asbestos--amosite and Lung-Diseases

The final results from this multi-dose, 90-day inhalation toxicology study in the rat with life-time post-exposure observation have shown a significant fundamental difference in pathological response and tumorgenicity between brake dust generated from brake pads manufactured with chrysotile or from chrysotile alone in comparison to the amphiboles, crocidolite and amosite asbestos. The groups exposed to brake dust showed no significant pathological or tumorigenic response in the respiratory track compared to the air control group at exposure concentrations and deposited doses well above those at which humans have been exposed. Slight alveolar/interstitial macrophage accumulation of particles was noted. Wagner grades were 1-2 (1 = control group), similar to the TiO

Topics: Air Pollutants; Animals; Asbestos, Amosite; Asbestos, Crocidolite; Dose-Response Relationship, Drug; Lung; Lung Diseases; Microscopy, Confocal; Rats; Time Factors

Hamsters breathed, nose-only, for 13 weeks, 5 days/week, 6 hr/day, either man-made vitreous fiber (MMVF)10a, MMVF33, or long amosite asbestos at approximately 300 World Health Organization (WHO) fibers/cc or long amosite at 25 WHO fibers/cc. [World Health Organization fibers are longer than 5 microm and thicker than 3 microm, with aspect ratio >3.] After sacrifice, fiber burden was estimated (left lungs) by ashing and scanning electron microscopy (ashing/SEM) or (right middle lobes) by confocal laser scanning microscopy (CLSM) in situ. In situ CLSM also provided three-dimensional views of fibers retained, undisturbed, in lung tissue. Fibers of each type were lodged in alveoli and small airways, especially at airway bifurcations, and were seen fully or partly engulfed by alveolar macrophages. Amosite fibers penetrated into and through alveolar septa. Length densities of fibers in parenchyma (total length of fiber per unit volume of lung) were estimated stereologically from fiber transsections counted on two-dimensional optical sections and were 30.5, 25.3, 20.0, and 81.6 mm/mm3 for MMVF10a, MMVF33, and low- and high-dose amosite, respectively. Lengths of individual fibers were measured in three dimensions by tracking individual fibers through series of optical sections. Length distributions of amosite fibers aerosolized, but before inhalation versus after retention in the lung were similar, whether determined by ashing/SEM or in situ CLSM. In contrast, the fraction of short MMVF10a and MMVF33 fibers increased and the geometric mean fiber lengths of both MMVFs decreased by approximately 60% during retention. Most likely due to fiber deposition pattern and differences in sampling, fiber burdens [MMVF10a, MMVF33, and amosite (high dose; 269 WHO fibers/cc)] determined by ashing/SEM were 1.4, 1. 5, and 3.5 times greater, respectively, than those calculated from in situ CLSM data. In situ CLSM is able to provide detailed information about the anatomic sites of fiber retention and also fiber lengths and burdens in good agreement with ashing/SEM results.

Topics: Administration, Inhalation; Aerosols; Air Pollutants; Animals; Asbestos, Amosite; Cricetinae; Glass; Lung Diseases; Male; Mesocricetus; Particle Size

A multidose, subchronic inhalation study was used to estimate the maximum tolerated dose (MTD) of 901 fiberglass (MMVF10.1) for a chronic inhalation study using hamsters. Subchronic study results indicated that 30 mg/m(3) [250-300 WHO fibers (>5 microm long)/cm(3) and 100-130 fibers/cm(3) >20 microm long] meets or exceeds the estimated MTD, and chronic study results confirmed this. For the subchronic study, hamsters were exposed 6 h/day, 5 days/wk, for 13 wk to MMVF10.1 at 3, 16, 30, 45, and 60 mg/m(3) (36, 206, 316, 552, or 714 WHO fibers/cm(3)), then monitored for 10 wk. Results demonstrating MTD were: inflammatory response (all fiber exposures); elevated lung cell proliferation with @ges;16 mg/m(3); lung lavage neutrophil elevations with @ges;16 mg/m(3) and lactate dehydrogenase (LDH) and protein elevations with > or = 30 mg/m(3); and persistent abnormal macrophage/fiber clumps in lungs exposed to 45 and 60 mg/m(3), which suggest overloading of clearance mechanisms. For the chronic study, hamsters were exposed for 78 wk to MMVF10a (901 fiber glass) or MMVF33 (special-application 475 fiberglass) at approximately 300 WHO fibers/cm(3) ( approximately 100 fibers/cm(3) @gt;20 @mu;m long), or to amosite asbestos at an equivalent concentration and 2 lower concentrations. All fiber-exposed animals had pulmonary inflammation, elevated lung lavage cells, and increased lung cell proliferation. Between 52 and 78 wk of exposure, lung burdens of all fibers increased at an accelerated rate, suggesting impairment of clearance mechanisms. MMVF33 and amosite induced fibrosis and pleural mesothelioma. These findings substantiate that exposures in the chronic study adequately tested the toxic potential of fiberglass.

Topics: Aerosols; Animals; Asbestos, Amosite; Body Burden; Body Weight; Bronchoalveolar Lavage Fluid; Carcinogens; Cell Division; Cricetinae; Glass; Inhalation Exposure; Lung; Lung Diseases; Male; Mesocricetus; Microspheres; Mineral Fibers; Models, Animal; Organ Size; Time Factors

Fiberglass (FG) is the largest category of man-made mineral fibers (MMVFs). Many types of FG are manufactured for specific uses building insulation, air handling, filtration, and sound absorption. In the United States, > 95% of FG produced is for building insulation. Several inhalation studies in rodents of FG building insulation have shown no indication of pulmonary fibrosis or carcinogenic activity. However, because of increasing use and potential for widespread human exposure, a chronic toxicity/carcinogenicity inhalation study of a typical building insulation FG (MMVF 10a) was conducted in hamsters, which were shown to be highly sensitive to the induction of mesotheliomas with another MMVF. A special-application FG (MMVF 33) and amosite asbestos were used for comparative purposes. Groups of 140 weanling male Syrian golden hamsters were exposed via nose-only inhalation for 6 h/day, 5 days/wk for 78 wk to either filtered air (chamber controls) or MMVF 10a, MMVF 33, or amosite asbestos at 250-300 WHO fibers/cm(3) with two additional amosite asbestos groups at 25 and 125 WHO fibers/cm(3). They were then held unexposed for 6 wk until approximately 10-20% survival. After 13, 26, 52, and 78 wk, various pulmonary parameters and lung fiber burdens were evaluated. Groups hamsters were removed from exposure at 13 and 52 wk and were held until 78 wk (recovery groups). Initial lung deposition of long fibers (>20 microm in length) after a single 6-h exposure was similar for all 3 fibers exposed to 250-300 fibers/cm(3). MMVF 10a lungs showed inflammation (which regressed in recovery hamsters) but no pulmonary or pleural fibrosis or neoplasms. MMVF 33 induced more severe inflammation and mild interstitial and pleural fibrosis by 26 wk that progressed in severity until 52 wk, after which it plateaued. While the inflammatory lesions regressed in the recovery animals, pulmonary or pleural fibrosis did not. A single multicentric mesothelioma was observed at 32 wk. No neoplasms were found in the remainder of the study. Amosite asbestos produced dose-related inflammation and pulmonary and pleural fibrosis as early as 13 wk in all 3 exposure levels. The lesions progressed during the course of the study, and at 78 wk severe pulmonary fibrosis with large areas of consolidation was observed in the highest 2 exposure groups. Progressive pleural fibrosis with mesothelial hypertrophy and hyperplasia was present in the thoracic wall and diaphragm in most animals and increased with

Topics: Animals; Asbestos, Amosite; Body Burden; Body Weight; Bronchoalveolar Lavage Fluid; Carcinogens; Cell Division; Cricetinae; Glass; Inhalation Exposure; Lung; Lung Diseases; Male; Mesocricetus; Mineral Fibers; Models, Animal; Organ Size; Pleura; Time Factors

Fibronectin (Fn) and tenascin (Tn) are two major extracellular matrix (ECM) glycoproteins that may have important roles both in fibrotic lung diseases and in lung tumors. The significance of Fn and Tn in human pleural mesothelial cells and pleural diseases is unclear. Transformed human pleural mesothelial cells (Met5A), primary cultures of mesothelial cells, and cultured mesothelioma cell lines were investigated for Fn and Tn immunoreactivity. Mesothelial cells were exposed for 48 to 96 h to transforming growth factor-beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha), amosite asbestos fibers, or oxidants (H2O2 and menadione, a compound that auto-oxidizes to produce superoxide). Immunofluorescence and Western blotting with monoclonal anti-Fn and anti-Tn antibodies, and Northern blotting with a complementary DNA (cDNA) probe for Tn showed that mesothelial cells are capable of producing Fn and Tn. The mRNA level and immunoreactivity of Tn was enhanced by TGF-beta and TNF-alpha, whereas Fn was intensified only by TGF-beta. A wide range of amosite, H2O2, or menadione concentrations had no clear effect on Fn or Tn reactivity. Fn and Tn were present at low or undetectable concentrations in five of six mesothelioma cell lines, whereas the organization of Fn immunoreactivity in these cell lines was variable. Furthermore, results obtained with the tumor tissue of these same mesothelioma patients suggested that Fn and Tn expressions do not necessarily parallel either each other or results obtained with the cultured cells.

Topics: Asbestos, Amosite; Fibronectins; Gene Expression Regulation; Humans; Hydrogen Peroxide; Immunohistochemistry; Lung Diseases; Pleural Neoplasms; RNA, Messenger; Tenascin; Transforming Growth Factor beta; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha; Vitamin K

To determine predictors of progression of pleural and parenchymal disease on the chest radiographs of workers exposed to a short term, intense exposure of amosite asbestos.. The first and last of a series of chest radiographs of 887 workers exposed to amosite was interpreted and coded according to International Labour Organisation (ILO) standards by two physicians. Significant predictors of disease progression were found by a linear stepwise regression analysis from among such variables as smoking history, latency (time since first exposure), duration and intensity of exposure, and cytology.. Although most radiographs remained normal, some showed progression of disease with about twice as many patients with abnormalities on the last film. Various combinations of age, intensity of exposure, and time between films were significant predictors of pleural and parenchymal disease and progression of such disease. No predominance of one sided disease was noted. Cytology and smoking were unreliable predictors of disease. Most disease progression was minor, usually of less than two scoring categories.. An intense, yet short, exposure to amosite asbestos can produce pleural and parenchymal changes on chest radiographs. The number of those affected roughly doubled over a period spanning 10 to 20 years after exposure. Age and intensity of exposure are the most important predictors of disease.

Topics: Adult; Age Factors; Asbestos, Amosite; Calcinosis; Cohort Studies; Disease Progression; Female; Follow-Up Studies; Humans; Lung Diseases; Male; Occupational Exposure; Pleural Diseases; Radiography; Regression Analysis; Risk Factors; Severity of Illness Index; United States

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

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

Chest radiographs were read from a sub-cohort of 386 factory workers with short term exposure to amosite asbestos (median exposure six months) and long follow up (median 25 years). Prevalence of abnormality was determined independently by two readers from the first film available after 20 years from first employment. Serial films were obtainable for 238 men (median interval from first to last film: nine years). Progression was classified with a direct progression scoring scale. Individual dust exposure estimates were derived from dust counts from two similar plants. With as little as one month or less of employment, about 20% of the films showed parenchymal abnormality and about a third showed pleural abnormality. Those in the lowest cumulative exposure stratum (less than 5 fibre-years/ml) were similarly found to have high rates of abnormality. Dose-response relations were present in the data of both readers. Smokers had higher rates of parenchymal abnormality. On multivariate analysis, cumulative exposure was the exposure variable most closely related to parenchymal abnormality, and time from first employment was the variable most closely related to pleural abnormality. Progression (including first attacks) 20 or more years after ceasing employment occurred and was more common for pleural than for parenchymal abnormality. It is concluded that with exposure to high concentrations to amosite such as existed in this factory and with follow up for at least 20 years, (1) exposure for as little as a month was sufficient to produce radiological signs of parenchymal and pleural fibrosis, (2) no cumulative exposure threshold for parenchymal and pleural fibrosis was detectable, and (3) parenchymal and pleural progression were still detectable >/= 20 years after the end of exposure.

Topics: Asbestos; Asbestos, Amosite; Asbestosis; Cohort Studies; Follow-Up Studies; Humans; Lung; Lung Diseases; Male; Middle Aged; Multivariate Analysis; Occupational Exposure; Pleura; Radiography; Smoking

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

In order to assess the effects of cigarette smoke and asbestos exposure, we divided guinea pigs into 4 groups: smoking or nonsmoking, and asbestos-exposed or not asbestos-exposed groups. Asbestos-exposed animals were given a single intratracheal instillation of 5 mg UICC amosite, a dose and method of administration that we have previously shown produces morphologic changes in the small airways as well as minimal interstitial fibrosis. Animals were smoked 5 days per week for 6 months. By itself, smoking did not affect lung collagen content, small airways wall thickness, or the volume fraction of tissue surrounding airways, but it did cause a significant increase in alveolar mean linear intercept (Lm). Asbestos alone increased collagen content, airway wall thickness, and tissue volume fraction surrounding airways, the latter measure used to assess interstitial fibrosis. An unexpected finding was that asbestos also increased Lm. The two agents administered together caused more severe changes of all types than were produced by either agent alone, and the interaction between the 2 was generally synergistic. Smoke-exposed animals retained 3 times the asbestos fiber burden of those not smoke-exposed; the increase in retention was greater for short than for long fibers. We conclude that cigarette smoke can potentiate the fibrosis induced by asbestos, possibly because of increased fiber retention. As well, in this model, asbestos or asbestos plus cigarette smoke produces increases in alveolar size.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Asbestos; Asbestos, Amosite; Female; Guinea Pigs; Hydroxyproline; Lung; Lung Diseases; Nicotiana; Plants, Toxic; Smoke

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

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