Isopropanol and methylformate exposure in a foundry: exposure data and neurobehavioural measurements

Objectives: The aim of this study was to determine the dose-effect relationship between solvent exposure and acute neurobehavioural effects at the worksite. Methods: In a balanced design, ten workers in a Swiss foundry were monitored for 15 days at ten different times during work. Urine samples were taken in the morning and at the time of examination, and personal exposure to isopropanol and methylformate was measured with active samplers. Neurobehavioural tests such as postural balance (bipedal, bipedal blind, monopedal), simple reaction time and digit span of the Neurobehavioural Evaluation System (NES2) and a combined memory and reaction-time test, the combi-test, were performed. A rating of well-being, and the last consumption of alcohol, caffeine, nicotine and medication were reported. Results: Average environmental concentrations of isopropanol were at 44 ppm (±16 ppm), and at 36 ppm (±21 ppm) for methylformate. Maximum values of personal exposure to isopropanol reached barely the maximal allowable concentration (MAC) value (400 ppm); the methylformate personal exposure of three workers exceeded the MAC value (100 ppm). Urine concentrations of methanol were high (3.1 ± 2.3 mg/l in the morning, 7.8 ± 4.9 mg/l after exposure) compared with the results of other studies; concentrations of isopropanol were rather low (0.88 ± 0.73 mg/l after exposure). Conclusions: Nevertheless, between personal exposure and biomonitoring, linear correlation was found. Methylformate exposure correlated with methanol and formic acid concentration in the urine, and isopropanol exposure with its concentration in the urine. With the neurobehavioural tests used, no solvent effect in relation to the dose could be determined. Received: 21 January 2000 / Accepted: 20 May 2000     

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     

Follow-up study of workers in a nylon carpet yarn plant after remedial actions taken against a contaminated humidification system

Objective: To investigate the effectiveness of remedial actions taken against a contaminated humidification system, after an outbreak of humidifier disease in a nylon carpet yarn plant. Methods: Two and 6 years after modification, a follow-up investigation of a stratified (age, smoking habits) sample of exposed (n=75) and non-exposed (n=56) workers was carried out. Outcome-parameters were: respiratory symptoms, spirometry, skin tests and serology with various humidifier fungi. In addition, the yearly incidence of work-disability because of chronic respiratory disease during the 2 years before, and 11 years after the modification was compared. Results: At follow-up, exposed workers, who remained at the same workplace no longer had significantly more frequent chronic respiratory symptoms. The prevalence of positive serology was still higher (P < 0.05) in exposed workers after 2 years, but at the 6 year follow-up investigation, the difference was no longer significant. Prevalence of positive skin tests after 2 years no longer differed from that of the non-exposed workers. Slopes (ml/years) of the graphs of forced vital capacity (FVC) and one-second forced expiratory volume (FEV₁) during the 6 year follow-up after the first investigation did not differ between exposed and non-exposed workers, both before and after adjustment for age, smoking habits and results of skin tests and serology before modification. Before modification, exposed workers with a positive late skin test had a lower FVC than non-exposed workers. After 6 years of follow-up their FVC was still lower, but the difference was no longer significant. There were no indications of selective loss to follow-up. After remedial actions no new cases of humidifier disease occurred. Moreover, the yearly incidence of work-disability in this plant because of chronic respiratory disease, decreased from 1.30% to 0.27% compared with a decrease from 0.30% to 0.12% in other synthetic fibre plants. Conclusion: Follow-up investigation of exposure-effects demonstrated the effectiveness of remedial actions taken against a contaminated humidification system. Received: 27 January 1999 / Accepted: 22 January 2000     

Study of some immunological parameters in workers occupationally exposed to benzene

Objective: The aim of the study was to investigate the immunotoxicity of benzene exposure, to establish the correlation between the exposure biomarkers and some immunological parameters, and to assess the possible influence of confounding factors on the results of immunological assay applicable in routine medical surveillance of benzene-exposed workers. Methods: Forty-nine female workers in the shoemaking industry who were exposed to solvent mixtures and 27 nonexposed controls were examined. Workers were exposed to benzene concentrations of up to 15 ppm, and to toluene of up to 50 ppm. Results: Significant differences in the levels of benzene and toluene in blood and phenols in post-shift urine between the exposed and the control group confirmed solvent exposure. The number of B-lymphocytes (P=0.01) was lower in the shoe workers than in the controls. Significant correlation was found between the level of immunoglobulin G and benzene in the work atmosphere, while confounding factors had no impact on immunological values. Conclusion: According to these results, exposure to benzene concentration lower than 15 ppm can induce depression of the circulating B-lymphocyte level and therefore this fact could be used to develop a promising method for health surveillance of benzene-exposed workers. However, considerably more effort in the research on benzene immunotoxicity, especially in the search for suitable health surveillance methods, is still required. Received: 15 July 1999 / Accepted: 22 January 2000     

Symptoms and serum precipitins in workers exposed to dry sausage mould: consequences of exposure to sausage mould

Objective: Hypersensitivity pneumonitis due to dry sausage mould has been reported in workers who brush off the excess mould which coats dry sausage. Prevalence of symptoms and sensitization to mould among these pork-butchery workers is unknown. The aim of the study was to assess the clinical, radiographic, functional, and immunological features in exposed and non-exposed workers in semi-industrial pork butcheries. Patients and methods: Symptoms, and serum precipitins against mould extracts, were studied in workers in semi-industrial pork butcheries. Of 600 workers asked to participate, 123 (20.5%) were included. Fifty-nine workers, exposed to dry (raw) sausage mould and Penicillium nalgiovense were compared with 64 non-exposed subjects, for symptoms, chest X-rays, spirometry and CO-transfer measurements. Precipitating antibodies were detected by immunoelectrophoresis and electrosyneresis. Results: Sneezing, cough, dyspnoea, nasal obstruction, headache, and discomfort were significantly more frequent in the exposed group at work and after work than in the control group (P < 0.05). The prevalence of precipitating antibodies for sausage mould was higher in the exposed group (37%) than in the non-exposed group (9%) (P < 0.01). The mean number of precipitating lines measured by electrosyneresis was higher in exposed workers than in non-exposed workers for mould extract (1.09 vs 0.28, P < 0.05) and for Penicillium nalgiovense (1.77 vs 0.33, P < 0.05). No specific X-ray opacity or lung function impairment was found in either group. Conclusions: Clinical symptoms and sensitization to Penicillium nalgiovense are frequent among workers exposed to mould during brushing in dry sausage plants. Received: 27 December 2000 / Accepted: 28 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     

Respiratory health and fluoride exposure in different parts of the modern primary aluminum industry

Objective: The aim of this cross-sectional study was to investigate possible acute and long-term respiratory health effects of work at different working places in the primary aluminum industry. Method: A cross-sectional study was carried out on 78 potroom workers, 24 foundry workers, and 45 carbon-plant workers (n = 147, exposed group), and 56 control workers (watchmen, craftsmen, office workers, laboratory employees) of a modern German prebake aluminum plant. The survey consisted of pre- and postshift spirometric and urinary fluoride measurements. Results: Potroom workers had significantly lower preshift results with regard to forced vital capacity (FVC, 99.5% versus the 107.2% predicted; P < 0.05) and peak expiratory flow (PEF, 85.2% versus the 98.4% predicted; P < 0.01) as compared with controls. In a multiple regression model a small but significant negative correlation was found between postshift urinary fluoride concentrations and FVC, FEV₁, and PEF. Across-shift spirometric changes were observed only in FVC among carbon-plant workers (103.0 ± 13.3% predicted preshift value versus 101.2 ± 13.6% predicted postshift value; P < 0.05). Conclusions: The results suggest that lung function impairment in the modern primary aluminum industry may be only partly due to fluoride exposure and that working in aluminum carbon plants may cause acute lung function changes. Received: 8 July 1998 / Accepted: 31 October 1998     

Superoxide anion release by peripheral polymorphonuclear leukocytes in welders

Objectives: To investigate peripheral blood neutrophil [polymorphonuclear leukocyte (PMN)] function in a group of 23 welders compared with that in an age- and smoking habit-matched non-exposed control group. Methods: Stimulated release of superoxide anions from PMN isolated from peripheral blood of welders and of a matched group was carried out. Results: The stimulated release of superoxide anions in PMNs from welders was significantly lower (P = 0.021) than that of a control group. Smokers and older workers had a lower function of PMNs than non-smokers and younger workers. Conclusions: PMN function of welders is lower than that of controls. This effect might indicate reduced immunological defences in oxidant-exposed individuals. It is possible that PMN function might serve as a biological marker of exposure in the periodic health surveillance of welders. Received: 23 June 2000 / Accepted: 27 January 2001     

Qualitative color vision impairment in toluene-exposed workers

Objective : The aim of this study was to evaluate whether toluene, like many other organic solvents and solvent mixtures, could impair color vision. Subjects and methods : We investigated color vision impairment in three groups of workers, two groups occupationally exposed to toluene and a nonexposed group. The first exposed group, group E₁, comprised 41 workers (median value of toluene in air 35.00 ppm, range 11.3–49.3 ppm) and the second exposed group, group E₂, comprised 32 subjects (median value of toluene in air 156.00 ppm, range 66.0–250.0 ppm). The nonexposed group, group NE, comprised 83 subjects. Color vision was evaluated by the Lanthony D-15 desaturated test according to Verriest's classification: type I, loss in the red-green range; type II, loss in the blue-yellow and red-green ranges, and type III, loss in the blue-yellow range. Subjects were classified as dyschromates if specific acquired loss was determined in at least one eye. In both exposed groups, exposure was evaluated by measurement of the concentration of toluene in the ambient air and in the blood. In group E₂, level of hippuric acid and orthocresol in urine after the work shift were also determined. The Mann-Whitney U-test, t-test, χ²-test, and Spearman's rank correlation and multiple regression analysis were used for statistical analysis. Results : Type III dyschromatopsia was detected in all groups examined: 26.6% of the workers in group NE, 31.7% of those in group E₁, and 50% of those in group E₂. As many as 15.6% of the workers in group E₂, 4.8% of those in group E₁, and only 1.2% of those in group NE had type II dyschromatopsia. A statistically significant difference in the prevalence of total dyschromatopsia (type III + type II) was established among the three examined groups together (χ²=14.13; df=2;P<0.01), between group E₂ and group E₁ (χ²=4.96;P<0.05), and between group E₂ and group NE (χ²=12.50;P< 0.005), whereas no significant difference was found between groups E₁ and NE. Type III dyschromatopsia was significantly correlated with age in group NE (P<0.01) and in group E₁ (P<0.005). In group E₂, both type II (P<0.05) and type III dyschromatopsia correlated with toluene in ambient air and with the duration of exposure to toluene (both P<0.005). In group E₂, total dyschromatopsia correlated significantly with toluene in ambient air and in blood (both P<0.05) as well as with hippuric acid in urine after the work shift (P<0.001). Conclusion: This study suggests that toluene can impair color vision. Received: 24 July 1996 / Accepted: 15 July 1997     

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     

Association between blood levels of lead, blood pressure and risk of diabetes and heart disease in workers

Background: Previous studies have supported the association between high levels of blood lead levels (BLL) and elevated blood pressure. In addition, significant correlations between BLL and a variety of risk factors for blood pressure and diabetes mellitus have been well-established. Objective: To examine the relationship between BLL, blood pressure and diabetes as well as other selected social and biochemical factors, among workers in the United Arab Emirates (UAE). Methods: This comparative study included 110 industrial workers (exposed to lead in the workplace) and 110 non-industrial workers (not exposed); all were recruited in the city of Al-Ain, Abu-Dhabi Emirate, UAE and the groups were evenly matched for age, gender and nationality. Results: The industrial workers had a significantly higher mean of BLL (median 81 and geometric mean (GM) 62 μg/dl) than did non-industrial workers (median 11 and GM 13 μg/dl). In the present study, the lead-exposed group also had significantly higher blood lead levels, body-mass index (BMI), systolic and diastolic blood pressures, fasting blood glucose and plasma levels of total cholesterol, lactate dehydrogenase and uric acid than did the non-exposed group. Furthermore a significant correlation between BLL and systolic blood pressure was observed. Conclusion: The study supports the hypothesis of a positive association between lead exposure, high blood pressure and risk of diabetes and heart disease. Received: 11 July 2000 / Accepted: 5 January 2001     

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     

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     

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     

Long-term monitoring of sister chromatid exchanges and micronucleus frequencies in pharmacy personnel occupationally exposed to cytostatic drugs

Objectives: Many antineoplastic drugs were found to have carcinogenic, mutagenic and teratogenic potential. The aim of this study was to carry out cytogenetic and internal dose monitoring of hospital pharmacy personnel regularly involved in the preparation of cytostatic agents, in order to test possible cytostatics-induced genotoxic effects due to occupational exposure under routine working conditions, and in cases of accidental contamination. Methods: Platinum in whole blood and anthracyclines in plasma were measured to assess internal exposure to cytostatics. The level of cytogenetic damage was determined in peripheral blood lymphocytes with the micronucleus test and the sister chromatid exchange assay. Five series of monitoring were performed over a period of 2 years. Results: No significant differences in the mean frequencies of sister chromatid exchanges (SCE) and micronuclei (MN) were found between occupationally exposed probands and controls (9.9 ± 1.4 vs 10.1 ± 1.2 SCEs/cell and 21.2 ± 7.2 vs 23.3 ± 7.5 MN/2000 binucleated (BN) cells, n=16). Significant elevations of SCE or MN were detected in seven out of 12 cases of accidental contamination at the workplace, whereas no increase in platinum in blood and anthracyclines in plasma was observed in these probands. Two cases of non-reported contamination were identified by measurement of epirubicin in plasma. Smoking was found to increase the SCE significantly. No correlation between individual SCE scores and MN scores was observed. Conclusions: Our findings support a transient increase in SCE or MN after relevant exposure to cytostatic drugs in cases of accidental contamination. The lack of significant differences in SCE and MN between hospital pharmacy personnel and unexposed controls, points to high standards of safety at the corresponding workplaces. Received: 11 October 1999 / Accepted: 25 April 2000     

Chromosome analysis of lymphocytes from radiation workers in tritium-applying industry

Objectives : The frequency of chromosomal aberrations (CA) and micronuclei (MN) in peripheral blood lymphocytes was compared in two groups of persons occupationally exposed to tritium either through the use of luminous paints or in the weapons industry, with the aim of finding a correlation between the CA and MN assays, the extent of radiation hazard, and the duration of occupational exposure to chemical forms of tritium and the ability of the latter to induce hazards in human lymphocytes. Methods : CA analysis and the cytochalasin B micronucleus test were performed. Urinary tritium in both groups was measured using a liquid scintillation method. For purposes of comparison, 2 control groups (40 persons) were examined; 24 exposed individuals were matched to their controls according to age, sex, and smoking habits. Results: Values recorded for the frequency of CA in the group of workers handling tritium in luminous dial painting were 0.015 ± 0.014 dicentrics/cell, 0.023 ± 0.017 total unstable CA/cell, and 0.035 ± 0.019 MN/binucleated cell. Urinary levels of tritium in this group of employees ranged from 1.35 to 9.43 MBq/l. As compared with their matched controls, in these workers the differences in the yield of CA as well as in MN were statistically highly significant (P<0.005 and P<0.003, respectively). The same parameters analyzed in workers employed in the armament industry gave values of 0.001 ± 0.003 dicentrics/cell, 0.010 ± 0.008 total unstable CA/cell, and 0.021 ± 0.029 MN/binucleated cell. No detectable concentration of urinary tritium was found. As compared with their matched controls, in these workers the differences were also statistically significant (P<0.027 and P<0.012, respectively). The yield of CA, particularly the yield of dicentrics, was significantly higher (P<0.005) in the group of luminous dial painters as compared with the weapons industry workers. The difference found in the yield of MN between the two groups of workers was also statistically significant (P<0.084). Intercontrol differences in the yields of spontaneous CA as well as in MN were insignificant (P<0.683 and P<0.735, respectively). The results are discussed with respect to individual variations in the response to low doses of ionizing radiation, disorders in the handling of radionuclides, the duration of occupational exposure, and the chemical properties of the radionuclides used. Conclusion : Tritium in the chemical form of luminous paint is a more powerful clastogenic agent than tritium gas. Statistical analysis demonstrated that lymphocyte effects are due to the concentration of tritium in urine rather than to the duration of occupational exposure. Since the radiation hazard measured by the MN assay did not differ from that determined by the CA assay, the MN test can be recommended as a rapid assay for screening purposes in cases of occupational exposure to low radiation doses. Received: 20 November 1996 / Accepted: 1 August 1997     

Experimental exposure to methylformate and its neurobehavioral effects

Objectives: The aim of the study was to investigate the acute effects of experimental methylformate exposure on the nervous system. Methods: In an exposure chamber, 20 subjects were exposed to methylformate at 100 ppm [Swiss maximum allowable concentration (MAC)] for 8 h. The same number of subjects with the same ages (between 20 and 30 years), gender and education level (university) were examined by the same procedure as a control group. The subjects did not know if they were exposed or not. Three times (morning, noon, evening) during these 8 h, mood [Profile of Mood States (POMS)], neurobehavioral performance (reaction, Stroop, nonverbal learning, determination, tracking; Wiener Test System), vision (visual acuity, contrast sensitivity, color sensitivity) and postural sway were tested. During an undemanding test (POMS) and a demanding performance task (determination test), pulse, electromyography (EMG) of the forehead and of the neck were recorded. In the morning and evening spirometry [forced vital capacity (FVC), forced one-second expiration volume (FEV), medium expiration flow (MEF) and peak expiration flow (PEF)] and the odor perception threshold were measured. Results: In the evening, in the exposed group, fatigue was significantly increased and the EMG of the forehead during a demanding task showed a different development during exposure. The other tests showed no significant solvent effect, but 16 of 43 test parameters showed a significant effect of time. Conclusions: The results of this study indicate a possible effect of methylformate exposure on the subjective feeling of fatigue after 8 h exposure at 100 ppm in young and healthy subjects, without measurable impairment of neurobehavioral performance. We assume that a similar effect in normal work, combined with a heavy workload and shift work, can lead to an impairment of productivity, and increase the risk of accidents. Received: 8 February 1998 / Accepted: 22 January 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     

Relationships between perceived workload, stress and oxidative DNA damage

Objectives: The present study was performed to investigate the relationship between work-related factors, including psychological stress, and the formation of a type of oxidative DNA damage, 8-hydroxydeoxyguanosine (8-OH-dG), in order to examine their possible risk factor for occupational carcinogenesis. Methods: A total of 54 healthy workers (27 male and 27 female, aged 41.2 ± 12.5 years) in a company were investigated for 8-OH-dG levels in the peripheral blood leukocytes at the time of a questionnaire survey regarding several factors, such as working hours, workload, fatigue, sleep, psychological stress and the prospect of alleviating it. Subjects were limited to non-smoking and non-drinking workers to exclude the influence of cigarette smoking and alcohol drinking, which have been reported to have associations with the formation of 8-OH-dG. Results: The levels of 8-OH-dG in female subjects were significantly related to the perceived workload (F=5.56, P=0.010), the perceived psychological stress (F=6.15, P=0.007), and the impossibility of alleviating stress (F=3.82, P=0.048). No associations were observed in male subjects. Conclusions: Psychological stress and perceived overwork appear to be related to the pathogenesis of cancer via the formation of 8-OH-dG, particularly in female workers. Received: 9 December 1999 / Accepted: 11 October 2000     

Exposure and acute exposure-effects before and after modification of a contaminated humidification system in a synthetic-fibre plant

Objective: Follow-up study of exposure and acute exposure-effects after modification to steam humidification of a contaminated cold water system which had caused an outbreak of humidifier fever in a synthetic-fibre plant. Methods: Before and after modification of the system aerobiological measurements were performed. Concentrations of fungi and bacteria, in colony forming units (cfu) per m³, were measured by stationary air sampling with an Andersen sampler. Endotoxin levels (pg/m³) were determined by Limulus Amoebocyte Lysate (LAL) assay in pooled dust from personal air sampling. An indication of exposure levels of oil-mist was obtained by monitoring with a direct reading optical photometer. Changes as acute exposure-effects in spirometry and white blood cell count, during an afternoon shift were compared in exposed and non-exposed workers before and after modification. Results: Measured levels of fungi, total bacteria, Gram-negative bacteria and endotoxins both before and after modification were below levels which would be expected to be associated with the exposure-effects. However, after modification, we found that the statistically significant differences in levels of bacteria and endotoxins with a department without humidification no longer existed. Mean oil-mist concentrations were below 1 mg/m³, with short-time peak exposure during certain tasks of up to 5 mg/m³. Before modification, in exposed workers there was significantly more decline of spirometry, and more increase of white blood cell count during the first afternoon shift, compared with non-exposed workers. In exposed workers, the white blood cell count increase was positively associated with decline of spirometry. After modification, differences between exposed and non-exposed workers no longer existed. Conclusion: Follow-up investigation of acute exposure-effects demonstrated the effectiveness of remedial actions taken against a contaminated humidification system. Follow-up of exposure-effects in particular is recommended when there is doubt about the interpretation of exposure measurements. Received: 27 January 1999 / Accepted: 22 January 2000