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Although there is no dispute among independent scientists about the carcinogenic and fibrogenic effects of chrysotile, the asbestos industry has been continuously and successfully acting to cast doubts on its harm. Another approach including asbestos insurance entities is to refuse compensation by raising the bar and fight criminal prosecution for asbestos-related diseases by the help of paid scientists. A recent publication on asbestos fibre burden in human lungs fits well in this context. The claim that chrysotile fibres are biopersistent in human lung is not based on the data provided by these authors, and, additionally, exhibits serious inconsistencies and obvious mismeasurements and significant methodological problems. The conclusion of the authors that fibre analysis of workers' lungs "is of high significance for differential diagnosis, risk assessment and occupational compensation" is unfounded and reprehensible. Also the available literature, the statements of the WHO, IARC, other decisive independent international organizations, and all our experience provide abundant evidence to the contrary. Note, the method is generally restricted to research only and is not recognized for diagnostic purpose and compensation in any other country. In conclusion, fibre counting in lung tissues should not be used to estimate former exposure to chrysotile comprising c. 94 % of applied asbestos in Germany. The authors claim that the analyses can improve the compensation rates in Germany. However, the opposite has been the case; it significantly worsens the non-justified denial of well-substantiated compensation claims., Competing Interests: During recent 3 years, H-JW and XB have testified in ligitation, XB also on behalf of statutory insurance institutions., (© Georg Thieme Verlag KG Stuttgart · New York.)

Lung cancer is one of the most frequently encountered cancer types. According to the latest WHO data, about 10 % of this disease are due to occupational exposure to cancerogens. Asbestos is still the number one carcinogen. Further frequent causes include quarz and ionizing radiation (uranium mining). Probable causes of the disease can be identified only with the help of detailed occupational history taken by a medical specialist and qualified exposure assessment. Without clarifying the cause of the disease, there is neither a correct insurance procedure nor compensation for the victim, and furthermore, required preventive measures cannot be initiated., (© Georg Thieme Verlag KG Stuttgart · New York.)

The silicate mineral asbestos is categorized into two main groups based on fiber structure: serpentine asbestos (chrysotile) and amphibole asbestos (crocidolite, amosite, anthophyllite, tremolite, and actinolite). Chrysotile is used in more than 2 000 applications and is especially prevalent in the construction industry. Although its use is banned or restricted in more than 52 countries, an estimated 107 000 workers die from asbestos exposure each year, and approximately 125 million workers continue to be exposed. Furthermore, ambient exposures persist to which the public is exposed, globally. Today, the primary controversies regarding the use of asbestos are the potencies of different types of asbestos, as opposed whether or not asbestos causes morbidity and mortality. The asbestos industry has promoted and funded research based on selected literature, ignoring both clinical and scientific knowledge. In this piece, we highlight a prominent example of a conflicted publication that sought to undermine the World Health Organization (WHO) campaign to stop the use of all forms of asbestos, including chrysotile asbestos. Independent and rigorous scientific data provide sufficient evidence that chrysotile asbestos, like other forms of asbestos, is a cause of asbestos-related morbidity and premature mortality.

An 81-year-old woman was dying from histologically confirmed pulmonary fibrosis without having had any asbestos exposure in the workplace. The lung dust fibre analysis showed significantly increased "asbestos bodies" (AB) (2,640 AB per gram of wet lung tissue) and asbestos fibre concentrations (8,600,000 amphibole fibres of all lengths and 540,000 amphibole fibres with a length ≥5 μm per gram of dry lung tissue). Asbestos exposure was revealed to have occurred during household contact after 27 years of washing her husband's industrial clothing that had been contaminated by asbestos at his workplace in an asbestos textile factory. Household asbestos dust exposure as a risk or co-factor in the aetiology of the fatal pulmonary fibrosis is discussed.

Due to the current query whether the predominantly used chrysotile (white) asbestos comprises health risks we performed a literature search including in vitro and animal experiments as well as epidemiological studies.As shown by epidemiological studies chrysotile causes less pleural fibrosis and mesotheliomas when compared with other asbestos types. However, its otherwise inflammatory, toxic, carcinogenic, and fibrosis-inducing effects correspond to those of other occupationally relevant asbestos types. This is based on clinical, animal as well as on in-vitro findings. This means that denying a causal relationship, e. g. in a case with lung fibrosis (= asbestosis) or lung cancer with an asbestos load of 25 fiber-years in the absence of identification of a significant concentration of asbestos fibers or asbestos bodies in the lung (see so-called "hit and run" phenomenon), contradicts the medical-scientific knowledge., (© Georg Thieme Verlag KG Stuttgart · New York.)

Due to latency periods that can last for decades, asbestos-related diseases show 18 years after the enforcement of the prohibition of asbestos application in Germany their highest numbers. In the centre of attention are asbestos-induced pleural fibroses, mesotheliomas, asbestoses, lung and laryngeal cancer. Diagnosing and expertizing these diseases causes difficulties, is hitherto non-uniform and does frequently not correspond to the current medico-scientific expertise. This induced the German Respiratory Society as well as the German Society of Occupational and Environmental Medicine in cooperation with the German Society of Pathology, the German Radiology Society and the German Society of Otorhinolaryngology, Head and Cervical Surgery, to develop the above mentioned guideline during seven meetings moderated by AWMF. The required thorough diagnosis is based on the detailed recording of a qualified occupational history. Since the sole radiological and pathological-anatomical findings cannot sufficiently contribute to the causal relationship the occupational history recorded by a general physician and a specialist is of decisive importance. These physicians have to report suspected occupational diseases and to advise patients on social and medical questions. Frequently, problems occur if the recognition of an occupational disease is neglected due to a supposedly too low exposure or too few ferruginous bodies or low fibre concentrations in lung tissue. The new S2k directive summarizing the current medico-scientific knowledge is for this reason, for diagnoses and expert opinions as well as for the determination of a reduced capacity for work a very important source of information., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: The aim of this study was to evaluate the diagnostic power of a fuzzy classifier and a marker panel (CYFRA 21-1, NSE, CRP) for the detection of lung cancers in comparison to asbestosis patients at high-risk of developing lung cancer., Patients and Methods: A panel of four tumour markers, i.e. CEA, CYFRA 21-1, NSE, SCC and CRP, was measured in newly diagnosed lung cancer patients of different histological types and stages in comparison to asbestosis patients. In this prospective study, a fuzzy classifier was generated with the data of 216 primary lung cancer patients and 76 patients suffering from asbestosis. The patients and controls were recruited in the clinics of the University in Giessen., Results: At 95%-specificity, it was possible with this tool to detect non-small cell lung cancers in 70% at stage I (n = 30), in 95% at stage II (n = 22), in 98% at stage III (n = 56), in 92% at stage IV (n = 50) and small cell lung cancers with limited disease status (n = 21) in 90.7% and with extensive disease status (n = 37) in 97.3%. In contrast, single markers had a detection rate significantly far below these. The application of the classifier was examined on an independent collective of 38 non-small cell lung cancers and 76 asbestosis patients. The latter underwent stationary rehabilitation in the clinics for occupational diseases in Bad Reichenhall or Falkenstein. The fuzzy classifier showed correct negative classification in 75 out of the 76 cancer-free asbestosis patients, which confirmed a specificity of 97.4%. The overall sensitivity for lung cancer detection in high risk populations was 73.6%. All large cell carcinomas were detected. The positive predictive value was 77.7%. The negative predictive value reached 94.8%., Conclusion: With the fuzzy classifier and a marker panel, a reliable diagnostic tool for the detection of lung cancers in a high risk population is available.

Ataxia-telangiectasia is an autosomal recessive disease characterized by neurological and immunological symptoms, radiosensitivity and cancer predisposition. Heterozygous carriers of an ataxia-telangiectasia gene mutation are predisposed to epithelial cancers. We initiated a study to elucidate the frequency and clinical relevance of ATM gene mutations in former uranium miners exposed to high levels of radiation from radon and its decay products. Former uranium miners with Schneeberg lung cancer (n=48), former uranium miners suffering from silicosis (n=60) and uranium miners without occupational lung disorders (n=102) were investigated for nine mutations in the ATM gene. One gastric and one prostate cancer occurred in the group of miners without occupational lung diseases. Mutation analyses for S707P, IVS10-6Tright curved arrow G, 2250Gright curved arrow A, E1978X, R2443X, 3801delG, S49C and D2625E-A2626P were performed using genomic DNA obtained from peripheral blood samples. Three ATM gene alterations (S707P, S49C or IVS10-6Tright curved arrow G) were observed. Of all cancer patients, 8.0% were heterozygous, but only 1.9% of the non-cancer controls were [OR=4.6; 95% confidence interval (CI), 0.8-26.8]. In this pilot study a major role of six ATM gene mutations could not be revealed for cancer predisposition in former uranium miners. The results leave the possibility of a moderate risk associated with more subtle ATM gene alterations.

Despite an extensive literature, the relationship between asbestos exposure and lung cancer remains the subject of controversy, related to the fact that most asbestos-associated lung cancers occur in those who are also cigarette smokers: because smoking represents the strongest identifiable lung cancer risk factor among many others, and lung cancer is not uncommon across industrialised societies, analysis of the combined (synergistic) effects of smoking and asbestos on lung cancer risk is a more complex exercise than the relationship between asbestos inhalation and mesothelioma. As a follow-on from previous reviews of prevailing evidence, this review critically evaluates more recent studies on this relationship--concentrating on those published between 1997 and 2004--including lung cancer to mesothelioma ratios, the interactive effects of cigarette smoke and asbestos in combination, and the cumulative exposure model for lung cancer induction as set forth in The Helsinki Criteria and The AWARD Criteria (as opposed to the asbestosis-->cancer model), together with discussion of differential genetic susceptibility/resistance factors for lung carcinogenesis by both cigarette smoke and asbestos. The authors conclude that: (i) the prevailing evidence strongly supports the cumulative exposure model; (ii) the criteria for probabilistic attribution of lung cancer to mixed asbestos exposures as a consequence of the production and end-use of asbestos-containing products such as insulation and asbestos-cement building materials--as embodied in The Helsinki and AWARD Criteria--conform to, and are further consolidated by, the new evidence discussed in this review; (iii) different attribution criteria (e.g., greater cumulative exposures) are appropriate for chrysotile mining/milling and perhaps for other chrysotile-only exposures, such as friction products manufacture, than for amphibole-only exposures or mixed asbestos exposures; and (iv) emerging evidence on genetic susceptibility/resistance factors for lung cancer risk as a consequence of cigarette smoking, and potentially also asbestos exposure, suggests that genotypic variation may represent an additional confounding factor potentially affecting the strength of association and hence the probability of causal contribution in the individual subject, but at present there is insufficient evidence to draw any meaningful conclusions concerning variation in asbestos-mediated lung cancer risk relative to such resistance/susceptibility factors.

The impact of genetic polymorphisms in GSTM1, GSTP1 or GSTT1 on susceptibility to lung cancer has received particular interest since these enzymes play a central role in detoxification of major classes of tobacco carcinogens. In the current German study we investigated the role of GSTM1, GSTT1 and GSTP1 polymorphisms as a genetic modifier of risk for individuals with lung cancer as susceptible genotypes especially in relation to tobacco smoking. The GSTM1, the GSTP1 as well as GSTT1-polymorphism were determined by real time PCR analysis in 446 lung cancer patients and 622 controls. The observed allele frequencies of the GSTP1 polymorphism in the population were within the range described for Caucasians. Multivariate analyses of lung cancer patients, who carried at least one mutant variant allele of GSTP1 (OR=1.03; 95%-CI: 0.76-1.39) did not show any elevated risks. GSTM1 or GSTT1 null-genotypes were found in 47.3% resp. 18.5% of the controls and in 52.5% resp. 16.8% of the cancer patients. The estimated risk of the GSTM1 null genotype for lung cancer was OR=1.34 (95%-CI: 0.99-1.81) and for the GSTT1 null genotype OR=0.88 (95%-CI: 0.59-1.32). When analyzed by histology no individual subtype of lung cancer was strongly associated with the polymorphisms. Lung cancer risk rose significantly with higher cumulative cigarette consumption confirming the association with smoking-related lung cancer risk. Stratified analysis between tobacco smoking and variant genotypes revealed for heavy smokers (>60 pack-years) increasing risks at the presence for at least one copy of the GSTP1 variant allele OR=50.56 (95%-CI: 15.52-164.79). The corresponding risks for GSTM1 null genotypes were OR=112.08 (95%-CI: 23.02-545.71) and for the GSTT1 null-genotype OR=158.49 (95%-CI: 17.75-1415.06) in smokers >60 pack-years. Analysing the interaction between tobacco smoking and the genotypes, combined smoking and having the susceptible genotypes did not show a joint effect. In this study polymorphisms of the GSTM1, GSTT1 or GSTP1 had no relevant modifying effect on lung cancer risk and cumulative smoking dose.

Background: The impact of genetic polymorphisms in CYP1A1 or CYP1B1 on susceptibility to lung cancer has received particular attention since these enzymes play a central role in the activation of major classes of tobacco carcinogens. Several polymorphisms in the CYP1A1 locus have been identified and their genotypes appear to exhibit population frequencies that depend on ethnicity. In the current German study, we investigated the role of CYP1A1 and CYP1B1 polymorphisms as a genetic modifier of risk for individuals with lung cancers as susceptible genotypes, especially in relation to tobacco smoking., Materials and Methods: Three polymorphisms, the CYP1A1 T6235C (CYP1A1 MspI), the CYP1A1 A4889G-position (CYP1A1 iva) as well as the CYP1B1 codon 432 polymorphism were determined by real-time PCR analysis in 446 lung cancer patients and in 622 controls., Results: The observed allele frequencies in the population were within the range described for Caucasians. Multivariate analyses of lung cancer patients, who carried at least one mutant variant allele of CYP1A1 T6235C (OR=1.06; 95%-CI: 0.7-1.6), CYP1A1 A4889G (OR=1.09; 95%-CI: 0.63-1.88) or CYP1B1 Val432Leu (OR=1.01 CI: 0.73-1.39) did not show any elevated risks. When analysed by histology, no individual subtype of lung cancer was significantly associated with the polymorphisms. Lung cancer risk rose significantly with higher cumulative cigarette consumption. Stratified analysis between tobacco smoking and variant genotypes revealed, for heavy smokers (>60 pack-years), increasing risks with the presence of at least one copy of the CYP1A1 T6235C variant allele OR=27.74 (95%-CI: 4.34-177.25), the CYP1A1 A4889G position OR=33.23 (95%-CI: 3.11-354.99) and the CYP1B1 OR=418.70 (95%-CI: 45.45-3856.89). By analysing the interaction between tobacco smoking and the genotypes, the combination of smoking and having the susceptible genotypes did not show a joint effect., Conclusion: In this study polymorphism of the CYP1A1 T6235C- or A4889G-position as well as CYP1B1-codon 432-polymorphisms had no relevant modifying effect on lung cancer risk and cumulative smoking dose., (Copyright© 2004 International Institute of Anticaner Research (Dr. John G. Delinassios), All rights reserved.)

The ILO (1980) Classification has been revised during recent years. The new version is now available as the International Classification of Radiographs of Pneumoconioses (Revised edition 2000). The Guidelines booklet is currently available only in English. Those involved felt it was important to maintain continuity with the ILO (1980) edition, in particular to retain the standard radiographs, despite their restricted quality, so as to ensure comparability with earlier national and international data sets. The standard films illustrating pleural abnormalities, and 'u'-shadows, have been modified and reconstituted. The most important changes relate to assessment of film quality, pleural abnormalities, and additional symbols. In Germany, film quality is characterised as "+", "+-", "+--" and "u" according to whether the ability to assess pneumoconiosis is judged to be unimpeachable ("+") to unusable ("u"). If a film is not classified as "+", then written comments regarding defects are required. For "diffuse" pleural thickening, the ILO (2000) edition now requires the presence also of obliteration of the costophrenic angle. This was not required in the earlier (1980) edition and, as previously, is also not stipulated in the German version. A minimum width of 3 mm (previously 0-5 mm), coded "a", is required both for plaques as well as for the margin to the lateral chest wall. Congruence is thus achieved for criteria, which, in German practice, lead to an indication of suspect occupational disease. Plaques on the diaphragm are not considered for measurement of extent; they are only coded as present or absent. If calcification is identified, then this must also be classified and measured as a localised plaque. Extent of calcification on its own, previously coded "0" to "3", is no longer specified. The following new symbols, illustrated by new diagrams, have been introduced: aa = atherosclerotic aorta; at = apical thickening; cg = calcified granuloma (or other non-pneumocononiotic nodules); me = mesothelioma (already previously differentiated from "ca" on the German record sheet); pa = plate atelectasis; pb= parenchymal bands; ra = rounded atelectasis; od = other disease. (Examples of the latter are illustrated diagrammatically by lobar pneumonia, aspergilloma, goiter and hiatal hernia.) Earlier national differences (ILO 1980/German Federal Republic) on particular issues have also been agreed among German "double-readers" ["Zweitbeurteiler"]. However, conformity between the original (ILO 2000) text and the national (German) modified text has been retained in large measure. The detailed descriptions of the standard films differ in certain respects from the German (1980) definitions. Some revision of individual descriptions of the films are proposed. Except for a few differences, agreement was reached here too. The definitive date for the change in Germany is expected to be in early 2004. The standard films are already available now through ILO offices in Geneva or Bonn (addresses in appendix.)

Background: Pulmonary siderosis is a well established disorder in welders. Internationally more than 150 cases of interstitial pulmonary siderofibrosis are associated with long-standing and heavy exposure to welding fumes at poorly ventilated working places., Patients: Characteristic job histories, lung function analyses and histological examinations as well as elemental microanalysis by energy dispersive X-ray analysis (EDX) are demonstrated from 3 welders with pulmonary siderofibrosis., Results: Histological examinations show a patchy interstitial fibrosis with accumulations of particulate material typical for welding fumes. EDX disclose an increase of iron-load in activated macrophages as well as in lung tissue and a close topographical relationship of welding fume particles and interstitial fibrotic reactions. Lung function analysis showed predominantly loss of pulmonary performance during spiroergometry., Conclusions: Regarding the actual knowledge about the pathomechanisms of ultrafine particles on lung tissue, the evidence from animal experiments, the histological and electron microscopical results, our own clinical examinations of welders and some epidemiological evidence, we assume a causal relationship of interstitial pulmonary siderofibrosis in welders with long-standing exposure to high concentrations of welding fumes under poor working conditions.

Background: Interstitial pulmonary fibrosis (IPF) is reported after long term, severe exposure to welding fumes in poorly ventilated workplaces., Methods: Fifteen welders with IPF were examined--13 in our outpatient clinic--from 1990 to 1997. Occupational histories and examinations, lung function analyses, symptoms and clinical findings, histological analyses in 13 patients partly including SEM/EDX-analyses, chest X-rays, chest computed tomographies were conducted., Results: Duration of work as welders was 28 years and the cumulative dose of welding fumes 221 mg/m(3) x years (median). Lung function studies found pattern of restriction or combined restriction-obstruction, lower diffusion capacity, and reduced blood oxygen tension at exercise. Histologically, patchy interstitial fibrosis was noted. Accumulations of particulate matter typically for welding fume were detected. EDX showed increase of iron load and close topographical relationship to welding fume particles embedded in areas of scattered fibrosis., Conclusion: While epidemiological data are limited, it is reasonable to conclude that a causal relationship exists between IPF in welders with long term exposure to high concentrations of welding fumes., (Copyright 2002 Wiley-Liss, Inc.)

Since 1977 the diffuse malignant mesothelioma of the pleura and peritoneum caused by asbestos represents one of the most often compensated occupational cancers in Germany. Because of the probability of an asbestos-related etiology, it is considered as a "signal tumour", mainly indicating exposure to asbestos dust at the workplace. Two cases of histologically confirmed rare malignant mesothelioma of the tunica vaginalis testis are presented. Previous exposure to asbestos at the workplace is to be considered as a causal factor in both tumors. If cases of mesothelioma occur the criteria for indicating an occupational disease (No. 4105 of the German Law of Occupational Diseases, BKV) are fulfilled.

Objective: To ascertain the lung burden of asbestos fibres in Hungarian lung cancer patients in comparison with the cumulative asbestos exposure estimated from the occupational history., Methods: For 25 Hungarian lung cancer patients, lung tissue fibre analysis was performed by scanning transmission electron microscopy (STEM) and counting of ferruginous bodies (FBs) by light microscopy. Cumulative asbestos exposure in fibre-years was assessed from a standardised occupational history using the report "fibre years" of the German Berufsgenossenschaften., Results: Median and maximum concentrations of fibres longer 5 microns per gram dry lung tissue (g dry) were 0.03 and 7.38 million fibres/g dry for chrysotile, 0.00 and 0.21 million fibres/g dry for amphibole and 0.22 and 0.62 million fibres/g dry for other mineral fibres (OMFs). The maximum values were observed in one patient for whom a high asbestos exposure was evident in advance from the occupational history., Conclusions: In comparison with reference values obtained by the same method for German patients with no indication of workplace asbestos exposure, increased concentrations of more than 0.2 million chrysotile fibres/g dry were obtained for six of the 25 Hungarian patients (24%). For one of them, the second highest estimate of a workplace exposure of 60 fibre-years and the highest tissue concentration of 7.38 million chrysotile fibres/g dry substantiate a high probability of a causal relationship to asbestos. A further comparison can be made with the results for 66 German patients treated by surgical lung resection for a disorder other than mesothelioma, mainly lung cancer. For the Hungarian lung cancer patients, similar amounts of chrysotile but distinctly lower amounts of amphibole fibres and distinctly higher amounts of OMFs were observed. A correlation between exposure estimates from occupational history and concentration of fibres in the lung tissue was observed for amphibole (Spearman: R = 0.66, P < 0.001, Pearson: R = 0.50, P = 0.01) and for chrysotile (Pearson: R = 0.48, P = 0.02).

Background: This study examines the role of occupational factors in the development of diffuse malignant mesothelioma with special emphasis on the dose-response relationship for asbestos and on the exposure to man-made vitreous fibers (MMVFs)., Methods: One hundred and twenty-five male cases, diagnosed by a panel of pathologists, were personally interviewed concerning their occupational and smoking history. The same number of population controls (matched for sex, age and region of residence) underwent similar interviews by trained interviewers. Odds ratios (OR) were calculated for an expert-based exposure index using conditional logistic regression., Results: Exposure to asbestos shows the expected sharp gradient with an OR of about 45 for a cumulative exposure > 1.5 fiber years (arithmetic mean 16 fiber years). A significant OR was calculated even for the lowest exposure category "> 0 - < or = 0.15 fiber years". Although the mean cumulative exposure to MMVF is roughly 10% of the exposure to asbestos, an increased OR is observed in an ever/never evaluation. This observation is heavily hampered by methodical problems. A corresponding case-control study was performed using a lung tissue fiber analysis in addition to interviews. Both interviews and the lung tissue analysis yielded similar OR levels between the reference and the maximum exposure intervals., Conclusions: Despite a possible influence as a result of selection and information bias, our results confirm the previously reported observation of a distinct dose-response relationship even at levels of cumulative exposure below 1 fiber year. Moreover, the study confirms that asbestos is a relevant confounder for MMVF. A causal relationship between exposure to MMVF and mesothelioma could neither be detected nor excluded, as in other studies., (Copyright 2001 Wiley-Liss, Inc.)

This case report concerns a 46-year-old woman, dying from histologically confirmed diffuse malignant mesothelioma after asbestos exposure, which was only caused by indoor pollution from crocidolite-containing spray asbestos in building materials. There was no other known occupational or environmental asbestos exposure during her life. The lung tissue fibre analysis by light microscopy showed significantly increased concentrations of ferruginous bodies (3162 FB per gram of wet lung tissue). By use of scanning transmission electron microscopy, clearly increased concentrations of amphibole fibres (8.6 x 10(6) fibres longer than 1 microm and 0.6 x 10(6) fibres longer than > or =5 microm per gram dry tissue), mainly classified as crocidolite, were observed. The disease was attributed to indoor exposure to sprayed asbestos, which occurred during her work as a decorator in the studio of a warehouse.

Former East German uranium miners who are known to have been exposed to radon are estimated to be at high risk for lung carcinogenesis. Among these miners over 200 occupationally caused lung cancer cases are expected to occur each year, resulting in a total of 7,000-24,000 excess lung cancer cases in the coming years. It is still unknown whether there is a correlation between biomarkers and the exposure of the uranium miners to ionizing radiation that might enable us to trace those miners with high lung cancer risk. The primary aim of this pilot study was to test the possibility of performing a biomarker study in this unique cohort of former uranium miners in spite of several limitations that had to be taken into consideration when comparing them with healthy controls, such as old age, age-dependent diseases and potential confounding artefacts from dissimilar smoking patterns. The second aim was to test a range of biomarkers for DNA damage and inflammation in leukocytes and bronchoalveolar fluid for their ability to detect biological effects. In this cohort of miners we found an increased frequency of chromosomal aberrations in blood lymphocytes and an increased prevalence of both fibronectin and tumour necrosis factor alpha in the bronchoalveolar fluid.

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.

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-CIPh as the main ClPh metabolite) in urine for reevaluation 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 microg/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 microg 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.

Certain subsets of the population are especially sensitive to carcinogens, and this can be determined using molecular biological methods. In the literature there has been evidence presented for the use of p21ras (ras) as a tumor marker for human carcinogenic substances such as asbestos, polycyclic aromatic hydrocarbons, and vinyl chloride in the workplace. In this study we have examined whether serum ras could serve as a biomarker for the early detection of occupationally derived lung cancer, with an emphasis on Schneeberger (radon-induced) lung cancer. Sera were taken from 65 male tumor patients. Fifty-nine patients suffered from primary lung cancer (including 18 patients with Schneeberger lung cancer and 12 patients with asbestos-related lung cancer). Additionally, 29 patients with non-malignant lung disease, and a healthy control group (44) including 32 former uranium miners of SDAG Wismut exposed to ionizing radiation (radon and its decay products) were examined. Ras protein was determined via three different methods: 1) immunoprecipitation followed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting; 2) SDS-PAGE using 5-17% gradient gels followed by Western blotting; 3) pre-incubation with Blue Sepharose, SDS-PAGE on 5-17% gradient gels, and Western blotting. The results show that 1 ng ras protein was measurable in serum standards. This protein could not be detected in patient sera or in sera from any of the study groups. Thus, ras cannot be considered useful as a marker for the early detection of asbestos-induced or Schneeberger lung cancer.

The results of standardized 8 h lasting exposures of n = 18 volunteers to ethylbenzene (EthBz) at levels of 25 and 100% of the maximum allowable concentrations at the workplace (MAK) value of 100 ppm as well as the results of field studies are considered to evaluate a biological tolerance (BAT) value for EthBz. On the basis of the relationship between the external and internal exposure a BAT value of 1.5 mg/l has been set for the EthBz concentration in blood as the most sensitive and specific parameter of exposure to this aromatic hydrocarbon. The interpretation of EthBz blood values has to take into account the short half-life of t1/2 = 0.5 +/- 0.08 h in the first hour after the end of exposure in which this aromatic hydrocarbon is eliminated from the blood. The additional determination of the EthBz metabolites mandelic acid (MA) and phenylglyoxylic acid (PGA), respectively, excreted in post shift urine as well as in urine samples at the beginning of the next shift shows good correlations with the external exposure. The biological half-life of MA was calculated to t1/2 = 5.3 +/- 1.1 h. Because the time of sampling can vary the relationship between the levels of MA to PGA the total concentration of the excreted metabolites depends less on this influence and is therefore better suited for monitoring exposed persons. On the basis of the standardized experiments a BAT value has been proposed of 2 g MA plus PGA corrected per gram creatinine. Both BAT values are adjusted to data which result from earlier standardized exposures during 30 min to EthBz under physical activity of 50 watt on a bicycle ergometer.

Background: The oncogene product EGF-receptor (EGF-R), the tumor suppressor gene product p53, and anti-p53 antibodies are detectable in serum of certain cancer patients. Increased levels of some of these products were reported in lung cancer patients after occupational asbestos exposure, after exposure to polycyclic aromatic hydrocarbons or vinyl chloride. This molecular epidemiological study investigated the use of serum EGF-R, p53-protein, and anti-p53 antibodies as biomarkers for detection of effects of radon and its decay products., Methods: Serum EGF-R, p53-protein, and anti-53 antibodies were measured using ELISA in former uranium miners of SDAG Wismut without lung disease (n=106) and miners with Schneeberg lung cancer (n=22). They were compared with healthy subjects (n=23), patients with lung cancer not due to ionizing radiation (n=88), and patients with non-malignant lung or pleural diseases (n=50)., Results: No significantly elevated or decreased serum values for p53 protein, EGF-R, or anti-p53 antibodies could be found. There was no correlation of these with Working Level Months (WLM)., Conclusions: p53 protein, EGF-R, or anti-p53 antibodies in serum are not useful as biomarkers for detection of lung cancer related to ionizing radiation (i.e., Schneeberg lung cancer)., (Copyright 1999 Wiley-Liss, Inc.)

The oncogene product epidermal growth factor receptor (EGF-R), the tumour suppressor gene product p53 and anti-p53 antibodies are detectable in the serum of certain cancer patients. Increased levels of some of these products were reported in lung cancer patients after occupational asbestos exposure and after exposure to polycyclic aromatic hydrocarbons or vinylchloride. In the first step, this study investigated the possible diagnostic value of serum EGF-R, p53-protein and anti-p53 antibodies, measured by an enzyme-linked immunosorbent assay, in lung tumour patients. In addition to being investigated on a molecular epidemiological basis, these parameters were examined as biomarkers of carcinogenesis, especially with regard to asbestos incorporation effects or of radon-induced lung cancers. Also, a possible effect of cigarette smoking and age dependence were studied. A total of 116 male patients with lung or pleural tumours were examined. The histological classification was four small-cell cancers, six large-cell cancers, 32 adenocarcinomas, 47 squamous carcinomas, 12 mixed lung carcinomas, five diffuse malignant mesotheliomas and ten lung metastasis of extrapulmonary tumours. Twenty-two lung cancers and all mesotheliomas were related to asbestos, 22 lung cancers were related to ionizing radiation and 61 patients had cigarette smoke-related lung cancer. Besides these patients 50 male patients with non-malignant lung or pleural diseases were included; of the latter eight subjects suffered from asbestosis. Controls were 129 male subjects without any lung disease. No significantly elevated or decreased serum values for p53 protein, EGF-R, or anti-p53 antibodies as a function of histological tumour type, age, or degree and type of exposure (asbestos, smoking, ionizing radiation) could be found. The utility of p53-protein, EGF-R and anti-p53 antibodies as routine biomarkers for screening occupationally derived lung cancers is limited.

In a mesothelioma case-control study, asbestos and other mineral fibers from lung burden were examined as causal factors. Diagnosis was confirmed by a panel of pathologists. For 66 cases and 66 controls from hospitals in five German towns, lung tissue fiber analysis by transmission electron microscopy was available. Control patients were treated by a surgical lung resection mostly because of lung cancer. For chrysotile and other mineral fibers a significantly increased odds ratio (OR) was not observed. A clear dose-response relationship was demonstrated for the concentration CA of amphibole fibers longer than 5 microm. Between 0.025 and 2.5 fibers/microg dry weight (f/microg) the relationship can be approximated as OR = CA/(0. 025 f/microg). Similar but less distinct dose-response relationships were found in a Canadian and an Australian study. It is concluded that among German mesothelioma patients factors not associated with amphibole fiber concentration are not predominating.

This report concerns two Turkish immigrant workers, aged 50 and 59, who developed histologically confirmed diffuse malignant mesothelioma in the absence of obvious occupational exposure to asbestos in Germany. Both patients had spent their childhood in central Anatolia, Turkey, where the presence of tremolite asbestos in the environment has been described. In both patients, the lung-dust burden showed a high concentration of amphibole fibers (186 x 10(6) resp. 59 x 10(6) per gram dry tissue), mainly classified as actionolite/tremolite fibers in scanning transmission electron microscopy. In both patients, the disease was thus attributed to early environmental exposure to tremolite asbestos.

In an interdisciplinary, multicentre case control study of the causal factors of the diffuse malignant mesothelioma (DMM) standardised histories where taken from n = 324 Patients suffering from DMM, n = 315 hospital control patients (KK) and n = 182 population controls (PK). For 66 DMM, 149 KK and 107 PK a risk from asbestos fibre dust at the workplace was not detectable. For latter persons indoor and outdoor asbestos exposure outside of the workplace were investigated. The following factors were examined: neighbourhood exposure from companies using asbestos, living in big cities and nearby main traffic roads, building materials containing asbestos, electric storage heaters and household contacts. For using electric storage heaters a statistically significant increased odds ratio (OR) was observed for DMM as well in comparison with KK (OR = 2.42; 95%-CI: 1.01-5.72) and in comparison for PK (OR = 2.91; 95%-CI: 1.08-7.80). Only outside of Hamburg an increased OR compared to KK was observed for people living in the neighbourhood of asbestos factories (OR = 16.3; 95%-CI: 1.35-196.8) and also, but only in Hamburg, compared to PK living nearby main traffic roads. There is only a trend for a mesothelioma-risk for household-contacts based on a few cases. In one DMM-patient without an occupational asbestos exposure the lung dust fibre analysis yielded 2.912 FB and 1.459 x 10(3) crocydolithe fibres per gram dried lung tissue. As a child he lived in the immediate vicinity of the blue asbestos mine in Wittenoom, Australia. Therefore in special cases a para-occupational asbestos or a neighbourhood asbestos exposure can be demonstrated as a risk factor of diffuse malignant mesothelioma.

Objective: A case-control study was performed to assess various nonoccupational factors (smoking, eating and drinking habits, intake of analgesics) that may be aetiological factors in the development of tumours of the lower urinary tract, while vitamins may be protective., Patients and Methods: 150 patients (125 men, mean age 66.4 years; 25 women, mean age 68.2 years) with histologically confirmed malignant tumour of bladder or other part of the lower urinary tract and a comparable group of controls, matched for age, sex and home location, were asked in a standardised personal interview about their life-long habits of smoking, eating and drinking, as well as intake of analgesics., Results: Smoking was the greatest risk factor. In men there was a significant positive dose-effect relationship between the number of cigarettes smoked and relative carcinoma risk, compared with nonsmokers, by a factor of 3.68 among those with the highest dosage (> 40 pack-years). Because of the small number of cases this relationship could not be proven in women, but twice as many female tumour patients than controls were smokers (8 vs 4). In men, even after adjusting for smoking, increased coffee consumption increased the risk by a factor of 2 (2-4 cups: odds ratio 2.14 [P < 0.05]; > 5 cups: odds ratio 2.22 [not significant]). An increased beer consumption had no apparent effect on the development of tumours. Findings regarding vitamin C were ambiguous. More prolonged and increased intake of phenacetin-containing analgesics in men showed a tendency towards a higher tumour risk., Conclusion: Smoking cigarettes is one of the main risk factors for the development of bladder and other lower urinary tract tumours. The influence of other risk factors needs to be elucidated.

This article discusses the development of asbestos-induced malignant mesotheliomas after non-occupational environmental exposure to asbestos through contact with occupationally exposed household members. In our policlinic, we have seen six fatal pleural mesothelioma cases (five wives and one son of asbestos-industry workers) with no history of occupational asbestos exposure. In five women, a causal relation was established between the fatal disease and inhalation of asbestos fibers while cleaning the contaminated work-clothes and shoes of their husbands at home. The son had also been exposed to asbestos throughout his childhood during daily visits with his father at the workplace.

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 micrograms-1 dry lung (WHO fibres longer than 5 microns 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.

The Authors evaluate the risk of lung cancer and mesothelioma among asbestos workers in Germany. 3,988 workers (3,372 male and 616 female) were included in the study, which took into consideration the branch of the asbestos industry in which they had worked, the duration of their employment and also their smoking habits. At the end of the 12 year follow-up, 3,315 workers were alive and 673 dead. The analysis of cause of death showed an increased risk of dying from lung cancer and pleural and peritoneal mesothelioma, in men as well as in women. The risk was shown to be greatest among workers in the asbestos textile industry and among insulators. A probable multiplicative effect of asbestos exposure and smoking on lung cancer causation was noted.