asbestos--crocidolite and Asbestosis

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

Asbestos has been recognised as a potential health hazard since the 1940s. Of the two major species of asbestos; white asbestos (chrysotile) and blue asbestos (crocidolite), both of which are hazardous. The workers at extraction facilities are at the greatest risk of exposure to asbestos and, therefore, the development of asbestos-related diseases, commonly mesothelioma. However, other individuals at a high risk of exposure include asbestos-cement workers, insulation workers and ship-yard workers. Environmental exposure to asbestos can occur as a result of living in areas either characterised by natural outcrops of asbestos or asbestos-related materials, or those close to asbestos-producing or -using plants. Unfortunately, man-made fibre alternatives to asbestos, such as rock and slag-wool and glass wool, have also been shown to have a detrimental effect on human health. A characteristic of mesothelioma is that there is a long latency period (20-30 years) before the signs and symptoms of the disease become apparent. In addition, diagnosis of the disease can be difficult. The use of biological markers, such as tissue polypeptide antigen, may play a useful role in the early detection of the disease in individuals at risk.

Topics: Asbestos, Crocidolite; Asbestosis; Environmental Exposure; Humans; Manufactured Materials; Mesothelioma; Mineral Fibers; Occupational Exposure; Risk Factors; Time Factors

Asbestos exposure has been linked to non-Hodgkin's lymphoma (NHL) and other types of hematolymphoid cancer (HL-CA) in several case reports and epidemiologic studies. This review covers the scientific and medical literature on the issue of whether asbestos exposure is a cause of NHL or other HL-CAs. Studies of animals exposed to asbestos have not shown an increase in NHL or other types of HL-CA. Although some patients with asbestosis have mild immunologic abnormalities, 32 of 35 epidemiologic studies of asbestos exposure in humans are negative for NHL or other HL-CAs. Therefore, it can be concluded that there is no increased risk of NHL or other HL-CAs associated with asbestos exposure.

Topics: Adult; Asbestos; Asbestos, Crocidolite; Asbestosis; Case-Control Studies; Cohort Studies; Construction Materials; Environmental Exposure; Female; Hematologic Neoplasms; Humans; Leukemia; Lymphoma, Non-Hodgkin; Male; Metallurgy; Mining; Occupational Diseases; Occupational Exposure; Risk; Transportation

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

MACs of asbestos are from 2 to 20 times higher in Poland than in other Western Europe countries. The analysis of occupational diseases reported between 1983 and 1988 among workers of asbestos-cement plants has showed that Polish MAC values do not protect people from work-related asbestosis. Asbestosis was frequently diagnosed in workers employed at mining and processing of nickel ore containing admixtures of fibrous antigorite. The risk of asbestosis in workers of a nickel++ metallurgical plant was 8 times higher that in those employed at an asbestos-cement plant. In an animal study, fibrogenic, carcinogenic and mutagenic activity of antigorite was similar to the biological aggressiveness of crocidolite. Based on own studies and literature data, the following MACs for asbestos and other natural fibrous minerals were established: a) for dusts containing asbestos and other fibrous minerals except crocidolite and fibrous antigorite, total dust concentration equals 1 mg/m3 and concentration of fibres longer than 5 microns = 0.5 fibre/cm3 b) for dusts containing crocidolite and fibrous antigorite total dust concentration = 0.5 mg/m3 and concentration of fibres longer than 5 microns = 0.2 fibre/cm3.

Topics: Air Pollutants, Occupational; Asbestos; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Europe; Humans; Magnesium Silicates; Maximum Allowable Concentration; Mining; Occupational Medicine; Particle Size; Poland; Silicic Acid

Topics: Aerosols; Air Pollutants; Animals; Asbestos; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Carbon; Chemotactic Factors; Electron Probe Microanalysis; Glass; Lung; Macrophages; Mice; Microscopy, Electron, Scanning; Minerals; Phagocytosis; Pneumoconiosis; Quartz; Rats

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

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

Thirty three pairs of chest radiographs taken up to 10 years apart were obtained for 33 subjects suffering from asbestosis who had applied for compensation to the Pneumoconiosis Medical Board of Western Australia. Multiple films from the period before the first radiograph in each pair, from the intervening period between the two, and from the period subsequent to the second radiograph were also available and all films were read by two independent readers according to the 1980 ILO classification of pneumoconiosis. Films were read twice as side by side pairs ten years apart, twice as two separate randomly ordered films ten years apart, and once as part of the full series of all available chest radiographs on each subject to assess which method provided the best consistency (between reader variation) and repeatability (within reader variation). Judging by consistency, the full series method performed as well as either of the other methods when assessing radiographic changes and significantly better when assessing the level of profusion of small opacities. There was little to choose between the other two methods either judging by consistency or repeatability, which could not be estimated for the full series method. Use of all available films for a subject is recommended for assessing single films, as in a prevalence study, as well as for documenting change in a longitudinal study.

Topics: Asbestos; Asbestos, Crocidolite; Asbestosis; Humans; Longitudinal Studies; Lung; Male; Observer Variation; Radiography; Western Australia; Workers' Compensation

Early events in an experimental model of mesothelioma development include increased levels of editing in double-stranded RNA (dsRNA). We hypothesised that expression of endogenous retroviruses (ERV) contributes to dsRNA formation and type-I interferon signaling. ERV and interferon stimulated genes (ISGs) expression were significantly higher in tumor compared to non-tumor samples. 12 tumor specific ERV ("MesoERV1-12") were identified and verified by qPCR in mouse tissues. "MesoERV1-12" expression was lower in mouse embryonic fibroblasts (MEF) compared to mesothelioma cells. "MesoERV1-12" levels were significantly increased by demethylating agent 5-Aza-2'-deoxycytidine treatment and were accompanied by increased levels of dsRNA and ISGs. Basal ISGs expression was higher in mesothelioma cells compared to MEF and was significantly decreased by JAK inhibitor Ruxolitinib, by blocking Ifnar1 and by silencing Mavs. "MesoERV7" promoter was demethylated in asbestos-exposed compared to sham mice tissue as well as in mesothelioma cells and MEF upon 5-Aza-CdR treatment. These observations uncover novel aspects of asbestos-induced mesothelioma whereby ERV expression increases due to promoter demethylation and is paralleled by increased levels of dsRNA and activation of type-I IFN signaling. These features are important for early diagnosis and therapy.

Topics: Animals; Asbestos, Crocidolite; Asbestosis; Cell Line, Tumor; Disease Models, Animal; DNA Methylation; Endogenous Retroviruses; Gene Expression Regulation, Neoplastic; Host-Pathogen Interactions; Interferon Regulatory Factors; Interferon Type I; Mesothelioma; Mice; Promoter Regions, Genetic; RNA Editing; RNA, Double-Stranded; Signal Transduction

Rare biallelic

Topics: Adult; Aged; Animals; Asbestos, Crocidolite; Asbestosis; Family; Female; Genetic Predisposition to Disease; Genomic Instability; Germ-Line Mutation; Heterozygote; Humans; Incidence; Inflammation; Male; Mesothelioma; Mice; Middle Aged; RecQ Helicases

Three hundred and thirty thousand Italians arrived in Australia between 1945 and 1966, many on assisted passage schemes where the worker agreed to a 2-year unskilled employment contract. Italians were the largest of 52 migrant groups employed at the Wittenoom blue asbestos mining and milling operation. We compare mortality from asbestos-related diseases among Italian and Australian workers employed at Wittenoom.. A cohort of 6500 male workers was established from employment records and followed up at state and national mortality and cancer registries. SMRs were calculated to compare mortality with the Western Australian male population. Time-varying Cox proportional hazards models compared the risk of mesothelioma between Australian and Italian workers.. 1031 Italians and 3465 Australians worked at Wittenoom between 1943 and 1966. Duration of employment was longer for the Italian workers, although the concentration of exposure was similar. The mesothelioma mortality rate per 100 000 was higher in Italians (184, 95% CI 148 to 229) than Australians (128, 95% CI 111 to 149). The risk of mesothelioma was greater than twofold (HR 2.27, 95% CI 1.43 to 3.60) in Italians at the lowest asbestos exposure category (<10 fibre years/per mL).. A hierarchy in migration, isolation and a shortage of workers led to Italians at Wittenoom incurring higher cumulative exposure to blue asbestos and subsequently a greater rate of malignant mesothelioma than Australian workers.. Poor working conditions and disparities between native and foreign-born workers has had a detrimental and differential impact on the long-term health of the workforce.

Topics: Adult; Asbestos; Asbestos, Crocidolite; Asbestosis; Cohort Studies; Emigrants and Immigrants; Employment; Ethnicity; Female; Humans; Italy; Lung Neoplasms; Male; Manufacturing Industry; Mesothelioma; Mesothelioma, Malignant; Mining; Occupational Exposure; Proportional Hazards Models; Transients and Migrants; Western Australia; Young Adult

Human exposure to asbestos can cause a wide variety of lung diseases that are still a current major health concern, even if asbestos has been banned in many countries. It has been shown in many studies that asbestos fibers, ingested by alveolar macrophages, disrupt lung iron homeostasis by sequestering iron. Calcium can also be deposited on the fibers. The pathways along which iron and above all calcium interact with fibers are still unknown. Our aim was that of investigating if the iron accumulation induced by the inhaled asbestos fibers also involves calcium ions accumulation. Lung sections of asbestos-exposed mice were analyzed using an extremely sensitive procedure available at the synchrotron facilities, that provides morphological and chemical information based on X-ray fluorescence microspectroscopy (μ-XRF). In this study we show that (1) where conventional histochemical procedures revealed only weak deposits of iron and calcium, μ-XRF analysis is able to detect significant deposits of both iron and calcium on the inhaled asbestos fibers; (2) the extent of the deposition of these ions is proportionally directly related and (3) iron and calcium deposition on inhaled asbestos fibers is concomitant with the appearance of inflammatory and hyperplastic reactions.

Topics: Animals; Asbestos, Crocidolite; Asbestosis; Calcium; Homeostasis; Humans; Inhalation Exposure; Iron; Lung; Lung Diseases; Macrophages, Alveolar; Male; Mice; Mice, Inbred C57BL; Microscopy; Microscopy, Fluorescence; Synchrotrons; Tissue Distribution; X-Rays; Zinc

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

Chrysotile has been frequently used in the past in manufacturing brakes and continues to be used in brakes in many countries. This study was designed to provide an understanding of the biokinetics and potential toxicology following inhalation of brake dust following short term exposure in rats. The deposition, translocation and pathological response of brake dust derived from brake pads manufactured with chrysotile were evaluated in comparison to the amphibole, crocidolite asbestos. Rats were exposed by inhalation 6 h/day for 5 days to either brake dust obtained by sanding of brake-drums manufactured with chrysotile, a mixture of chrysotile and the brake dust or crocidolite asbestos. No significant pathological response was observed at any time point in either the brake dust or chrysotile/brake dust exposure groups. The long chrysotile fibers (>20 μm) cleared quickly with T(½) estimated as 30 and 33 days, respectively in the brake dust and the chrysotile/brake dust exposure groups. In contrast, the long crocidolite fibers had a T(½)>1000 days and initiated a rapid inflammatory response in the lung following exposure resulting in a 5-fold increase in fibrotic response within 91 days. These results provide support that brake dust derived from chrysotile containing brake drums would not initiate a pathological response in the lung following short term inhalation.

Topics: Animals; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Chemical Phenomena; Disease Models, Animal; Dust; Half-Life; Industry; Inhalation Exposure; Lung; Male; Materials Testing; Motor Vehicles; Occupational Diseases; Protective Devices; Rats; Rats, Wistar; Respiratory Mucosa; Tissue Distribution; Toxicity Tests, Acute

The purpose of this study was to develop an improved method for collagen and protein assessment of fibrotic lungs while decreasing animal use.. 8-10 week old, male C57BL/6 mice were given a single intratracheal instillation of crocidolite asbestos or control titanium dioxide. Lungs were collected on day 14 and dried as whole lung, or homogenized in CHAPS buffer, for hydroxyproline analysis. Insoluble and salt-soluble collagen content was also determined in lung homogenates using a modified Sirius red colorimetric 96-well plate assay.. The hydroxyproline assay showed significant increases in collagen content in the lungs of asbestos-treated mice. Identical results were present between collagen content determined on dried whole lung or whole lung homogenates. The Sirius red plate assay showed a significant increase in collagen content in lung homogenates however, this assay grossly over-estimated the total amount of collagen and underestimated changes between control and fibrotic lungs, conclusions: The proposed method provides accurate quantification of collagen content in whole lungs and additional homogenate samples for biochemical analysis from a single animal. The Sirius-red colorimetric plate assay provides a complementary method for determination of the relative changes in lung collagen but the values tend to overestimate absolute values obtained by the gold standard hydroxyproline assay and underestimate the overall fibrotic injury.

Topics: Analysis of Variance; Animals; Asbestos, Crocidolite; Asbestosis; Azo Compounds; Biomarkers; Collagen; Colorimetry; Coloring Agents; Disease Models, Animal; Hydroxyproline; Lung; Male; Mice; Mice, Inbred C57BL; Pulmonary Fibrosis; Reproducibility of Results; Severity of Illness Index; Spectrophotometry; Up-Regulation

Little is known about neighborhood exposure to asbestos and mesothelioma risk among residents around an industrial source of asbestos.. To investigate the magnitude of the risk among residents by asbestos exposure levels and to determine the range of the area affected by asbestos.. We calculated standardized mortality ratios of mesothelioma from 1995 to 2006 among the estimated population at risk that lived around a former large asbestos cement pipe plant in Amagasaki City, Japan, between 1957 and 1975, the time when the plant had used crocidolite and chrysotile. The distance between the plant and homes and relative asbestos concentrations obtained by diffusion equations involving meteorological conditions were used to determine asbestos exposure levels among residents.. We identified 73 mesothelioma deaths of 35 men and 38 women who had no occupational exposure to asbestos. Among persons who had lived within a 300-m radius of the plant, the standardized mortality ratio of mesothelioma was 13.9 (95% confidence interval, 5.6-28.7) for men and 41.1 (95% confidence interval, 15.2-90.1) for women. When the study area was divided into five regions by relative asbestos concentration, standardized mortality ratios of mesothelioma declined, for both sexes, in a linear dose-dependent manner with concentration. The regions with a significantly elevated standardized mortality ratio reached 2,200 m from the plant in the same direction in which the wind predominantly blew.. Neighborhood exposure to asbestos can pose a serious risk to residents across a wide area.

Topics: Aged; Air Pollutants; Asbestos, Crocidolite; Asbestosis; Cluster Analysis; Dose-Response Relationship, Drug; Environmental Exposure; Female; Humans; Japan; Male; Mesothelioma; Middle Aged; Pleural Neoplasms; Risk Assessment

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

Blue asbestos was mined and milled at Wittenoom in Western Australia between 1943 and 1966.. Nearly 7000 male workers who worked at the Wittenoom mine and mill have been followed up using death and cancer registries throughout Australia and Italy to the end of 2000. Person-years at risk were derived using two censoring dates in order to produce minimum and maximum estimates of asbestos effect. Standardised mortality ratios (SMRs) compare the mortality of the former Wittenoom workers with the Western Australian male population.. There have been 190 cases of pleural and 32 cases of peritoneal mesothelioma in this cohort of former workers at Wittenoom. Mortality from lung cancer (SMR = 1.52), pneumoconiosis (SMR = 15.5), respiratory diseases (SMR = 1.58), tuberculosis (SMR = 3.06), digestive diseases (SMR = 1.47), alcoholism (SMR = 2.24) and symptoms, signs and ill defined conditions (SMR = 2.00) were greater in this cohort compared to the Western Australian male population.. Asbestos related diseases, particularly malignant mesothelioma, lung cancer and pneumoconiosis, continue to be the main causes of excess mortality in the former blue asbestos miners and millers of Wittenoom.

Topics: Aged; Asbestos, Crocidolite; Asbestosis; Cause of Death; Follow-Up Studies; Humans; Italy; Lung Neoplasms; Male; Mesothelioma; Mining; Occupational Exposure; Peritoneal Neoplasms; Pleural Neoplasms; Respiratory Tract Diseases; Western Australia

The extracellular signal-regulated kinases 1 and 2 (ERK1/2) are phosphorylated after inhalation of asbestos. The effect of blocking this signaling pathway in lung epithelium is unclear. Asbestos-exposed transgenic mice expressing a dominant-negative mitogen-activated protein kinase kinase-1 (dnMEK1) (i.e., the upstream kinase necessary for phosphorylation of ERK1/2) targeted to lung epithelium exhibited morphologic and molecular changes in lung. Transgene-positive (Tg+) (i.e., dnMEK1) and transgene-negative (Tg-) littermates were exposed to crocidolite asbestos for 2, 4, 9, and 32 days or maintained in clean air (sham controls). Distal bronchiolar epithelium was isolated using laser capture microdissection and mRNA analyzed for molecular markers of proliferation and Clara cell secretory protein (CCSP). Lungs and bronchoalveolar lavage fluids were analyzed for inflammatory and proliferative changes and molecular markers of fibrogenesis. Distal bronchiolar epithelium of asbestos-exposed wild-type mice showed increased expression of c-fos at 2 days. Elevated mRNA levels of histone H3 and numbers of Ki-67-labeled proliferating bronchiolar epithelial cells were decreased at 4 days in asbestos-exposed Tg+ mice. At 32 days, distal bronchioles normally composed of Clara cells in asbestos-exposed Tg+ mouse lungs exhibited nonreplicating ciliated and mucin-secreting cells as well as decreased mRNA levels of CCSP. Gene expression (procollagen 3-a-1, procollagen 1-a-1, and IL-6) linked to fibrogenesis was also increased in lung homogenates of asbestos-exposed Tg- mice, but reduced in asbestos-exposed Tg+ mice. These results suggest a critical role of MEK1 signaling in epithelial cell proliferation and lung remodeling after toxic injury.

Topics: Animals; Asbestos, Crocidolite; Asbestosis; Cell Proliferation; Extracellular Signal-Regulated MAP Kinases; Lung; MAP Kinase Kinase 1; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Mice, Transgenic; Phosphorylation; Respiratory Mucosa

We sought to examine the relationships between plasma concentrations of retinol, carotene, and vitamin E and mortality associated with asbestosis in people previously exposed to crocidolite.. Cox regression modeling was applied to examine these relationships at the first measurement of each vitamin, at the measurement at each visit, and with the rate of change of each vitamin during the follow-up.. There were 76 deaths of people with asbestosis during the follow-up period and 1885 subjects censored. Mortality in subjects with asbestosis was inversely related to plasma levels of retinol and Vitamin E concentrations and to their rate of increase during the follow-up. Carotene concentrations at first visit were associated with lower mortality but not during the follow up period.. Chronically low levels of these vitamins are associated with an increased risk of dying with asbestosis.

Topics: Aged; Asbestos, Crocidolite; Asbestosis; Carotenoids; Cohort Studies; Humans; Male; Middle Aged; Occupational Exposure; Proportional Hazards Models; Vitamin A; Vitamin E; Western Australia

To determine if the presence of asbestosis is a prerequisite for lung cancer in subjects with known exposure to blue asbestos (crocidolite).. Former workers and residents of Wittenoom with known amounts of asbestos exposure (duration, intensity, and time since first exposure), current chest x ray and smoking information, participating in a cancer prevention programme (n = 1988) were studied. The first plain chest radiograph taken at the time of recruitment into the cancer prevention programme was examined for radiographic evidence of asbestosis according to the UICC (ILO) classification. Cox proportional hazards modelling was used to relate asbestosis, asbestos exposure, and lung cancer.. Between 1990 and 2002 there were 58 cases of lung cancer. Thirty six per cent of cases had radiographic evidence of asbestosis compared to 12% of study participants. Smoking status was the strongest predictor of lung cancer, with current smokers (OR = 26.5, 95% CI 3.5 to 198) having the greatest risk. Radiographic asbestosis (OR = 1.94, 95% CI 1.09 to 3.46) and asbestos exposure (OR = 1.21 per f/ml-year, 95% CI 1.02 to 1.42) were significantly associated with an increased risk of lung cancer. There was an increased risk of lung cancer with increasing exposure in those without asbestosis.. In this cohort of former workers and residents of Wittenoom, asbestosis is not a mandatory precursor for asbestos related lung cancer. These findings support the hypothesis that it is the asbestos fibres per se that cause lung cancer, which can develop with or without the presence of asbestosis.

Topics: Aged; Asbestos, Crocidolite; Asbestosis; Environmental Exposure; Female; Humans; Lung; Lung Neoplasms; Male; Middle Aged; Occupational Exposure; Odds Ratio; Proportional Hazards Models; Radiography; Risk Assessment; Smoking; Western Australia

To further study the pathogenic mechanism of crocidolite, the imperceptible changes of crocidolite surface in rat were observed.. The animal model was established and the changes in the rat infected with dust were observed by use of microscopy, SEM, differential thermal analysis and IR spectroscopy.. In the course of interaction between organism protein and crocidolite, the protein symmetry decreased and structure loosened. The silicon of crocidolite was bonded with the alkyl, amido- of protein. New absorption bands of Si-O-C(N), Si-R clearly appeared. The organism cleared the dust by means of dissolution, enwrapping, winding or in the way of biochemical dissolution, and the fibre became shortened, broken, bifurcated, ends-rounded, and also it could dissolve, transfer and chemically react on surface.. The results showed that the surface radicals of asbestos fibre reacted with some albumen in tissue and hence formed new surface mediator. It is a new form of dissolution and reaction of fibre in vivo that fibres in alveoli transform to carbonate. The residual substances of crocidolite are mainly Si-O. Tissue membrane is the retardation cingulum of dust transference in vivo.

Topics: Animals; Asbestos, Crocidolite; Asbestosis; Dust; Microscopy, Electron, Scanning; Mineral Fibers; Pleural Diseases; Pulmonary Fibrosis; Rats; Silicon

In the first half of the twentieth century, asbestos was a controversial mineral because of its association with asbestosis and asbestos-related lung cancer. It has proved no less so since the 1960s, when another asbestos cancer, mesothelioma, was identified. Mesothelioma appeared to be more strongly linked with blue asbestos (crocidolite) than with the other asbestos varieties, brown (amosite) and white (chrysotile). This finding triggered a fierce debate between "chrysophiles" (those who declared chrysotile innocuous) and "chrysophobes" (those who believed it was a mortal hazard). This essay attempts the first history of the chrysotile controversy, which shows that a scientific consensus on the safety of white asbestos was very slow to emerge. This was only partly due to the complexities of scientific research. Political, economic, and social factors have militated against a speedy resolution of the debate, facilitating the continued production and use of asbestos in the developing world.

Topics: Asbestos; Asbestos, Amphibole; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Global Health; History, 20th Century; Humans; Lung Neoplasms; Mesothelioma; Risk Factors

Increased rates of death from asbestos related diseases have been reported in former workers and residents exposed to crocidolite (blue asbestos) at Wittenoom, Western Australia. Exposure to asbestos is associated with reduced static lung volumes, gas transfer and lung compliance, and a restrictive ventilatory abnormality.. The effects of crocidolite exposure and smoking history on levels and rates of change of lung function were evaluated using a linear mixed model. Lung function was measured as forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC.. Cumulative doses of asbestos and the presence of radiographic asbestosis were associated with lower levels of FEV1 and FVC and a steeper decline during the period of observation. Subjects exposed to asbestos at a younger age had lower levels of FEV1 and FVC. Current smokers had lower levels and a steeper decline in lung function than never smokers. No significant interactions between crocidolite exposure and smoking on the levels or rates of change of lung function were found.. The deleterious effects of crocidolite exposure on lung function persist in this population, despite asbestos exposure having ceased more than 30 years ago. No significant interactions were found in this population between asbestos and smoking at the first visit or longitudinally.

Topics: Asbestos, Crocidolite; Asbestosis; Environmental Exposure; Female; Forced Expiratory Volume; Humans; Lung Diseases; Male; Middle Aged; Radiography; Regression Analysis; Smoking; Vital Capacity; Western Australia

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

This article reconstructs how workers perceived asbestos hazards, using narratives from a group of migrant workers at the crocidolite mine of Wittenoom Gorge, Western Australia. The mine employed about 7000 workers over the entire period of its operation from 1943 to 1966-relying heavily on migrant workers. The exposure to asbestos dust caused a huge number of occupational respiratory diseases in workers, leading Wittenoom later to be labelled as a modern industrial disaster. Fieldwork involved 137 interviews with Italians who had worked at Wittenoom. They constituted 18% of the mine's work-force and were employed as miners or millers between 1951 and 1966. We interviewed workers who had returned to Italy, relatives of Italian workers now deceased, and workers who had settled in Australia. The results confirm the seriousness of the occupational exposure to asbestos and the weaknesses of the health surveillance program. Although workers were given no health-related information, they felt they were at risk and left the job as soon as possible. From the early 1950s onward, some of the workers became aware of a long-term connection between work at Wittenoom and lung illnesses that required hospitalisation and caused deaths. However, up to the early 1960s, workers at the mine were led to believe that the respiratory disease spreading among them was tuberculosis.

Topics: Adult; Asbestos, Crocidolite; Asbestosis; Attitude to Health; Humans; Interviews as Topic; Italy; Male; Middle Aged; Mining; Narration; Occupational Exposure; Population Surveillance; Qualitative Research; Respiration Disorders; Risk Assessment; Social Control, Formal; Social Perception; Transients and Migrants; Western Australia; Workforce

Asbestos fibers up-regulate the extracellular signal-regulated kinase (ERK1/2) pathway in mesothelial and pulmonary epithelial cells in vitro, but the cell-type expression patterns and intracellular localization of activated, ie, phosphorylated, ERK in the lung after inhalation of asbestos are unclear. C57/BL6 mice were exposed to 7-mg/m(3) air of crocidolite asbestos for 5 and 30 days, the times required for the development of epithelial cell hyperplasia and fibrotic lesions, respectively. Exposure to asbestos caused striking increases in both unphosphorylated and phosphorylated ERK (p-ERK), which were most marked at 30 days and co-localized in bronchiolar and alveolar epithelial cells using an antibody to cytokeratin. Alveolar macrophages, detected with an anti-macrophage antibody, did not express p-ERK. p-ERK was localized at the apical cell surface of bronchiolar and alveolar type II epithelial cells exposed to asbestos fibers, and was most marked in areas of epithelial hyperplasia in association with fibrotic lesions. Because translocation of p-ERK to the nucleus is associated with activation of early response genes and transcription factors, laser scanning cytometry was used to determine the kinetics of activation and nuclear translocation of p-ERK in an alveolar type II epithelial cell line in vitro after exposure to asbestos or the ERK stimuli, epidermal growth factor, or H(2)O(2). Results showed that cytoplasmic to nuclear translocation of p-ERK occurred in a protracted manner in cells exposed to asbestos. The immunolocalization of p-ERK at the membrane surface, a site of initial exposure to asbestos fibers, and the chronic activation of p-ERK in epithelial cells at sites of fibrogenesis are consistent with the concept that epithelial cell signaling through the ERK pathway contributes to remodeling of the lung during the development of pulmonary fibrosis.

Topics: Administration, Inhalation; Animals; Asbestos, Crocidolite; Asbestosis; Disease Models, Animal; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Respiratory Mucosa

Topics: Asbestos, Crocidolite; Asbestosis; Ascorbic Acid; Calcium Oxalate; Humans; Iron; Lung; Mineral Fibers; Occupational Exposure; Oxidation-Reduction

We report on a deposition of oxalate crystals on ferruginous bodies after occupational exposure to asbestos demonstrated in 3 patients. We investigated the mechanism and possible significance of this deposition by testing the hypothesis that oxalate generated through nonenzymatic oxidation of ascorbate by asbestos-associated iron accounts for the deposition of the crystal on a ferruginous body. Crocidolite asbestos (1000 microg/mL) was incubated with 500 micromol H(2)O(2) and 500 micromol ascorbate for 24 hours at 22 degrees C. The dependence of oxalate generation on iron-catalyzed oxidant production was tested with the both the metal chelator deferoxamine and the radical scavenger dimethylthiourea. Incubation of crocidolite, H(2)O(2), and ascorbate in vitro generated approximately 42 nmol of oxalate in 24 hours. Oxalate generation was diminished significantly by the inclusion of either deferoxamine or dimethylthiourea in the reaction mixture. Incubation of asbestos bodies and uncoated fibers isolated from human lung with 500 micromol H(2)O(2) and 500 micromol ascorbate for 24 hours at 22 degrees C resulted in the generation of numerous oxalate crystals. We conclude that iron-catalyzed production of oxalate from ascorbate can account for the deposition of this crystal on ferruginous bodies.

Topics: Asbestos, Crocidolite; Asbestosis; Ascorbic Acid; Calcium Oxalate; Crystallization; Crystallography, X-Ray; Deferoxamine; Fatal Outcome; Humans; Hydrogen Peroxide; Iron; Iron Chelating Agents; Lung; Male; Middle Aged; Oxidation-Reduction; Thiourea

Recent studies have suggested that inducible nitric oxide synthase (iNOS) plays a role in the development of asbestos-related pulmonary disorders. The pulmonary reactions of rats and hamsters upon exposure to asbestos fibers are well known to be disparate. In addition, in vitro experiments have indicated that mononuclear phagocytes from hamsters, in contrast to those from rats, lack the iNOS pathway. Therefore, the purpose of this study was to investigate whether rats and hamsters differ in lung iNOS expression in vivo upon exposure to asbestos fibers and whether differences in iNOS induction are associated with differences in the acute pulmonary inflammatory reaction. Body weight, alveolar-arterial oxygen difference, differential cell count in bronchoalveolar lavage fluid, total protein leakage, lung myeloperoxidase activity and lipidperoxidation, wet/dry ratio, iNOS mRNA and protein expression, and nitrotyrosine staining of lung tissue were determined 1 and 7 days after intratracheal instillation of asbestos fibers in CD rats and Syrian golden hamsters. Exposure of rats to asbestos fibers resulted in enhanced pulmonary iNOS expression and nitrotyrosine staining together with an acute inflammation that was characterized by an influx of neutrophils, enhanced myeloperoxidase activity and lipid peroxidation, damage of the alveolar-capillary membrane, edema formation, and impairment of gas exchange. In comparison, instillation of asbestos fibers in hamsters resulted in a significantly milder inflammatory reaction of the lung with no induction of iNOS in pulmonary cells. The data obtained provide important information to understand the underlying mechanisms of species differences in the pulmonary response upon exposure to asbestos fibers.

Topics: Animals; Asbestos, Crocidolite; Asbestosis; Body Weight; Bronchoalveolar Lavage Fluid; Cell Count; Cricetinae; Disease Models, Animal; Inhalation Exposure; Intubation, Intratracheal; Lung; Mesocricetus; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Oxygen; Peroxidase; Rats; RNA, Messenger; Species Specificity; Thiobarbituric Acid Reactive Substances; Tyrosine

Recent studies have shown that iron is an important factor in the chemical activity of asbestos and may play a key role in its biological effects. The most carcinogenic forms of asbestos, crocidolite and amosite, contain up to 27% iron by weight as part of their crystal structure. These minerals can acquire more iron after being inhaled, thereby forming asbestos bodies. Reported here is a method for depositing iron on asbestos fibers in vitro which produced iron deposits of the same form as observed on asbestos bodies removed from human lungs. Crocidolite and amosite were incubated in either FeCl(2) or FeCl(3) solutions for 2 h. To assess the effect of longer-term binding, crocidolite was incubated in FeCl(2) or FeCl(3) and amosite in FeCl(3) for 14 days. The amount of iron bound by the fibers was determined by measuring the amount remaining in the incubation solution using an iron assay with the chelator ferrozine. After iron loading had been carried out, the fibers were also examined for the presence of an increased amount of surface iron using X-ray photoelectron spectroscopy (XPS). XPS analysis showed an increased amount of surface iron on both Fe(II)- and Fe(III)-loaded crocidolite and only on Fe(III)-loaded amosite. In addition, atomic force microscopy revealed that the topography of amosite, incubated in 1 mM FeCl(3) solutions for 2 h, was very rough compared with that of the untreated fibers, further evidence of Fe(III) accumulation on the fiber surfaces. Analysis of long-term Fe(III)-loaded crocidolite and amosite using X-ray diffraction (XRD) suggested that ferrihydrite, a poorly crystallized hydrous ferric iron oxide, had formed. XRD also showed that ferrihydrite was present in amosite-core asbestos bodies taken from human lung. Auger electron spectroscopy (AES) confirmed that Fe and O were the only constituent elements present on the surface of the asbestos bodies, although H cannot be detected by AES and is presumably also present. Taken together for all samples, the data reported here suggest that Fe(II) binding may result from ion exchange, possibly with Na, on the fiber surfaces, whereas Fe(III) binding forms ferrihydrite on the fibers under the conditions used in this study. Therefore, fibers carefully loaded with Fe(III) in vitro may be a particularly appropriate and useful model for the study of chemical characteristics associated with asbestos bodies and their potential for interactions in a biosystem.

Topics: Adenocarcinoma; Aged; Asbestos, Amosite; Asbestos, Crocidolite; Asbestosis; Chlorides; Ferric Compounds; Ferrous Compounds; Humans; In Vitro Techniques; Lung; Lung Neoplasms; Male; Microscopy, Atomic Force; Microscopy, Electron, Scanning; Models, Biological; Spectrometry, X-Ray Emission

This study was undertaken to determine whether certain criteria could be used to select among asbestos-exposed subjects those who could benefit from computed tomography screening.. Search for criteria enabling the selection of patients who should undergo a CT screening exam after occupational exposure to asbestos was conducted in 150 subjects. All subjects were explored with selected high-resolution CT scans. Studied parameters were age, exposure data, pulmonary function test results.. None of the exposure data or pulmonary function test results suggested with certainty the presence or absence of asbestos-related pleural and parenchymal lung disease. The studied parameters could not be used to select patients who could benefit from CT screening.. None of the studied parameters enabled a selection of asbestos-exposed subjects who should undergo chest CT screening.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Asbestos; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Carcinogens; Female; Humans; Male; Mass Screening; Maximal Expiratory Flow-Volume Curves; Middle Aged; Occupational Exposure; Patient Selection; Pleural Diseases; Pulmonary Diffusing Capacity; Residual Volume; Spirometry; Time Factors; Tomography, X-Ray Computed; Vital Capacity

Topics: Adult; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Child; Humans; Lung Neoplasms; Mesothelioma; Mining; South Africa

Asbestosis is a fibrotic lung disease resulting from inhalation of asbestos fibres. Its pathogenesis is poorly understood but probably involves stimulation of fibroblast proliferation and collagen production by mediators released from inflammatory and resident lung cells. In vitro studies have implicate PDGF, TNF-alpha, IGF-1, TGF-beta, and IL-1 in asbestosis, but the role of these mediators in vivo is not known. This study aimed to characterize mediators in bronchoalveolar lavage (BAL) fluid from patients exposed to asbestos with (n = 24) or without (n = 34) asbestosis, compared with ten normal subjects. Human lung fibroblasts were exposed to serial dilutions of BAL fluids and the effects on fibroblast proliferation were assessed. The median mitogenic activity of BAL fluid from asbestos-exposed (17 per cent above medium control, range 3-44 per cent) and asbestosis (14 per cent, range 2-60 per cent) groups was higher than that of BAL fluid from controls (10 per cent, range 2-20 per cent; P < 0.01 and P < 0.05, respectively), but there was no significant difference between the patient groups. The mitogenic activity of BAL fluids was not reduced by incubation with neutralizing antibodies to PDGF-AA, PDGF-AB, PDGF-BB, TNF-alpha, IGF-1, and IL-1 beta. We conclude that BAL fluids from patients exposed to asbestos contain mitogens for human lung fibroblasts, but that PDGF, TNF-alpha, IGF-1, or IL-1 beta do not contribute to this activity.

Topics: Adult; Aged; Antibodies; Asbestos, Crocidolite; Asbestosis; Bronchoalveolar Lavage Fluid; Cell Division; Cells, Cultured; Fibroblasts; Humans; Inflammation Mediators; Insulin-Like Growth Factor I; Interleukin-1; Middle Aged; Mining; Occupational Exposure; Platelet-Derived Growth Factor; Tumor Necrosis Factor-alpha

To investigate effects of asbestos on the process of cancer development, the capacity of asbestos which increases cellular uptake of external carcinogens was tested for asbestos-mediated viral RNA transfection in cultured cells. For the transfection, crocidolite, amosite, anthophyllite and chrysotile were placed onto Vero-E6 cells with poliovirus RNA inoculum, respectively. All asbestos samples mediated viral RNA transfection compared with the background including only viral RNA. The transfection was much greater with combined exposure to asbestos and kaolin than with exposure to asbestos alone.

Topics: Animals; Asbestos; Asbestos, Amosite; Asbestos, Amphibole; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Chlorocebus aethiops; Kaolin; Neoplasms; Poliovirus; RNA, Viral; Transfection; Vero Cells

The largest Italian asbestos cement factory had been active in Casale Monferrato until 1986: in previous studies a substantial increase in the incidence of pleural mesothelioma was found among residents without occupational exposure to asbestos. To estimate exposure to asbestos in the population, this study evaluated the presence of histological asbestosis and the lung burden of asbestos fibres (AFs) and asbestos bodies (ABs).. The study comprises the consecutive series of necropsies performed at the Hospital of Casale Monferrato between 1985 and 1988. A sample of lung parenchima was collected and stored for 48 out of 55 necropsies. The AF concentration was measured with a TEM electron microscope with x ray mineralogical analysis. The ABs were counted and fibrosis evaluated by optical microscopy. The nearest relative of each subject was interviewed on occupational and residential history. Mineralogical and histological analyses and interviews were conducted in 1993-4.. Statistical analyses included 41 subjects with AF, AB count, and interview. Subjects without occupational exposure who ever lived in Casale Monferrato had an average concentration of 1500 AB/g dried weight (gdw); Seven of 18 presented with asbestosis or small airway lung disease (SAL). G2 asbestosis was diagnosed in two women with no occupational asbestos exposure. One of them had been teaching at a school close to the factory for 12 years. Ten subjects had experienced occupational asbestos exposure, seven in asbestos cement production: mean concentrations were 1.032 x 10(6) AF/gdw and 96,280 AB/gdw. Eight of the 10 had asbestosis or SAL.. The high concentration of ABs and the new finding of environmental asbestosis confirm that high asbestos concentration was common in the proximity of the factory. Subjects not occupationally exposed and ever living in Casale Monferrato tended to have higher AB concentration than subjects never living in the town (difference not significant). The concentrations of ABs and AFs were higher than those found in other studies on nonoccupationally exposed subjects.

Topics: Adult; Aged; Aged, 80 and over; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Construction Materials; Environmental Exposure; Female; Humans; Italy; Male; Middle Aged; Occupational Exposure

To analyze the correlation between asbestos lung burden and lung cancer, lungs of 211 female cases with and without lung cancer were examined. Phase-contrast microscopic (PCM) counting of ferruginous (FBs) and uncoated fibers (UFs), which had length longer than 5 microns and aspect ratios greater than 3:1, revealed a significantly higher level of FBs plus UFs in urban lung cancer cases than urban non-lung cancer cases (1380.5 vs. 550.3; p < 0.001). No difference was noted between rural lung cancer and non-lung cancer cases. Analytical electron microscopic studies identified various kinds of mineral fibers with an aspect ratio greater than 3:1 in the lung tissue including chrysotile, actinolite/tremolite, amosite/crocidolite, fibrous talc, mica, silica, iron, wollastonite, chlorite, kaoline, and others. The most frequently detected fibers were thin, short chrysotile fibers, most of which could not be found by PCM, followed by relatively thick, long actinolite/tremolite fibers, fibrous talc, and in a smaller number, amosite/crocidolite of intermediate length and width. Amosite/crocidolite and fibrous talc counts in urban lung cancer cases were greater than those of urban non-lung cancer cases, rural lung cancer, and rural non-lung cancer cases; these findings were consistent with PCM analysis. Therefore, it is suggested that fibers detected in PCM observation may be mainly amosite/crocidolite with some parts fibrous talc and that fibrous talc in urban environments may be another candidate for carcinogenic or cocarcinogenic factors of female lung cancer.

Topics: Adult; Aged; Asbestos, Amosite; Asbestos, Crocidolite; Asbestosis; Carcinogens; Case-Control Studies; Female; Humans; Japan; Lung Neoplasms; Microscopy, Electron, Scanning Transmission; Microscopy, Phase-Contrast; Middle Aged; Rural Health; Talc; Urban Health

Asbestos exposure causes pulmonary fibrosis by mechanisms that remain uncertain. There is increasing evidence that iron from asbestos is responsible for many of its effects. In this paper, we investigated the effect of iron mobilized from crocidolite asbestos on collagen content in rat lung fibroblast cultures under serum-free conditions. Crocidolite (2, 4, 6 microg/cm2 well) increased collagen content in a dose-dependent manner (+42 +/- 8, +92 +/- 10, and +129 +/- 13% vs controls). This effect was specific for collagen, since it did not alter total protein content and was inhibited by the iron chelator deferoxamine (DFO). Preincubation of crocidolite with citrate (1 mM) for 48 hr resulted in iron mobilization (51 microM) and increased collagen production (>3-fold) in treated cells. These effects occurred without the intervention of serum factors. The absence of cell damage, proliferation or lipid peroxidation leads to the supposition that iron from crocidolite per se may act as a profibrogenic agent. Although the in vivo participation of other cells and factors cannot be excluded, we conclude that iron released from crocidolite plays a role in collagen increase occurring during asbestosis.

Topics: Animals; Asbestos, Crocidolite; Asbestosis; Cells, Cultured; Collagen; DNA; Fibroblasts; Iron; Lung; Proteins; Rats

Asbestosis is a fibrotic and inflammatory interstitial lung disease occurring after chronic occupational exposure to asbestos. An alveolitis has been described with activated alveolar macrophages and increased neutrophils as sampled by bronchoalveolar lavage (BAL). Animal models and in vitro studies demonstrate that asbestos can stimulate alveolar macrophages to release neutrophil chemotactic factor. We performed BAL on 18 nonsmoking individuals with asbestos exposure and observed a twofold increase in percent neutrophils recovered. Alveolar macrophages cultured in vitro from the asbestos-exposed individuals spontaneously released significant amounts of the neutrophil chemotaxin, interleukin-8 (IL-8). In addition, the alveolar macrophages expressed a 2.7-fold increase in steady state mRNA levels compared to unexposed normal controls utilizing the reverse transcriptase/polymerase chain reaction. In vitro experiments confirmed that crocidolite or chrysotile asbestos could stimulate the release of IL-8 from mononuclear phagocytes in a dose-dependent fashion. We conclude that asbestos exposure causes a mild neutrophilic alveolitis, and that IL-8 is one potential mediator capable of contributing to this inflammation in the lower respiratory tract.

Topics: Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Base Sequence; Humans; Interleukin-8; Macrophages, Alveolar; Molecular Sequence Data; RNA, Messenger

Topics: Asbestos, Crocidolite; Asbestosis; Case-Control Studies; Confidence Intervals; Humans; Italy; Logistic Models; Male; Mining; Occupational Exposure; Odds Ratio; Respiratory Tract Neoplasms; Transients and Migrants; Western Australia

The present study was undertaken to further define the role of alveolar macrophages (AM) in the pulmonary response to crocidolite fibers. Briefly, groups of 4 male F344 rats were intratracheally instilled with saline or saline suspensions of crocidolite at 2 or 20 mg/kg body weight. Animals were sacrificed 3, 7, 14, and 28 d after exposure and the lung response was characterized by analysis of bronchoalveolar lavage fluid (BALF) for markers of lung injury and inflammation. AM obtained in BALF were cultured and their production of the pro-inflammatory cytokines, tumor necrosis factor alpha (TNF alpha), and interleukin-1 (IL-1) were characterized along with fibronectin, a protein known to stimulate fibroblast migration and proliferation. Lung hydroxyproline content was determined 28 d after exposure and lung histopathology was characterized on d 28 and 90 after exposure. Crocidolite instillation resulted in transient dose-related pulmonary inflammation as evidenced by increased numbers of BALF neutrophils at the low dose and neutrophils, macrophages, and lymphocytes at the high dose. Cytotoxicity and increased permeability were demonstrated by increased levels of BALF lactate dehydrogenase (LDH) and total protein, respectively. AM TNF alpha and IL-1 production were increased only at the high crocidolite dose. This cytokine response was greatest at d 3 and decreased thereafter. AM TNF alpha and IL-1 release were positively correlated with the increased BALF neutrophils. In contrast to TNF alpha and IL-1, AM fibronectin release was increased at both the low and high doses, with the magnitude of response increasing over time. Consistent with previous acute asbestos inhalation studies, histopathology revealed inflammation localized at the level of the terminal bronchioles and alveolar ducts. Fibrosis was demonstrated at both doses by increased trichrome staining of lung tissue sections. Only the high dose resulted in a detectable increase in lung hydroxyproline. Given the bioactivities of TNF alpha, IL-1, and fibronectin, their increased production after crocidolite exposure indicates they contribute to the pulmonary inflammation and fibrosis occurring with this mineral fiber. In addition, the correlation of increased AM TNF alpha and IL-1 production with increased BALF neutrophils supports a role for these cytokines in crocidolite-induced inflammatory cell recruitment. Lastly, association of a persistent increase in AM fibronectin production with an eventual i

Topics: Analysis of Variance; Animals; Asbestos, Crocidolite; Asbestosis; Bronchoalveolar Lavage Fluid; Cells, Cultured; Cytokines; Fibronectins; Growth Substances; Hydroxyproline; Interleukin-1; Intubation, Intratracheal; Macrophages, Alveolar; Male; Pulmonary Fibrosis; Rats; Rats, Inbred F344; Specific Pathogen-Free Organisms; Tumor Necrosis Factor-alpha

A series of 206 necropsies in Western Australia (WA) have had routine counts made of asbestos bodies in samples of lung tissue using conventional light microscopy. Thirty-two cases had worked in the asbestos industry at Wittenoom, WA and (log) counts of asbestos bodies in their lung tissue correlated well with estimates of their (log) cumulative airborne exposure to crocidolite fibers (r = 0.60). There was no association between the number of asbestos bodies and time since exposure to asbestos ceased. In subjects without known exposure to asbestos, there was a weak but nonsignificant increase in number of asbestos bodies with increasing age, with 26% of cases having no asbestos bodies present. It is concluded that the relatively simple technique of light microscopy for counting of asbestos bodies in lung tissue provides a reliable indication of the level of past occupational exposure to crocidolite in subjects whose exposure has been only to crocidolite. This could be extremely useful in follow-up studies of cohorts that lack reliable measures of airborne exposure to crocidolite asbestos.

Topics: Adult; Aged; Aged, 80 and over; Asbestos, Crocidolite; Asbestosis; Feasibility Studies; Female; Humans; Lung; Male; Middle Aged; Mineral Fibers; Occupational Exposure

The aim of the study was to review existing cases, calculate rates, and predict future numbers of occupational and environmental mesotheliomas from Wittenoom.. On the basis of information contained in occupational and environmental histories, Wittenoom cases were extracted from national records collected since 1979. Occupational and residential population estimates were obtained from company and government records. The proportional latency method was used to predict the numbers of mesotheliomas prior to and after the data collection phase. Airborne fiber monitoring was used to calculate risk due to current levels of contamination in the mine and town environments.. During 1979-1994, Wittenoom cases (N = 176) comprised approximately 6% of the mesothelioma cases recorded in Australia. Of these 122 were employed directly in the mining and milling activities, another 18 were involved in the transport of raw fiber or tailings, and 34 were town residents or visitors. Due to past exposures, additional occupational (N = 301) and environmental (N = 83) cases can be expected. Dependent on residential time, existing levels of contamination may result in a risk of between < 1 to 57 per million of the population.. Latency effects will result in considerable numbers of mesotheliomas appearing over the next 10-20 years in Wittenoom. The cessation of mining activities and major clean up of the town will result in reduced mesothelioma cases.

Topics: Adolescent; Adult; Asbestos, Crocidolite; Asbestosis; Child; Environmental Exposure; Female; Humans; Incidence; Lung Neoplasms; Male; Mesothelioma; Middle Aged; Mining; Occupational Diseases; Occupational Exposure; Registries; Risk Assessment; Western Australia

We treated a 63-year-old man in whom asbestosis developed after he had sprayed asbestos for 24 years. He was admitted with the chief complaint of dyspnea and was managed for 4 years with artificial ventilation. We believe that he survived for this long because he was free of severe pneumonia and because the lower lung, which is primarily affected by asbestos, was relatively intact so his pulmonary function did not deteriorate rapidly. Pathological findings included plate-like atelectasis in both upper lung fields and marked thickening of the pleura. Lung fibrosis was centrilobular but showed no honeycombing. The lung tissue contained 265 X 10(6) asbestos particles and 910 X 10(6) asbestos fibers per gram (dry weight), and the pleura also had 805 asbestos particles and 3,035 asbestos fibers. Most of these asbestos fibers were 20 microns or longer and were crocidolite.

Topics: Asbestos, Crocidolite; Asbestosis; Humans; Lung; Male; Middle Aged; Pleura; Respiration, Artificial

The different pulmonary macrophage (airway macrophages, alveolar macrophages, interstitial macrophages, intravascular macrophages, pleural macrophages) are an important part of the lungs' defences against non-fibrous and fibrous particles deposited by inhalation. The first line of defence is airway macrophages and alveolar macrophages (AM) which initially interact with deposited chrysotile fibres and subsequently release a number of mediators including growth regulatory and chemotactic proteins, arachidonic acid metabolites, proteases, NO and active oxygen species, all of which can affect--also adversely--specific target cells in the lung. Mechanical clearance via the mucociliary escalator and dissolution of phagocytized fibres in the acidic milieu of the phagolysosome in pulmonary macrophages are further important functions of AM. Chrysotile appears to be more toxic or at least has the same toxicity to AM as amphibole fibres when doses of a similar mass are administered. However, on a fibre number basis chrysotile appears to be less toxic to AM. The importance of the appropriate dose parameter--i.e. fibre mass, number or surface area--needs to be considered in in vitro as well as in in vivo studies. Short chrysotile fibres are cleared from rat lungs very rapidly whereas longer ones are cleared at a much slower rate. This is due to efficient phagocytosis of short fibres by AM accompanied by dissolution in the acidic milieu of the phagolysosome. Prediction of chrysotile clearance in primate lung based on results from rat studies result in an overall retention half-time of approximately 105 days, based on which no long-term accumulation of chrysotile in the primate lung is to be expected. Long-term inhalation studies in baboons exposed to chrysotile confirm the very fast build up of a low steady-state lung burden, consistent with a pulmonary retention half-time for chrysotile of approximately 90 days. Despite the fast clearance and low pulmonary accumulation of chrysotile, the resulting effects, such as asbestosis, were found to be of the same severity in rats as those induced by amphibole exposure. In the amphibole-exposed rats, the fibre lung burden continued to increase with exposure time. The potential contamination of chrysotile with tremolite cannot explain these results since there was no increased pulmonary accumulation of fibres in the chrysotile-exposed rats. Effects due to lung particle overload are not to be expected in long-term chrysotile inha

Topics: Animals; Asbestos, Amosite; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Coal Mining; Cytokines; Dogs; Dust; Humans; Lung; Lymph; Macrophages, Alveolar; Papio; Pneumoconiosis; Quartz; Rats; Silicosis; Time Factors

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

We focused here on steady-state mRNA levels of genes involved in antioxidant defense, i.e., manganese superoxide dismutase and copper-zinc superoxide dismutase, and in cell proliferation, i.e., ornithine decarboxylase, c-jun, and glyceraldehyde-3-phosphate-dehydrogenase in whole-lung homogenates from Fischer 344 rats at 3 h to 20 d after exposure to crocridolite asbestos. Changes in gene expression were correlated with histopathologic findings, total and differential cell counts in bronchoalveolar lavage, and levels of hydroxyproline in lung. Dosage-dependent increases in mRNA levels of antioxidant enzymes and proliferation-related genes were observed. Differential cell counts revealed a dose-related infiltration of neutrophils that preceded elevations in gene expression. Neutrophil infiltration into lung and focal lesions of fibrosis as well as increased levels of hydroxyproline were observed only at high concentrations of asbestos. These results indicate that high airborne concentrations of asbestos cause molecular changes in lung that may be related to antioxidant defense and the triggering of cell proliferation, a feature of asbestosis and lung cancer.

Topics: Administration, Inhalation; Animals; Asbestos, Crocidolite; Asbestosis; Blotting, Northern; Blotting, Western; Bronchoalveolar Lavage Fluid; Cell Count; Cell Division; Dust; Female; Gene Expression; Glyceraldehyde-3-Phosphate Dehydrogenases; Hydroxyproline; Lung; Ornithine Decarboxylase; Proto-Oncogene Proteins c-jun; Pulmonary Fibrosis; Rats; Rats, Inbred F344; RNA, Messenger; Superoxide Dismutase

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

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

Plain chest radiographs from a one in six random sample of the workforce of the asbestos industry at Wittenoom, Western Australia between 1943 and 1966 have been classified for degree of profusion and pleural thickening by two independent observers according to the 1980 UICC-ILO Classification of Radiographs for the pneumoconioses to clarify the effect of degree of radiological abnormality on survival. A total of 1106 subjects were selected. Each subject's age, cumulative exposure to crocidolite, and time since first exposure were determined from employment records, the results of a survey of airborne concentrations of fibres > 5 mu in length conducted in 1966, and an exposure rating by an industrial hygienist and an ex-manager of the mine and mill at Wittenoom. By the end of 1986 193 subjects had died. Conditional logistic regression was used to model the relative risk of death in five separate case-control analyses in which the outcomes were deaths from: (1) all causes, (2) malignant mesothelioma, (3) lung cancer, (4) asbestosis, and (5) other causes excluding cancer and asbestosis. Up to 20 controls per case were randomly chosen from all men of the same age who were not known to have died before the date of death of the index case. After adjustment for exposure and time since first exposure, there were significant and independent effects of radiographic profusion and pleural thickening on all cause mortality. The effect of profusion was largely a result of the effect on mortality from malignant mesothelioma and asbestosis but not lung cancer. The effect of pleural thickening was greatest on mortality from other causes, mainly ischaemic heart disease. This study has shown that degree of radiographic abnormality has an independent effect on mortality from malignant mesothelioma, asbestosis, and all causes even after allowing for the effects of age, degree of exposure, and time since first exposure.

Topics: Asbestos, Crocidolite; Asbestosis; Cause of Death; Cohort Studies; Humans; Male; Mesothelioma; Neoplasms; Occupational Diseases; Occupational Exposure; Pleura; Pleural Diseases; Radiography; Random Allocation; Western Australia

This study reports an association between pleural plaques and resting hyperventilation in a group of workers exposed to asbestos. Information on exposure level, pack-years of cigarette smoking, chest radiographs, ventilation parameters, single-breath diffusing lung capacity, and arterial gases were obtained for 344 workers. After the exclusion of 37 workers for isolated parenchymal fibrosis, combined pleuroparenchymal fibrosis, or diffuse pleural thickening, 55 subjects with isolated pleural plaques were evaluated against 252 no-plaque workers. A quantitative pleural score revealed mild pleural disease. Forty-four workers with plaques (80%) had hypocapnia induced by resting hyperventilation. The quantitative pleural score correlated significantly with the partial pressure of carbon dioxide in arterial blood (correlation coefficient = 0.7). A decrement in forced vital capacity was associated with plaques, whether controlled for age, smoking, and exposure or not. It was concluded that the resting hyperventilation observed in some asbestos-exposed subjects is related to the presence of mild pleural plaques and a restrictive disorder.

Topics: Adult; Aged; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Croatia; Cross-Sectional Studies; Humans; Hyperventilation; Lung; Lung Volume Measurements; Male; Middle Aged; Pleura; Pulmonary Diffusing Capacity; Radiography; Rest; Smoking

Urinary recovery of intratracheally instilled polyethylene glycol polymers (PEG:s) in the molecular weight range 722-1294 Da (PEG 1000) was studied under normal conditions and during experimentally induced lung damage in rats. The urinary PEG recoveries were between 30-60% under normal conditions, with a selectivity for smaller PEG:s. No significant differences in the urinary PEG molecular weight profiles were found between 30 days old and adult rats; i.e. they had similar PEG 1162/810 (molecular weights) urinary recovery ratios (0.78 +/- 0.25 and 0.69 +/- 0.27, respectively, p > 0.05). In rats instilled with PEG 1000 and ferritin (5 mg.kg-1 body weight), the urinary recovery was increased for PEG:s with molecular weights greater than 1030 Da; i.e. a higher PEG 1162/810 recovery ratio (1.44 +/- 0.58, p < 0.01) was obtained. Rats instilled with PEG 1000 and crocidolite asbestos fibres (5 mg.kg-1 body weight) showed higher urinary recoveries for PEG:s greater than 854 Da, resulting in a higher PEG 1162/810 ratio (1.47 +/- 0.59, p < 0.01). By adding the iron-chelator, desferrioxamine, to the crocidolite-instillate, the urinary recoveries and the PEG 1162/810 ratio (0.97 +/- 0.47) were reduced, indicating a restored molecular weight selectivity of the lung. Thus, in rats, PEG 1000 passes via the respiratory tract in large amounts which is dependent on the molecular weight. This passage was increased after ferritin- or crocidolite instillation, indicating that the barrier function of the respiratory tract was impaired due to local tissue damage, and that iron may play an important role in this.

Topics: Aging; Animals; Asbestos; Asbestos, Crocidolite; Asbestosis; Blood-Air Barrier; Ferritins; Instillation, Drug; Lung Diseases; Molecular Weight; Polyethylene Glycols; Rats; Rats, Sprague-Dawley; Trachea

Topics: Adult; Aged; Animals; Asbestos; Asbestos, Crocidolite; Asbestosis; China; Female; Humans; Lung Neoplasms; Male; Mesothelioma; Middle Aged; Prevalence; Rats; Risk Factors

Metal content in the chemical structure of asbestos and man-made mineral fibres can affect their carcinogenic properties. As the chemical composition (metal content) of man-made silicate substitutes for asbestos can be varied almost at will in the process of their manufacture, the search for potentially least carcinogenic silicates appears to be of utmost importance. This paper presents diffractometric characteristics, dimensional analysis and morphology data for 4 synthetic amphibole fibres with chemical compositions differing from that of natural crocidolite amphibole. Those included the following synthetic amphiboles: Na2Mg6Ge8O22(OH)2; Na2Ni6Si8O22(OH)2; Na2Mg6Si8O22(OH)2; Na2Co6Si8O22(OH)2. The studied amphiboles differed in fibre length and diameter. The magnesium amphibole contained the longest (6.03 microns) fibres, and the nickel amphibole contained the shortest (2.7 microns) fibres, resembling those of crocidolite. The highest content (54.7%) of respirable fibres was found in the magnesium amphibole, and the lowest (15.9%) in the natural crocidolite. The authors suggest that the detected differences in the physical and chemical characteristics of the synthetic amphiboles may affect their biological properties.

Topics: Asbestos; Asbestos, Crocidolite; Asbestosis; Cobalt; Humans; Lung Neoplasms; Magnesium; Mesothelioma; Microscopy, Electron; Nickel; Particle Size; X-Ray Diffraction

We have studied the effects of in vivo asbestos exposure on the surface immune-associated (Ia) antigen expression and distribution of alveolar macrophage subpopulations defined by continuous iso-osmotic Percoll gradients (density range: 1.006 to 1.123 g/ml) using a rat model of asbestos inhalation. Two groups of rats were exposed by intermittent inhalation (6 hr/day for 5 days/week over 4 weeks) to either amphibole (crocidolite) or serpentine (chrysotile) asbestos. A group of control rats was sham-exposed to clean air only. Alveolar macrophages from rats of three groups were obtained by bronchoalveolar lavage. During exposure, distinct differences appeared within 7 days of asbestos exposure, and some of these findings persisted in the crocidolite-exposed group for as long as 2 to 5 months after the cessation of exposure. Furthermore, relatively greater proportions of Ia-antigen positive cells were detected in several density fractions obtained from both asbestos-exposed groups (especially the crocidolite-exposed group). Multinucleated alveolar macrophages were seen frequently in all Percoll fractions after both types of asbestos inhalation. A significant proportion of multinucleated alveolar macrophages in these fractions expressed surface Ia-antigen positivity. The finding of enriched numbers of higher-density phagocytes in bronchoalveolar lavage cell subpopulations from asbestos-exposed rats may reflect the presence of newly recruited-immature monocytes and/or macrophages at sites of intrapulmonary asbestos deposition. Also, increased proportions of Ia-antigen positive cells suggest that a part of them were functionally activated.

Topics: Administration, Inhalation; Animals; Asbestos; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Centrifugation, Density Gradient; Disease Models, Animal; Histocompatibility Antigens Class II; Macrophages, Alveolar; Male; Rats; Rats, Inbred F344

In 1979 all former workers from the Wittenoom asbestos industry who could be traced to an address were sent a questionnaire to determine smoking history. Occupational exposure to crocidolite was known from employment records. Of 2928 questionnaires sent, satisfactory replies were received from 2400 men and 149 women. Eighty per cent of these had smoked at some time and 50% were still smoking. Since that time 40 cases of lung cancer and 66 cases of compensatable asbestosis have occurred in this cohort. The incidence of both lung cancer and asbestosis was greatest in those subjects with the highest levels of exposure to crocidolite and in ex-smokers. Statistical modelling of the joint effects of these exposures on the incidence of each disease indicated that crocidolite exposure multiplied the rates of lung cancer due to smoking and that smoking has no measurable effect on the rates of asbestosis. There was also some evidence that the incidence rate of lung cancer is falling with time.

Topics: Asbestos; Asbestos, Crocidolite; Asbestosis; Humans; Incidence; Lung Neoplasms; Occupational Diseases; Occupational Exposure; Risk Factors; Smoking; Time Factors; Western Australia

Projections have been made of the number of mesotheliomas, lung cancers, and cases of asbestosis that might occur over the period 1987 to 2020 in former workers at the Wittenoom crocidolite asbestos mine in Western Australia. Predictions were based on the observed mortality to the end of 1986 and modelling of the mesothelioma rate. Elimination of crocidolite from the lungs was included in the model. Between the years 1987 and 2020 it is predicted that between 250 and 680 deaths will occur due to mesothelioma. This wide range is due to uncertainty on the functional form of the relation between mesothelioma rate and time, and insufficient data to estimate the elimination rate of crocidolite from the lungs. The most likely range is the lower half of this total range--that is, between 250 and 500. It is predicted that between 340 and 465 deaths will occur due to lung cancer. About 45% of these deaths would be attributable to exposure to asbestos. It is estimated that currently there are up to 200 cases of undiagnosed asbestosis. Of these about 50 will die of lung cancer or mesothelioma and are therefore also included in the figures above. Up to 60 former workers may develop the first signs of asbestosis in the future but any such cases are likely to progress to more serious disease at a much slower rate than the cases that have already been identified.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Asbestos; Asbestos, Crocidolite; Asbestosis; Cause of Death; Female; Forecasting; Humans; Lung Neoplasms; Male; Mesothelioma; Middle Aged; Mining; Time Factors; Western Australia

Although the pathogenesis of asbestos-induced pulmonary damage is still not completely understood, an important role has been attributed to active oxygen species. In the present paper we present results of a study investigating the effect of crocidolite asbestos inhalation on different lung antioxidant enzymes in rats. During the development of pulmonary fibrosis induced by crocidolite asbestos, lung superoxide dismutase, catalase and selenium-dependent glutathione peroxidase activities increased, indicating an adaptive response to increased pulmonary oxidant stress. However, this adaptive response obviously is not sufficient to protect the lung from asbestos-induced pulmonary damage. Considering the role of active oxygen species in both the fibrotic process and tumor promotion, it is hypothesized that antioxidants may also protect the lung from chronic asbestos-induced pulmonary damage such as bronchogenic carcinoma.

Topics: Animals; Asbestos; Asbestos, Crocidolite; Asbestosis; Catalase; Enzyme Induction; Glutathione Peroxidase; Lung; Male; Oxygen; Rats; Rats, Inbred F344; Superoxide Dismutase

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

After long-term asbestos inhalation, the lung tissue burden is much less for chrysotile (CHRY) than for crocidolite (CRO) exposure. Nonetheless CHRY does not appear to be less fibrogenic. To study mechanisms responsible for the low retention of CHRY and the relationships with fibrogenesis, 15 sheep received a single intratracheal injection of either CHRY or CRO. Exposures in 100 ml saline consisted of 100 mg of 1-micron latex beads for the five control sheep, 100 mg UICC CRO fibres for the five CRO sheep and 100 mg UICC B CHRY fibres for the five CHRY sheep. Bronchoalveolar lavage (BAL) was carried out at months 2, 4, 6 and 8 after exposure and necropsy at month 8. BAL and tissue samples were analysed for fibres by transmission electron microscopy. At month 2, mass concentration in BAL was 108 +/- 30 ng/ml for CRO and 0.6 +/- 0.1 ng/ml for CHRY. BAL CRO decreased afterward but BAL CHRY did not. The mass concentration in the lung at month 8 was 40.6 +/- 8.7 ng/mg dry tissue for CRO and 11.5 +/- 7.0 ng/mg for CHRY. BAL fibrogenic activity at month 8 assessed by macrophage fibronectin production was less than 0.2 ng/10(6) cells/24 h in control sheep, 5 +/- 2 in CRO sheep and 11 +/- 2 in CHRY sheep (P less than 0.05 CRO vs CHRY). Histologic score of tissue injury fibrosis was 0 in control sheep, 1.9 +/- 0.3 in CRO sheep and 2.8 +/- 0.1 in CHRY sheep (P less than 0.05). At necropsy, the number size distribution of fibres per microgram of tissue from the (CRO)/(CHRY) sheep was respectively: (127 +/- 54)/(15 +/- 14) for fibres less than 5 microns, (18 +/- 17)/(32 +/- 14) for fibres greater than 5 microns, (1.6 +/- 8)/(7 +/- 13) for fibres greater than 20 microns. This study documented that the low pulmonary retention of CHRY was largely related to the faster alveolar clearance rate of CHRY mass. Fibrogenicity of CHRY remained higher and appeared to be related at least in part to the preferential retention of long and very long CHRY fibres.

Topics: Animals; Asbestos; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Bronchoalveolar Lavage Fluid; Lung; Male; Pulmonary Alveoli; Sheep

Topics: Asbestos; Asbestos, Crocidolite; Asbestosis; Australia; Humans; Incidence; Lung Neoplasms; Mesothelioma; Models, Statistical; Risk; Survival Rate

Several in vitro studies suggest the involvement of active oxygen metabolites in cell damage caused by asbestos. To determine if lung injury, inflammation, and asbestosis could be inhibited in vivo in a rapid-onset, inhalation model of disease, a novel method of chronic administration of antioxidant enzymes was developed. In brief, Fischer 344 rats were treated with polyethylene glycol-conjugated (PEG-) superoxide dismutase or catalase in osmotic pumps over a 10-day (5 days/wk for 2 wk) or 20-day (5 days/wk for 2 wk) period of exposure to crocidolite asbestos. Control rats included sham-exposed animals and those exposed to asbestos but receiving chemically inactivated enzymes. After 10 days of exposure to asbestos, lactic dehydrogenase (LDH), alkaline phosphatase, and total protein in bronchoalveolar lavage (BAL) were measured in one group of rats. Total and differnetial cell counts in BAL also were assessed. After 20 days of exposure, lungs of an additional group of rats were evaluated by histopathology and by measurement of hydroxyproline. Asbestos-associated elevations in LDH, protein, and total cell numbers in BAL were reduced in rats receiving PEG-catalase. Decreases in numbers of alveolar macrophages, polymorphonuclear leukocytes, and lymphocytes occurred in these animals. Exposure to asbestos for 20 days caused significant increases in both the amount of hydroxyproline in lung and the severity and extent of fibrotic lesions as determined by histopathology. These indicators of asbestosis were inhibited in a dosage-dependent fashion in rats receiving PEG-catalase. Use of inactivated PEG-catalase failed to boost serum levels of catalase and did not inhibit asbestos-induced elevation of hydroxyproline in lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Asbestos; Asbestos, Crocidolite; Asbestosis; Bronchoalveolar Lavage Fluid; Catalase; Disease Models, Animal; Hydroxyproline; Lung; Male; Polyethylene Glycols; Pulmonary Fibrosis; Rats; Rats, Inbred F344; Superoxide Dismutase

Topics: Adult; Aged; Asbestos; Asbestos, Crocidolite; Asbestosis; Humans; Lung Neoplasms; Male; Middle Aged; Survival Rate; Time Factors

Pulmonary inflammation has been evaluated in 43 crocidolite-exposed asbestos (ASB) workers and 12 control subjects, using a quantitative index of gallium uptake (GI). The GI was compared with chest roentgenographs (CXRs) graded by the ILO classification. The ASB workers included 15 with asbestosis (CXR greater than or equal to 1/0), 19 with a normal CXR (CXR 0/0), and 9 with equivocal CXR changes (CXR 0/1). In individuals with asbestosis the GI was 3.6 +/- 0.3 (mean +/- SEM), P less than 0.01 compared with exposed patients without asbestosis. In exposed patients with equivocal CXR changes (0/1) the GI was 3.1 +/- 0.3, and in exposed patients with a normal CXR (0/0) the GI was 2.4 +/- 0.2. The GI for subjects without lung disease was 1.2 +/- 0.2, P less than 0.01 compared with exposed patients without asbestosis. The scans were scored independently by two observers, and the correlation coefficient of the two sets of GI was 0.95. These data demonstrate that subjects with crocidolite-induced asbestosis and exposed patients with equivocal CXR changes or a normal CXR have significantly increased GI.

Topics: Asbestos; Asbestos, Crocidolite; Asbestosis; Gallium Radioisotopes; Humans; Image Processing, Computer-Assisted; Lung; Middle Aged; Radionuclide Imaging; Western Australia

Gallium lung scanning is widely used to evaluate pulmonary inflammation in patients with interstitial lung disease but has not previously been reported in crocidolite-exposed workers. In order to characterize the pulmonary inflammation caused by crocidolite inhalation, GLS and BAL findings were related to chest x-ray film changes graded according to the ILO classification of roentgenograms of pneumoconioses. In individuals with roentgenographic evidence of asbestosis (CXR greater than or equal to 1/0, n = 15), 13 had a positive GLS and 13 had an abnormal BAL. In asbestos-exposed individuals with equivocal chest x-ray film changes (CXR 0/1, n = 12), six had a positive GLS and six had BAL changes (both GLS and BAL abnormal in three). In individuals with a normal chest x-ray film (CXR 0/0 n = 8), two had a positive GLS and two BAL changes (both abnormal in 1). These data demonstrate that most subjects with crocidolite-induced asbestosis have an abnormal GLS and BAL. In addition, many individuals with asbestos exposure and equivocal or no chest x-ray film changes have an abnormal GLS and/or BAL, suggesting the presence of active subclinical pulmonary inflammation in these individuals.

Topics: Asbestos; Asbestos, Crocidolite; Asbestosis; Bronchoalveolar Lavage Fluid; Citrates; Citric Acid; Female; Gallium Radioisotopes; Humans; Lung; Male; Middle Aged; Mining; Radionuclide Imaging; Time Factors; Western Australia

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

To estimate the effects on health of occupational exposure to crocidolite, a highly toxic form of asbestos, we studied a cohort of 33 men who worked in 1953 in a Massachusetts factory that manufactured cigarette filters containing crocidolite fibers from 1951 to 1957. Twenty-eight of the men have died, as compared with 8.3 deaths expected. This increased mortality was attributable to asbestos-associated diseases. Fifteen deaths were caused by cancer, as compared with 1.8 expected (relative risk, 8.2; 95 percent confidence interval, 4.6 to 13.4), including eight from lung cancer, five from malignant mesothelioma, and two from other types of cancer. There were seven deaths from nonmalignant respiratory disease, as compared with 0.5 expected (relative risk, 14.7; 95 percent confidence interval, 5.9 to 30.3), of which five were due primarily to asbestosis. In contrast, the mortality rates from cardiovascular diseases and all other causes were not increased. Four of the five living workers have pulmonary asbestosis; three of them have recently diagnosed cancers, including two additional lung cancers. We conclude that the extremely high morbidity and mortality in these workers were caused by intense exposure to crocidolite asbestos fibers.

Topics: Asbestos; Asbestos, Crocidolite; Asbestosis; Cohort Studies; Humans; Lung Neoplasms; Male; Massachusetts; Mesothelioma; Nicotiana; Occupational Diseases; Plants, Toxic

It is known that 6505 men and 411 women were employed in the mining and milling of crocidolite at Wittenoom in the Pilbara region of Western Australia between 1943 and 1966. Employment was usually brief (median duration four months) and exposure intense (median estimated cumulative exposure 6 fibres/cc years). The vital status of 73% of the men and 58% of the women employed in the industry was known at 31 December 1980, providing 95 264 person-years of follow up with 820 deaths in men and 4914 person-years with 23 deaths in women. The standardised mortality ratio (SMR) for all causes in men was 1.53 (95% confidence interval 1.43 to 1.64). Statistically significant excess death rates were observed in men for neoplasms, particularly malignant mesothelioma (32 deaths), neoplasms of the trachea, bronchus, and lung (SMR 2.64), and neoplasms of the stomach (SMR 1.90); respiratory diseases, particularly pneumoconiosis (SMR 25.5); infections, particularly tuberculosis (SMR 4.09); mental disorders particularly alcoholism (SMR 4.87); digestive diseases, particularly peptic ulceration (SMR 2.46) and cirrhosis of the liver (SMR 3.94); and injuries and poisonings, particularly non-transport accidents (SMR 2.36). The excess mortality from pneumoconiosis, malignant mesothelioma, and respiratory cancers, but not stomach neoplasms, was dependent on time since first exposure and cumulative exposure. There was no increase in mortality from laryngeal cancer (SMR 1.09) or neoplasms other than those listed. The SMR for all causes in women was 1.47 (95% confidence interval 0.98-2.21) and for neoplasms 1.99; there was one death from malignant pleural mesothelioma.

Topics: Adult; Asbestos; Asbestos, Crocidolite; Asbestosis; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Mesothelioma; Mining; Pleural Neoplasms; Western Australia

Topics: Air Pollutants; Air Pollutants, Occupational; Asbestos; Asbestos, Amosite; Asbestos, Amphibole; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Humans; Neoplasms; Risk

Topics: Animals; Asbestos; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Cell Membrane; Epithelium; Erythrocyte Membrane; Fibroblasts; Macrophages; Microscopy, Electron, Scanning; Particle Size; Phagocytosis; Pulmonary Alveoli; Rats

Topics: Animals; Asbestos; Asbestos, Crocidolite; Asbestosis; Cell Line; Fibroblasts; Lung; Procollagen; Rats; Rats, Inbred F344

The course of pulmonary asbestosis and its determinants have been examined in 280 applicants for compensation among former workers of the crocidolite mine and mill at Wittenoom Gorge, Western Australia. Serial chest radiographs accrued over more than 3 decades were graded for parenchymal disease separately by two observers according to the 1980 ILO Classification of Radiographs for Pneumoconioses and without knowledge of exposure histories or compensation details. In 136 subjects whose median duration of exposure was 37 months, radiographic asbestosis appeared between 1 and 34 yr after initial exposure and then progressed continuously. Total exposure to asbestos and time from first exposure to the appearance of definite radiographic asbestosis were significant determinants of the rate of progression of profusion of radiographic abnormality. Asbestosis should be considered to be an active disease even 3 decades after exposure has ended.

Topics: Adult; Asbestos; Asbestos, Crocidolite; Asbestosis; Australia; Humans; Male; Mining; Models, Theoretical; Pneumoconiosis; Radiography; Retrospective Studies; Severity of Illness Index; Time Factors

An estimate has been made of the prevalence of unrecognised pneumoconiosis in former crocidolite workers from Wittenoom, Western Australia. All plain chest radiographs relating to a one in six random sample (1025 men) of all former Wittenoom workers who had never entered a compensation claim to the Pneumoconiosis Medical Board of Western Australia were sought from Perth teaching hospitals and from the Perth Chest Clinic where compulsory examination of all workers in the mining industry takes place. Radiographs were recovered for 83% of the men and read independently by two observers. By means of logistic regression analysis a current prevalence of parenchymal abnormality (defined as a radiographic profusion of small opacities of category 1/0 or greater on the ILO classification) of nearly 20% was calculated after adjustment for age, time since first exposure, and cumulative exposure level. One hundred men randomly selected from those known to be alive in the sample were invited to attend for a new radiographic examination. Seventy four men attended and the predicted prevalence was confirmed. It is estimated from these data that there were between 450 and 900 former Wittenoom workers in Australia at the end of 1980 who had radiographic abnormality consistent with pneumoconiosis but had not claimed compensation or had asbestosis diagnosed. The data are consistent with there being no threshold dose of crocidolite exposure for the development of radiographic abnormality in this group.

Topics: Adult; Age Factors; Asbestos; Asbestos, Crocidolite; Asbestosis; Australia; Humans; Lung; Male; Middle Aged; Mining; Radiography; Retrospective Studies; Time Factors

Bronchoalveolar lavage (BAL) findings in 27 individuals with crocidolite- or chrysotile-induced asbestosis were compared to BAL findings in 29 unexposed control subjects. Alveolitis, defined as an increase in the proportions and/or absolute numbers of inflammatory cells present in BAL fluid compared to values in control subjects, was present in 26 (96 percent) subjects with asbestosis. Most exhibited a neutrophil-eosinophil alveolitis, with neutrophil proportions increased to 7.4 +/- 0.7 percent and eosinophil proportions increased to 2.2 +/- 0.4 percent, compared to 2 +/- 0.5 percent and 0.4 +/- 0.01 percent, respectively, in control subjects (p less than 0.01 for both neutrophils and eosinophils). An increase in the total number of neutrophils and eosinophils per ml of lavage fluid was also seen (neutrophils 23 +/- 5 and eosinophils 13 +/- 4 per ml; p less than 0.05 compared to control subjects). Severity of the alveolitis, defined by the neutrophil or eosinophil proportions, was independent of a history of exposure to cigarette smoke. The pattern and severity of alveolitis in crocidolite- and chrysotile-induced asbestosis were similar. There was a significant correlation between duration of exposure to asbestos and neutrophil proportions (p less than 0.01). No significant difference in the severity of the alveolitis was observed between individuals with radiologic and physiologic evidence of asbestosis compared to those with asbestos exposure and crackles alone, suggesting that, in asbestosis as in other chronic interstitial lung diseases, radiologic and physiologic parameters do not reflect the severity of the alveolitis. This study demonstrates that a neutrophil-eosinophil alveolitis is present in individuals with crocidolite- and chrysotile-induced asbestosis, that this alveolitis is independent of cigarette smoking, and that the severity of the BAL changes is not reflected in radiologic and physiologic changes.

Topics: Asbestos; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Cell Count; Eosinophils; Female; Humans; Male; Middle Aged; Neutrophils; Pulmonary Alveoli; Smoking; Therapeutic Irrigation

Asbestos-associated damage to cells of the respiratory tract in vitro can be prevented by the simultaneous addition of scavengers of active oxygen species to cultures. To determine if administration of scavenger enzymes to animals and humans is a plausible approach to the prevention of asbestos-induced lung disease, osmotic pumps were filled with various concentrations of PEG-coupled catalase and implanted subcutaneously into Fischer 344 rats over a 28-day period. At 3, 14, and 28 days after implantation of the pumps, the animals were evaluated for levels of catalase in serum and lung. In addition, lung tissue and lavage fluids were examined at 28 days for biochemical and morphologic indications of cell injury, inflammation, and fibrotic lung disease. At all time points examined, the administration of PEG-catalase caused a dosage-dependent increase in serum levels of catalase. The levels of lung catalase were evaluated at 28 days but not at earlier time periods. In comparison to control rats, the amounts of enzymes (lactic dehydrogenase, alkaline phosphatase), protein, and cells in lavage fluids from treated animals were unaltered. Moreover, the lungs showed no evidence of inflammation or fibrotic disease as determined by differential cell counts in lavage and measurement of hydroxyproline. These studies suggest that administration of PEG-catalase does not cause injury or other alterations in lung tissue and can be pursued as a feasible approach to prevention of asbestosis.

Topics: Animals; Antioxidants; Asbestos; Asbestos, Crocidolite; Asbestosis; Catalase; Free Radicals; Infusion Pumps; Lung; Polyethylene Glycols; Rats; Rats, Inbred F344

The survival of 354 claimants for compensation for pulmonary asbestosis among former workers of the Wittenoom crocidolite mine and mill in Western Australia has been examined. There were 118 deaths up to December 1982. The median time between start of work and claim for compensation was 17 years. The standardised mortality ratio (SMR) for deaths from all causes was 2.65 (p less than 0.0001). The SMR for pneumoconiosis was 177.2 (p less than 0.0001), bronchitis and emphysema 2.6 (p = 0.04), tuberculosis 44.6 (p less than 0.0001), respiratory cancer (including five deaths from malignant pleural mesothelioma) 6.4 (p less than 0.0001), gastrointestinal cancer 1.6 (p = 0.22), all other cancers 1.6 (p = 0.17), heart disease 1.4 (p = 0.07), and all other causes 2.18 (p = 0.004). Plain chest radiographs taken within two years of claiming compensation were found for 238 subjects and were categorised independently by two observers according to the International Labour Organisation criteria without knowledge of exposure or compensation details. Profusion of radiographic opacities, age at claiming compensation, work in the Wittenoom mill, and degree of disability awarded by the pneumoconiosis medical board were significant predictors of survival, but total estimated exposure to asbestos was not. Radiographic profusion and degree of disability were, however, predictable by total exposure. The median survival from claim for compensation was 17 years in subjects with ILO category 1 pneumoconiosis, 12 years in category 2, and three years in category 3.

Topics: Asbestos; Asbestos, Crocidolite; Asbestosis; Australia; Disability Evaluation; Humans; Male; Radiography; Time Factors; Workers' Compensation

Serial plain chest radiographs taken between 1943 and 1982 for 280 claimants for compensation for asbestosis and 32 claimants for malignant pleural mesothelioma from the Wittenoom asbestos industry were reviewed by two observers to identify diffuse pleural thickening and pleural effusion. A pleural effusion which appeared and resolved within two years without radiographic or clinical evidence of underlying malignancy, infection or cardiac failure was seen in 15 cases by reader 1 and 24 cases by reader 2. Eighteen cases of effusion, determined from clinical records to be caused by malignant pleural mesothelioma, were seen by reader 1 and 20 by reader 2. The latent periods between commencing work and the first radiograph showing effusion were much shorter for subjects with benign asbestos pleural effusion than for subjects with effusion due to malignant pleural mesothelioma, although there was considerable overlap in the range. The longest latent period for benign asbestos pleural effusion was 22 years and the shortest period for effusion due to malignant pleural mesothelioma was 12 years. The latent period for benign asbestos pleural effusion was inversely related to total cumulative exposure, whereas that for effusion due to malignant pleural mesothelioma was significantly shorter for subjects who had worked in the mill than for those who had worked in the mine. A long latent period and a history of working in the mill were significant discriminators for a malignant as opposed to a benign basis for an effusion. The appearance of a benign asbestos pleural effusion appeared to be a risk factor for the severity of subsequent diffuse pleural thickening.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Asbestos; Asbestos, Crocidolite; Asbestosis; Diagnosis, Differential; Humans; Male; Mass Chest X-Ray; Mesothelioma; Mining; Pleura; Pleural Effusion; Pleural Neoplasms; Regression Analysis; Time Factors

This account reviews the clinical and pathological features of asbestosis, with a brief comment on the incidence of asbestosis in workers exposed occupationally to Western Australian crocidolite at Wittenoom Gorge. In keeping with common usage, the term "asbestosis" is restricted to pulmonary parenchymal fibrosis--with or without associated visceral pleural fibrosis--related to inhalation of asbestos fibres, thereby excluding parietal pleural fibrous plaques. The mechanisms underlying the development of the interstitial fibrosis are incompletely understood, but they appear to involve complex interactions of asbestos with alveolar macrophages, fibroblasts, lymphocytes and the complement system.

Topics: Asbestos; Asbestos, Crocidolite; Asbestosis; Australia; Biological Transport; Biomechanical Phenomena; Disease Susceptibility; Dose-Response Relationship, Drug; Humans; Lung; Pulmonary Fibrosis; Radiography

The pleura is a main target for various reactions related to asbestos exposure. However there are great radiological and clinical differences between the various reactions, and there is also increasing evidence that they have different prognoses. The main reactions are pleural plaques on the one hand and acute pleurisy and diffuse pleural fibrosis on the other. In a population with a low mesothelioma risk, the anthophyllite-exposed population of Northern Karelia in Finland, there are very few reactions of the second type, while plaques are very common. In Turkey, where the exposure is to erionite, the mesothelioma level is extremely high, and reactions of type two are very common in the exposed population. Thus it seems that careful discrimination of the various pleural changes can have prognostic value. There are also indications that plaques do not have any relation to a disturbed immunologic system, while pleurisy and diffuse pleurisy have.

Topics: Aluminum Silicates; Asbestos; Asbestos, Crocidolite; Asbestosis; Finland; Humans; Mesothelioma; Pleural Diseases; Pleural Neoplasms; Pneumoconiosis; Radiography; Risk; Sweden; Turkey; Zeolites

Topics: Administration, Intranasal; Animals; Asbestos; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Female; Histocompatibility Antigens Class II; Macrophages; Male; Phagocytosis; Pulmonary Alveoli; Rats; Rats, Inbred ACI; Rats, Inbred F344

Topics: Asbestos; Asbestos, Amosite; Asbestos, Crocidolite; Asbestosis; Disease Susceptibility; Humans; Male; Mining; Risk; South Africa

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

Analysis of numbers and types of asbestos fibers present in lung tissue may provide insights into the pathogenesis of asbestos-induced disease, as well as diagnostic information concerning the relationship of a given lesion to asbestos exposure. This type of analysis requires extraction of fibers and asbestos bodies from lung tissue, preferably by means of a digestion-and-concentration technique, and examination with a combination of electron optical techniques, including electron diffraction and energy-dispersive x-ray spectroscopy. The combination permits definitive identification of asbestos fibers. Asbestos bodies have been shown to contain asbestos no matter what population they are found in, but they appear to be of value in ascertaining unusual exposure only when present in very large numbers. Numbers of asbestos bodies markedly underestimate total numbers of fibers present in lung. In patients from the general population, the mean number of asbestos fibers is about 1 X 10(6)/g dry lung; of this number, more than 80 per cent are fibers of chrysotile less than 5 microns long. Patients in the general population who have pleural plaques have about the same total number of fibers, but their lungs contain about a 50-fold increase in long thin amphibole fibers of commercial origin. Patients who have asbestosis and most patients who have mesothelioma have 100 to 200 X 10(6) fibers/g dry lung; the grade of asbestosis appears to be related to total fiber content. Occasional patients may develop mesotheliomas with much smaller fiber burdens. Both benign and malignant pleural diseases appear to be closely related to the presence of long thin amphibole fibers. Analysis of pulmonary fiber burden suggest that asbestos-related disease is not merely a matter of total numbers of fibers present, but that factors such as fiber type and size are equally important.

Topics: Asbestos; Asbestos, Amphibole; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Environmental Exposure; Humans; Lung; Lung Neoplasms; Pleural Neoplasms; Silicon Dioxide

Incubation of chrysotile and amphibole asbestos fibers with normal human peripheral blood polymorphonuclear leukocytes (PMN) resulted in a significant stimulation of PMN metabolic activity and generation of toxic oxygen by-products as measured by chemiluminescence (CL). Although all asbestos fibers tested were cytotoxic to PMN, cytotoxicity and CL varied disproportionately with fiber type. Anthophyllite asbestos produced the greatest PMN cytotoxicity. It also depressed PMN phagocytosis of latex beads the most and induced the greatest PMN CL response of the fiber types examined. We postulate that asbestos-induced release of toxic oxygen by-products from PMN which have infiltrated into the pulmonary alveoli may contribute to disease pathogenesis in asbestosis.

Topics: Asbestos; Asbestos, Amosite; Asbestos, Amphibole; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Cell Survival; Humans; Luminescent Measurements; Neutrophils; Phagocytosis; Silicon Dioxide

Topics: Asbestos; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; England; Female; Humans; Lung Neoplasms; Mesothelioma; Occupational Diseases; Ovarian Neoplasms; Respiratory Protective Devices; Time Factors