Exposure and mineralogical correlates of pulmonary fibrosis in chrysotile asbestos workers.

OBJECTIVES: The relation between lifetime cumulative exposure to asbestos, pathological grade of pulmonary fibrosis, and lung burden of asbestos at death, was explored in a necropsy population of former workers in a chrysotile asbestos textile plant in South Carolina. METHODS: Estimates of cumulative, mean, and peak exposures to asbestos were available for 54 workers. Necropsy records and lung tissue samples were obtained from hospital files. Matched control cases were selected from consecutive necropsies performed at the same hospitals. The extent and severity of pulmonary fibrosis was graded on tissue sections. Mineral fibres in lung tissue were characterised by transmission electron microscopy combined with x ray spectroscopy. RESULTS: A significant positive correlation (r = 0.67, P < 0.0001) was found between lifetime cumulative exposure to asbestos and total lung burden of asbestos fibres. This relation was also found for the individual types of asbestos associated with the exposure: chrysotile and tremolite. Pulmonary fibrosis was correlated with both cumulative exposure to asbestos (r = 0.60, P < 0.01) and the concentration of asbestos fibres in the lung (r = 0.62, P < 0.0001). The concentration of tremolite fibres in the lung provided a better estimate of lung fibrosis than did the concentration of chrysotile. Asbestosis was usually present in asbestos textile workers with more than 20 fibre-years cumulative exposure. The lengths and aspect ratios of chrysotile asbestos, but not amphibole asbestos, were greater in the lungs of asbestos fibre workers than in the control population. Textile workers with lung cancer had significantly greater cumulative exposures and fibrosis scores than workers without lung cancer. CONCLUSIONS: Both cumulative exposure to asbestos and lung fibre burden are strongly correlated with severity of asbestosis. The data also support the hypothesis that the high prevalence of asbestosis and lung cancer in this population resulted from exposure to long fibres of chrysotile asbestos in the workplace.     

Amphibole fibres in Chinese chrysotile asbestos

Ten chrysotile bulk samples originating from six Chinese chrysotile mines were studied for amphibole fibres. Five of the mines operate on ultramafic rocks whereas one exploits a dolomite-hosted deposit. The asbestos fibre content in lung tissue was examined from seven deceased workers of the Shenyang asbestos plant using these raw materials. The bulk samples were pretreated with acid/alkali-digestion, and thereafter, scanning and transmission electron microscopy, X-ray microanalysis, selected area electron diffraction and X-ray powder diffractometry were used to identify the minerals. Sample preparation of lung tissue involved drying and low-temperature ashing.All of the bulk samples contained amphibole fibres as an impurity. The amphibole asbestos contents were between 0.002 and 0.310 w-%. Tremolite fibres were detected in every sample but anthophyllite fibres were present only in the sample originating from the dolomite-hosted deposit. In comparison, anthophyllite (71%), tremolite (9%) and chrysotile (10%) were the main fibre types in the lung tissue samples indicating faster pulmonary clearance of chrysotile fibres. The total levels ranged from 2.4 to 148.3 million fibres (over 1 microm in length) per gram of dry tissue, and they were consistent with heavy occupational exposure to asbestos.     

Role of occupational asbestos exposure in Hungarian lung cancer patients

Objective: What is the frequency of occupational asbestos exposure among patients suffering from malignant respiratory tumours and how many of these tumours are associated with asbestos in Hungary? Methods: An internationally established questionnaire with 29 questions, covering the most characteristic activities of asbestos exposure at the workplace was completed for 300 patients with respiratory malignancies, i.e. 297 patients with lung cancer and three with mesothelioma of the pleura. From the questionnaire, the smoking habits were estimated and cumulative asbestos exposure was assessed in fibre-years. Additionally, lung X-rays were classified and the national data on the incidence of malignant pleura mesothelioma were analysed. Results: A cumulative asbestos exposure of 25?fibre-years or more was detected in 11 patients with lung cancer (4%) and in each of the three patients with pleural mesothelioma (100%). In a further 72 patients (24%), cumulative occupational asbestos exposure was assessed as below 25?fibre-years (between 0.01 and 23.9?fibre-years). In this group, car and truck mechanics, and installation and construction workers using asbestos-cement were registered. Among patients with an asbestos exposure of 25?fibre-years or more, six asbestos-cement production workers were observed, among them the three mesothelioma cases. A weak but significant association between positive X-ray findings and exposure estimates could be demonstrated. Additionally, results of the lung tissue fibre counts by scanning transmission electron microscopy were available for 25 of the lung cancer patients. A good correlation was observed between the asbestos fibre counts and the assessment of cumulative asbestos exposure. In Hungary, 84 cases of pleural mesothelioma were registered in 1997 and 73 in 1998. These numbers correspond to an annual incidence of about one new case per 100,000 inhabitants older than 15?years. Conclusions: The annual incidence of lung cancer in Hungary is about 6,000. Since in our series of lung cancer patients about 4% were observed, which could be accepted as representing occupational disease because of a cumulative exposure to 25?fibre-years or more, the annual asbestos related lung tumour incidences may be estimated to be approximately 150 or more. The proportion of nearly two estimated cases of lung cancer per case of pleural mesothelioma corresponds to international experience. Up to now, lung cancer cases only exceptionally have been registered as occupational diseases, i.e. they were seriously under-diagnosed in Hungary. For improving this situation, diagnostic assistance by a self-interview with a questionnaire covering the working history for all newly diagnosed lung cancer patients would be helpful.     

Malignant mesothelioma--German mesothelioma register 1987-1999

Objectives: The study group comprised a collective of 1,605 patients with malignant mesotheliomas and with lung tissue available for lung dust analyses. Method: Clinical features, occupational histories, expositions and individual data were evaluated, and the asbestos bodies concentrations (asbestos bodies/cm³ lung tissue or g wet tissue) were determined. Results: Mesotheliomas developed mainly in men (94.5%). Of the cases, 96.4% were of pleural origin and only 3.3% were peritoneal mesotheliomas. The biphasic subtype predominated (61.3%), followed by the epithelioid type (29.3%). The sarcomatoid subtype was rarely developed (9.4%). Mean age at first diagnosis was 60.4 years. The mean survival time from time of symptom onset was 13.5 months. Patients with epithelioid subtypes had a longer survival time (16.9 months) than those with biphasic (13.1 months) and sarcomatoid subtypes (5.5 months). Of the patients, 73% presented pleural effusions as initial symptoms of the disease. An increased asbestos burden was identified by light microscopy in 84.8% of the patients. There was no association between histological subtypes and the asbestos burden of the lungs. Patients with peritoneal mesotheliomas had distinctly higher asbestos burdens in the lungs than patients with pleural mesotheliomas. There exists no association between lung asbestos burdens and survival times. The mean latency period was 37.8 years. A trend: higher asbestos burden of the lung/shorter latency periods was suggested. About 70% of the patients had a history of occupational exposure to asbestos dust. Most patients worked in the building trade, the locksmith and machine building industries and in the steel and blast-furnace industries. Of the patients, 25.6% had asbestos-associated lung fibroses, in 40.7% of the cases pleural plaques were identified. Conclusions: The most important causal factor for development of mesotheliomas is still asbestos, primarily amphibole asbestos. The recurring occurrence of mesotheliomas in younger people without known asbestos exposure needs the urgent investigation of other inducing factors for mesotheliomas. Received: 11 September 2000 / Accepted: 20 February 2001     

Asbestosis and small cell lung cancer in a clutch refabricator

OBJECTIVES: To present a case of asbestosis and small cell lung cancer caused by asbestos in a clutch refabricator. METHODS: Exposed surfaces of used clutches similar to those refabricated in the worker's workplace were rinsed, and the filtrate analysed by analytical transmission electron microscopy. Tissue samples were also analysed by this technique. RESULTS: Numerous chrysotile fibres of respirable dimensions and sufficient length to form ferruginous bodies (FBs) were detected from rinsed filtrates of the clutch. Bronchoalveolar lavage fluid contained many FBs, characteristic of asbestos bodies. Necropsy lung tissue showed grade 4 asbestosis and a small cell carcinoma in the right pulmonary hilum. Tissue analysis by light and analytical electron microscopy showed tissue burdens of coated and uncoated asbestos fibres greatly exceeding reported environmental concentrations (3810 FBs/g dry weight and 2,080,000 structures > or = 0.5 micron/g dry weight respectively). 72% Of the cores were identified as chrysotile. CONCLUSIONS: Clutch refabrication may lead to exposure to asbestos of sufficient magnitude to cause asbestosis and lung cancer.

 

     

Risk of lung cancer in workers producing stainless steel and metallic alloys

Objectives: The mortality of workers involved in the production of stainless and alloyed steel from 1968 to 1992 was studied, in order to investigate the risk of lung cancer due to exposure to metals, i.e. iron oxides, chromium and/or nickel compounds. Methods: The study design was a historical cohort mortality study and a nested case-control study concerning lung cancer. Standardized mortality ratios (SMRs) were computed using regional mortality rates as an external reference for comparing observed and expected numbers of deaths, adjusting for age, sex and calendar time. Conditional logistic regression was used to estimate odds ratios (ORs). Occupational exposure was assessed through the complete job histories of cases and controls and a specific job-exposure matrix. Results: The cohort comprised 4,288 male and 609 female workers. The observed overall mortality was significantly lower than expected [649 deaths; SMR = 0.91; 95% confidence interval (CI) 0.84–0.98]. No significant SMR was observed for mortality from lung cancer (54 deaths; SMR = 1.19; CI 0.88–1.55). The case-control study was based on 54 cases and 162 individually matched controls. Smoking habits were available for 71%. No lung cancer excess was observed for exposure to (1) metals and/or their compounds, i.e. iron (OR = 0.94, CI 0.48–1.86), chromium and/or nickel (OR = 1.18, CI 0.62–2.25), and cobalt (OR = 0.64, CI 0.33–1.25), (2) acid mists (OR = 0.43, CI 0.17–1.10), and (3) asbestos (OR =  1.00, CI 0.54–1.86). With respect to exposure to polycyclic aromatic hydrocarbons (PAHs) and silica, which are often found together in workplaces, (1) high and statistically significant lung cancer excesses were observed, the ORs being 1.95 (CI 1.03–3.72) and 2.47 (CI 1.28–4.77) respectively, (2) quantitative exposure parameters revealed upward trends reaching statistical significance (P < 0.05), and (3) adjustments for tobacco consumption did not reveal any confounding factors from smoking. Conclusion: This study failed to detect any relationship between lung cancer and exposure to iron, chromium, nickel and/or their compounds. High and statistically significant relative risks, along with increasing trends, were observed for simultaneous exposure to PAHs and silica. Received: 12 April 1999 / Accepted: 2 October 1999     

Asbestos concentration and fiber size in lungs of the urban residents]

Asbestos fiber concentrations and fiber size distribution in lung tissues of 53 urban residents (males: 34, female: 19) were analyzed by low temperature ashing-analytical transmission electronmicroscopy. The following findings were obtained. 1. Pulmonary asbestos fibers were found in 51 out of 53 patients. The types of asbestos fibers were chrysotile, amosite, crocidolite, actinolite and tremolite. 2. Thirty-six of 53 patients had no history of occupational asbestos exposure, and their geometric mean concentration of asbestos fibers was 1.67 x 10(6) fibers/g dry lung. Most of these asbestos fibers are probably attributable to general environmental contamination. Thirteen patients who had a history of occupational asbestos exposure showed a geometric mean of their pulmonary asbestos concentrations (5.82 x 10(6) fibers/g dry lung) which was significantly higher than that of patients without occupational asbestos exposure (p less than 0.01). 3. The geometric mean concentration of asbestos fiber in males (2.70 x 10(6)) was higher than in females (1.59 x 10(6)), probably due to a difference in the occupational asbestos exposure between males and females. 4. Regardless of the patient's sex, the geometric mean concentration of asbestos fibers in patients without a history of smoking (male: 4.91 x 10(6), female: 1.78 x 10(6)) was higher than that in patients with a smoking history (male: 2.76 x 10(6), female: 1.37 x 10(6)). The difference, however, was not statistically significant, and no correlation was seen between the concentration of asbestos fibers and smoking history. 5. Although most asbestos fiber utilized in Japan is chrysotile, the geometric mean concentration of chrysotile (0.87 x 10(6)) was almost identical to that of amphibole asbestos fiber (0.90 x 10(6)). 6. Of the asbestos fibers observed, 95% of chrysotile and 85% of amphibole asbestos were less than 5 microns in length and 93% of the total asbestos fibers were too small to be visible by light microscopy.     

Chrysotile and tremolite asbestos fibres in the lungs and parietal pleura of Corsican goats

Methods: Ten goats from areas with asbestos outcrops and two from other areas were slaughtered. Fibre content of lung and parietal pleural samples was determined by analytical transmission electron microscopy.

Results: Both chrysotile and tremolite fibres were detected. In the exposed goats, the geometric mean concentrations of asbestos fibres longer than 1 µm were 0.27 x 10⁶ fibres/g dry lung tissue and 1.8 x 10⁶ fibres/g dry pleural tissue. Asbestos fibres were not detected in the lungs of the two control goats. Chrysotile fibres shorter than 5 µm were predominant in the parietal pleura. Tremolite fibres accounted for 78% and 86% of the fibres longer than 5 µm in lung and parietal pleural samples, respectively.

Conclusions: Environmental exposure in northeast Corsica results in detectable chrysotile and tremolite fibre loads in the lung and parietal pleura of adult goats. Tremolite fibres of dimensions with a high carcinogenic potency are detected in the parietal pleura.

     

The quantitative risks of mesothelioma and lung cancer in relation to asbestos exposure

Mortality reports on asbestos exposed cohorts which gave information on exposure levels from which (as a minimum) a cohort average cumulative exposure could be estimated were reviewed. At exposure levels seen in occupational cohorts it is concluded that the exposure specific risk of mesothelioma from the three principal commercial asbestos types is broadly in the ratio 1:100:500 for chrysotile, amosite and crocidolite respectively. For lung cancer the conclusions are less clear cut. Cohorts exposed only to crocidolite or amosite record similar exposure specific risk levels (around 5% excess lung cancer per f/ml.yr); but chrysotile exposed cohorts show a less consistent picture, with a clear discrepancy between the mortality experience of a cohort of xhrysotile textile workers in Carolina and the Quebec miners cohort. Taking account of the excess risk recorded by cohorts with mixed fibre exposures (generally<1%), the Carolina experience looks uptypically high. It is suggested that a best estimate lung cancer risk for chrysotile alone would be 0.1%, with a highest reasonable estimate of 0.5%. The risk differential between chrysotile and the two amphibole fibres for lunc cancer is thus between 1:10 and 1:50.Examination of the inter-study dose response relationship for the amphibole fibres suggests a non-linear relationship for all three cancer endpoints (pleural and peritoneal mesotheliomas, and lung cancer). The peritoneal mesothelioma risk is proportional to the square of cumulative exposure, lung cancer risk lies between a linear and square relationship and pleural mesothelioma seems to rise less than linearly with cumulative dose. Although these non-linear relationships provide a best fit ot the data, statistical and other uncertainties mean that a linear relationship remains arguable for pleural and lung tumours (but not or peritoneal tumours).Based on these considerations, and a discussion fo the associated uncertainties, a series of quantified risk summary statements for different elvels of cumulative exposure are presented.     

Mineral fibres, fibrosis, and asbestos bodies in lung tissue from deceased asbestos cement workers

Lung tissue from 76 deceased asbestos cement workers (seven with mesothelioma) exposed to chrysotile asbestos and small amounts of amphiboles, has been studied by transmission electron microscopy, together with lung tissue from 96 controls. The exposed workers with mesothelioma had a significantly higher total content of asbestos fibre in the lungs than those without mesothelioma, who in turn, had higher concentrations than the controls (medians 189, 50, and 29 x 10(6) fibres/g (f/g]. Chrysotile was the major type of fibre. The differences were most pronounced for the amphibole fibres (62, 4.7, and 0.15 f/g), especially crocidolite (54, 1.8 and less than 0.001 f/g), but were evident also for tremolite (2.9, less than 0.001, and less than 0.001 f/g) and anthophyllite (1.7, less than 0.001, and less than 0.001 f/g). For amosite, there was no statistically significant difference between lungs from workers with and without mesothelioma; the lungs of workers had, however, higher concentrations than the controls. Strong correlations were found between duration of exposure and content of amphibole fibres in the lungs. Asbestos bodies, counted by light microscopy, were significantly correlated with the amphibole but not with the chrysotile contents. Fibrosis was correlated with the tremolite but not the chrysotile content in lungs from both exposed workers and controls. Overall, similar results were obtained using fibre counts and estimates of mass.     

Asbestos lung fibre concentrations in South African chrysotile mine workers

Mesothelioma has not been found in South African chrysotile miners and millers despite decades of producing about 100000 tons of the mineral per year. One possible explanation for the scarcity or absence of the cancer may be a relative lack of contaminating fibrous tremolite, an amphibole that variably occurs with chrysotile ores. The fibre content in the lungs of nine former chrysotile mine workers was ascertained by transmission electron microscopy. Despite fairly long service in most cases (median 9.5 yr; range 32-4 yr) the concentrations of chrysotile fibres were relatively low: only two cases exceeded 1.14 million fibres/g dried lung. Tremolite fibre levels were even lower: less than 1 million fibres/g dried lung in all but one case. Tremolite fibre concentrations exceeded those of chrysotile in only two cases. These results support the contention that South African chrysotile is not heavily contaminated by tremolite.     

Mineral fibres, fibrosis, and asbestos bodies in lung tissue from deceased asbestos cement workers.

Lung tissue from 76 deceased asbestos cement workers (seven with mesothelioma) exposed to chrysotile asbestos and small amounts of amphiboles, has been studied by transmission electron microscopy, together with lung tissue from 96 controls. The exposed workers with mesothelioma had a significantly higher total content of asbestos fibre in the lungs than those without mesothelioma, who in turn, had higher concentrations than the controls (medians 189, 50, and 29 x 10(6) fibres/g (f/g]. Chrysotile was the major type of fibre. The differences were most pronounced for the amphibole fibres (62, 4.7, and 0.15 f/g), especially crocidolite (54, 1.8 and less than 0.001 f/g), but were evident also for tremolite (2.9, less than 0.001, and less than 0.001 f/g) and anthophyllite (1.7, less than 0.001, and less than 0.001 f/g). For amosite, there was no statistically significant difference between lungs from workers with and without mesothelioma; the lungs of workers had, however, higher concentrations than the controls. Strong correlations were found between duration of exposure and content of amphibole fibres in the lungs. Asbestos bodies, counted by light microscopy, were significantly correlated with the amphibole but not with the chrysotile contents. Fibrosis was correlated with the tremolite but not the chrysotile content in lungs from both exposed workers and controls. Overall, similar results were obtained using fibre counts and estimates of mass.     

Airborne fibre concentrations and lung burden compared to the tumour response in rats and humans exposed to asbestos

The excess risk of tumours exposed to asbestos were previously compared with the results of rat inhalation experiments. It could be demonstrated that humans at the workplace suffer from a tumour risk at fibre concentrations which are 300 times lower than those needed in the rat inhalation model to produce the same risk. However, the estimation of human risk was based on the study of workers at a chrysotile textile factory, whereas animal experimental results were related to exposure to amphiboles. Since for this comparison the risk of cancer due to exposure to amosite or crocidolite fibres at the workplace is of interest, quantitative exposure-response relationships for lung cancer and mesothelioma for the white workforce of South African amosite and crocidolite mines were discussed. On comparing the risk of lung cancer in this study with the risk of lung cancer for chrysotile textile workers, it can be concluded, that the risk of lung cancer and mesothelioma from crocidolite and amosite was higher than in the chrysotile textile factory.It could be also demonstrated, on the basis of a study of the lung burden of mesothelioma cases and of controls, that a significantly increased odds ratio of about 5 was established at amphibole concentrations of between 0.1 and 0.2 f μg⁻¹ dry lung (WHO fibres longer than 5 μm from TEM analysis). On the other hand, carcinogenic response was observed at a fibre concentration 6000 times higher in animal inhalation experiments with crocidolite asbestos (SEM analysis of WHO fibres). As a result of these findings, it has been concluded that inhalation studies in rats are not sufficiently sensitive for the detection of hazards and risks to humans exposed to man-made fibres.     

Retention patterns of asbestos fibres in lung tissue among asbestos cement workers.

Retention patterns in lung tissue (determined by transmission electron microscopy and energy dispersive spectrometry) of chrysotile, tremolite, and crocidolite fibres were analysed in 69 dead asbestos cement workers and 96 referents. There was an accumulation of tremolite with time of employment. Among workers who died within three years of the end of exposure, the 13 with high tremolite concentrations had a significantly longer duration of exposure than seven in a low to intermediate category (medians 32 v 20 years; p = 0.018, one sided). Crocidolite showed similar patterns of accumulation. In workers who died more than three years after the end of exposure, there were no correlations between concentrations of amphibole fibres and time between the end of exposure and death. Chrysotile concentrations among workers who died shortly after the end of exposure were higher than among the referents (median difference in concentrations 13 million fibres (f)/g dry weight; p = 0.033, one sided). No quantitative differences in exposure (duration or intensity) could be shown between workers with high and low to intermediate concentrations. Interestingly, all seven workers who had had a high intensity at the end of exposure (> 2.5 f/ml), had low to intermediate chrysotile concentrations at death, whereas those with low exposure were evenly distributed (31 subjects in both concentration categories); hence, there was a dependence between last intensity of exposure and chrysotile concentration (p = 0.014). Among 14 workers with a high average intensity of exposure, both those (n = 5) with high tissue concentrations of chrysotile and those (n = 10) with high tissue concentrations of tremolite fibres had more pronounced fibrosis than those with low to intermediate concentrations (median fibrosis grades for chrysotile: 2 v 1, p = 0.021; for tremolite: 2 v 0.5, p = 0.012). Additionally, workers who died shortly after the end of exposure with high concentrations of chrysotile and crocidolite had smoked more than those with low intermediate concentrations (medians for chrysotile 35 v 15 pack-years, p = 0.030; for crocidolite 37 v 15 pack-years, p = 0.012). The present data indicate that chrysotile has a relatively rapid turnover in human lungs, whereas the amphiboles, tremolite and crocidolite, have a slower turnover. Further, chrysotile retention may be dependent on dose rate. Chrysotile and crocidolite deposition and retention may be increased by tobacco smoking; chrysotile and tremolite by fibrosis.     

Occupational asbestos exposure among respiratory cancer patients in Lithuania

BACKGROUND: Despite intensive use of asbestos, no cancer case has ever been diagnosed as asbestos related in Lithuania. This paper attempts to estimate the proportion of those occupationally exposed to asbestos among respiratory cancer patients. MATERIAL AND METHODS: Occupational exposure to asbestos was assessed retrospectively for 298 lung cancer and four mesothelioma patients, admitted to the Institute of Oncology, Vilnius. The evaluation was based on personal interview data using an internationally established questionnaire covering most likely activities of asbestos exposure at the workplace. Cumulative exposure to asbestos at work was estimated in fiber years. Lung tissue asbestos fiber burden analysis was conducted by scanning transmission electron microscopy on 23 samples. RESULTS: A cumulative asbestos exposure of > or =25 fiber years was found for 10 lung cancer patients (3.4%). They worked in foundries, construction, installation, shipyard, power plant, railway, asbestos cement, glass and chemical industry. In a further 56 lung cancer patients (18.8%) and for one (25%) mesothelioma patient, a cumulative exposure from 5 to 24.9 fiber years was assessed. Asbestos fibers were detected in 18 cases, the burden ranged from 0.1 to 4.1 million fibers/g dry lung tissue; concentrations exceeding 1 million f/g dry lung tissue were found in four cases. All fibers were chrysotile. CONCLUSIONS: Findings indicate that a fraction (3.4%) of the lung cancer cases could be attributed to heavy occupational exposure to asbestos using the Helsinki criterion of > or =25 fiber years. Therefore, approximately 50 lung cancer cases per year in Lithuania could be asbestos-related compensable occupational diseases.     

Pulmonary mineral fibers after occupational and environmental exposure to asbestos in the Russian chrysotile industry

BACKGROUND: As an indicator of occupational, domestic, and environmental exposure, the level and type of asbestos fibers were determined from lung tissue samples of workers and residents who resided in the area of the world's largest asbestos mine at Asbest, Russia. METHODS: Electron microscopy was used to analyze and measure the concentration of asbestos fibers in a series of 47 autopsies at the Asbest Town Hospital. Work histories were obtained from pathology reports and employment records. RESULTS: In 24 chrysotile miners, millers, and product manufacturers, the pulmonary concentrations of retained fibers (over 1 microm in length) were 0. 8-50.6 million f/g for chrysotile, and < 0.1-1.9 million f/g for amphiboles (tremolite and anthophyllite). The concentrations were lower in 23 persons without any known occupational contact with asbestos; 0.1-14.6 million f/g for chrysotile, and < 0.1-0.7 million f/g for amphiboles. On average, 90% of all inorganic fibers were chrysotile, and 5% tremolite/anthophyllite. No amosite or crocidolite fibers were detected in any of the samples. CONCLUSIONS: The mean and range of pulmonary chrysotile concentrations were about the same as reported previously from the Canadian mining and milling industry. In the Russian samples, the mean concentration of tremolite fibers were less by at least one order of magnitude. Occupational contact was the most important source of asbestos exposure.     

Occupational exposure to asbestos as evaluated from work histories and analysis of lung tissues from patients with mesothelioma

The past occupational exposure to asbestos of 23 patients with mesothelioma (21 men and two women) has been evaluated by a personal interview of their work history and by determination of the fibre burden in their lung tissue with scanning electron microscopy (SEM) and x ray microanalysis. According to the work history, nine patients (39%) had definitely been or probably been exposed to asbestos, six patients (26%) had had possible exposures, and eight patients (35%) unlikely or unknown exposure to asbestos. The two female patients were in the unknown exposure category. The fibre concentrations in the patients' lung tissue ranged from less than 0.1 million to 370 million fibres (f) per g dry tissue. Concentrations of over one million f per g dry tissue were found in 15 patients (65%). The lung fibre concentrations of all nine male office workers analysed for reference were less than one million f per g dry tissue. Seventy eight per cent of the patients with mesothelioma had at least possible exposure according to their history of work or concentrations of more than one million f per g dry tissue.     

Occupational exposure to asbestos as evaluated from work histories and analysis of lung tissues from patients with mesothelioma.

The past occupational exposure to asbestos of 23 patients with mesothelioma (21 men and two women) has been evaluated by a personal interview of their work history and by determination of the fibre burden in their lung tissue with scanning electron microscopy (SEM) and x ray microanalysis. According to the work history, nine patients (39%) had definitely been or probably been exposed to asbestos, six patients (26%) had had possible exposures, and eight patients (35%) unlikely or unknown exposure to asbestos. The two female patients were in the unknown exposure category. The fibre concentrations in the patients' lung tissue ranged from less than 0.1 million to 370 million fibres (f) per g dry tissue. Concentrations of over one million f per g dry tissue were found in 15 patients (65%). The lung fibre concentrations of all nine male office workers analysed for reference were less than one million f per g dry tissue. Seventy eight per cent of the patients with mesothelioma had at least possible exposure according to their history of work or concentrations of more than one million f per g dry tissue.     

Changes in low molecular weight DNA fragmentation in white blood cells of workers highly exposed to asbestos

Objective: The aim of this study was to determine low molecular weight (LMW)-DNA fragmentation changes after white blood cell (WBC) incubation in lysis buffer followed by constant-field gel electrophoresis (CFGE). WBCs were isolated from blood samples of workers highly exposed to asbestos fibres at the workplace in Germany, and were compared with those from healthy adults. This study was conducted parallel to the study presented in our preceding paper (Marczynski et al. 2000b) in which we described significant increases in the levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG) adducts in the DNA of white blood cells from the same highly exposed workers relative to the levels found in the control group in all three study years (1994 to 1997). Method: We found that 15-h incubation in lysis buffer of WBCs embedded in agarose-plugs from healthy control donors with 2% SDS, proteinase K and Na₂-EDTA at 42 °C followed by 0.5 h at 4 °C produced a characteristic DNA fragmentation pattern below 23 kbp using CFGE. Results: In the 1st year of the study (1994–1995) changes were found in LMW-DNA fragmentation in 54.8% of the asbestos workers studied, compared with the DNA fragmentation pattern of controls. Interestingly, in the 2nd year of the study (1995–1996) changes in DNA fragmentation were found in only 39.9% of exposed subjects. In the 3rd year of the study (1996–1997) the highest number of workers exposed to asbestos (67.3%) with changes in the LMW-DNA fragmentation pattern was found. The Chi-square test for each year of the study revealed significant changes (P < 0.001). These changes may be due to the presence of hydrogen peroxide (H₂O₂), as has been shown in vitro. It is likely that a Fenton reaction involving the heterolytic reduction of H₂O₂ by traces of reduced transition metals such as Fe²⁺ and Cu⁺ is involved in the fragmentation of DNA. No difference was found in the changes in DNA fragmentation between asbestos-exposed subjects with and without benign asbestos-associated diseases (asbestosis, asbestos-associated pleural plaques). Significant correlations were not found after analysis of the changes in DNA fragmentation in relation to different possible occupational and non-occupational confounding factors, such as the duration of asbestos exposure, the latency period, estimated cumulative fibrous dust dose (“fibre-years”), and non-occupational confounding factors, such as age, smoking status, acute febrile infections, the intake of medicines, aspirin, Ca²⁺, Mg²⁺ and/or hormones, the intake of vitamins, and cases of cancer. Conclusions: Our data confirm that oxidative stress occurs in the WBCs of workers highly exposed to asbestos fibres, thus supporting the hypothesis that asbestos fibres damage cells through an oxidative mechanism. Oxidative stress and oxidative DNA damage may be induced by long-term exposure to asbestos. The new insights into the oxidative effects of asbestos fibres are of great importance because they provide a way forward for new preventive strategies. Preventive and therapeutic approaches using antioxidants should be taken into consideration. Received: 2 October 2000 / Accepted: 27 January 2001     

Lung asbestos burden in shipyard and construction workers with mesothelioma: comparison with burdens in subjects with asbestosis or lung cancer

Although mesothelioma is generally considered to be caused by asbestos, epidemiologic studies indicate that some cases have another cause. In order to determine whether pulmonary asbestos burden can be used to define asbestos-related mesotheliomas, asbestos burden was quantified in 27 shipyard or construction workers with diffuse malignant mesothelioma of the pleura or peritoneum and a history of asbestos exposure. Their burden was significantly greater than the burden found in 19 unexposed men (P less than 0.001). The burdens were also compared to those of previously reported subjects with asbestosis or lung cancer. The median concentration for total amphibole fibers (2.7 million/g dry lung) in subjects with mesothelioma did not differ significantly from our previously reported median values for 14 subjects with asbestosis (1.3 million/g dry lung) or for 60 asbestos workers with lung cancer (1.3 million/g dry lung). Fiber size distribution for amosite, the most prevalent fiber type, was similar in all three subject groups. Fifteen of 25 (60%) subjects with mesothelioma had mild asbestosis. Asbestos body (AB) concentrations were greater than or equal to 1900/g dry lung, and total amphibole fiber concentrations were greater than or equal to 390,000/g dry lung. Counts of ABs greater than or equal to 0.5/cm2 in histologic sections always signified both of these concentrations in extracts. Thus, histologic sections showing greater than or equal to 0.5 ABs/cm2 or extracts containing asbestos body or amphibole fiber concentrations of at least 1900 or 390,000/g dry lung, respectively, will confirm an asbestos-related mesothelioma.