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BACKGROUND: Workers on dredgers and lighters on rivers are potentially exposed to a variety of substances. AIMS: To determine the internal load of heavy metals and arsenic as well as levels of cytogenetic markers in workers exposed to river silt aerosols. METHODS: One hundred exposed workers were examined up to eight times within three years. Additionally, 100 control workers were studied once. Blood samples were analysed for lead, mercury, and cadmium. Additionally, micronuclei frequency and sister chromatid exchange (SCE) rates were determined. Urinary samples were analysed for cadmium, mercury, nickel, chromium, and arsenic. Information on potential confounders, such as smoking habits and consumption of fish were assessed. RESULTS: Apart from some increased concentrations of mercury in blood (maximum 14.6 microg/l) and arsenic in urine (maximum 356.5 microg/l) all measurements were within reference values. None of the exposure and effect markers were found to be significantly increased in exposed workers compared to non-exposed controls. In multiple linear regression models, mercury levels in blood as well as the concentration of arsenic in urine were strongly related to fish consumption. Cadmium levels in blood as well as urinary cadmium concentrations were strongly related to smoking habits. After adjusting for smoking habits, SCE rates were associated with cadmium levels in blood. CONCLUSION: Increased exposure levels or enhanced levels of cytogenetic markers were not found in workers exposed to river silt aerosols. However, cadmium exposure in blood was related to SCE frequency.

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BACKGROUND: The aim of the European Farmers' Project was to estimate the prevalence of respiratory diseases in farmers across Europe. Furthermore, risk factors for respiratory symptoms in different parts of agricultural production should be assessed. METHODS: In the first part of the study, 7496 farmers from four European countries answered a written questionaire. Of these, 229 were visited at their farms in the second part of the survey. On site, spirometry, allergy tests, as well exposure measurements were performed. RESULTS: Farmers with animal production had a significantly lower prevalence of allergic diseases than the general population. In contrast, the prevalence of chronic phlegm was higher in animal farmers. Organic dust toxic syndrome (ODTS) was a major predictor of chronic bronchitis. It was indicated that allergens found in the working environment could be transfered to the living environment of the farmer. Poor ventilation as well as high temperatures inside the animal buildings were shown to have a negative impact on respiratory symptoms and lung function parameters. CONCLUSION: Animal farmers are at high risk of chronic bronchitis. Intervention studies on the efficacy of different types of ventilation are now warranted. Furthermore, prospective studies on the associaton between ODTS and COPD should be done.

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A 63-year-old nonatopic female suffering from type II diabetes with severe local and systemic immediate-type allergic reactions to injections of different recombinant human insulin products has been reported. Skin testing as well as IgE measurements not only proved immediate-type sensitization to human insulin but also to porcine and bovine insulin which had never been administered and indicated immunological cross-reactivity. Cross-reactivity was proved by an IgE inhibition test. Independent of this reaction, the patient showed IgE-mediated sensitization to protamine.

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BACKGROUND: Although fungal phytase is frequently used as an additive to animal feed few investigations of its allergenic property have been conducted. METHODS: Fifty-three subjects occupationally exposed to powdered phytase from Aspergillus niger were studied. Exposure data and symptoms were registered by the company physician. RESULTS: Thirty-eight subjects complained of work-related respiratory symptoms and 14 of them showed phytase-specific IgE antibodies; only one asymptomatic subject revealed such antibodies. IgE antibodies were significantly more frequently found in the high-exposure group (technical centre) when compared with the low-exposure group (laboratories, experimental animal husbandry). Phytase-specific IgG antibodies were present in 19 symptomatic (50%) and five (33%) asymptomatic subjects. CONCLUSIONS: Our results demonstrate that powdered fungal phytase is a highly sensitizing substance whose inhalation exposure should be avoided. Hypersensitivity symptoms could be prevented by means of extensive hygienic measures and ongoing medical surveillance.

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The present study was conducted to evaluate characteristics of pig houses that are associated with the development of respiratory morbidity in 100 swine producers with work-related respiratory symptoms. A standardized questionnaire for farm characteristics was used, and lung function was assessed immediately before and after feeding the pigs. Exposure to dust and endotoxin was determined by personal sampling. Among these farmers, baseline lung function results were shown to be negatively associated with duration of employment, number of pigs on the farm, manual feeding, and ventilation. The decrease in forced vital capacity and forced expiratory volume in 1 second over the feeding period was negatively correlated with air velocity, whereas respirable dust concentrations were shown to be significant predictors of maximal midexpiratory flow (MMEF25/75) decline. In conclusion, among symptomatic pig farmers, those with higher numbers of pigs and longer duration of employment are at highest risk for developing functional impairment.

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BACKGROUND: The aim of the present study was to determine the distribution of mite allergens in pig-farming environments in comparison to urban homes and the relationship between exposure to mite allergens and sensitization to the respective allergens in 100 pig farmers with work-related respiratory symptoms. METHODS: The concentration of storage mite (Lep d 2) and house-dust-mite (Der p 1, Der f 1, and Der 2) allergens in dust collected from five different sampling sites (floor, wall, grain mill, transit area between confinement house and farmer's kitchen, and farmers' mattresses) was studied in relationship to the respective sensitization rates. Allergen concentrations in the mattresses were compared to those determined in mattresses from 22 urban dwellers. RESULTS: Median concentrations of Der p 1 and Der 2 in the mattresses of the farmers were significantly higher than in the urban dwellers' samples (53.4 microg/g dust vs 1.05 microg/g dust, P=0.001; 19.6 microg/g dust vs 2.2 microg/g dust, P<0.0001, respectively). Allergen concentrations in the transit areas were strongly related to bedroom exposure. In a multiple logistic regression model, a weak but significant relationship between Der p 1 exposure and sensitization to Der p 1 was found. Despite these findings, the prevalence of sensitization to mite allergens in the farmers (18%) was comparable to the prevalence in the general population. CONCLUSIONS: Allergen exposure at the workplace is strongly related to the concentration of allergens in farmers' beds. Exposure to domestic mite allergens should be taken into account when assessing occupational exposure to allergens and the respiratory health of farmers.

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The authors studied cultured skin fibroblasts of 64 patients with lung cancer for constitutive mutations of the p53 tumor suppressor gene by using polymerase chain reaction and single-strand conformation polymorphism covering the entire coding region. The patients were considered to be genetically predisposed because lung cancer had developed in 25 of them before age 46 and because 42 of them had at least one first-degree relative with lung cancer. One mutation was detected at position 235 coding for serine instead of asparagine in the conserved DNA binding domain. The Pro/Pro genotype at codon 72 of p53, considered to harbor an increased risk for lung cancer, could not be detected with increased frequency in this study's patients. From these data, the authors conclude that constitutive variations of the p53 gene do not represent a major genetic determinant for lung cancer.

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OBJECTIVE: To determine the incidence of cancer in Odijk and the connection if any of the occurrence of cancer with the presence of a high-voltage cable constructed there in the fifties. DESIGN: Descriptive. SETTING: Public Health Services, South-East Utrecht, the Netherlands. METHOD: Data on the numbers of new cancer patients in Odijk over the period 1985/'96 were obtained from general practitioners, from the Integral Cancer Centre Mid-Netherlands (IKMN) and from the Foundation Dutch Study Group Leukaemia in Children. The classifications were according to age and to distance from the home to the high-voltage cable. The electric and magnetic field strengths in dwellings situated less than 28 m from the cable were calculated. RESULTS: Cancer was diagnosed in 131 patients in the period 1985/'96, 127 adults and four children. The cases in 3 of 4 children occurred in the period 1993/'96. Over the period 1990-1994, the registered cancer incidence did not deviate from the expected incidence in the IKMN region, nor from the mean incidence in the Netherlands. Neither for adults nor for children was a relationship found between cancer and living in the vicinity of the high-voltage cable. The exposure to the electric field of persons living in houses near the cable was maximally 7%, and exposure to the magnetic field maximally 6.5% of the maximal liminal values applied in the Netherlands on recommendation of the Health Council. CONCLUSION: No relationship existed between development of cancer and the presence of a high-voltage cable.

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OBJECTIVE: The aim of this study was to investigate the effect of environmental tobacco smoke (ETS) exposure in the evening on inflammatory changes in bronchoalveolar (BAL) and nasal lavage (NAL) fluid. METHODS: Ten subjects with mild asthma [mean (+/- SD) age, 25 +/- 2 years, FEV1% pred., 93 +/- 6%, PC20FEV1 0.44 x 5.11 mg/ml methacholine] were exposed to ETS (22.4 +/- 1.2 ppm CO) or ambient air (sham) for 3 h (7.00 to 10.00 p.m). Bronchoscopy was performed the following morning at 7.00 a.m. A visual endoscopic score was assessed, and BAL fluids were analyzed for cellular composition and concentrations of histamine, albumin, eosinophilic cationic protein, myeloperoxidase, hyaluronic acid, tryptase, prostanoids and leukotrienes. Nasal lavages were performed 30 min prior to and 30 min after exposures, and NAL fluids were analyzed for histamine, albumin, eosinophilic cationic protein, myeloperoxidase, hyaluronic acid, and tryptase. RESULTS: There was a significant rise in symptoms after ETS exposure compared with sham (P < 0.05). Spirometric lung function did not change during or after exposure compared with pre-session values. Visual bronchoscopic scoring revealed no significant effect of ETS exposure, nor did BAL cells and mediators or NAL mediators as compared with pre-challenge or post-sham values. CONCLUSION: In the subjects tested, a 3-h ETS exposure in the evening appeared not to have an inflammatory effect detectable in BAL or NAL fluid.

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OBJECTIVES: Low exposures to volatile aromatic hydrocarbons and cytogenetic effects in peripheral white blood cells were determined in 25 healthy workers employed in different areas of a styrene production plant in the former German Democratic Republic. The results were compared with 25 healthy unexposed controls (matched for age and sex) employed in the same company. METHODS: The concentrations of aromatic hydrocarbons determined from active air sampling in all areas of the factory (styrene: 73-3540 micrograms/m3 (< 0.01-0.83 ppm); ethylbenzene 365-2340 micrograms/m3 (0.08-0.53 ppm); benzene 73-3540 micrograms/m3 ( < 0.02-1.11 ppm); toluene 54-2960 micrograms/m3 (0.01-0.78 ppm); xylenes 12-94 micrograms/m3 ( < 0.01-0.02 ppm)) were considerably lower than in the pump house ( > 4000 micrograms/m3 styrene, ethylbenzene, benzene, and toluene; > 500 micrograms/m3 xylenes), which was only intermittently occupied for short periods. Passive personal monitoring, biomonitoring of exhaled air and metabolites (mandelic, phenylglyoxylic, trans, trans-muconic, hippuric, o-, m- and p-methylhippuric acids, and phenol) in urine samples collected before and after an eight hour working shift was used to assess individual exposure. Questionnaires and examination of company records showed that the historical exposure was far higher than that measured. Genotoxic monitoring was performed by nuclease P1-enhanced 32P-postlabelling of DNA adducts in peripheral blood monocytes, and DNA single strand breaks, sister chromatid exchange, and micronuclei in lymphocytes. The content of kinetochores in the micronuclei was determined by immunofluorescence with specific antibodies from the serum of CREST patients. RESULTS: No genotoxic effects related to exposure were detected by DNA adducts or DNA single strand breaks and sister chromatid exchange. The only effect related to exposure was an increase in kinetochore positive micronuclei in peripheral lymphocytes; the frequency of total micronuclei in peripheral lymphocytes did not change. Smoking was confirmed by measurement of plasma cotinine, and no confounding effect was found on any of the cytogenetic variables. CONCLUSIONS: Low occupational exposure to styrene, benzene, and ethylbenzene did not induce alterations of genotoxicological variables except kinetochore positive micronuclei. This is the first reported use of the CREST technique for an in vivo study in occupational toxicology, which thus could serve as a valuable and sensitive technique for toxicogenic monitoring.

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In a controlled study, ten male volunteers (five smokers and five nonsmokers) were subjected to different smoking conditions and compared to five nonsmokers, not exposed to cigarette smoke. During the 4 days of the study, nonsmoking periods were strictly controlled. On the first day the ten subjects were sham exposed. On the second day the five smokers smoked 24 cigarettes in 8 h, while the five nonsmokers were exposed to the environmental tobacco smoke. After another day of sham exposure the smoke exposure was repeated under the same conditions. Blood was drawn before and after exposure and DNA single-strand breaks (SSBs) were analyzed in lymphocytes immediately (1 h) after isolation of cells and after 4 h incubation at 37 degrees C, using a modified assay based on the nick translation reaction. Base levels of unscheduled DNA synthesis (UDS) and UDS levels were determined after 1 h incubation with methyl methanesulfonate. Duplicate analysis using the same method was performed in a second laboratory after transportation of blood samples at 0 degree C on a train from Munich to Hamburg. Tobacco smoke exposure of the subjects increased COHb and plasma cotinine levels. SSBs could be detected in all probands with some interindividual day-to-day and morning-to-evening variations. In four of five active smokers, SSB increases were found after smoking. In nonsmokers exposed to tobacco smoke no exposure-related variation in SSB levels could be detected.(ABSTRACT TRUNCATED AT 250 WORDS)

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The induction of micronuclei was studied in human diploid fibroblasts incubated in the presence of the tobacco-specific nitrosamine NNK. We used four fibroblast strains having a high capacity of O6-alkylguanine DNA alkyltransferase (13.0-23.3 pmol O6-methylguanine repaired per 8 x 10(6) cells) and four strains that showed no detectable repair capacity. Incubation with NNK doubled the frequency of micronuclei in repair-deficient cells but failed to evoke any effect in the proficient cell strains. Control experiments were performed with the direct methylating agent MNNG and in the presence of inhibitors of either metabolic activation or alkyltransferase. The results showed that the genotoxicity of NNK is dependent on the relationship between its metabolic activation and the constitutive DNA repair. This supports earlier findings that low constitutive levels of O6-alkylguanine DNA alkyltransferase may increase susceptibility to lung cancer after exposure to DNA methylating agents.

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