asbestos--crocidolite and tremolite

It has been more than 40 years since occupational crocidolite exposure in South African miners was found to be associated with development of malignant mesothelial tumors 30 to 40 years later. Similar cases were not seen in the amosite and chrysotile miners. Since then, epidemiological and toxicological knowledge have increased enormously, but mortality continues to rise steeply (5% to 10% per year) in most industrialized countries. Even with widespread asbestos abatement efforts, this increase is likely to continue in Western Europe and the United State well into the next century, at least until 2020. Unregulated use of asbestos in less industrialized countries may cause the epidemic to continue throughout the next century in those regions. Asbestos abatement seems to be successful as evidenced by a decline in the proportion of patients with peritoneal tumors, which are the most common malignancies in heavily exposed individuals. Whereas in the 1960s peritoneal tumors comprised up to 30% of the total, in recent years the proportion has fallen to about 10%, This changing ratio could also be due to the steady increase in pleural tumors. The difficulty in formulating the connection as to the etiology of mesothelioma resulted from an unforeseeable difference in the carcinogenicity of various asbestos and mineral fiber types and was compounded by the very long latency of the disease. Unfortunately, the use of a single term, "asbestos," to describe at least five fibrous silicate minerals, each with unique physical, chemical, and biological properties and not infrequently and naturally admixed, severely hampered scientific investigation into the occupational health risks. The field became confused and filled with debate. At the heart of the fiber type controversy lies a fundamentally differing view of the importance of biopersistence of various asbestos fibers in carcinogenesis. This review will deal with the epidemiology of mesothelioma with particular attention to the studies that elucidate the impact of various asbestos fiber types on the etiology of the disease.

Topics: Asbestos; Asbestos, Amphibole; Asbestos, Crocidolite; Case-Control Studies; Cohort Studies; Global Health; Humans; Lung Neoplasms; Mesothelioma; Occupational Diseases; Occupational Exposure; Pleural Neoplasms

Primary malignant mesothelial tumours were recognized by pathologists before asbestiform minerals (chrysotile, crocidolite and amosite) were mined commercially. The discovery, 40 yrs ago, of a causal link with crocidolite and the wide-ranging epidemiological studies which followed are the subject of this review. Early case-control and descriptive surveys, supplemented by cohort studies in insulation workers and chrysotile miners, quickly demonstrated major occupational and geographical differences, with high risk in naval dockyard areas and in the heating trades. In the 1980s, reliable cohort surveys showed that in mining and in the manufacture of asbestos products the mesothelioma risk was much higher when exposure included crocidolite or amosite than chrysotile alone. However, qualitative and quantitative information on exposure was too often inadequate for this evidence to be conclusive. Well-controlled lung fibre analyses have reduced these deficiencies and demonstrated the probable implications of the greater biopersistence of amphibole fibres. Chrysotile for industrial use often contains low concentrations of fibrous tremolite, which may well explain the few cases of mesothelioma associated with this type of asbestos. Progress in this field has been much retarded by controversy, for which the 20 year gap between the availability of reliable estimates of risk for the mining of chrysotile and that for crocidolite or amosite may have been largely responsible.

Topics: Asbestos; Asbestos, Amosite; Asbestos, Amphibole; Asbestos, Crocidolite; Asbestos, Serpentine; Carcinogens; Case-Control Studies; Cohort Studies; Female; History, 20th Century; Humans; Lung Neoplasms; Male; Mesothelioma; Mineral Fibers; Mining; Occupational Diseases; Reproducibility of Results; Risk Factors

Tissues obtained at autopsy or biopsy from 81 workers and 2 household persons, were chemically digested. The asbestos fibres recovered were characterized by analytical transmission electron microscopy. Among the 83 causes of death were 33 mesotheliomas, 35 lung cancers, 12 asbestosis and 3 from other cancers. Of the three major commercial asbestos fibre types, amosite was found to be the most prevalent fibre, occurring in approximately 76% of the cases, followed by chrysotile in approximately 60% and crocidolite in approximately 24%. Amosite and chrysotile were observed as the single commercial fibre in approximately 22 and approximately 17% of the cases respectively, whereas crocidolite and tremolite were found as the single fibre type in only approximately 2.5% of the cases. Among the fifteen cases where chrysotile and tremolite occurred together, the amount of chrysotile fibre always exceeded tremolite. However, tremolite was also found in ten additional cases where chrysotile was not detected. Amosite was present in four, amosite plus crocidolite in three, and crocidolite alone in one. Amosite was present in all of the insulation workers' lungs studied and was found in the highest concentration in this exposure category. The highest chrysotile concentration was found among workers in general trades. Although most prevalent in shipyard workers lungs, crocidolite concentration is not statistically different among the exposure groups studied. Although crocidolite was found in twenty cases, amosite accompanied it in eighteen of these. Eleven of the 20 cases were from shipyard workers. Of the 8 mesothelioma cases, 7 also contained amosite. Crocidolite alone only occurred in 1 of the 33 mesothelioma cases analysed. We concluded the following: crocidolite exposure occurred among USA insulators and a large percentage of other workers as well; insulation workers are primarily exposed to amosite; mixed fibre exposures are associated with more mesotheliomas than single fibre exposures; chrysotile only exposure is associated with approximately 12% of the mesothelioma cases studied; and if tremolite exposure is associated with chrysotile exposure, the chrysotile amount exceeds that for the associated tremolite.

Topics: Aged; Asbestos; Asbestos, Amosite; Asbestos, Amphibole; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Autopsy; Biopsy; Female; Humans; Lung; Lung Neoplasms; Male; Microscopy, Electron; Middle Aged; Occupational Exposure; Organ Culture Techniques; United States

The Fe content and the morphometry of asbestos are two major factors linked to its toxicity. This study explored the use of microbe-mineral interactions between asbestos (and asbestos-like) minerals and thermophilic chemolithoautotrophic microorganisms as possible mineral dissolution treatments targeting their toxic properties. The removal of Fe from crocidolite was tested through chemolithoautotrophic Fe(III) reduction activities at 60°C. Chrysotile and tremolite-actinolite were tested for dissolution and potential release of elements like Si and Mg through biosilicification processes at 75°C. Our results show that chemolithoautotrophic Fe(III) reduction activities by Deferrisoma palaeochoriense were supported with crocidolite as the sole source of Fe(III) used as a terminal electron acceptor during respiration. Microbial Fe(III) reduction activities resulted in higher Fe release rates from crocidolite in comparison to previous studies on Fe leaching from crocidolite through Fe assimilation activities by soil fungi. Evidence of biosilicification in Thermovibrio ammonificans did not correspond with increased Si and Mg release from chrysotile or tremolite-actinolite dissolution. However, overall Si and Mg release from chrysotile into our experimental medium outmatched previously reported capabilities for Si and Mg release from chrysotile by fungi. Differences in the profiles of elements released from chrysotile and tremolite-actinolite during microbe-mineral experiments with

Topics: Asbestos; Asbestos, Crocidolite; Asbestos, Serpentine; Bacteria, Anaerobic; Ferric Compounds; Iron; Minerals

The onset of malignant mesothelioma (MM) is linked to exposure to asbestos fibers. Asbestos fibers are classified as serpentine (chrysotile) or amphibole, which includes the crocidolite, amosite, anthophyllite, tremolite, and actinolite types. Although few studies have been undertaken, anthophyllite has been shown to be associated with mesothelioma, and tremolite, a contaminant in talc and chrysotile, is a risk factor for carcinogenicity. Here, after characterizing the length and width of these fibers by scanning electron microscopy, we explored the cytotoxicity induced by tremolite and anthophyllite in cells from an immortalized human mesothelial cell line (MeT5A), murine macrophages (RAW264.7), and in a rat model. Tremolite and short anthophyllite fibers were phagocytosed and localized to vacuoles, whereas the long anthophyllite fibers were caught on the pseudopod of the MeT5A and Raw 264.7 cells, according to transmission electron microscopy. The results from a 2-day time-lapse study revealed that tremolite was engulfed and damaged the MeT5A and RAW264.7 cells, but anthophyllite was not cytotoxic to these cells. Intraperitoneal injection of tremolite in rats induced diffuse serosal thickening, whereas anthophyllite formed focal fibrosis and granulomas on peritoneal serosal surfaces. Furthermore, the loss of Cdkn2a/2b, which are the most frequently lost foci in human MM, were observed in 8 cases of rat MM (homozygous deletion [5/8] and loss of heterozygosity [3/8]) by array-based comparative genomic hybridization techniques. These results indicate that tremolite initiates mesothelial injury and persistently frustrates phagocytes, causing subsequent peritoneal fibrosis and MM. The possible mechanisms of carcinogenicity based on fiber diameter/length are discussed.

Topics: Animals; Asbestos; Asbestos, Amphibole; Asbestos, Crocidolite; Asbestos, Serpentine; Comparative Genomic Hybridization; Cyclin-Dependent Kinase Inhibitor p15; Cyclin-Dependent Kinase Inhibitor p16; Homozygote; Humans; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Rats; Risk Factors; Sequence Deletion

Humans exposed to asbestos and/or asbestiform fibers are at high risk of developing many lung diseases including asbestosis, lung cancer, and malignant mesothelioma. However, the disease-causing potential and specific metabolic mechanisms and pathways associated with various asbestos/asbestiform fiber exposures triggering different carcinogenic and non-carcinogenic outcomes are still largely unknown. The aim of this this study was to investigate gene expression profiles and inflammatory responses to different asbestos/asbestiform fibers at the acute/sub-acute phase that may be related to delayed pathological outcomes observed at later time points. Mice were exposed to asbestos (crocidolite, tremolite asbestos), asbestiform fibers (erionite), and a low pathogenicity mineral fiber (wollastonite) using oropharyngeal aspiration. Similarities in inflammatory and tissue damage responses, albeit with quantitative differences, were observed at day 1 and 7 post treatment. Exposure to different fibers induced significant changes in regulation and release of a number of inflammatory cytokines/chemokines. Comparative analysis of changes in gene regulation in the lung on day 7 post exposure were interpretable in the context of differential biological responses that were consistent with histopathological findings at days 7 and 56 post treatment. Our results noted differences in the magnitudes of pulmonary responses and gene regulation consistent with pathological alterations induced by exposures to four asbestos/asbestiform fibers examined. Further comparative mechanistic studies linking early responses with the long-term endpoints may be instrumental to understanding triggering mechanisms underlying pulmonary carcinogenesis, that is lung cancer versus mesothelioma.

Topics: Animals; Asbestos, Amphibole; Asbestos, Crocidolite; Calcium Compounds; Female; Inflammation; Lung; Mice; Mice, Inbred C57BL; Silicates; Transcriptome; Zeolites

Topics: Air Pollutants, Occupational; Animals; Asbestos, Amosite; Asbestos, Amphibole; Asbestos, Crocidolite; Asbestos, Serpentine; Carcinogens; Humans; Lung; Minerals; Particulate Matter

Mineral fibers are potential carcinogens to humans. In order to help clarify the etiology of the pathological effects of asbestos, cellular reactions to natural and synthetic asbestos fibers were compared using a lung alveolar cancer cell line (A549 epithelial cells), considered the first target of inhaled micro-environmental contaminants. Natural asbestos tremolite (NAT) fibers were collected from rocks in NW Italy. Synthetic asbestos tremolite (SAT) was iron-free and therefore considered as standard tremolite. Both fibers, subjected to mineralogical characterization by X-ray powder diffractometry, electron microscopy and energy dispersive spectrometry, fell within the definition of respirable and potentially carcinogenic fibers. Several signs of functional and structural cell damage were found after treatment with both fibers, documented by viability, motility, and morphological perturbations. Phalloidin labeling showed irregular distribution of cytoskeletal F-actin, whereas immunohistochemical investigations showed abnormal expression of VEGF, Cdc42, β-catenin, assessed as risks indicators for cancer development. Both fibers caused significant loss of viability, even compared to UICC crocidolite, but, while SAT fibers exerted a more direct cytotoxic effect, survival of damaged cells expressing high VEGF levels was detected after NAT contact. This in vitro pilot study outlines potential health risks of NAT fibers in vivo related to their iron content, which could trigger signaling networks connected with cell proliferation and neoplastic transformation.

Topics: Actins; Apoptosis; Asbestos; Asbestos, Amphibole; Asbestos, Crocidolite; beta Catenin; cdc42 GTP-Binding Protein; Cell Line, Tumor; Cell Survival; Cytoskeleton; Humans; Immunohistochemistry; Iron; Microscopy, Electron; Mitosis; Necrosis; Phalloidine; Pilot Projects; Tetrazolium Salts; Thiazoles; Time Factors; Vascular Endothelial Growth Factor A; X-Rays

Given the role of phosphoinositide-specific phospholipase C (PLC) isozymes in the control of cell growth and differentiation we were prompted to analyze the expression of some of these PLC in human bronchoalveolar carcinoma-derived alveolar epithelial A549 cells. The effects of several fluoro-edenite fibers were compared with those of tremolite, a member of the calcic amphibole group of asbestos that originates from Calabria (Italy), and crocidolite, that, due to its high toxicity, is one of the most studied asbestos amphiboles. Our data show an increased expression of both PLC beta1 and PLC gamma1 in A549 cells treated with asbestos-like fibers, hinting at a role of PLC signalling in those cancerous cells.

Topics: Adenocarcinoma, Bronchiolo-Alveolar; Asbestos, Amphibole; Asbestos, Crocidolite; Cell Line, Tumor; Enzyme Activation; Humans; Lung Neoplasms; Phosphatidylinositols; Phospholipase C beta; Phospholipase C delta; Second Messenger Systems

Lung tissue from 15 women who died from mesothelioma was evaluated for tissue burden of ferruginous bodies and uncoated asbestos fibers. The group contained individuals who had occupational exposure to asbestos and others had family members whose work history included vocations where contact with asbestos containing materials occurred.. Tissue samples from tumor free lung were digested and filtered and then investigated for ferruginous bodies by light microscopy and asbestos and non-asbestos fibers by analytical transmission electron microscopy (ATEM). Size and type of fibers were also analyzed.. Asbestos bodies were found in 13 of the 15 samples and asbestos fibers were found in all cases. The most commonly found uncoated asbestos fiber in these individuals was amosite whereas tremolite was the second most commonly found form. The asbestos fiber burden in these females was often of mixed types.. The asbestos body and fiber burden in these cases show variation in tissue burden. Some cases in this study had appreciable burden, which was attributed to secondhand exposure from occupationally exposed family members. Mesothelioma can occur also in individuals with comparatively low tissue burdens of asbestos.

Topics: Aged; Aged, 80 and over; Asbestos, Amosite; Asbestos, Amphibole; Asbestos, Crocidolite; Asbestosis; Body Burden; Environmental Exposure; Female; Humans; Lung; Lung Neoplasms; Mesothelioma; Microscopy, Electron; Middle Aged; Mineral Fibers; Occupational Exposure; Reproducibility of Results

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.. 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.. 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.. 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.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asbestos; Asbestos, Amosite; Asbestos, Amphibole; Asbestos, Crocidolite; Asbestos, Serpentine; Employment; Environmental Exposure; Female; Humans; Infant; Lung; Male; Microscopy, Electron; Middle Aged; Mineral Fibers; Mining; Occupational Exposure; Russia

Twenty cases of mesothelioma among miners of the township of Asbestos, Quebec, Canada, have been reported. To further explore the mineral characteristics of various fibrous material, we studied the fibrous inorganic content of postmortem lung tissues of 12 of 20 available cases. In each case, we measured concentrations of chrysotile, amosite, crocidolite, tremolite, talc-anthophyllite, and other fibrous minerals. The average diameter, length, and length-to-diameter ratio of each type of fiber were also calculated. For total fibers > 5 microns, we found > 1,000 asbestos fibers per mg tissue (f/mg) in all cases; tremolite was above 1,000 f/mg in 8 cases, chrysotile in 6 cases, crocidolite in 4 cases, and talc anthophyllite in 5 cases. Among cases with asbestos fibers, the tremolite count was highest in 7 cases, chrysotile in 3 cases, and crocidolite in 2 cases. The geometric mean concentrations of fibers > or = 5 microns were in the following decreasing order: tremolite > crocidolite > chrysotile > other fibers > talc-anthophyllite > amosite. For total fibers < 5 microns, we found > 1,000 fibers per mg tissue (f/mg) in all cases; tremolite was above 1,000 f/mg in 12 cases, chrysotile in 8 cases, crocidolite in 7 cases, and talc-anthophyllite in 6 cases. Tremolite was highest in 8 cases, chrysotile in 2 cases, and crocidolite and amosite in 2 cases. The geometric mean concentrations of fibers < 5 microns were in the following decreasing order: tremolite > other fibers > chrysotile > crocidolite > talc-anthophyllite > amosite. We conclude, on the basis of the lung burden analyses of 12 mesothelioma cases from the Asbestos township of Quebec, that the imported amphibole (crocidolite and amosite) were the dominant fibers retained in the lung tissue in 2/12 cases. In 10/12 cases, fibers from the mine site (chrysotile and tremolite) were found at highest counts; tremolite was clearly the highest in 6, chrysotile in 2, and 2 cases had about the same counts for tremolite and chrysotile. If a relation of fiber burden-causality of mesothelioma is accepted, mesothelioma would be likely caused by amphibole contamination of the plant in 2/12 cases and by the mineral fibers (tremolite and chrysotile) from the mine site in the 10 other cases.

Topics: Aged; Asbestos; Asbestos, Amosite; Asbestos, Amphibole; Asbestos, Crocidolite; Asbestos, Serpentine; Culture Techniques; Humans; Lung Neoplasms; Male; Mesothelioma; Middle Aged; Mining; Occupational Diseases; Quebec; Textile Industry

Studies of human lungs indicate that, for virtually all types of exposure, the relative proportion of amphibole asbestos retained in the lung far exceeds the proportion in the original dust and, conversely, the relative proportion of chrysotile is far less than that in the original dust. Although amphiboles appear to accumulate in lung in proportion to exposure and chrysotile does not, failure of chrysotile deposition is probably not the reason for the disproportionate retention of amphibole fibres. The available data suggest that chrysotile is deposited in the parenchyma but is cleared extremely rapidly, with the vast bulk of fibres removed from human lungs within weeks to months after inhalation; by comparison, amphibole clearance half-lives are of the order of years to decades. The mechanisms of preferential chrysotile clearance remain uncertain, but fragmentation of chrysotile into short fibres, possibly accompanied by extremely rapid dissolution of such fibres, appears to be important in this process. Chrysotile fibres do penetrate to the periphery of the lung, so that differences in mesothelial pathogenicity of chrysotile and amphiboles in regard to mesothelioma are not caused by failure of chrysotile to reach the pleura. The theory that the tremolite contaminant rather than the chrysotile itself is the cause of 'chrysotile-induced' disease (especially mesothelioma) is consistent with the available human data, but the contrary ideas that disease is caused either by the total transient burden of inhaled chrysotile fibres or by a small, sequestered, long-retained fraction of chrysotile fibres still need to be excluded.

Topics: Animals; Asbestos, Amosite; Asbestos, Amphibole; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Guinea Pigs; Humans; Lung; Mesothelioma; Mining; Occupational Exposure; Pleura; Pleural Neoplasms; Textile Industry; Time Factors

Topics: Asbestos; Asbestos, Amosite; Asbestos, Amphibole; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Humans; Mesothelioma; Pleural Neoplasms; Risk Factors

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

Topics: Aged; Asbestos, Amphibole; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Female; Humans; Industry; Lung; Male; Microscopy, Electron; Occupational Exposure; Silicate Cement; Smoking; Time Factors

For many years, the main source of asbestos in Cyprus was thought to be the chrysotile mine in the central mountains. When a woman, who had no connection with the mine, developed mesothelioma, it was surprising to discover tremolite asbestos bodies within her lung. However, further studies have shown that tremolite occurs as a contaminant within the chrysotile ore body. In this study we have shown that both chrysotile and tremolite can be found in domestic and environmental samples throughout the mountain region; in particular, numerous fine fibres of both materials are present in stucco. Preliminary radiological studies have shown pleural disease in the village population and 5 out of 13 known cases of mesothelioma have arisen in persons unconnected with the mine. This suggests an environmental contribution to asbestos-related disease on the island.

Topics: Air Pollutants; Animals; Asbestos; Asbestos, Amphibole; Asbestos, Crocidolite; Asbestos, Serpentine; Cyprus; Humans; Lung; Mesothelioma; Mining; Pleural Neoplasms; Radiography; Sheep; Silicic Acid