, fluorene, phenanthrene and acenaphthene, exceeded 1 μg/m³, and that of benzo(a)pyrene was 0.07 μg/m³. Naphthalene was by far the main PAH contaminant, with a mean concentration (±standard deviation) of 28.7 ± 23.4 μg/m³, representing on average 60–70% of total PAH concentration. Carbon monoxide mean concentration (±standard deviation) was 42 ± 31 mg/m³, and correlated with total PAH concentration. Geometric mean urinary 1-OHP excretion (range) in people living in traditional houses was 1.50 (0.26–15.62) μmol/mol creatinine, a value which is on average 30 times higher than that of people living in the capital (0.05 (0.009–0.17) μmol/mol creatinine). Conclusions: It appears that the substantially high concentrations of the studied contaminants constitute a potential health hazard to the rural population of Burundi. Received: 15 July 1999 / Accepted: 20 November 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     

Exposure-response relationships in rhinitis and conjunctivitis caused by methyltetrahydrophthalic anhydride

Objective: To examine exposure-response relationships in the occurrence of symptoms of the eyes and airways in workers exposed to methyltetrahydrophthalic anhydride (MTHPA). Methods: A population of 111 workers from 2 condenser plants (A and B) using epoxy resin with MTHPA underwent a questionnaire survey and serology investigations, and data obtained on 95 subjects in assembly and inspection lines were analyzed for this study. Results: In all, 24 (65%) of 37 workers in plant A and 38 (66%) of 58 workers in plant B had positive MTHPA-specific IgE. The air levels of MTHPA detected in assembly and inspection lines were higher in plant A than in plant B (geometric mean 25.5–63.9  and 4.93–5.49 μg/m³, respectively). IgE-sensitized workers in each plant had significantly (P < 0.05) more complaints regarding the eyes and nose than did unsensitized workers, suggesting that there is an IgE-mediated mechanism in most of these symptoms. The sensitized workers in plant A had higher frequencies for symptoms of the eyes, nose, and pharynx than did those in plant B (P < 0.02). Furthermore, only 15% of persons often displayed work-related symptoms among the 20 symptomatic workers in plant B as compared with 73% of the 26 symptomatic workers in plant A (P < 0.0001). These results can be explained by the difference in the MTHPA levels measured in the lines between the two plants. In plant B the minimal level of MTHPA that was associated with work-related symptoms was 15–22 μg/m³, which was lower than the geometric mean levels detected in assembly and inspection lines in plant A. Conclusions: These results suggest that MTHPA exposure at levels above 15 μg/m³ should be avoided to prevent the development of occupational allergic diseases in most workers. Received: 4 May 1998 / Accepted: 4 August 1998     

Comparison between blood and urinary toluene as biomarkers of exposure to toluene

Objectives: To compare blood toluene (TOL-B) and urinary toluene (TOL-U) as biomarkers of occupational exposure to toluene, and to set a suitable procedure for collection and handling of specimens. Method: An assay based on headspace solid-phase microextraction (SPME) was used both for the determination of toluene urine/air partition coefficient (λ_urine/air) and for the biological monitoring of exposure to toluene in 31 workers (group A) and in 116 non-occupationally exposed subjects (group B). Environmental toluene (TOL-A) was sampled during the work shift (group A) or during the 24 h before specimen collection (group B). Blood and urine specimens were collected at the end of the shift (group A) or in the morning (group B) and toluene was measured. Results: Toluene λ_urine/air was 3.3 ± 0.9. Based on the specimen/air partition coefficient, it was calculated that the vial in which the sample is collected had to be filled up to 85% of its volume with urine and 50% with blood in order to limit the loss of toluene in the air above the specimen to less than 5%. Environmental and biological monitoring of workers showed that the median personal exposure to toluene (TOL-A) during the work-shift was 80 mg/m³, the corresponding TOL-B was 82 μg/l and TOL-U was 13 μg/l. Personal exposure to toluene in environmentally exposed subjects was 0.05 mg/m³, TOL-B was 0.36 μg/l and TOL-U was 0.20 μg/l. A significant correlation (P < 0.05) was observed between TOL-B or TOL-U and TOL-A (Pearson's r=0.782 and 0.754) in workers, but not in controls. A significant correlation was found between TOL-U and TOL-B both in workers and in controls (r=0.845 and 0.681). Conclusion: The comparative evaluation of TOL-B and TOL-U showed that they can be considered to be equivalent biomarkers as regards their capacity to distinguish workers and controls and to correlate with exposure. However, considering that TOL-U does not require an invasive specimen collection, it appears to be a more convenient tool for the biological monitoring of exposure to toluene. Received: 20 October 1999 / Accepted: 4 March 2000     

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     

Measured exposures by personal monitoring for respirable suspended particles and environmental tobacco smoke of housewives and office workers resident in Bremen, Germany

Objective : Exposures to respirable suspended particles (RSP) and environmental tobacco smoke (ETS) were assessed in Bremen, Germany, as part of a European air quality study. The range and level of personal exposures were assessed for housewives and office workers. Design : Nonsmokers were randomly selected from a representative sample of the population of Bremen. Housewives were recruited into one group primarily for assessment of exposures in the home and office workers, into a second group for assessment of the contribution of the workplace to overall exposure. Methods : A total of 190 subjects collected air samples from areas close to their breathing zone by wearing personal monitors for 24 h. Samples collected were analysed for RSP, ultraviolet-absorbing particulate matter (UVPM), fluorescing particulate matter (FPM), solanesol-related particulate matter (SolPM), nicotine and 3-ethenylpyridine (3-EP). Saliva cotinine levels for all subjects were also established. Results : Overall the levels found were quite low, with the majority of results being below the limit of quantification. Workers both living and working with smokers were exposed to the highest 24-h median quantities of RSP (789 μg) and ETS particles (128 μg) measured by FPM. The highest nicotine levels, based on median 24-h time-weighted average concentrations, were experienced by office workers working with smokers (0.69 μg m⁻³). These workers were also found to have␣the highest median cotinine levels (1.6 ng ml⁻¹). Conclusions: The most highly exposed workers, both living and working with smokers, would potentially inhale over 20 cigarette equivalents (CE) per annum as based on the upper decile levels. Housewives living with smokers could inhale up to 11 CE per annum as based on the upper decile levels. Locations outside the workplace, including the home, contribute most to overall RSP and ETS particle exposure. Consideration should be given to extending the personal monitoring period in cities where levels appear to be quite low. Received: 9 May 1997 / Accepted: 17 October 1997     

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 μg/m³ was exceeded in two cases. The mean values of the sum of eight PAHs were 12.6 μg/m³ (stationary air measurement) and 22.2 μg/m³ (personal air measurement). Urinary 1-hydroxypyrene excretion predominated, with a median of 11.1 μg/g creatinine (creat.), followed by 3-hydroxyphenanthrene (median 2.2 μg/g creat.), 1-hydroxyphenanthrene (median 1.9 μg/g creat.) and 2-hydroxyphenanthrene (median 1.6 μg/g creat.). 4-Hydroxyphenanthrene (median 0.3 μg/g creat.) and 3-hydroxybenz(a)anthracene (median 0.17 μg/g creat.) were found in far lower concentrations, while 3-hydroxybenzo(a)pyrene was found only in very low concentrations (median 0.014 μg/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. Received: 3 November 1999 / Accepted: 26 January 200     

Liver function in workers exposed to N,N-dimethylformamide during the production of synthetic textiles

In a factory producing synthetic fibers the hepatotoxic effects of the solvent N,N-dimethylformamide (DMF) were investigated in 126 male employees, especially with regard to the combination effects of DMF exposure and ethyl alcohol consumption. A collective of similar structure from the same factory served as a control collective. Methods: Reference is made to the results of air measurements and biological monitoring presented in a previous publication. The DMF concentrations in the air ranged from <0.1 (detection limit) to 37.9 ppm (median 1.2 ppm). Concentrations of the DMF metabolite N-methylformamide (NMF) in urine were 0.05–22.0 mg/l (preshift) and 0.9–100.0 mg/l (postshift), corresponding to 0.02–44.6 mg/g creatinine (preshift) and 0.4–62.3 mg/g creatinine (postshift). A standardized anamnesis was drawn up for relevant previous illnesses and other factors influencing liver function. The laboratory tests included parameters especially relevant to the liver (e.g., AST, ALT, γ-GT, hepatitis B and C antibodies, and carbohydrate-deficient transferrin). Results: The results indicate a statistically significant toxic influence of DMF on liver function. Alcohol has a synergistic effect. The effects of DMF and those of alcohol are dose-dependent. Under the existing workplace conditions the hepatotoxic effects of alcohol are more severe than those of DMF. In the exposed group there was a statistically significantly greater number of persons who stated that they had drunk less since the beginning of exposure (13% versus 0). This corresponded with the data on symptoms occurring after alcohol consumption (71% versus 4%). In the work areas with lower-level exposure to DMF there was greater alcohol consumption. It corresponded to that of the control collective not exposed to DMF. Conclusion: In this study we tried to differentiate and quantify the interaction between DMF exposure and alcohol consumption and the influence of both substances on liver function. The experience gained from former occupational health surveillance in DMF-exposed persons and from the present study show that there are individual differences in tolerance of interactions between DMF and ethyl alcohol. Further studies are necessary for the evaluation of these individual degrees of susceptibilitiy. Received: 23 February 1998 / Accepted: 19 August 1998     

Biological monitoring of occupational exposure to N,N -dimethylformamide – the effects of co-exposure to toluene or dermal exposure

Objectives: The objective of this study is to assess the exposure and intake dose of N,N-dimethylformamide (DMF) and the correlation between them, according to the type of exposure for the workers in the DMF industry. Methods: We monitored 345 workers occupationally exposed to DMF, from 15 workshops in the synthetic fiber, fiber coating, synthetic leather and paint manufacturing industries. Ambient monitoring was carried out with personal samplers to monitor the external exposure. Biological monitoring was done to determine the internal dose by analyzing N-methylformamide (NMF) in end-shift urine. Work procedure and exposure type of each DMF workshop was carefully surveyed, to classify workers by exposure type according to work details. Workers were classified into three groups (Group A: continuous and direct exposure through inhalation and skin; Group B: intermittent and short-term exposure through inhalation and skin; Group C: continuous and indirect exposure mostly through inhalation). Results: Geometric mean of DMF concentration in air was 2.62 (GSD 5.30) ppm and that of NMF in urine was 14.50 (GSD 3.89) mg/l. In the case of continuous absorption through inhalation and dermal exposure (Group A), the value of NMF in urine corresponding to 10 ppm of DMF was 45.3 mg/l (r=0.524, n=178), 39.1 mg/g creatinine (r=0.424), while it was 37.7 mg/l (r=0.788, n=37), 24.2 mg/g creatinine (r=0.743) in the case of absorption mostly through inhalation (Group C). Creatinine correction reduced the correlation between two parameters. Conclusion: The NMF in urine corresponding to 10 ppm DMF, of the dermal and inhalation exposure group was 39.1 mg/g creatinine (r=0.424, n=178), while that of the inhalation exposure-only group was 24.2 mg/g creatinine (r=0.743, n=37). Co-exposure with toluene reduced the NMF excretion in urine. Received: 4 October 1999 / Accepted: 25 April 2000