asbestos--amosite and Mesothelioma

An earlier meta-analysis of mortality studies of asbestos-exposed worker populations, quantified excess mesothelioma and lung cancer risks in relation to cumulative exposure to the three main commercial asbestos types. The aim of this paper was to update these analyses incorporating new data based on increased follow-up of studies previously included, as well as studies of worker populations exposed predominantly to single fibre types published since the original analysis. Mesothelioma as a percentage of expected mortality due to all causes of death, percentage excess lung cancer and mean cumulative exposure were abstracted from available mortality studies of workers exposed predominantly to single asbestos types. Average excess mesothelioma and lung cancer per unit of cumulative exposure were summarised for groupings of studies by fibre type; models for pleural and peritoneal mesothelioma risk and lung cancer risk in terms of cumulative exposure for the different fibre types were fitted using Poisson regression. The average mesothelioma risks (per cent of total expected mortality) per unit cumulative exposure (f/cc.yr), R

Topics: Asbestos; Asbestos, Amosite; Asbestos, Amphibole; Asbestos, Crocidolite; Asbestos, Serpentine; Humans; Lung Neoplasms; Mesothelioma; Microscopy, Phase-Contrast; Occupational Diseases; Occupational Exposure

The term asbestos collectively refers to a group of naturally occurring fibrous minerals which have been exploited in numerous commercial and industrial settings and applications dating to antiquity. Its myriad uses as a "miracle mineral" owe to its remarkable properties of extreme resistance to thermal and chemical breakdown, tensile strength, and fibrous habit which allows it to be spun and woven into textiles. Abundant in nature, it has been mined considerably, and in all continents save Antarctica. The nomenclature concerning asbestos and its related species is complex, owing to the interest held therein by scientific disciplines such as geology, mineralogy and medicine, as well as legal and regulatory authorities. As fibrous silicates, asbestos minerals are broadly classified into the serpentine (chrysotile) and amphibole (crocidolite, amosite, tremolite, anthophyllite, actinolite) groups, both of which may also contain allied but nonfibrous forms of similar or even identical chemical composition, nonpathogenic to humans. Recently, fibrous amphiboles, not historically classified or regulated as asbestos (winchite, richterite), have been implicated in the causation of serious disease due to their profusion as natural contaminants of vermiculite, a commercially useful and nonfibrous silicate mineral. Although generally grouped, classified, and regulated collectively as asbestos, the serpentine and amphibole groups have different geologic occurrences and, more importantly, significant differences in crystalline structures and chemical compositions. These in turn impart differences in fiber structure and dimension, as well as biopersistence, leading to marked differences in relative potency for causing disease in humans for the group of minerals known as asbestos.

Topics: Asbestos; Asbestos, Amosite; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Humans; Mesothelioma; Mineral Fibers

Mesothelioma is a "new" malignant disease strongly associated with exposure to amphibole asbestos exposure (amosite and crocidolite) environmentally and in the work place. Nonetheless, in recent years, we have learned that many cases of mesothelioma are idiopathic, while some are caused by therapeutic irradiation or chronic inflammation in body cavities. This paper reviews the key epidemiological features of the malignancy in the context of the biological and mineralogical factors that influence mesothelioma development. These tumors challenge the diagnostic pathologist's acumen, the epidemiologist's skill in devising meaningful and definitive studies, the industrial hygienist's knowledge of environmental hazards in diverse occupational settings, and the clinician's skill in managing an intrepid and uniformly fatal malignancy.

Topics: Asbestos, Amosite; Asbestos, Amphibole; Asbestos, Crocidolite; Asbestos, Serpentine; Female; History, 20th Century; Humans; Lung Neoplasms; Male; Mesothelioma; Mining; Occupational Diseases

The strong relationship between mesothelioma and asbestos exposure is well established. The analysis of lung asbestos burden by light and electron microscopy assisted to understand the increased incidence of mesothelioma in asbestos mining and consuming nations.The data on the occupational exposure to asbestos are important information for the purpose of compensation of occupational disease No. 4105 (asbestos-associated mesothelioma) in Germany.However, in many cases the patients have forgotten conditions of asbestos exposure or had no knowledge about the used materials with components of asbestos. Mineral fiber analysis can provide valuable information for the research of asbestos-associated diseases and for the assessment of exposure. Because of the variability of asbestos exposure and long latency periods, the analysis of asbestos lung content is a relevant method for identification of asbestos-associated diseases. Also, sources of secondary exposure, so called "bystander exposition" or environmental exposure can be examined by mineral fiber analysis.Household contacts to asbestos are known for ten patients (1987-2009) in the German mesothelioma register; these patients lived together with family members working in the asbestos manufacturing industry.Analysis of lung tissue for asbestos burden offers information on the past exposure. The predominant fiber-type identified by electron microscopy in patients with mesothelioma is amphibole asbestos (crocidolite or amosite). Latency times (mean 42.5 years) and mean age at the time of diagnose in patients with mesothelioma are increasing (65.5 years). The decrease of median asbestos burden of the lung in mesothelioma patients results in disease manifestation at a higher age.Lung dust analyses are a relevant method for the determination of causation in mesothelioma. Analysis of asbestos burden of the lung and of fiber type provides insights into the pathogenesis of malignant mesothelioma. The most important causal factor for the development of mesothelioma is still asbestos exposure.

Topics: Aged; Asbestos; Asbestos, Amosite; Asbestos, Amphibole; Asbestos, Crocidolite; Asbestos, Serpentine; Female; Germany; Humans; Lung Neoplasms; Male; Mesothelioma; Microscopy, Electron; Middle Aged; Mineral Fibers; Occupational Diseases; Occupational Exposure; Pleural Neoplasms

Grunerite asbestos (amosite) has been shown in epidemiological and experimental animal studies to cause lung cancer, mesothelioma and pulmonary fibrosis commonly referred to as asbestosis. An overview of the human and experimental animal studies describing the health hazards of grunerite asbestos (amosite) is presented. Of the many human studies describing the health hazards of asbestos, only three factories using mainly, if not exclusively, grunerite asbestos (amosite) have been studied. The first is a series of reports on a cohort of 820 workers from a plant located in Paterson, NJ. Among this cohort, 18.7% died of lung cancer and 17 mesotheliomas occurred. The Paterson factory closed in 1954 and moved to Tyler, Texas where it operated until 1972. Among the 1130 former workers in the Tyler plant 6 mesotheliomas were reported with 15.8% lung cancer mortality. The third grunerite asbestos (amosite) exposed cohort was an insulation board manufacturing facility in Uxbridge, United Kingdom. Here 17.1% of the workers died of lung cancer and 5 mesotheliomas occurred. The lung content from 48 Uxbridge workers was analyzed by analytical transmission electron microscopy for mineral fibers. The relationship between grunerite asbestos (amosite) concentrations in the lung correlated with grades of fibrosis and asbestos bodies and was lower than the concentration found in the cases with malignant tumors. The lung cancer cases contained more grunerite asbestos (amosite) than mesothelioma cases, and in the cases of non-malignant disease the concentrations were still lower. In both types of malignancies the concentration of grunerite asbestos (amosite) was very high-over a billion fibers per gram of dried lung tissue. Occupational exposure to airborne concentrations of between 14 and 100 fibers of grunerite asbestos (amosite) per milliliter after 20 year latency causes marked increases in lung cancer, mesothelioma and pulmonary fibrosis (asbestosis).

Topics: Air Pollutants, Occupational; Animals; Asbestos, Amosite; Asbestosis; Cohort Studies; Disease Models, Animal; Humans; Lung; Lung Neoplasms; Mesothelioma; New Jersey; Texas; United Kingdom

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

A review of the literature on chronic inhalation studies in which rats were exposed to mineral fibres at known fibre number concentrations was undertaken to examine the specific roles of fibre length and composition on the incidences of both lung cancer and mesothelioma. For lung cancer, the percentage of lung tumours (y) could be described by a relation of the form y = a + bf + cf2, where f is the concentration of fibre numbers and a, b, and c are fitted constants. The correlation coefficients for the fitted curves were 0.76 for > 5 microns f/ml, 0.84 for > 10 microns f/ml, and 0.85 for > 20 microns f/ml. These seemed to be independent of fibre type. It has been shown that brief inhalation exposures to chrysotile fibre produces highly concentrated fibre deposits on bifurcations of alveolar ducts, and that many of these fibres are phagocytosed by the underlying type II epithelial cells within a few hours. Churg has shown that both chrysotile and amphibole fibres retained in the lungs of former miners and millers do not clear much with the years since last exposure. Thus, lung tumours may be caused by that small fraction of the inhaled fibres that are retained in the interstitium below small airway bifurcations where clearance processes are ineffective. By contrast, for mesothelioma, the (low) tumour yields seemed to be highly dependent upon fibre type. Combining the data from various studies by fibre type, the percentage of mesotheliomas was 0.6% for Zimbabwe (Rhodesian) chrysotile, 2.5% for the various amphiboles as a group, and 4.7% for Quebec (Canadian) chrysotile. This difference, together with the fact that Zimbabwe chrysotile has 2 to 3 orders of magnitude less than tremolite than Quebec chrysotile, provides support for the hypothesis that the mesotheliomas that have occurred among chrysotile miners and millers could be largely due to their exposures to tremolite fibres. The chrysotile fibres may be insufficiently biopersistent because if dissolution during translocation from their sites of deposition to sites where more durable fibres can influence the transformation or progression to mesothelioma.

Topics: Asbestos; Asbestos, Amosite; Asbestos, Serpentine; Humans; Incidence; Lung Neoplasms; Mesothelioma

The authors briefly reviewed the literature concerning the risk factors for primary pleural tumors in humans. The results from the most relevant studies emphasize the fact that the large majority of mesotheliomas are associated with exposure to asbestos or asbestiform fibers. Exposure to asbestos is mainly through industrial use, and mesotheliomas result from occupational, para-occupational, or environmental exposure. Fibers of crocidolite, amosite, and chrysotile appear to be, in descending order, more carcinogenic for pleural tissues. The authors summarize the available data on consumption of asbestos and asbestos-based products in Italy. The chrysotile-asbestos mine in Balangero (Piedmont) stimulated the industrial production of asbestos-cement; asbestos has been largely sprayed among shipyards and user for insulating railroad coaches and carriages. Italy had the greatest consumption of crocidolite in Europe, which was not banned until 1986. The authors discuss the major findings derived from descriptive epidemiological data presented in previous papers dealing with this issue. In addition, standardized mortality rates of primary pleural tumors for European countries are shown. A clearly increasing trend for mortality is observed in Italy, which has also the provinces with the highest mortality rates in Europe. Among Italian provinces, the mortality rates are consistent with the number of asbestosis cases receiving workman's compensation. The authors present the results of both cohort and case-control analytical studies performed in Italy, and provide suggestions for further research.

Topics: Asbestos; Asbestos, Amosite; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Construction Materials; Europe; Female; Humans; Italy; Lung Neoplasms; Male; Mesothelioma; Occupational Diseases; Pleural Neoplasms; Prevalence; Risk Factors

Topics: Asbestos; Asbestos, Amosite; Asbestos, Crocidolite; Asbestos, Serpentine; Canada; Humans; Lung Neoplasms; Maximum Allowable Concentration; Mesothelioma; New Zealand; Occupational Diseases; Risk; South Africa; United Kingdom; United States

Prior to its termination, asbestos mining in South Africa was centred on the large crocidolite fields of the present day Northern Cape, the amosite (grunerite)-crocidolite fields of Limpopo, and chrysotile fields of Mpumalanga provinces. The legacy of these activities continues to affect surrounding communities in contemporary South Africa. The asbestos fields of Limpopo host two important former mining areas at Penge and at the Bewaarkloof near Chuenespoort. A large abandoned site is located southeast of Penge at Weltevreden, where there is no evidence of any rehabilitation. Two former mines, Lagerdraai and Uitkyk, are rehabilitated sites in an extensive string of closed mines that operated in the southern Bewaarkloof. Samples from the abandoned and rehabilitated mine sites were studied using semi-quantitative X-ray powder diffraction (XRD) to determine asbestos contamination levels in soils, and to assess distribution patterns of asbestos mineral species in the surrounding soils. Only where below detection (typically 1-3 mass%) from XRD, samples were assessed optically. The Weltevreden site, with no observable rehabilitation efforts, contrasts with the rehabilitated sites at Lagerdraai and Uitkyk. The predominant asbestiform mineral species at each site were successfully identified, with underlying geological asbestos mineral distribution trends recognised in the soils at the Bewaarkloof. Trace amounts of asbestiform minerals were identified in soils downstream of the Weltevreden mine, as well as in surrounding hillsides. The results indicate that XRD is a potentially useful tool for benchmarking sites yet to be rehabilitated as well as monitoring the effectiveness of previous rehabilitation efforts. The method is also a suitable first-pass for target areas that may require more detailed, time-consuming, and costly analysis.

Topics: Asbestos; Asbestos, Amosite; Asbestos, Crocidolite; Asbestos, Serpentine; Humans; Mesothelioma; Soil; South Africa

We have conducted a population-based study of pleural mesothelioma patients with occupational histories and measured asbestos lung burdens in occupationally exposed workers and in the general population. The relationship between lung burden and risk, particularly at environmental exposure levels, will enable future mesothelioma rates in people born after 1965 who never installed asbestos to be predicted from their asbestos lung burdens.. Following personal interview asbestos fibres longer than 5 µm were counted by transmission electron microscopy in lung samples obtained from 133 patients with mesothelioma and 262 patients with lung cancer. ORs for mesothelioma were converted to lifetime risks.. Lifetime mesothelioma risk is approximately 0.02% per 1000 amphibole fibres per gram of dry lung tissue over a more than 100-fold range, from 1 to 4 in the most heavily exposed building workers to less than 1 in 500 in most of the population. The asbestos fibres counted were amosite (75%), crocidolite (18%), other amphiboles (5%) and chrysotile (2%).. The approximate linearity of the dose-response together with lung burden measurements in younger people will provide reasonably reliable predictions of future mesothelioma rates in those born since 1965 whose risks cannot yet be seen in national rates. Burdens in those born more recently will indicate the continuing occupational and environmental hazards under current asbestos control regulations. Our results confirm the major contribution of amosite to UK mesothelioma incidence and the substantial contribution of non-occupational exposure, particularly in women.

Topics: Adult; Aged; Asbestos, Amosite; Asbestos, Amphibole; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Employment; Female; Humans; Lung; Lung Neoplasms; Male; Mesothelioma; Mesothelioma, Malignant; Middle Aged; Mineral Fibers; Occupational Diseases; Occupational Exposure; Pleural Neoplasms; Risk Assessment

In 2013 the International Journal of Surgical Pathology published a case report of intrasplenic malignant mesothelioma (MM) in a 48-year-old man: it was the first report in literature describing a case of primitive intra-splenic MM, described without  a history of asbestos exposure.. To verify the possible past exposure to asbestos, ignored by the patient himself, by studying in depth his environmental and occupational history.. Information about the occupational and non-occupational history of the subject was collected by Experts of the Operational Unit of Occupational Health and Safety Control (UOC PSAL) of the Local Health Unit Umbria 1 - Perugia, using the Italian National Mesothelioma Register (ReNaM) questionnaire and guide lines; an inspection was  carried out at the past canning industry where the patient worked in the period 1982-1990 and material was taken to be analysed by MOCF and SEM.. Samples showed the presence of asbestos  fibres belonging to the amphibole class (amosite and crocidolite) and to the serpentine class (chrysotile).. The survey described the past occupational exposure to asbestos in a canning industry, where  the subject worked in the period 1982-1990,  unknown to the patient himself. The authors strongly confirm the  usefulness of standardized methods, such as the ReNaM Questionnaire, and the importance of technical expertise of the investigator to find and analyse the suspect materials and to demonstrate  possible past occupational exposure to asbestos.

Topics: Asbestos; Asbestos, Amosite; Asbestos, Crocidolite; Asbestos, Serpentine; Carcinogens; Food Packaging; Humans; Lung Neoplasms; Male; Medical History Taking; Mesothelioma; Mesothelioma, Malignant; Middle Aged; Risk Assessment; Splenic Neoplasms

In former mine workers of Libby, MT, exposure to amphibole-containing vermiculite was linked to increased rates of asbestosis, lung cancer, and mesothelioma. Although many studies showed adverse effects following exposure to Libby amphibole (LA; a mixture of winchite, richterite, and tremolite), little is known regarding the relative toxicity of LA compared to regulated asbestos, or regarding the risks associated with acute high-dose exposures relative to repeated low-dose exposures. In this study, pulmonary function, inflammation, and pathology were assessed after single or multiple intratracheal (IT) exposures of LA or a well-characterized amosite (AM) control fiber with equivalent fiber characteristics. Male F344 rats were exposed to an equivalent total mass dose (0.15, 0.5, 1.5, or 5 mg/rat) of LA or AM administered either as a single IT instillation, or as multiple IT instillations given every other week over a 13-wk period, and necropsied up to 20 mo after the initial IT. When comparing the two fiber types, in both studies LA resulted in greater acute neutrophilic inflammation and cellular toxicity than equal doses of AM, but long-term histopathological changes were approximately equivalent between fibers, suggesting that LA is at least as toxic as AM. In addition, although no dose-response relationship was discerned, mesothelioma or lung carcinomas were found after exposure to low and high dose levels of LA or AM in both studies. Conversely, when comparing studies, an equal mass dose given over multiple exposures instead of a single bolus resulted in greater chronic pathological changes in lung at lower doses, despite the initially weaker acute inflammatory response. Overall, these results suggest that there is a possibility of greater long-term pathological changes with repeated lower LA dose exposures, which more accurately simulates chronic environmental exposures.

Topics: Air Pollutants, Occupational; Animals; Asbestos, Amosite; Asbestos, Amphibole; Dose-Response Relationship, Drug; Drug Administration Schedule; Inflammation; Lung; Lung Neoplasms; Male; Mesothelioma; Rats; Rats, Inbred F344; Toxicity Tests, Acute; Toxicity Tests, Chronic

Asbestos is a potent carcinogen associated with increased risks of malignant mesothelioma and lung cancer in humans. Although the mechanism of carcinogenesis remains elusive, the physicochemical characteristics of asbestos play a role in the progression of asbestos-induced diseases. Among these characteristics, a high capacity to adsorb and accommodate biomolecules on its abundant surface area has been linked to cellular and genetic toxicity. Several previous studies identified asbestos-interacting proteins. Here, with the use of matrix-assisted laser desorption ionization-time of flight mass spectrometry, we systematically identified proteins from various lysates that adsorbed to the surface of commercially used asbestos and classified them into the following groups: chromatin/nucleotide/RNA-binding proteins, ribosomal proteins, cytoprotective proteins, cytoskeleton-associated proteins, histones and hemoglobin. The surfaces of crocidolite and amosite, two iron-rich types of asbestos, caused more protein scissions and oxidative modifications than that of chrysotile by in situ-generated 4-hydroxy-2-nonenal. In contrast, we confirmed the intense hemolytic activity of chrysotile and found that hemoglobin attached to chrysotile, but not silica, can work as a catalyst to induce oxidative DNA damage. This process generates 8-hydroxy-2'-deoxyguanosine and thus corroborates the involvement of iron in the carcinogenicity of chrysotile. This evidence demonstrates that all three types of asbestos adsorb DNA and specific proteins, providing a niche for oxidative modification via catalytic iron. Therefore, considering the affinity of asbestos for histones/DNA and the internalization of asbestos into mesothelial cells, our results suggest a novel hypothetical mechanism causing genetic alterations during asbestos-induced carcinogenesis.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aldehydes; Animals; Asbestos, Amosite; Asbestos, Crocidolite; Asbestos, Serpentine; Chromatin; Cytoskeleton; Deoxyguanosine; DNA; DNA Damage; Hemoglobins; Histones; Iron; Lung Neoplasms; Mesothelioma; Mice; Oxidation-Reduction; Proteins; Rats; Ribosomal Proteins; RNA-Binding Proteins; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Surface Properties

We obtained lifetime occupational and residential histories by telephone interview with 622 mesothelioma patients (512 men, 110 women) and 1420 population controls. Odds ratios (ORs) were converted to lifetime risk (LR) estimates for Britons born in the 1940s. Male ORs (95% confidence interval (CI)) relative to low-risk occupations for >10 years of exposure before the age of 30 years were 50.0 (25.8-96.8) for carpenters (LR 1 in 17), 17.1 (10.3-28.3) for plumbers, electricians and painters, 7.0 (3.2-15.2) for other construction workers, 15.3 (9.0-26.2) for other recognised high-risk occupations and 5.2 (3.1-8.5) in other industries where asbestos may be encountered. The LR was similar in apparently unexposed men and women (approximately 1 in 1000), and this was approximately doubled in exposed workers' relatives (OR 2.0, 95% CI 1.3-3.2). No other environmental hazards were identified. In all, 14% of male and 62% of female cases were not attributable to occupational or domestic asbestos exposure. Approximately half of the male cases were construction workers, and only four had worked for more than 5 years in asbestos product manufacture.

Topics: Adult; Aged; Asbestos; Asbestos, Amosite; Case-Control Studies; Environmental Exposure; Female; Humans; Male; Mesothelioma; Middle Aged; Occupational Exposure; Odds Ratio; Risk

This study focuses on the amosite mining region in South Africa and associated health effects, compared to other mined asbestos fiber types. Historically, dust and fiber levels were high in the amosite mills and mines, and many miners and members of the surrounding communities were exposed to the fibers. Research has shown that amosite produces both benign and malignant disease. Nevertheless, the mesotheliomagenic potential of amosite is several fold lower than crocidolite. The risk of disease associated with amosite exposure is difficult to quantify. Reasons for this include the scarcity of available information, including fiber measurements, and case ascertainment, as well as the juxtaposition of the amosite and crocidolite asbestos seams in South Africa.

Topics: Asbestos, Amosite; Asbestosis; Environmental Exposure; Female; History, 20th Century; Humans; Male; Mesothelioma; Mineral Fibers; Mining; South Africa; Space-Time Clustering

South Africa (SA), a country in which all three commercially important asbestos minerals have been mined and milled, has retained proven cases of mesothelioma linked with environmental exposure to asbestos. This study illustrates the importance of fiber type in the occurrence of environmental mesothelioma. Four studies have reviewed the source of occupational or environmental asbestos exposure in 504 histologically proven cases of mesothelioma in South Africa. One hundred and eighteen cases (23%) were thought to be related to environmental exposure to asbestos. In the vast majority of these cases, exposure was linked to crocidolite mining activities in the Northern Cape Province. Two cases were thought to have occurred in relation to amosite and Transvaal crocidolite exposure in the Limpopo Province. In the balance of cases there was some uncertainty. No cases were reported with exposure to South African chrysotile. Consequently, in the vast majority of cases of mesothelioma, environmental exposure to asbestos occurred in the Northern Cape Province, in proximity to mines, mills and dumps where crocidolite was processed. Crocidolite appears to be far more mesotheliomagenic than amosite, and chrysotile has not been implicated in the disease. This is true for both occupationally and environmentally exposed individuals.

Topics: Asbestos; Asbestos, Amosite; Asbestos, Crocidolite; Asbestosis; Carcinogens; Environmental Exposure; Female; Humans; Male; Mesothelioma; Mineral Fibers; Mining; Occupations; South Africa

Topics: Air Pollutants, Occupational; Asbestos, Amosite; Asbestosis; Environmental Exposure; Humans; Mesothelioma; Mineral Fibers; Mining; New Jersey; South Africa; Texas; United Kingdom

Topics: Asbestos, Amosite; Asbestos, Amphibole; Carcinogens, Environmental; Female; Humans; Male; Mediterranean Region; Mesothelioma; Mineral Fibers; Minnesota; South Africa

Topics: Asbestos; Asbestos, Amosite; Asbestos, Crocidolite; History, 19th Century; History, 20th Century; Mesothelioma; Mining; Occupational Medicine; Pathology; Physicians; Public Health; Research; Research Personnel; Respiratory Tract Diseases; Silicosis; South Africa; Workplace

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

A factory fire in Tranmere, Merseyside, England, deposited asbestos containing fallout in an urban area. There was considerable community anxiety for months after the incident. Therefore an assessment of the long term health risks of this acute environmental incident were requested by the local health authority.. The facts of the incident were gathered and appraised from unpublished and press reports, involved personnel, and further analysis of material collected at the time of the incident. The literature on the long term health risks of asbestos was reviewed, and combined with evidence on asbestos exposure to estimate community health risk.. Risk was almost entirely from exposure to fire fallout of chrysotile in asbestos bitumen paper covering the factory roof. Amosite was only detected in a few samples and in trace amounts. The number of people who lived in the area of fallout was 16 000 to 48 000. From a non-threshold model with assumptions likely to overestimate risk, the lung cancer risk is estimated to be undetectably small. Risk of mesothelioma from chrysotile exposure, and risks of lung cancer and mesothelioma from amosite exposure were based on observational studies and were estimated to be even lower than that of lung cancer risk from chrysotile exposure. Academically, there are assumptions that while reasonable cannot be proven, for example, the validity of extrapolating observed risk from much higher exposures to lower exposures, estimates of individual exposure, and that there is no threshold for asbestos to cause cancer.. The author is unaware of a similar study on long term health risks in a community exposed to asbestos in a fire. It is concluded that, using methods that do not underestimate risk, risk is undetectably small. Practical lessons from this methodology and approach to health risk assessment are discussed.

Topics: Asbestos; Asbestos, Amosite; Asbestos, Serpentine; England; Environmental Exposure; Environmental Pollutants; Fires; Humans; Industry; Linear Models; Lung Neoplasms; Mesothelioma; Risk Assessment; Survival Rate

This article describes the activity of an E-glass microfiber (104E) during chronic inhalation and intraperitoneal injection studies in rats. Results are compared with another microfiber of similar dissolution rate (k(dis)), code 100/475, and the more durable amosite asbestos, both of which we had previously used in similar experiments (Davis et al., 1996). Rats were exposed to aerosol concentrations of 1000 fibers (longer than 5 microm)/ml, as measured by optical microscopy, for 7 h/day, 5 days/wk. Subgroups of rats were followed for mean lung burden, early and late signs of fibrosis, and tumor incidence. At the end of 12 mo of exposure, the mean number of 104E fibers of all lengths in the lungs was approximately double that for amosite but two-thirds of that for 100/475. For fibers longer than 15 microm, the mean 104E burden was similar to that for the amosite and more than twice that of the 100/475. After a 12-mo recovery period, the retained lung burdens (of fibers of all lengths) were approximately 30% of those at 12 mo for both microfibers, and somewhat higher (approximately 44%) for amosite. Amosite and 100/475 fibers longer than 15 microm were more persistent in the lungs than 104E fibers. The chemical composition of 104E fibers did not appear to have been significantly altered by up to 24 mo of residence in lung tissue, whereas the composition of 100/475 was substantially altered over the same time period. From the inhalation study, out of the pathology subgroup of 43 animals exposed to 104E microfibers, 10 had lung tumors (7 carcinoma, 3 adenoma) and 2 had mesotheliomas, whereas in 42 rats exposed to amosite asbestos, there were 16 lung tumors (7 carcinoma, 9 adenoma) and 2 mesotheliomas. The 104E- and amosite-treated animals had similar levels of fibrosis. In contrast, 38 animals treated with 100/475 had little fibrosis, 4 lung tumors (adenomas), and no mesotheliomas. The greater pathogenicity of the 104E fibers, compared to 100/475 fibers, might be partly explained by the greater numbers of long fibers retained in the lung after 12 mo of inhalation. However, we speculate that modification of surface properties by extensive selective leaching of some glass components reduces the toxic potential of 100/475. In a parallel intraperitoneal injection study, 104E caused considerably more mesotheliomas (21 rats out of 24) than 100/475 (8 rats out of 24). In addition, 104E appeared to be more active than amosite asbestos, since mesotheliomas appeared mu

Topics: Administration, Inhalation; Aerosols; Animals; Asbestos, Amosite; Body Burden; Carcinoma; Glass; Inhalation Exposure; Injections, Intraperitoneal; Lung; Lung Neoplasms; Male; Mesothelioma; Mineral Fibers; Neoplasms, Experimental; Particle Size; Pulmonary Fibrosis; Rats; Rats, Wistar; Survival Analysis; Survival Rate; Toxicity Tests

Normal human mesothelial cells from individual donors were studied for susceptibility to asbestos-induction of apoptosis and generation of an extended lifespan population. Such populations were generated after death of the majority of cells and arose from a subset of mesothelial cultures (4/16) whereas fibroblastic cells (5/5) did not develop extended lifespan populations after asbestos exposure. All mesothelial cultures were examined for the presence of SV40 T antigen to obtain information on (i) the presence of SV40 T antigen expression in normal human mesothelial cells and (ii) the relationship between generation of an extended lifespan population and expression of SV40 T antigen. Immunostaining for SV40 T antigen was positive in 2/38 normal human mesothelial cultures. These cultures also had elevated p53 expression. However, the two isolates expressing SV40 T antigen did not exhibit enhanced proliferative potential or develop an extended lifespan population. Asbestos-generated extended lifespan populations were specifically resistant to asbestos-mediated but not to alpha-Fas-induced apoptosis. Deletion of p16Ink4a was shown in 70% of tumor samples. All mesothelioma cell lines examined showed homozygous deletion of this locus which extended to exon 1beta. Extended lifespan cultures were examined for expression of p16Ink4a to establish whether deletion was an early response to asbestos exposure. During their rapid growth phase, extended lifespan cultures showed decreased expression of p16Ink4a relative to untreated cultures, but methylation was not observed, and p16Ink4a expression became elevated when cells entered culture crisis. These data extend the earlier observation that asbestos can generate extended lifespan populations, providing data on frequency and cell type specificity. In addition, this report shows that generation of such populations does not require expression of SV40 T antigen. Extended lifespan cells could represent a population expressing early changes critical for mesothelioma development. Further study of these populations could identify such changes.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Polyomavirus Transforming; Apoptosis; Asbestos; Asbestos, Amosite; Carcinogens; Cell Division; Cell Line; Cellular Senescence; Cyclin-Dependent Kinase Inhibitor p16; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Dose-Response Relationship, Drug; Drug Resistance; Epithelial Cells; Female; Gene Expression Regulation; Genes; Humans; Immunohistochemistry; Male; Mesothelioma; Methylation; Middle Aged; Pleural Neoplasms; Time Factors; Tumor Suppressor Protein p53

A range of respirable man-made mineral fibres were tested for evidence of carcinogenicity by injection into the peritoneal cavity of male SPF Wistar rats; and differences in carcinogenicity were related to the dimensions and biopersistence of the injected fibres. The fibres tested included an amosite asbestos, a silicon carbide whisker, a special purpose glass microfibre, and a range of other man-made vitreous fibres (MMVFs) and refractory ceramic fibres (RCFs) from the TIMA fibre repository. The injected dose of each was designed as the estimated mass required to contain 10(9) fibres > 5 microns in length, as determined by optical microscopy. The numbers of long fibres (> 15 microns) contained in these doses ranged across fibres from 0.1 x 10(9) to 0.8 x 10(9) fibres; the number of long fibres thinner than 0.95 micron ranged from 0.015 x 10(9) to 0.4 x 10(9). The treatment groups contained between 18 and 24 animals. Animals were killed when they showed signs of debilitation. At autopsy, the diagnosis of mesothelioma was usually obvious macroscopically. Otherwise, histological examination of peritoneal organs was used to search for early tumour development. Judged by median survival time, four of the fibre types, in the doses administered, presented higher mesothelioma activity than amosite asbestos. The other fibres tested were less carcinogenic than the amosite. Only a ceramic material derived by extreme heating to simulate the effect of furnace or oven conditions, produced no mesotheliomas. Attempts were made, using regression models, to relate these differences to fibre dimensions and to measures of durability from separate experiments. The results pointed principally to a link with the injected numbers of fibres > 20 microns in length and with biopersistence in the rat lung of fibres longer than 5 microns. Improved quantification of the relative importance of fibre dimensions and biopersistence indices requires experimentation with a range of doses.

Topics: Animals; Asbestos, Amosite; Biodegradation, Environmental; Carbon Compounds, Inorganic; Carcinogenicity Tests; Disease Models, Animal; Dose-Response Relationship, Drug; Glass; Male; Mesothelioma; Mineral Fibers; Neoplasms, Experimental; Peritoneal Neoplasms; Rats; Rats, Wistar; Silicon Compounds; Survival Analysis; Time Factors

To describe the exposure experiences of South African mesothelioma cases, with emphasis on the contribution made to the caseload by different fibre types, the proportion of subjects with no recall of asbestos exposure and only environmental contact, and the importance of putative causes other than asbestos.. A multi-centred case-control study.. 123 patients with mesothelioma interviewed by trained interviewers in study centres established in Johannesburg, Kimberley, Pretoria, Bloemfontein, Cape Town and Port Elizabeth.. A convincing history of asbestos exposure was obtained in the overwhelming majority of cases (only 5 cases had unlikely asbestos exposure). Twenty-three subjects had worked on Cape crocidolite mines, 3 at Penge (an amosite mine), 3 on mines producing amosite and Transvaal crocidolite and 1 on a Transvaal crocidolite mine. Exclusively environmental exposure accounted for at least 18% of cases; 91% of these cases (20/22 subjects) had had contact with Cape crocidolite. There was a relative paucity of cases linked to amosite and no convincing chrysotile case. Non-asbestos causes occur rarely, if at all, in South Africa.. The preponderance of crocidolite cases, followed by amosite and then chrysotile cases, is consistent with the view that there is a fibre gradient of mesotheliomagenic potential for South African asbestos (crocidolite > amosite > chrysotile).

Topics: Asbestos, Amosite; Asbestos, Crocidolite; Carcinogens; Case-Control Studies; Disease Outbreaks; Female; Humans; Male; Mesothelioma; Middle Aged; Mining; Occupational Exposure; South Africa

To examine the causes of death among 1130 former workers of a plant in Tyler, Texas dedicated to the manufacture of asbestos pipe insulation materials. This cohort is important and unusual because it used amosite as the only asbestiform mineral in the production process. High level exposure of such a specific type was documented through industrial hygiene surveys in the plant.. Deaths were ascertained through various sources including data tapes from the Texas Department of Health and the national death index files. As many death certificates as possible were secured (304/315) and cause of death assigned. After select exclusions, 222 death certificates were used in the analysis. Causes of death were compared with age, race, and sex specific mortalities for the United States population with a commercial software package (OCMAP Version 2.0).. There was an excess of deaths from respiratory cancer including the bronchus, trachea, and lung (standardised mortality ratio (SMR) 277 with 95% confidence interval (95% CI) 193 to 385). Four pleural mesotheliomas and two peritoneal mesotheliomas were identified. The analysis also showed an increasing risk of respiratory malignancy with increased duration of exposure including a significant excess of total deaths from respiratory cancer with less than six months of work at the plant (SMR 268 with 95% CI 172 to 399).. The importance of the cohort lies with the pure amosite exposure which took place in the plant and the extended period of latency which has followed. The death certificate analysis indicates the pathogenicity of amosite, the predominant commercial amphibole used in the United States. These data confirm a link between amosite asbestos and respiratory malignancy as well as mesothelioma.

Topics: Adult; Aged; Asbestos, Amosite; Asbestosis; Cohort Studies; Humans; Male; Mesothelioma; Middle Aged; Occupational Exposure; Respiratory Tract Neoplasms; Retrospective Studies; Texas; Time Factors

A cohort study was carried out in order to evaluate the cancer risk in the asbestos-cement industry workers. The cohort consisted of workers employed in four asbestos-cement plants. One of those plants was established in 1924, the other three in the 1960s and 1970s. Currently only two of these plants continue their production. The plants used mainly chrysotile asbestos as well as crocidolite and amosite. Amphibolite asbestos was used before the mid-nineteen eighties in production of pressure pipes utilising about 15% of the total quantity of asbestos used. The measurements of the asbestos fibre concentration at work-sites have been taken occasionally since the mid 1980s, thus, the determination of a cumulative dose for individual persons in the cohort and the evaluation of the dose-effect relationship were not feasible. It could only be supposed that the concentrations at the preparatory work-site during first years of the plants' operation accounted for several tens fibres/cm3 in the production that employed the dry method. The cohort consisted of workers employed in the plant for at least three months between beginning of the plant during the post-war period, and 1980, that is during the period when amphibolite asbestos was in use. The retrospective observation was completed on 31 December 1991. The analysis of the death risk by causes was based on a standardized mortality ratios (SMRs) calculated using the person-years method. Statistical significance of SMRs was assessed by means of Poisson distribution one-sided test. The general population of Poland was used as the reference population to estimate the death risk. The cohort comprised 4,712 persons (3,563 males and 1,149 females). Of this number 4,500 persons (3,405 males and 1,095 females) were followed. The cohort availability were 95.5%. Male mortality, both total (473 deaths; SMR = 83) and due to malignant neoplasms (108 deaths; SMR = 86) was lower than in the general population. An excess of deaths from neoplasm of the pleura was by about 23 times higher (5 deaths; SMR = 2,288) and from neoplasm of the large intestine by two times higher (7 deaths; SMR = 214). Among females (41 deaths; SMR = 50) death risk was lower than in the reference population. At a low level of total mortality from neoplasms (13 deaths; SMR = 52) a statistically significant excess of deaths from neoplasm of the pleura (2 deaths; SMR = 2,112) was observed. In the plants investigated the analysis revealed a considerably dive

Topics: Aged; Asbestos; Asbestos, Amosite; Asbestos, Crocidolite; Cohort Studies; Environmental Monitoring; Epidemiological Monitoring; Female; Humans; Incidence; Male; Mesothelioma; Middle Aged; Neoplasms; Occupational Diseases; Pleural Neoplasms; Poland; Risk Assessment; Sex Distribution; Survival Rate

About 8% of our cases of mesothelioma occur in women, with a median age of 59 years. Our percentage is lower than other series reported in the literature because of the large number of occupationally exposed men referred to our laboratory. Tumor arose in the pleura in 86% of the women in our study, and the majority were epithelial. Pleural plaques were found in half of the women for which this information was available, and asbestosis was found in only 16%. A history of exposure to asbestos was identified in three quarters of the women, more than half of whom were household contacts of asbestos workers. Occupational exposure to asbestos was identified in only 19% of patients. An elevated tissue asbestos burden was noted in 70% of women from whom lung tissue was available for analysis. The main fiber type identified was amosite, followed by tremolite and chrysotile. These findings and those from other countries suggest a need for reassessment of the background rate of mesothelioma in industrialized nations.

Topics: Adult; Aged; Aged, 80 and over; Asbestos, Amosite; Asbestos, Amphibole; Asbestos, Serpentine; Asbestosis; Female; Humans; Male; Mesothelioma; Middle Aged; Mineral Fibers; Peritoneal Neoplasms; Peritoneum; Pleura; Pleural Neoplasms

Standard asbestos samples to be used for biomedical research were first prepared by the International Union Against Cancer (UICC) in 1966 in the United Kingdom and South Africa. Using modern techniques, X-ray diffractometry, analytical transmission electron microscopy, and thermal analysis, we have now analyzed these UICC samples to determine the mineral compositions (mineral phases) and their respective quantities. UICC chrysotile A (from Zimbabwe) contains 2% fibrous anthophyllite as impurity; chrysotile B (from Canada) does not contain any fibrous impurities, only non-fibrous minerals. UICC amosite and crocidolite are almost pure. UICC anthophyllite has 20-30% talc as impurity. The chemical compositions and fiber size distributions of the UICC asbestos samples have also been determined. The mean widths of the fibers of chrysotile A and B are smaller than those of the amphibole fibers. This agrees well with the earlier results which showed the two chrysotile samples to have a larger respirable fraction than the amphiboles.

Topics: Asbestos, Amosite; Asbestos, Amphibole; Asbestos, Crocidolite; Asbestos, Serpentine; Canada; Carcinogens; Differential Thermal Analysis; Humans; Lung Neoplasms; Mesothelioma; Microscopy, Electron; Mineral Fibers; Occupational Diseases; Reference Standards; X-Ray Diffraction; Zimbabwe

Data from inhalation studies in which AF/HAN rats were exposed to nine different types of asbestos dusts (in 13 separate experiments) are employed in a statistical analysis to determine if a measure of asbestos exposure (expressed as concentrations of structures with defined sizes, shapes and mineralogy) can be identified that satisfactorily predicts the observed lung tumor or mesothelioma incidence in the experiments. Due to limitations in the characterization of asbestos structures in the original studies, new exposure measures were developed from samples of the original dusts that were re-generated and analyzed by transmission electron microscopy using a direct transfer technique. This analysis provided detailed information on the mineralogy (i.e., chrysotile, amosite, crocidolite or tremolite), type (i.e., fiber, bundle, cluster, or matrix), size (length and width) and complexity (i.e., number of identifiable components of a cluster or matrix) of each individual structure. No univariate measure of exposure was found to provide an adequate description of the lung tumor responses observed among the inhalation studies, although the measure most highly correlated with tumor incidence is the concentration of structures > or = 20 microns in length. Multivariate measures of exposure were identified that do adequately describe the lung tumor responses. Structures contributing to lung tumor risk appear to be long (> or = 5 microns) thin (0.4 microns) fibers and bundles, with a possible contribution by long and very thick (> or = 5 microns) complex clusters and matrices. Potency appears to increase with increasing length, with structures longer than 40 microns being about 500 times more potent than structures between 5 and 40 microns in length. Structures < 5 microns in length do not appear to make any contribution to lung tumor risk. This analysis did not find a difference in the potency of chrysotile and amphibole toward the induction of lung tumors. However, mineralogy appears to be important in the induction of mesothelioma with chrysotile being less potent than amphibole.

Topics: Administration, Inhalation; Animals; Asbestos; Asbestos, Amosite; Asbestos, Crocidolite; Asbestos, Serpentine; Dust; Environmental Exposure; Incidence; Information Systems; Likelihood Functions; Lung Neoplasms; Male; Mesothelioma; Microscopy, Electron; Multivariate Analysis; Rats; Rats, Inbred Strains; Risk Factors; Surface Properties

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

This study investigates reactive oxygen species generation and oxidant-related cytotoxicity induced by amosite asbestos fibers and polymorphonuclear leucocytes (PMNs) in human mesothelial cells and human bronchial epithelial cells in vitro. Transformed human pleural mesothelial cells (MET 5A) and bronchial epithelial cells (BEAS 2B) were treated with amosite (2 micrograms/cm2) for 48 h. After 24 h of incubation, the cells were exposed for 1 h to nonactivated or amosite (50 micrograms) activated PMNs, washed, and incubated for another 23 h. Reactive oxygen species generation by the PMNs and the target cells was measured by chemiluminescence. Cell injury was assessed by cellular adenine nucleotide depletion, extracellular release of nucleotides, and lactate dehydrogenase (LDH). Amosite-activated (but also to a lesser degree nonactivated) PMNs released substantial amounts of reactive oxygen metabolites, whereas the chemiluminescence of amosite-exposed mesothelial cells and epithelial cells did not differ from the background. Amosite treatment (48 h) of the target cells did not change intracellular adenine nucleotides (ATP, ADP, AMP) or nucleotide catabolite products (xanthine, hypoxanthine, and uric acid). When the target cells were exposed to nonactivated PMNs, significant adenine nucleotide depletion and nucleotide catabolite accumulation was observed in mesothelial cells only. In separate experiments, when the target cells were exposed to amosite-activated PMNs, the target cell injury was further potentiated compared with the amosite treatment alone or exposure to nonactivated PMNs. In conclusion, this study suggests the importance of inflammatory cell-derived free radicals in the development of amosite-induced mesothelial cell injury.

Topics: Adenine Nucleotides; Antioxidants; Asbestos, Amosite; Bronchi; Cell Death; Cell Line, Transformed; Epithelial Cells; Epithelium; Free Radicals; Humans; Hydrogen Peroxide; Inflammation; L-Lactate Dehydrogenase; Luminescent Measurements; Lung Neoplasms; Mesothelioma; Neutrophils; Pleura; Reactive Oxygen Species

The Cape Boards Plant at Uxbridge produced insulation board containing amosite asbestos between 1947 and 1973 with only small amounts of chrysotile. After 1973 only amosite was used. In this study we examined lung samples from 48 workers who had been employed at the plant and who had come to autopsy. The study investigated the fiber levels against the lung pathology including amount of interstitial fibrosis and numbers of ferruginous bodies. The degree of interstitial fibrosis and number of asbestos bodies were graded and the tissues were analyzed by transmission electron microscopy and energy dispersive X-ray analysis and the fibers counted and typed. The 48 cases included 5 mesotheliomas and 14 lung cancers. The mineral analysis results were dominated by the amosite fiber levels. The amounts of chrysotile were relatively small. There were higher levels in lung cancer cases than mesotheliomas and higher levels in mesothelioma cases than those who had died from nonasbestos related diseases. Analysis of the lung tissues showed a consistent pattern of high amosite levels, which confirms the impression that amosite was the predominant form of asbestos used and also indicates that the factory had been a very dusty one.

Topics: Asbestos, Amosite; Asbestosis; Humans; Lung Diseases; Lung Neoplasms; Mesothelioma; Occupational Diseases; Pulmonary Fibrosis

Experimental inhalation in a number of studies has demonstrated that chrysotile asbestos can cause pulmonary fibrosis and both benign and malignant pulmonary tumours, two lesions which are associated in that the studies reporting high tumour rates also found high levels of asbestosis. One comparison reported that animals with malignant tumours had approximately twice the amount of fibrosis in the lung parenchyma as those of similar age without tumours. Many studies have examined the pathogenicity of asbestos administered by ingestion and most of these included chrysotile asbestos: the results have been universally negative apart from one study with amosite that contained no control animals and is best discarded. Only one inhalation study has reported an examination of the larynxes of animals: this found no pathological changes. In many studies, tumours other than the lung had been listed, but significant numbers of kidney tumours have never been recorded. Injection studies inducing mesothelioma have indicated that fibre geometry is important with long thin fibres (> 8 microns in length and < 0.25 microns in diameter) being the most carcinogenic. This has been difficult to confirm for inhaled fibres although fibres less than 5 microns in length appear to cause neither fibrosis nor pulmonary tumours. Similar results have been found with amosite for fibres up to 10-15 microns although longer fibres do produce these conditions. It is suggested that to produce pulmonary fibrosis and neoplasia fibres may need to be longer than 20 microns. Chrysotile has been shown in many studies to be removed from lung tissue much more rapidly than amphibole fibres.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Inhalation; Animals; Asbestos, Amosite; Asbestos, Amphibole; Asbestos, Serpentine; Asbestosis; Cricetinae; Dust; Injections; Laryngeal Neoplasms; Lung Neoplasms; Mesothelioma; Pleural Neoplasms; Pulmonary Fibrosis; Rats

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, Crocidolite; Asbestos, Serpentine; Asbestosis; Humans; Mesothelioma; Pleural Neoplasms; Risk Factors

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

Pulmonary fiber content of both asbestos and nonasbestos types were evaluated in Japanese patients with malignant pleural mesotheliomas.. Pulmonary fiber content was analyzed in 16 patients and 16 case-matched control subjects by transmission electron microscopy with energy-dispersive X-ray analysis using a low-temperature ashing procedure.. The geometric mean content of total asbestos was significantly higher in the patients (22.0 x 10(6) fibers/g dry lung) than in the control subjects (2.24 x 10(6) fibers/g dry lung) (P < 0.01). When the asbestos content was analyzed by fiber type, the geometric means were also consistently and significantly higher among the patients compared with the control subjects (P < 0.01). Results were as follows: (1) amosite: patients 3.94 times 10(6) versus control subjects 0.23 x 10(6); (2) crocidolite: patients 3.56 times 10(6) versus control subjects 0.35 times 10(6); (3) total amphiboles: patients 16.0 times 10(6) versus control subjects 0.77 times 10(6); and (4) chrysotile: patients 3.76 times 10(6) versus control subjects 1.01 times 10(6). However, when individual total asbestos content was considered, 7 of the 16 patients (44%) had levels lower than the highest value noted among the control subjects. Pulmonary fiber content of patients and control subjects also revealed the presence of nonasbestos fibers. The geometric mean of nonasbestos fibers was significantly higher in the patients (87.3 x 10(6)) than in control subjects (33.8 x 10(6)) (P < 0.01). The major type of nonasbestos fibers in both groups was aluminum silicates. The mean of ratios of nonasbestos fiber contents to total asbestos contents in the patients and control subjects was 7.0 and 17.3, respectively.. The results were mainly in agreement with the findings of earlier investigations, but fiber content of both chrysotile and nonasbestos fiber as well as those of amphibole asbestos were significantly higher in the patients than in the control subjects.

Topics: Adult; Aged; Aluminum Silicates; Asbestos; Asbestos, Amosite; Asbestos, Amphibole; Asbestos, Crocidolite; Asbestos, Serpentine; Case-Control Studies; Electron Probe Microanalysis; Female; Humans; Lung; Male; Mesothelioma; Microscopy, Electron; Middle Aged; Occupational Exposure; Pleural Neoplasms; Silicates

A previous study using intrapleural administration of surface-modified amosite asbestos showed a difference in the number of pleural mesotheliomas induced with C18-hydrocarbon derivatised fibres compared to native amosite asbestos. The study has been repeated with larger groups of animals (30) under specific pathogen free conditions, resulting in an increase in the mean animal survival time for both fibre-treated groups. Under these conditions there was no significant difference between the numbers of pleural mesotheliomas induced by C18 hydrocarbon-modified amosite asbestos and native amosite asbestos. The major difference between the two studies was the mean time to death from tumour of rats exposed to fibres. The C18 amosite treated rats in the first study may not have had a mean survival time long enough to allow mesotheliomas to develop.

Topics: Animals; Asbestos, Amosite; Male; Mesothelioma; Pleural Neoplasms; Rats; Rats, Wistar; Silanes; Time Factors

Ten out of 12 South African baboons (Papio ursinus) survived exposure to amosite asbestos dust for periods ranging from 242 days to 898 days at an aerosol level ranging between 1,100 and 1,200 fibers per milliliter. After exposure, they were kept under observation until they died; the total residence time of amosite varied from 1.2-10.2 years. All underwent detailed postmortem necropsy examinations. All baboons had asbestosis. Five of the baboons developed malignant diffuse mesothelioma; three peritoneal, and two pleural with peritoneal invasion. These results indicate that amosite is highly carcinogenic. Since it is difficult to accomplish follow-up of persons exposed to amosite asbestos because of the geographic location of the amosite mines and mills in South Africa (a majority of the workers being migrant laborers from countries bordering on the Transvaal), it is therefore probable that cases of peritoneal mesothelioma have been missed. If human beings are likely to react to amosite as do baboons, epidemiological follow-up should include identification of abdominal as well as thoracic neoplasms.

Topics: Animals; Asbestos, Amosite; Atmosphere Exposure Chambers; Dust; Environmental Exposure; Male; Mesothelioma; Papio; Peritoneal Neoplasms; Pleural Neoplasms

To determine and compare the fiber types and size distributions in the lung tissue of mesothelioma patients in Finland, samples from 29 patients with known work history were analyzed with transmission electron microscopy (TEM) and X-ray microanalysis. Compared with the earlier results using scanning electron microscopy (SEM), the fiber concentrations were about three times as high and ranged from 0.1 million to 5,200 million fibers per gram of dry tissue. In 15 patients (52%), crocidolite/amosite were the dominating fiber types, representing more than 70% of all fibers. Anthophyllite asbestos was the most prevalent fiber type in eight patients (28%), and it was found in the samples of 13 patients (45%). One-half of the anthophyllite fibers were longer than 5 microns, whereas other fiber types were somewhat smaller.

Topics: Adult; Aged; Asbestos; Asbestos, Amosite; Asbestos, Amphibole; Asbestos, Crocidolite; Female; Finland; Humans; Male; Mesothelioma; Microscopy, Electron; Microscopy, Electron, Scanning; Middle Aged; Occupational Diseases

We conducted a clinical, environmental, pathologic, and mineral lung burden investigation of a 61-year-old man with malignant mesothelioma. For 35 years, up until three weeks prior to pneumonectomy, the patient made asbestos soldering forms at a costume jewelry production facility. Only chrysotile asbestos was used at the plant during the last decade of the patient's employment, and recent environmental sampling of the work-place identified no other asbestos fiber type. Anticipating that the patient would add to the very small number of cases of mesothelioma attributable solely to chrysotile, we found instead that the patient's lung tissue contained large numbers of both coated and uncoated amosite asbestos fibers but, surprisingly, no chrysotile. We subsequently learned that a distributor of both chrysotile and amosite supplied the company during the first 25 years the patient was fabricating soldering forms. The findings underscore the futility of estimating environmental exposure to chrysotile on the basis of fiber counts in lung tissue. Although we previously described non-neoplastic asbestos-related disease among patients engaged in similar work, this case, to the best of our knowledge, represents the first report of mesothelioma in the commercial jewelry industry. As such, it prompted us to initiate a public health campaign to replace asbestos soldering forms in this industry with readily available, safer alternatives.

Topics: Air Pollutants, Occupational; Asbestos; Asbestos, Amosite; Asbestos, Serpentine; Humans; Lung Neoplasms; Male; Mesothelioma; Middle Aged; Occupational Diseases

Histological observations were performed on female Syrian hamsters 2 years after the intratracheal administration of amphibole asbestos, amosite, and crocidolite to evaluate the tumorigenicity of six types of fine manmade fibers (reported previously). A mesothelioma and a lung tumor were induced in 20 animals administered amosite, but no tumors were found in the crocidolite group. Because this incidence is not higher than that of manmade fibers, such as basic magnesium sulfate fiber [9 tumor-bearing hamsters in 20 hamsters (9/20)], metaphosphate fiber (5/20), calcium sulfate fiber (3/20), and fiberglass (2/20), it is suggested that some types of manmade fibers have a greater ability than asbestos to induce tumors. Moreover, as a specific observation in manmade fiber groups, tumors were induced at intracelial organs rather than at the pleural cavity. On the other hand, the average thickness of visceral pleura was higher in all asbestos and manmade fiber groups than in the control (2.9 microns), for instance, 36.95 microns in potassium titanate fiber group, 15.90 microns crocidolite group, 13.00 microns basic magnesium sulfate fiber group, and 10.45 microns in the rockwool group. Although both pleural thickening and mesothelioma are known as peculiar lesions in asbestos-exposed people, it might also be suggested that these lesions could be induced by different mechanisms from the result that there was no relation between the pleural thickening and mesothelioma incidence in hamsters.

Topics: Adenoma; Animals; Asbestos; Asbestos, Amosite; Asbestos, Amphibole; Asbestos, Crocidolite; Calcium Sulfate; Carbon; Cricetinae; Female; Glass; Lung Neoplasms; Magnesium Sulfate; Mesocricetus; Mesothelioma; Pleura; Pleural Neoplasms; Silicon Dioxide; Titanium

To determine if asbestos exposure could contribute to mesothelial cell carcinogenesis by selection and/or expansion of an initiated cell population, we compared normal human pleural mesothelial cells to either human mesothelioma cell lines or mesothelial cells transfected with cancer-related genes for sensitivity to amosite fibers in vitro. Neither normal nor mesothelioma cells were directly stimulated to replicate or increase DNA synthesis by any of the asbestos exposure conditions tested. The potential selective effect of asbestos exposure was demonstrated by a differential sensitivity of normal mesothelial cells and mesothelioma cells to amosite: for example, up to 20-fold higher concentrations of amosite fibers were required to inhibit replication of mesothelioma cell lines than normal mesothelial cells. In addition, a significant resistance (4-fold) to amosite toxicity was observed for SV40 immortalized mesothelial cell lines that had previously been selected in vitro for resistance to asbestos. SV40 immortalized cells that have become tumorigenic after transfection with either Ha-ras or PDGF A-chain genes were not significantly more resistant to the cytotoxic effects of amosite than primary normal cells, and the primary cells were equally sensitive to amosite as mesothelial cells that were only immortalized by SV40. The sensitivity of normal mesothelial cells to asbestos does not appear to be simply a result of general fragility of the mesothelial cells, since similar levels of hydrogen peroxide and silica were cytotoxic for normal mesothelial cells and mesothelioma cell lines. Because mesothelioma cells have a greater resistance to asbestos cytotoxicity than normal mesothelial cells, we hypothesize that a differential resistance to cell killing by asbestos fibers in vivo may result in a selective expansion of an initiated or transformed cell population and thus contribute to the carcinogenesis process. Since tumorigenicity and asbestos resistance occur independently of one another in genetically altered mesothelial cell lines, genotypic and phenotypic alterations that lead to tumorigenic conversion may not be the same changes that provide resistance to cell killing by asbestos.

Topics: Asbestos; Asbestos, Amosite; Cells, Cultured; Colony-Forming Units Assay; DNA Replication; Dose-Response Relationship, Drug; Epithelium; Humans; Hydrogen Peroxide; Lethal Dose 50; Lung Neoplasms; Mesothelioma; Silicon Dioxide; Tumor Cells, Cultured

The clinical characteristics and the results of mineral fibre and cytogenetic analyses were coordinated prospectively for 41 patients with confirmed malignant pleural mesothelioma. A correlation was found between high total fibre concentration, and partial or total loss of chromosomes 1, 4 and 9 and chromosomal rearrangements involving a breakpoint at 1p11-p22. There was also a correlation between crocidolite/amosite as the main fibre type and partial or total loss of chromosomes 1, 3 and 4 and chromosomal rearrangements involving del (3p). Positive prognostic factors were female gender, low total fibre concentration (less than 10(6) fibres per g dried lung tissue), anthophyllite as the main fibre type and normal chromosome 7. In addition, we found 4 patients with malignant mesothelioma who had been exposed mainly to anthophyllite fibres (total lung fibre concentrations of 1.2, 0.4, 0.2 and 0.1 x 10(6) fibres per g dried lung tissue). This would seem to indicate that there may be a carcinogenic role for anthophyllite.

Topics: Adult; Aged; Aged, 80 and over; Asbestos; Asbestos, Amosite; Asbestos, Amphibole; Asbestos, Crocidolite; Chromosome Aberrations; Chromosome Disorders; Chromosomes, Human, Pair 7; Female; Humans; Karyotyping; Male; Mesothelioma; Middle Aged; Pleural Neoplasms; Prognosis; Sex Factors

A cohort was established in 1981 of all 7317 white male employees in the amosite and crocidolite mines in South Africa whose names had appeared in the personnel records (initiated between 1945 and 1955) of the major companies. Some of the men had been employed as early as 1925, but only 8% had had more than 10 years of service. Three subcohorts were defined: 3212 men whose only exposure to asbestos was to amosite; 3430 exposed to crocidolite; and 675 to both amphiboles. No deaths or losses to view occurred before 1946, and 5925 men (81%) were known to be alive at the end of 1980. Losses to view numbered 167 (2%), and there had been 1225 deaths (17%), an excess of 331 over the number of deaths expected on the basis of the mortality of all white South African males. The fibre related excesses were of mesothelioma, lung cancer, and other respiratory diseases, but there were other excesses perhaps mainly related to socioeconomic factors including lifestyle. When cause of death was determined according to "best evidence" (after study of clinical, radiological, biopsy, and necropsy reports in conjunction with the death certificate), there were 30 deaths due to mesothelioma (22 pleural, six peritoneal, two other) and 65 due to cancer of trachea, bronchus, and lung. Various analyses of these deaths showed that crocidolite had higher toxicity than amosite for lung cancer and this was most pronounced for mesothelioma; there can now be no question that crocidolite is far more dangerous than amosite at least in so far as mesothelioma is concerned. Nevertheless, crocidolite induced mesothelioma appeared only in men who had been exposed for long periods, at least 12 months, but on average about 15 years.

Topics: Asbestos; Asbestos, Amosite; Asbestos, Crocidolite; Cause of Death; Cohort Studies; Humans; Incidence; Lung Neoplasms; Male; Mesothelioma; Mining; Neoplasms; Occupational Diseases; Risk Factors; South Africa; Survival Analysis

All ascertainable cases of malignant mesothelioma in Australia were notified to a national surveillance program in the period January 1, 1980 to December 31, 1985. There were 854 cases obtained and 823 confirmed on clinical (77) or histologic (746) ground. Tumor site was known in 759 cases (685 pleural and 74 peritoneal). Lung fiber content analyses by light microscopy and analytic transmission electron microscopy with energy-dispersive x-ray analysis were done on 226 cases in which postmortem material was available, using the method of Rogers. Cell type was determined by a five-member expert panel of pathologists appointed by the Royal College of Pathologists of Australasia. There was a statistically significant trend between lung fiber content (fibers/g dry lung) and cell type from epithelial (low fiber content) through mixed to sarcomatous (high fiber content). This trend was most apparent for total uncoated fibers (chi-square = 6.8, df = 1, P less than 0.01) and crocidolite (chi-square = 6.7, df = 1, P less than 0.01). Lung fiber content also was associated with tumor site; higher lung fiber content being associated with peritoneal tumors. This relationship was significant for all fiber content measures except chrysotile and was independent of the fiber content-cell type relationship (log-linear analysis). Survival from time of provisional diagnosis was significantly longer for epithelial (mean, 13 months; standard deviation [SD], 12.8) and mixed (mean, 10.2 months; SD, 8.7) types than sarcomatous cell types (mean, 5.8 months; SD, 6.5; P less than 0.0001, by analysis of variance on log10 survival time). Survival time was significantly greater for pleural tumors (mean, 11.4 months; SD, 13.4) than peritoneal tumors (mean, 8.6 months; SD, 12.5) (P less than 0.005, by Student's t test on log10 survival time).

Topics: Asbestos; Asbestos, Amosite; Asbestos, Crocidolite; Asbestos, Serpentine; Humans; Lung; Mesothelioma; Peritoneal Neoplasms; Pleural Neoplasms; Survival Rate

Asbestos exposure is associated with an increased incidence of several malignancies, including malignant mesothelioma (MM). This study evaluates the relationship between asbestos exposure and the in vitro generation and function of LAK cells, an immune effector cell population with powerful lytic activity against MM cells. Both serpentine (chrysotile) and amphibole (amosite and crocidolite) forms of asbestos fibres suppress LAK cell generation, viability (by 5-11%, P less than 0.02) and cell recovery (by 13-15%, P less than 0.02). However, the LAK cells generated in the presence of the amphiboles were as effective as unexposed cells in lysing both standard tumour cell targets (K562, 56.4% lysis versus 61.5%, respectively, P greater than 0.5; NS; Daudi, 60.5% lysis versus 64.5% P greater than 0.5; NS), and MM tumour cell targets (mean of three MM cell lines 48.3% versus 46.3%, P greater than 0.5; NS), whereas the function of LAK cells generated in the presence of chrysotile was significantly reduced against three out of the five tumour cell targets tested (P less than 0.03). In the presence of asbestos fibres, LAK cell function was reduced against all five tumour cell targets (P less than 0.01), irrespective of whether the cell donors were healthy individuals or patients with MM. NK cell activity was also suppressed (P less than 0.01). The serpentine form of asbestos, chrysotile, was significantly more suppressive of both effector cell functions than either of the amphiboles (P less than 0.01). These findings suggest that asbestos exposure may suppress the function and in some instances the generation of immune effector cell mechanisms, thereby increasing the risk of disease and malignancy.

Topics: Asbestos; Asbestos, Amosite; Asbestos, Crocidolite; Asbestos, Serpentine; Cell Survival; Cytotoxicity Tests, Immunologic; Female; Humans; In Vitro Techniques; Interleukin-2; Killer Cells, Lymphokine-Activated; Killer Cells, Natural; Male; Mesothelioma; Tumor Cells, Cultured

Lung tissue from 221 definite and probable cases of malignant mesothelioma reported to the Australian Mesothelioma Surveillance Program from January 1980 through December 1985 and from an age-sex frequency matched control series of 359 postmortem cases were examined by light microscopic (LM) and analytical transmission electron microscopic (TEM) analysis and energy dispersive x-ray analysis (EDAX). Concentrations of total fibers (coated and uncoated) (LM), crocidolite, amosite, chrysotile, and unidentified amphibole (TEM) (fibers/g dry lung tissue) were measured. Fiber concentrations less than 10 microns in length and greater than or equal to 10 microns in length were separately quantified. By comparing cases (221) and controls (359 LM, 103 TEM), odds ratios for increasing fiber concentrations compared with less than 15,000 fibers/g (LM) and less than 200,000 fibers/g (TEM) (the respective detection limits) were calculated. Univariate analyses showed statistically significant dose-response relationships between odds ratio and fiber concentration for all fiber concentration measures. The relationship between log(odds ratio) and log(fiber concentration) was linear. Multiple logistic regression analysis showed that a model containing crocidolite greater than or equal to 10 microns, amosite less than 10 microns, and chrysotile less than 10 microns as explanatory variables best described the data. The odds ratios for a X10 increase in fiber concentration (fibers/micrograms) were as follows: crocidolite greater than or equal to 10 microns, 29.4 (95% confidence interval [CI], 3.6 to 241); chrysotile less than 10 microns, 15.7 (95% CI, 6.1 to 40); amosite less than 10 microns, 2.3 (95% CI, 1.0 to 5.3). An additive risk model gave similar results. In a subgroup of cases and controls with only chrysotile in the lungs, a significant trend in odds ratio with increasing fiber content was found.

Topics: Adult; Aged; Aged, 80 and over; Asbestos; Asbestos, Amosite; Asbestos, Crocidolite; Asbestos, Serpentine; Case-Control Studies; Female; Humans; Male; Mesothelioma; Middle Aged; Particle Size

The concentration of airborne fibers longer than 5 microns, thinner than 3 microns, and with an aspect ratio exceeding 3 as counted by phase contrast optical microscopy is the most widely used fiber exposure index. Recently, more adequate, specific exposure indices for asbestosis, lung cancer, and mesothelioma risk have been suggested by Lippmann (1988, Environ. Res., 46, 86-106). The consequences of using these indices are examined on the basis of calculations for a broad range of theoretical and published size distributions. Optical microscopy appears to be a good predictor of the exposure indices for asbestosis and for lung cancer after scaling. Only fibers longer than about 3 microns need to be counted in a transmission electron microscope. The lung cancer index still cannot explain the large differences of risk among chrysotile exposures. Both the mesothelioma exposure index and the ratio mesothelioma to lung cancer index ranks in order of increasing risk: wollastonite, glass and mineral wool, amosite, glass microfibers, chrysotile, and crocidolite. Amosite is thus not ranked according to epidemiological evidence. Detailed size information should be made available so that the size criteria can be adjusted. It may still prove necessary to use fiber type specific concentration limits.

Topics: Asbestos; Asbestos, Amosite; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Environmental Exposure; Environmental Monitoring; Humans; Lung Neoplasms; Mesothelioma; Microscopy, Electron; Microscopy, Phase-Contrast; Minerals; Risk Factors

In a family with a remarkable aggregation of malignant mesothelioma the father, mother, and a son all died of the condition, whereas two other sons and a daughter were unaffected. From 1944 to 1961 the family produced a material that was used to fix screws in drilled holes and consisted of amosite, gypsum, and sand. It was produced in the basement of their villa and was described as being a dusty job. The father died in 1984 aged 74, the son in 1985 aged 45, and the mother in 1987 aged 79. It is concluded that there is a high risk of malignant mesothelioma after massive exposure to amosite and the risk and latency period are independent of age during the exposure.

Topics: Aged; Asbestos; Asbestos, Amosite; Cluster Analysis; Denmark; Family; Family Health; Female; Humans; Male; Mesothelioma; Middle Aged; Occupational Diseases; Peritoneal Neoplasms; Pleural Neoplasms

A sample of amosite asbestos was modified by effectively adding C8 and C18 hydrocarbon chains to the fibre surfaces. The altered fibres interacted less readily with cells in vitro and were less cytotoxic. In whole animals the number of mesotheliomas produced by the C8 material was the same as that with the parent material but the tumours occurred earlier. The C18 derivatized fibre was markedly less active in the production of tumours. This is the first report demonstrating that similar size fibres with differing surfaces have different pathogenic properties.

Topics: Animals; Asbestos; Asbestos, Amosite; Carcinogenicity Tests; Carcinogens; Cell Line; Cell Survival; Mesothelioma; Rats; Reference Values; Surface Properties

In a family with a remarkable aggregation of malignant mesothelioma the father, mother, and a son all died of the condition, whereas two other sons and a daughter were unaffected. From 1944 to 1961 the family produced a material that was used to fix screws in drilled holes and consisted of amosite, gypsum, and sand. This was produced in the basement of their villa and was described as being a dusty job. The father died in 1984 aged 74, the son in 1985 aged 45, and the mother in 1987 aged 79. It is concluded that there is a high risk of malignant mesothelioma after massive exposure to amosite and the risk and latency period are independent of age during the exposure.

Topics: Adult; Aged; Asbestos; Asbestos, Amosite; Environmental Exposure; Female; Humans; Male; Mesothelioma; Middle Aged; Pleural Neoplasms

Normal human mesothelial (NHM) cells were transfected with a plasmid containing SV40 early region DNA. Individual colonies of transformed cells from several donors were subcultured for periods of 5 to 6 months and 60 to 70 population doublings (PDs) before senescence, in contrast to a culture lifespan of approximately 1 month and 15 PDs for NHM cells. One such culture, designated MeT-5A, escaped senescence and has been passaged continuously for more than 2 years. These cells had a single integrated copy of SV40 early region DNA in their genome, expressed SV40 large T antigen, and exhibited features of mesothelial cells including sensitivity to the cytotoxic effects of asbestos fibers. One year after injection subcutaneously or intraperitoneally in athymic nude mice, these cells remain nontumorigenic, and therefore are a potential model system for in vitro fiber carcinogenesis studies.

Topics: Animals; Antigens, Polyomavirus Transforming; Asbestos; Asbestos, Amosite; Carcinogenicity Tests; Cell Survival; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Glycoproteins; Growth Substances; Humans; Karyotyping; Mesothelioma; Mice; Mice, Nude; Plasmids; Plasminogen Activators; Plasminogen Inactivators; Pleural Neoplasms; RNA, Messenger; Simian virus 40; Transfection

The lungs from 36 former workers at an East London asbestos factory dying of asbestos-related disease were compared with lung tissue from 56 matched control patients operated on in East London for carcinoma of the lung. The severity of asbestosis and the presence of pulmonary carcinoma or mesothelioma of the pleura or peritoneum were correlated with an asbestos exposure index and with the type and amount of mineral fibre of the lungs. Asbestosis was associated with far heavier fibre burdens than mesothelioma. Moderate or severe asbestosis was more common among those with carcinoma of the lung than in those with mesothelial tumours. Crocidolite and amosite asbestos were strongly associated with asbestosis, carcinoma of the lung and mesothelial tumours, whereas no such correlation was evident with chrysotile or mullite. It is suggested that greater emphasis should be placed on the biological differences between amphibole and serpentine asbestos fibre.

Topics: Aluminum Silicates; Asbestos; Asbestos, Amosite; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Female; Humans; London; Lung; Lung Diseases; Lung Neoplasms; Male; Mesothelioma; Middle Aged; Occupational Diseases; Pleural Neoplasms

The assessment of asbestos fibres in the lungs at post mortem in groups of mesotheliomas, groups occupationally exposed to asbestos, and controls has shown that all these groups contain significant levels of asbestos as a lung burden. The amounts in each group are dependent on the degree of past exposure, being highest in those cases with a known or extrapolated occupational exposure, less in those cases with recorded neighbourhood or environmental exposure, and less again in those cases with no evidence of exposure to asbestos and in controls. Relative risk estimates and the use of models developed for occupational situations do not provide good estimates of the relevance of environmental fibres in producing mesotheliomas in the general population. This may be the result of differences between the groups in their time periods of exposure and long-term elimination of asbestos from the lungs. The number of mesotheliomas that might be due to low-level environmental exposure to asbestos cannot be determined from lung contents alone, but an assessment based on detailed occupational histories from the Australian Mesothelioma Surveillance Program show that the problem is not one of great importance when compared with other public health issues.

Topics: Air Pollutants; Asbestos; Asbestos, Amosite; Asbestos, Amphibole; Asbestos, Crocidolite; Australia; Humans; Lung; Mesothelioma; North America; Silicon Dioxide; Tissue Distribution; United Kingdom

A cohort of 820 asbestos workers with a short duration of exposure to amosite between 1941 and 1945 was followed. These men were alive five years after starting work and were observed until 1988. Seventeen cases of malignant mesothelioma (eight pleural, nine peritoneal) were found. The mean age at the onset of exposure was 33 years for men with pleural mesothelioma and 30 years for those with peritoneal mesothelioma. Chest pain was the main symptom in pleural mesothelioma and abdominal pain in peritoneal mesothelioma. Open lung biopsy was the most useful diagnostic approach for pleural mesothelioma, whereas for peritoneal mesothelioma it was exploratory laparotomy. Pleural patients died of pulmonary insufficiency, and peritoneal patients of wasting and inanition. In both groups the death certificate diagnosis was less accurate than the clinical diagnosis at death. The mean survival was 12.5 months from first symptom to death for the pleural group and 5.4 months for the peritoneal group.

Topics: Adult; Aged; Asbestos; Asbestos, Amosite; Humans; Male; Mesothelioma; Middle Aged; New Jersey; Occupational Diseases; Peritoneal Neoplasms; Pleural Neoplasms

We have previously shown that there are differences in the sizes of fibers of amosite asbestos in different parts of the lung in workers with relatively high asbestos exposure and malignant pleural mesothelioma. To determine whether this distribution pattern is specific to cases of mesothelioma, we compared the fiber distribution in the lungs of 20 cases of mesothelioma and 10 cases of carcinoma of the lung. The two test groups were statistically identical in terms of age, and exposure period, and overall both groups had very similar mean fiber concentrations and mean fiber sizes. When individual sampling sites within the lung were considered, neither group showed preferential fiber concentration in any area. However, there were definite differences in the intrapulmonary fiber size distribution both within and between the two groups: Cases of mesothelioma showed accumulation of lung fibers in the peripheral upper lobe with shorter central upper lobe fibers. The lung cancer cases demonstrated a reverse pattern, with shorter fibers in the peripheral compared to central upper lobe, but accumulations of long fibers in the peripheral lower lobe. Fiber surfaces and masses showed similar differences among sample sites. We conclude that (1) there is no evidence for fiber concentration variations in different portions of the lung; (2) there is strong evidence for variations in fiber sizes in different portions of the lung, and these differences are most clearly related to fiber length, surface area, and mass; (3) contrary to data from experimental animals, there are no clear gravitational effects on fiber distribution in humans; and (4) there are reproducible differences in intrapulmonary fiber size distribution between mesothelioma and lung cancer cases. These differences may be a manifestation of individual handling of mineral particles because of structural variations in individual lungs.

Topics: Aged; Asbestos; Asbestos, Amosite; Carcinoma; Humans; Lung Neoplasms; Mesothelioma; Middle Aged; Smoking; Tissue Distribution

Animal studies suggest that mesothelioma is most effectively induced by fibers longer than 8 mu. However, studies of asbestos fibers recovered from human lungs in cases of mesothelioma indicate that, at least in large-scale samples, relatively few fibers meet this size criterion, perhaps implying that the animal data do not apply to man. Since asbestos concentration in lung is known to be extremely inhomogeneous, it is also possible that long fibers may selectively accumulate in specific sites, such as under the pleura. To examine this possibility, we selected ten cases of mesothelioma that contained relatively large amounts of amosite asbestos and extracted fibers from an 0.5-cm-thick strip of subpleural tissue and an area 3-cm deep to the subpleural sample for upper and lower lobes. Amosite fibers were identified and sized by electron microscopic techniques. Fibers in the peripheral upper lobe were significantly longer, broader, and of higher aspect ratio than those in the central upper lobe. The lower lobe showed a reverse pattern, with longer fibers and broader fibers in the central sample. These data indicate that the two lobes behave differently in regard to fiber size, with selective accumulation of long fibers in the peripheral upper lobe, but not in the peripheral lower lobe. Whether these differences reflect differences in initial deposition of fibers within the lung, or, more likely, specific redistribution of fibers, is unclear, but in either case, accumulation of long fibers immediately under the upper lobe pleura may be important in the genesis of mesothelioma.

Topics: Asbestos; Asbestos, Amosite; Humans; Lung; Lung Neoplasms; Male; Mesothelioma; Occupational Diseases; Particle Size

A cohort of 820 men in a Paterson, New Jersey, amosite asbestos factory which began work during 1941-1945 was observed from 5 to 40 years after start of work. Most of the cohort had limited duration of work experience (days, weeks, months), though some men worked for several years until the factory closed in 1954. With white males of New Jersey as the control population, Standardized Mortality Ratios (SMRs) of 500 are evident for the cohort for lung cancer and for noninfectious pulmonary diseases (including asbestosis), while being almost 300 for total cancer and about 170 for all causes of death. A statistically significant SMR of almost 200 is seen for colon-rectum cancer. Mesothelioma incidence initially shows a strong relationship with advancing time since onset of exposure and then tails off. The main concern of the study is with dose-response patterns. Response is measured by the mortality for relevant causes of death, while the direct asbestos dosage was measured in two ways. One way was the length of time worked in the factory and the other was the individual's accumulated fiber exposure, calculated by multiplying the aforementioned length of time worked by the estimated fiber exposures associated with the particular job that the worker had in the factory. Whichever measure of dosage is used, it was found that, in general, the lower the dose, the longer it took for adverse mortality to become evident and, also, the smaller the magnitude of that adverse mortality.

Topics: Adult; Asbestos; Asbestos, Amosite; Colonic Neoplasms; Dose-Response Relationship, Drug; Humans; Lung Diseases; Lung Neoplasms; Male; Mesothelioma; Middle Aged; New Jersey; Occupational Diseases; Rectal Neoplasms; Risk; Time Factors

Topics: Asbestos; Asbestos, Amosite; Humans; Male; Mesothelioma; Pleural Neoplasms

The carcinogenicity of asbestos (amosite and chrysotile) and zeolite (fibrous erionite, mordenite, and synthetic zeolite 4A) were studied in the peritoneum of 586 BALB/C male mice after a single intraperitoneal or intraabdominal wall injection. As controls, 182 mice treated with and without saline solution were used. Both asbestos types and fibrous erionite frequently produced malignant peritoneal tumors after long latency; tumors developed in 93 of 394 animals (23.6%) treated with asbestos or fibrous erionite 7 months or more after administration. All of the induced peritoneal tumors were intimately associated with marked peritoneal fibrosis, in which asbestos or erionite fibers were regularly detected. Histopathologically, 83 (73 fibrous, 9 biphasic, and 1 epithelial) of 93 were consistent with malignant mesotheliomas. Other tumors consisted of 6 plasmacytomas, 1 histiocytoma, 1 liposarcoma, 1 osteosarcoma, and 1 adenocarcinoma of the pancreas. Two of the cases of mesotheliomas were associated with plasmacytoma. In many instances, the primary site of the mesotheliomas seemed to be multiple, the favorite sites being the omentum, mesentery, serosae of the gastrointestinal and genital organs, the diaphragm, the capsule of the liver and spleen, and the abdominal wall peritoneum. In these cases, asbestos or erionite-tissue burden followed by fibrosis was frequently observed. In addition to the 93 peritoneal tumors, 3 extraperitoneal tumors (1 fibrosarcoma and 2 rhabdomyosarcomas) were induced by amosite which was probably accidentally injected into the extraperitoneal connective tissue and the striated muscle tissue of the abdominal wall, respectively. These three tumors were also intimately associated with focal fibrosis in which amosite fibers were detected. Among the three different types of zeolite, only fibrous erionite showed striking carcinogenicity and marked fibrogenicity. The erionite-induced mesotheliomas were similar to those induced by asbestos in exhibiting long latency, in gross appearance, in histology, and in close association with fibrosis. Long-term persistence of asbestos or fibrous erionite around progenitor cells of the induced tumors and the consequent fibrosis seemed to be an important precondition of the malignant transformation of the progenitor cells.

Topics: Aluminum Silicates; Animals; Asbestos; Asbestos, Amosite; Asbestos, Serpentine; Male; Mesothelioma; Mice; Mice, Inbred BALB C; Neoplasms, Multiple Primary; Peritoneal Neoplasms; Plasmacytoma; Zeolites

Topics: Adult; Aged; Asbestos; Asbestos, Amosite; Asbestos, Crocidolite; Asbestos, Serpentine; Australia; Humans; Lung; Lung Neoplasms; Male; Mesothelioma; Microscopy, Electron; Middle Aged

Numbers and sizes of fibers from the lungs of 10 patients who had an amphibole asbestos-induced malignant pleural mesothelioma were analyzed. Amosite was found in 10 lungs and crocidolite in 9; the average ratio of amosite to crocidolite was approximately 14:1. In the 8 patients who were not long-time asbestos insulators , the mean number of amosite fibers was 2.3 X 10(6) fibers/g dry lung, and of crocidolite fibers, 0.2 X 10(6)/g; these values represent an approximately 250-fold increase over those found in the general population. Crocidolite fibers were significantly narrower than amosite fibers (mean width, 0.13 versus 0.23 mu), were significantly shorter (mean length, 4.0 versus 5.8 mu), and had a significantly higher mean aspect (length to width) ratio (48 versus 34). Aspect ratios in general increased with increasing fiber length and decreasing fiber width, but the highest values were found for thin amosite fibers at about 13 mu in length, and thin crocidolite fibers at 8 or 15-17 mu in length. Comparison with data from other asbestos-exposed populations indicates that mesothelioma can be induced by relatively small numbers of amphibole fibers and also indicates that amosite is an effective mesothelial carcinogen in humans. Comparison of these data with epidemiologic and experimental predictions of carcinogenic size ranges for mesothelioma induction implies that either the carcinogenic size range is much broader than has been claimed (in particular, fibers considerably shorter than 8 mu and broader than 0.05 mu can produce mesothelioma), or, alternately, that extraordinarily small absolute numbers of fibers in certain size ranges can induce tumors in humans.

Topics: Aged; Asbestos; Asbestos, Amosite; Asbestos, Amphibole; Asbestos, Crocidolite; Female; Humans; Lung; Male; Mesothelioma; Middle Aged; Occupational Diseases; Particle Size; Pleural Neoplasms; Silicon Dioxide

This report describes the second in a series of three parallel cohort studies of asbestos factories in South Carolina, Pennsylvania, and Connecticut to assess the effects of mineral fibre type and industrial process on mortality from malignant mesothelioma, respiratory cancer, and asbestosis. In the present plant (in Pennsylvania) mainly chrysotile, with some amosite and a small amount of crocidolite, were used primarily in textile manufacture. Of a cohort of 4137 men comprising all those employed 1938-59 for at least a month, 97% were traced. By the end of 1974, 1400 (35%) had died, 74 from asbestosis and 70 from lung cancer. Mesothelioma was mentioned on the certificate in 14 deaths mostly coded to other causes. All these deaths occurred after 1959, and there were indications that additional cases of mesothelioma may have gone unrecognised, especially before that date. The exposure for each man was estimated in terms of duration and dust concentration in millions of dust particles per cubic foot (mpcf) from available measurements. Analyses were made both by life table and case referent methods. The standardised mortality ratio for respiratory cancer for the whole cohort was 105.0, but the risk rose linearly from 66.9 for men with less than 10 mpcf.y to 416.1 for those with 80 mpcf.y or more. Lines fitted to relative risks derived from SMRs in this and the textile plant studied in South Carolina were almost identical in slope. This was confirmed by case referent analysis. These findings support the conclusion from the South Carolina study that the risk of lung cancer in textile processing is very much greater than in chrysotile production and probably than in the friction products industry. The much greater risk of mesothelioma from exposure to processes in which even quite small quantities of amphiboles were used was also confirmed.

Topics: Adult; Aged; Asbestos; Asbestos, Amosite; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Dust; Humans; Lung Neoplasms; Male; Mesothelioma; Middle Aged; Occupational Diseases; Textile Industry

The predominant asbestos fibre type used in the production of asbestos cement is chrysotile. The use of asbestos in relation to fibre type in a Norwegian asbestos cement plant during 1942-80 was 91.7% chrysotile, 3.1% amosite, 4.1% crocidolite, and 1.1% anthophyllite respectively. Electron microscopy and x ray microanalysis of lung tissue samples of asbestos cement workers who had died of malignant pleural mesothelioma or bronchogenic carcinoma showed a completely inverse ratio with regard to fibre type. The percentage of chrysotile asbestos in lung tissue varied between 0% and 9% whereas the corresponding numbers for the amphiboles were 76% and 99%. These differences are discussed with respect to the behaviour of different fibre types in the human body and to the occurrence of malignant mesothelioma in this asbestos cement factory.

Topics: Aged; Asbestos; Asbestos, Amosite; Asbestos, Amphibole; Asbestos, Crocidolite; Asbestos, Serpentine; Carcinoma, Bronchogenic; Humans; Lung; Lung Neoplasms; Mesothelioma; Middle Aged; Occupational Diseases; Pleural Neoplasms; Silicon Dioxide

Topics: Animals; Asbestos; Asbestos, Amosite; Asbestos, Serpentine; Dust; Male; Mesothelioma; Neoplasms, Experimental; Peritoneal Neoplasms; Rats; Rats, Inbred Strains