asbestos--amosite and Disease-Models--Animal

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

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

In former mine workers and residents of Libby, Montana, exposure to amphibole-contaminated vermiculite has been associated with increased incidences of asbestosis and mesothelioma. In this study, long-term effects of Libby amphibole (LA) exposure were investigated relative to the well-characterized amosite asbestos in a rat model. Rat-respirable fractions of LA and amosite (aerodynamic diameter≤2.5 μm) were prepared by water elutriation. Male F344 rats were exposed to a single dose of either saline, amosite (0.65 mg/rat), or LA (0.65 or 6.5 mg/rat) by intratracheal (IT) instillation. One year after exposure, asbestos-exposed rats displayed chronic pulmonary inflammation and fibrosis. Two years postexposure, lung inflammation and fibrosis progressed in a time- and dose-dependent manner in LA-exposed rats, although the severity of inflammation and fibrosis was smaller in magnitude than in animals exposed to amosite. In contrast, gene expression of the fibrosis markers Col 1A2 and Col 3A1 was significantly greater in LA-exposed compared to amosite-exposed rats. There was no apparent evidence of preneoplastic changes in any of the asbestos-exposed groups. However, all asbestos-exposed rats demonstrated a significant increase in the expression of epidermal growth factor receptor (EGFR) 2 yr after instillation. In addition, only LA-exposed rats showed significant elevation in mesothelin (Msln) and Wilms' tumor gene (WT1) expression, suggesting possible induction of tumor pathways. These results demonstrate that a single IT exposure to LA is sufficient to induce significant fibrogenic, but not carcinogenic, effects up to 2 yr after exposure that differ both in quality and magnitude from those elicited by amosite administration at the same mass dose in F344 rats. Data showed that LA was on a mass basis less potent than amosite.

Topics: Animals; Asbestos, Amosite; Asbestos, Amphibole; Biomarkers; Disease Models, Animal; Dose-Response Relationship, Drug; Environmental Exposure; ErbB Receptors; Fibrosis; Gene Expression Regulation; Genes, Wilms Tumor; GPI-Linked Proteins; Inflammation; Lung; Male; Mesothelin; Rats; Rats, Inbred F344

Asbestos bodies (ABs) form as asbestos fibers become coated by a cellular iron- and protein-rich matrix. ABs have been reported in lymph nodes and a few extrapulmonary sites, but no data exist as to their formation outside of the lung. It is not clear whether the AB found in these extrapulmonary areas have been transported as mature structures from the lung or formed at the extrapulmonary site. This study was designed to determine if ABs are produced in extrapulmonary sites. The guinea pig efficiently forms ferruginous bodies in the lung and so it was chosen as a model to test the coating efficiency of amosite asbestos fibers in lung, liver and spleen.. Sized amosite asbestos (5 mg) was administered either endotracheally into lung (n = 2) or directly into liver (n = 4) and spleen (n = 4) of healthy 10-week-old male guinea pigs. The lung, liver and splenic tissues were removed at 40 and 180 days post inoculation and were examined histologically for the presence of AB via light microscopy. Uncoated fibers isolated from the tissues were characterized by electron microscopy. The coating efficiency was calculated as a ratio of uncoated/coated fibers per organ.. The coating efficiency ratios of fibers that were collected at 40 days post-injection from the individual sites were: lung - 350:1, liver - 4200:1, and spleen - 220,000:1. At 6 months post-injection the ratios for the individual sites consisted of: lung - 176:1, liver - 11,000:1, and spleen - 1000:1.. This study indicates that AB can be formed in extrapulmonary sites and that the coating efficiency in the lung is much greater than that within the liver or spleen.

Topics: Animals; Asbestos, Amosite; Asbestosis; Disease Models, Animal; Ferritins; Foreign Bodies; Guinea Pigs; Liver; Lung; Male; Mineral Fibers; Spleen

The study objectives were to assess the ability of intratracheal injection methods to discriminate between nine fibre types in respect of pulmonary biopersistence, and to provide approximate estimates of relative biopersistence and durability for a study of general relationships with biological and toxicological responses. The test fibres included six samples of size-selected fibre types specially prepared for research purposes, two commercially available fibres, and amosite. A 1 mg dose of each fibre type was administered to rats by intratracheal injection. The relative biopersistence of fibres in different size categories was assessed from the changes in mean lung burden, as determined by electron microscopy, at 3 days and 1, 6 and 12 months after injection. The ability of the test materials to resist dissolution was measured in a parallel series of simple in vitro acellular experiments at two pHs and in a continuous flow dissolution test. The observed differences in the persistence of fibres of differing length recovered from rat lungs were consistent with the current hypothesis that short fibres are cleared by cellular processes and long fibres by dissolution and disintegration. Differences in persistence of long (> 20 microns) fibres were correlated with measured rates of dissolution in vitro. Differences in persistence among those fibre types also studied by others workers were consistent with their findings after inhalation and intratracheal injection. Overall, the differences in the biopersistences of the test fibres following intratracheal injection were sufficient to enable an examination of the relationship of biopersistence with other biological and toxicological responses. Biopersistence was influenced by both fibre dimensions and solubility.

Topics: Air Pollutants, Occupational; Animals; Asbestos, Amosite; Biodegradation, Environmental; Disease Models, Animal; Environmental Monitoring; Hydrogen-Ion Concentration; Inhalation; Injections; Lung; Male; Mineral Fibers; Rats; Rats, Wistar; Reproducibility of Results; Time Factors; Trachea

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

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

To determine whether asbestos dust produces pathologic changes in the small airways, and to determine where the anatomic lesions of asbestosis commence, the authors examined lungs from guinea pigs exposed to 10 or 30 mg of amosite asbestos by intratracheal instillation and sacrificed 6 months later. Measurement of airway wall thickness revealed that membranous and respiratory bronchioles of all sizes in exposed animals were significantly thicker than those of controls. Amosite fibers were found embedded in the walls of bronchi and in membranous and respiratory bronchioles; where these fibers penetrated the airway walls, an interstitial inflammatory and fibrotic reaction (asbestosis) occurred. It is concluded that 1) amosite asbestos produces diffuse abnormalities throughout the noncartilagenous airways and possibly the cartilagenous airways as well; 2) this effect is independent of interstitial fibrosis of the parenchyma (classical asbestosis); 3) asbestosis, at least that induced by amosite, commences at any site in the parenchyma to which the asbestos fibers can gain access, either by deposition in alveoli and alveolar ducts or by direct passage of fibers through the walls of all types and sizes of small airways.

Topics: Animals; Asbestos; Asbestos, Amosite; Asbestosis; Bronchi; Disease Models, Animal; Guinea Pigs; Pulmonary Fibrosis

The early response of the lung to a single exposure of amosite asbestos was examined via scanning electron microscopy and correlated light microscopy in the guinea pig model. At 2 h post-exposure, lesions consisted of discrete areas of atelectasis with influx of neutrophils and macrophages. Free asbestos fibres were evident in affected areas. By 4 h post exposure, affected regions were more extensive with phagocytic cell numbers increased both in reactive sites and in adjacent tissue. By 1 day post-exposure, the inflammatory response was well developed and encompassed wide areas of the lung. Activated phagocytes were congregated in atelectatic regions and on blood vessel walls. Numerous macrophages were present even in alveoli distant to reactive loci. The 6 day and 12 day time frames marked a subsiding of the inflammatory response in which macrophages outnumbered PMNs in the comparably fewer reactive areas. There was a notable decrease both in marginated leucocytes and in accumulations of phagocytes in tissue adjacent to affected regions.

Topics: Acute Disease; Animals; Asbestos; Asbestos, Amosite; Asbestosis; Bronchi; Disease Models, Animal; Female; Guinea Pigs; Leukocytes; Lung; Male; Microscopy, Electron, Scanning; Phagocytosis; Pulmonary Alveoli; Sodium Chloride; Time Factors