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     

Urinary methanol and formic acid as indicators of occupational exposure to methyl formate

Objective: To evaluate the validity of methanol (MeOH) and formic acid (FA) in urine as biological indicators of methyl formate (MF) exposure in experimental and field situations. Methods: The subjects were 28 foundrymen and two groups of volunteers (20 control and 20 exposed). Exposure assessment of the workers was performed by personal air and biological monitoring. Methyl formate vapour collected on charcoal tube was analysed by gas chromatography. The concentration of MF in the exposure chamber (volunteer-study) was monitored by two independent methods [flame ionisation detection (FID) and Fourier transformation infra-red detection (FTIR)]. Urinary metabolites (MeOH and FA) were analysed separately by head-space gas chromatography. Results: The volunteers exposed to 100 ppm MF vapour at rest for 8 h excreted 3.62 ± 1.13 mg MeOH/l (mean ± SD) at the end of the exposure. This was statistically different (P < 0.001) from pre-exposure MeOH excretion (2.15 ± 0.80 mg/l), or from that of controls (1.69 ± 0.48 mg/l). The urinary FA excretion was 32.2 ± 11.3 mg/g creatinine after the exposure, which was statistically different (P < 0.001) from pre-exposure excretion (18.0 ± 9.3 mg/g creatinine) or that of controls (13.8 ± 7.9 mg/g creatinine). In foundrymen, the urinary FA excretion after the 8 h workshift exposure to a time weighted average (TWA) concentration of 2 to 156 ppm MF showed a dose-dependent increase best modelled by a polynomial function. The highest urinary FA concentration was 129 mg/g creatinine. The pre-shift urinary FA of the foundrymen (18.3 ± 5.6 mg/g creatinine) did not differ from that of controls (13.8 ± 7.9 mg/g creatinine). The urinary MeOH excretion of the foundrymen after the shift, varied from <1 to 15.4 mg/l, while the correlation with the preceding MF exposure was poor. The foundrymen excreted more (P=0.01) FA (2.12 ± 3.56 mg/g creatinine) after the workshift than experimentally, once-exposed volunteers (0.32 ± 0.11 mg/g creatinine) at a similar inhaled MF level of 1 ppm). Conclusions: In spite of its high background level in non-exposed subjects, urinary FA seems to be a useful biomarker of methyl formate exposure. The question remains as to what is the reason for the differences in chronic and acute exposure respectively. Received: 27 September 1999 / Accepted: 25 March 2000     

Adjustment to concentration-dilution of spot urine samples: correlation between specific gravity and creatinine

Objective: Spot urine samples were investigated to determine correlations between urinary creatinine and specific gravity, and intra- and inter-day variations other than gender- and age-dependence of urinary concentrations. Methods: Urinary creatinine concentrations and specific gravity were determined in 534 spot samples (385 from men and 149 from women). Subjects' ages ranged between 18 and 68 years. Spot urine samples were also collected from 14 male subjects before and after a 1-week work-shift for the evaluation of intra- and inter-day variations of creatinine and specific gravity. Results: In spot samples, creatinine concentrations ranged between 0.16 and 4.36 g/l and specific gravity between 1.002 and 1.037. A high correlation (r=0.82, P < 0.001) was observed between creatinine and specific gravity; male subjects showed significantly higher values of creatinine (P < 0.001) than did female subjects (1.90 ± 0.74 and 1.41 ± 0.72 g/l, respectively) and specific gravity (1.023 ± 0.006 and 1.020 ± 0.007, respectively). In addition, creatinine but not specific gravity significantly decreased (P < 0.02) in subjects older than 50 years, compared with those under 40. Conclusions: Results confirm the gender-dependence of creatinine concentrations in spot specimens and also show age-dependence, indicating the need for these aspects to be considered when the range of acceptable samples is to be set. No significant intra- or inter-day variations were observed for the two parameters. Lastly, the possibility of a comparison of differently adjusted values was indicated by a conversion formula derived from adjustments to creatinine and the corresponding specific gravity of a hypothetical urinary value, as follows: specific gravity adjusted values= 1.48 × creatinine adjusted values. Received: 14 February 2000 / Accepted: 26 July 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     

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     

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.     

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     

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     

Correspondence between occupational exposure limit and biological action level values for alkoxyethanols and their acetates

Objectives: The Finnish occupational exposure limit (OEL) values for alkoxyethanols and their acetates were lowered in 1996. A reevaluation of the correspondence between the new OEL value and the biological action level (BAL) was thus needed. This study was conducted in silkscreen printing enterprises, where 2-alkoxyethanols and their acetates are mainly used as solvents. The air/urine correlations between 2-methoxyethylacetate, 2-ethoxyethylacetate, 2-butoxyethanol, 2-butoxyethylacetate, and 2-methoxyacetic (MAA), 2-ethoxyacetic (EAA), and 2-butoxyacetic acid (BAA) were evaluated on an individual and time-related basis at four different enterprises. Methods: Inhalation exposure to alkoxyalcohols and their acetates was monitored with diffusion badges (n = 38) for an entire work week. Urinary excretion of alkoxyacetic acids immediately after the shift and at 14–16 h after exposure (n = 112) was analyzed by a gas chromatograph equipped with a flame-ionization detector. Results: Inhalation exposure to 2-methoxyethylacetate at 0.5 cm³/m³ corresponded to MAA excretion of 3 mmol/mol creatinine in urine at 14 to 16 hours after exposure. The next-morning urinary EAA excretion of 37 mmol/mol creatinine corresponded to an 8-h 2-ethoxyethylacetate exposure of 2 cm³/m³ when all collected data were included. This average EAA excretion was 69% of the German BAT value and only 34% of the American biological exposure index (BEI) value. Urinary EAA excretion was 30–40% lower at the beginning of the work week than at the end of the work week. On the other hand, EAA excretion was 10–20% higher than that measured at 14–16 h after exposure. Urinary BAA excretion of 75 mmol/mol creatinine in postshift urine corresponded to an 8-h 2-butoxyethanol and 2-butoxyethylacetate exposure of 5 cm³/m³. This BAA excretion was 87% of the German BAT value. Conclusion: According to these results, it seems that the BAL for MAA and EAA should be 3 and 50 mmol/mol creatinine as measured at 14–16 h after exposure, respectively. The BAL value for BAA seems to be 70 mmol/mol creatinine in postshift samples. These recommendations are valid only if samples are collected at the end of the work week. Received: 29 January 1997 / Accepted: 2 July 1997     

Human biomonitoring of antimony

Objectives : The aim of the study was to test the suitability of 24-h urine, blood, and scalp-hair samples as surrogates for the determination of internal exposure to antimony in case of a strongly elevated soil contamination with antimony. Methods : The biomonitoring was performed using graphite-furnace atomic absorption spectrometry. Blood and scalp-hair samples were decomposed by microwave digestion. Results : No elevated content of antimony could be detected in 24-h urine, blood, or scalp-hair samples from the study participants geogenically exposed to antimony. The results did not show a correlation between the antimony contents in the soil of the housing area and those in urine, blood, or hair. Surprisingly, the reference group (n=47) showed a significantly higher median antimony excretion rate than did the exposed group (n=89; 1.23 versus 0.60 μg Sb/24 h). Additionally, the scalp-hair contents of the reference group were also significantly higher than those of the exposed persons (0.045 versus 0.026 mg Sb/kg). Blood contents of the two study groups were 0.57 and 0.48 μg Sb/l, respectively. The detection limit for urine and blood was 0.5 μg Sb/l and that for scalp hair was 0.005 mg Sb/kg. Of all samples of urine, blood, and scalp hair analyzed, 31.2%, 49.3%, and 10.3%, respectively, were below the limit of analytical detection. Conclusions : The antimony contents recorded for both study groups in urine, blood, and scalp hair can be judged as being within the normal range. The rate of transfer of antimony from the soil to humans in the exposure case described seemed to be very low. With respect to analytical practicability and validity, urine was the surrogate which deemed most useful for determination of internal exposure to antimony. Received: 21 July 1997 / Accepted: 5 November 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     

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     

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     

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     

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     

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     

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 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