Toluene in blood as a marker of choice for low-level exposure to toluene

The validity of two new biological exposure markers of toluene in blood (TOL-B) and toluene in urine (TOL-U) was examined in comparison with that of the traditional marker of hippuric acid in urine (HA-U) in 294 male workers exposed to toluene in workroom air (TOL-A), mostly at low levels. The exposure was such that the geometric mean for toluene was 2.3 ppm with a maximum of 132 ppm; the workers were also exposed to other solvents such as hexane, ethyl acetate, styrene, and methanol, but at lower levels. The chance of cutaneous absorption was remote. Higher correlation with TOL-A and better sensitivity in separating the exposed workers from the nonexposed subjects were taken as selection criteria. When workers exposed to TOL-A at lower concentrations (< 50 ppm, < 10 ppm, < 2 ppm, etc.) were selected and correlation with TOL-A was examined, TOL-B showed the largest correlation coefficient which was significant even at TOL-A of < 1 ppm, whereas correlation of HA-U was no longer significant when TOL-A was < 10 ppm. TOL-U was between the two extremes. The sensitivities of TOL-B and TOL-U were comparable; HA-U showed the lowest sensitivity. Thus, it was concluded that TOL-B is the indicator of choice for detecting toluene exposure at low levels.     

Toluene itself as the best urinary marker of toluene exposure

Head-space gas chromatography (GC) and high-performance liquid chromatography (HPLC) (with fluorescence detectors) methods were developed for toluene (TOL-U) and o-cresol (CR-U) in urine, respectively. In order to identify the most sensitive urinary indicator of occupational exposure to toluene vapor (TOL-A) among TOL-U, CR-U, and hippuric acid in urine (HA-U), the two methods together with an HPLC (with untraviolet detectors) method for determination of HA-U were applied in the analysis of end-of-shift urine samples from 115 solvent-exposed workers (exposed to toluene at 4 ppm as geometric mean). Regression analysis showed that TOL-U correlated with TOL-A with a significantly higher correlation coefficient than did HA-U or CR-U. With regard to the TOL-A concentrations at which the exposed subjects could be separated from the nonexposed by the analyte, TOL-U achieved separation at < 10 ppm TOL-A, whereas both HA-U and CR-U did so only when TOL-A was 30 ppm or even higher. The ratio of the analyte concentrations at 50 ppm TOL-A to those at 0 ppm TOL-A was also highest for TOL-U. Overall, the results suggest that TOL-U is a better marker of exposure to toluene vapor than HA-U or CR-U.     

Comparison between urinary o-cresol and toluene as biomarkers of toluene exposure

The characteristics of urinary o-cresol (o-C) and urinary toluene (TOL-U) as biomarkers of occupational exposure to toluene were comparatively evaluated. One hundred healthy male rotogravure printing workers and 161 male and female control subjects were studied. Personal exposure to airborne toluene (TOL-A) during the shift was determined as a time-weighted average. Simple analytical procedures based on solid phase microextraction followed by gas chromatography/mass spectometry analysis were applied to the determination of end-shift o-C and TOL-U. Median TOL-A was 48 (6.0-162.0) mg/m3 in printers and 0.021 (<0.003-0.137) mg/m3 in controls. o-C was 0.185 (0.032-0.948) mg/g creatinine in printers and 0.027 (<0.006-0.330) mg/g creatinine in the controls. TOL-U was 7.6 (1.8-23.9) microg/L in printers and 0.140 (0.094-0.593) microg/L in the controls. According to all indices, exposure to toluene was higher in printers than in the controls. Nevertheless, the distribution of o-C in the two groups partially overlapped, whereas such behavior was not found in TOL-U. Both o-C and TOL-U in printers were correlated with TOL-A (Pearson's on log10-transformed variables r = 0.704 and 0.844, respectively) and with each other (r = 0.683). Smoking habits significantly increased the excretion of o-C but not of TOL-U. From the point of view of sampling conditions and analytical requirements, TOL-U and o-C showed similar properties, but comparison of their intrinsic characteristics showed that TOL-U had higher specificity and sensitivity, lower background values, was better correlated with airborne exposure, and was not influenced by cigarette smoking. Therefore TOL-U may be considered superior to o-C as a biomarker of occupational exposure to toluene.     

High-pressure liquid chromatographic determination of toluenein urine as a marker of occupational exposure to toluene

Objective: To establish a convenient method by high-pressure liquid chromatography (HPLC) to measure toluene in urine as a marker of occupational exposure to toluene. Methods: As soon after sampling as possible, 1 ml of urine was mixed with an equal volume of acetonitrile in a 2.2-ml HPLC glass bottle, and the bottle was tightly sealed and stored at 4 °C. Immediately before HPLC determination, 100 μl methanol was added to the mixture to prevent confounding effects of glycosuria, and the bottle was spun to remove any suspended matter. An aliquot of the supernate was introduced into the HPLC system and analyzed on a PRODIGY column, with an acetonitrile – perchloric acid – phosphoric acid – water mixture serving as the mobile phase. The effluent was monitored at 191 nm. Results: The method can measure toluene in urine every 20 min; the detection limit was 2 μg/l, the coefficient of variation was less than 5%, and the recovery rate was 100%. No significant reduction in toluene concentration was observed for 1 week after storage at 4 °C. When the method was applied to end-of-shift urine samples from 13 male workers exposed to toluene at 18–140 ppm and also to urine samples from 10 nonexposed male controls, toluene in urine was linearly related to toluene exposure concentration, with a regression line passing close to the origin. The correlation coefficient was as high as 0.97 (n = 23). No toluene was detected in control urine samples. Calculations suggest that urinary toluene accounts for as little as less than 0.01% of the toluene absorbed via inhalation and that the absorbed toluene is converted almost quantitatively to hippuric acid and, by less than 0.1%, to o-cresol. Received: 25 August 1997 / Accepted: 13 February 1998     

Self-collected urine sampling to study the kinetics of urinary toluene (and <Emphasis Type="Italic">o</Emphasis>-cresol) and define the best sampling time for biomonitoring

Purpose  To study the excretion kinetics of urinary toluene, TOL-U, and o-cresol, o-C, following occupational exposure to toluene in order to define the best time for sample collection, to apply a non-invasive approach based on self-collected urine sampling. Methods  Five rotogravure printing workers exposed to uncontrolled levels of toluene collected spot urine samples over three consecutive working days and the following day of rest. In each sample TOL-U and o-C were measured and kinetics of excretion evaluated. Results  Toluene exposure ranged from 48.3 to 75.3 mg/m³; TOL-U and o-C ranged from 1.4 to 34.6 μg/L and from 0.013 to 1.012 mg/L. A time course trend was obtained: TOL-U and o-C increased during the shift and peaked at the end of exposure and up to 2 h later, respectively; afterwards they rapidly decreased following apparent first order kinetics. Considering TOL-U, the elimination half-life for the first fast phase was 79 (±35 standard error) min, and for the second slow phase was 1,320 (±1,162) min. For o-C the elimination half-life for the first fast phase was 231 (±48) min. Considering a toluene uptake of 86%, TOL-U and o-C excreted in urine were about 0.0067 and 0.18% of the up taken. Conclusion  Our results support the use of end shift TOL-U as a short term biomarker of occupational exposure to toluene and show the feasibility of self-collected urine sampling to investigate the elimination kinetics of industrial toxics in humans.     

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     

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     

Cognitive functions in workers exposed to toluene: evaluation at least 48 hours after removal from exposure

Objectives: Long-term exposure to toluene may result in subtle impairment of cognitive functions. However, it is not clear whether this impairment is due to the presence of the solvent in the body or if it persists after its elimination from blood. The aim of this study is to compare cognitive functions between toluene-exposed workers (at least 48 h after removal from exposure) and non-exposed workers. Methods: Seventy-two workers exposed for at least 5 years to toluene (9 to 467 ppm) completed a questionnaire and psychometric tests. The results were compared with those of 61 non-exposed workers. An alveolar air sample was taken just before the tests to ensure the absence of toluene. Results: Results of the vocabulary test were slightly better in exposed (correct words: 21 ± 0.6) than in non-exposed workers (19 ± 0.8) (P < 0.05). No differences were found for simple reaction time, digit symbol, digit span, continuous tracking test, color word and switching attention test. Conclusions: The results of this study do not support the notion of the persistence of cognitive effects of toluene after elimination of the solvent from blood. Received: 5 June 2000 / Accepted: 9 December 2000     

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     

Biological monitoring of controlled toluene exposure

Objectives: Widespread exposure to toluene occurs in the printing, painting, automotive, shoemaking, and speaker-manufacturing industries. The relationship between air concentrations and the absorbed dose is confounded by dermal exposure, personal protective devices, movement throughout the workplace, and interindividual differences in toluene uptake and elimination. Methods: To determine the best biological indicator of exposure we examined the blood and alveolar breath concentrations of toluene as well as the urinary excretion rates of hippuric acid and of o-, m-, and p-cresols from 33 controlled human inhalation exposures to 50 ppm for 2 h. Results: Among the metabolites, o-cresol was least influenced by background contributions, whereas the p-cresol and hippuric acid rates were obscured by endogenous and dietary sources. Toluene levels in alveolar breath proved to be the most accurate and noninvasive indicator of the absorbed dose. A physiologic model described blood and breath data using four measured anthropometric parameters and the fit values of extrahepatic metabolism and adipose-tissue blood flow. Conclusions: After breathing rate and extrahepatic metabolism had been set to conservative (protective) values (the 97.5th and 2.5th percentiles, respectively) the model predicted that pre-final-shift breath levels of ≤10 μmol/m³ and post-final-shift levels of ≤150 μmol/m³ corresponded to average workplace exposure levels of ≤50 ppm toluene. Alternately, we used the distributions and covariances of the measured and fit model parameters to yield conservative pre-final-shift levels of ≤7.3 μmol/m³ and post-final-shift breath levels of ≤120 μmol/m³ that were reflective of workplace exposure levels of ≤50 ppm toluene. Received: 30 December 1997 / Accepted: 12 June 1998     

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     

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     

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     

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     

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     

TTCA measurements in biomonitoring of low-level exposure to carbon disulphide

Objectives: The biomonitoring of carbon disulphide exposure is currently performed by measuring the concentration of 2-thiothiazolidine-4-carboxylic acid (TTCA) in the urine of exposed workers. Methods: In this study the effect of TTCA, which is found in some vegetables, on the biomonitoring of low-level carbon disulphide exposure was evaluated. In addition the upper reference limit (URL) of TTCA in the non-exposed Finnish population was estimated by analysing TTCA in urine samples from 116 people. The samples were collected at health centres all over Finland from people in employment and in the age group 24–64 years. The analytical measurements were made using a modern column-switching technique and the results were compared with those from the same samples using the extraction method generally in use and, until now, recommended for the determination of TTCA in urine. Results: The results obtained with the two analytical methods correlated very well with each other (r=0.9). The liquid-liquid extraction method gave results constantly about 3.5 μmol/l higher than the column-switching method. The results of this study also confirmed that many cruciferous vegetables (Cruciferae) contain endogenous TTCA (0.6–5.0 mg/kg), which is excreted unchanged in the urine. After a normal meal which included these vegetables, the TTCA concentration did not rise above the biomonitoring action level even if this was as low as 2 mmol/mol creatinine, but was easily above the URL of TTCA in the non-exposed population. The URL, calculated as the 95th percentile, was 0.3 mmol/mol creatinine. Conclusion: The results showed that the extraction method was not sufficiently specific or sensitive when the TTCA concentrations were lower than 10 μmol/l. In contrast, the column-switching method seemed to give reliable results even at these low levels, which are the levels of interest in current practice. Received: 29 September 1999 / Accepted: 27 December 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     

Biological monitoring of methylhexahydrophthalic anhydride by determination of methylhexahydrophthalic acid in urine and plasma from exposed workers

Objective: To investigate whether methylhexahydrophthalic acid (MHHP acid) in urine and plasma can be used as a biomarker for exposure to methylhexahydrophthalic anhydride (MHHPA). Methods: MHHPA in air was sampled by Amberlite XAD-2 and analysed by gas chromatography (GC) with flame ionisation detection. MHHP acid in urine and plasma was analysed by GC with mass spectrometric detection. Workers occupationally exposed to MHHPA were studied. Air levels of MHHPA were determined by personal sampling in the breathing zone. Urinary levels of MHHP acid, a metabolite of MHHPA, were determined in 27 workers. In eight workers all urine was collected at intervals during 24 h. Plasma levels of MHHP acid were determined in 20 workers. Results: The time-weighted average (TWA) air levels ranged from 5 to 60 μg MHHPA/m³ during 8-h work-shifts. The urinary levels of MHHP acid increased during exposure and decayed after the end of exposure with an estimated half-life of about 6 h. A correlation was found between the TWA air levels of MHHPA and creatinine-adjusted MHHP acid levels in urine collected during the last 4 h of exposure. A correlation was also seen between the TWA air levels of MHHPA and the plasma concentrations of MHHP acid. An exposure to 20 μg MHHPA/m³ corresponded to about 140 nmol MHHP acid/mmol creatinine and about 40 nmol MHHP acid/l plasma. Conclusion: The results indicate that MHHP acid in urine or plasma may be used for biological monitoring of the exposure to MHHPA. Received: 4 October 1996 / Accepted: 2 January 1997     

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     

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.