tremolite and Pulmonary-Fibrosis

The physical properties of different types of asbestos may strongly affect health outcomes in exposed individuals. This study was designed to provide understanding of the comparative toxicity of naturally occurring asbestos (NOA) fibers including Libby amphibole (LA), Sumas Mountain chrysotile (SM), El Dorado tremolite (ED), and Ontario ferroactinolite (ON) cleavage fragments. Rat-respirable fractions (PM₂.₅) were prepared by water elutriation. Surface area was greater for SM (64.1 m²/g) than all other samples (range: 14.1-16.2 m²/g), whereas mean lengths and aspect ratios (ARs) for LA and SM were comparable and greater than ED and ON. Samples were delivered via a single intratracheal (IT) instillation at doses of 0.5 and 1.5mg/rat. One day post-IT instillation, low-dose NOA exposure resulted in a 3- to 4-fold increase in bronchoalveolar lavage fluid (BALF) cellularity compared with dispersion media (DM) controls, whereas high-dose exposure had a more severe effect on lung inflammation which varied by source. Although inducing less neutrophilic inflammation than ON and ED, exposure to either LA or SM resulted in a greater degree of acute lung injury. Three months post-IT instillation, most BALF parameters had returned to control levels, whereas the development of fibrosis persisted and was greatest in SM-exposed rats (SM > LA > ON > ED). These data demonstrate that fiber length and higher AR are directly correlated with the severity of fibrosis and that, in the rat, exposure to SM is more fibrogenic than LA which suggests that there may be cause for concern for people at risk of being exposed to NOA from the Sumas Mountain landslide.

Topics: Animals; Asbestos, Amphibole; Asbestos, Serpentine; Bronchoalveolar Lavage Fluid; Dose-Response Relationship, Drug; Inflammation Mediators; Inhalation Exposure; Lung; Particle Size; Pulmonary Fibrosis; Rats; Rats, Inbred F344; Risk Assessment; Severity of Illness Index; Time Factors

Lung fibre content was determined for 86 former chrysotile miners and millers in two Québec mining regions: Thetford mines (TM) and the Asbestos region (AR).. Fibres were assessed using transmission electron microscopy (TEM) and energy dispersive X-ray spectrometry (EDS). Asbestos body (AB) concentrations were assessed by microscopy of tissue digests. Corresponding histological lung tissue sections were quantitatively graded for the severity of interstitial fibrosis on a 12-point scale. Fibrosis score and its associations with (1) fibre concentrations and fibre dimensions within three fibre length intervals (less than 5 microm, 5-10 microm, and over 10 microm), and (2) several exposure variables were evaluated using correlation coefficients and regression techniques.. Concentration of short (<5 microm) tremolite fibres was the best predictor of fibrosis grade in both mining groups (r=0.44, P<0.01 and r=0.39, P<0.01 for TM and AR, respectively). Chrysotile fibre concentration showed a lower correlation with the fibrosis grade for subjects from TM only. Long (>10 microm) amosite fibre concentration showed a linear relationship with the fibrosis score in miners and millers from AR. Exposure variables, including smoking, had no predictive value for fibrosis grade. Within fibre length categories, fibre dimension was not related to the fibrosis score.. Lung fibre concentration as measured by TEM/EDS, especially that of short (<5 microm) tremolite fibres, is a better predictor of fibrosis grade in these two groups of chrysotile miners than either the concentration of ABs or the duration of exposure. Due to the limitation of our counting method, almost all fibres longer than 10 microm observed in this study were shorter than 14 microm. Thus, if length plays a role in fibrogenesis, it may be related to fibres of greater length than those covered in this study.

Topics: Asbestos, Amphibole; Asbestos, Serpentine; Extraction and Processing Industry; Humans; Lung; Microscopy, Electron, Transmission; Occupational Diseases; Occupational Exposure; Pulmonary Fibrosis; Quebec; Spectrometry, X-Ray Emission

The differences between chrysotile asbestos, a serpentine mineral, and amphibole asbestos have been debated extensively. Many studies have shown that chrysotile is cleared from the lung more rapidly than amphibole. In order to quantify the comparative clearance of chrysotile and the amphibole asbestos tremolite, both fibers were evaluated in an inhalation biopersistence study that followed the European Commission recommended guidelines. In addition, the histopathological response in the lung was evaluated following the short-term exposure. This article presents the results of this study through 90 days after cessation of exposure. Following the termination of the study, a subsequent article will provide the complete results through 12 mo after cessation of exposure. In order to quantify the dynamics and rate by which these fibers are removed from the lung, the biopersistence of a sample of commercial grade chrysotile from the Coalinga mine in New Idria, CA, of the type Calidria RG144 and of a long-fiber tremolite were studied. For synthetic vitreous fibers, the biopersistence of the fibers longer than 20 microm has been found to be directly related to their potential to cause disease. This study was designed to determine lung clearance (biopersistence) and the histopathological response. As the long fibers have been shown to have the greatest potential for pathogenicity, the aerosol generation technique was designed to maximize the number of long respirable fibers. The chrysotile samples were specifically chosen to have 200 fibers/cm3 longer than 20 microm in length present in the exposure aerosol. These longer fibers were found to be largely composed of multiple shorter fibrils. The tremolite samples were chosen to have 100 fibers/cm3 longer than 20 microm in length present in the exposure aerosol. Calidria chrysotile fibers clear from the lung more rapidly (T1/2, fibers L > 20 microm = 7 h) than any other commercial fiber tested including synthetic vitreous fibers. With such rapidly clearing fibers, the 5-day exposure would not be expected to result in any pathological change in the lung, and the lungs of animals that inhaled Calidria chrysotile showed no sign of inflammation or pathology and were no different than the lungs of those animals that breathed filtered air. Following this 5-day exposure to tremolite, the tremolite fibers once deposited in the lung parenchyma do not clear and almost immediately result in inflammation and a pathological respon

Topics: Aerosols; Animals; Asbestos, Amphibole; Asbestos, Serpentine; Inhalation Exposure; Lung; Male; Mineral Fibers; Pulmonary Fibrosis; Rats

To examine how fiber type, fiber concentration, and fiber size correlate with the presence of asbestos-related disease in workers with heavy chrysotile exposure, we used analytic electron microscopy to determine the fiber content of the lungs of 94 long-term chrysotile miners and millers from the region of Thetford Mines, Quebec. Mesothelioma, airway fibrosis, and asbestosis were strongly associated with a high tremolite fiber concentration, whereas pleural plaques and carcinoma of the lung showed no relationship to tremolite burden. Similar patterns were seen for chrysotile concentration, but further analysis suggested that the apparent effect of chrysotile probably was due to the high correlation (r = 0.70) between chrysotile and tremolite concentration rather than to an independent effect of chrysotile. Increased tremolite-chrysotile ratio was marginally associated with the presence of pleural plaques but not with any other disease. Very high correlations (r > 0.90) between the concentrations of fibers longer or shorter than 8 microns prevented assessment of the effects of long compared with short fibers. Pleural plaques were very strongly associated with higher mean tremolite fiber aspect ratios, but no differences in mean fiber size (length, width, aspect ratio, surface area, and mass) were seen for any other disease. Total fiber size measures (total fiber length/g and others) showed differences similar to fiber concentration for mesothelioma, airways fibrosis, and asbestosis, but no one measure was clearly better than another or better than fiber concentration. We conclude that, in this population of heavily exposed chrysotile miners and millers, the presence of airways fibrosis and asbestosis and, probably, mesothelioma reflects high tremolite burden.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Asbestos; Asbestos, Amphibole; Asbestos, Serpentine; Asbestosis; Humans; Lung; Lung Neoplasms; Mesothelioma; Microscopy, Electron; Middle Aged; Mining; Particle Size; Pleural Diseases; Pulmonary Fibrosis; Quebec; Regression Analysis; Silicic Acid

Lung tissue from 76 deceased asbestos cement workers (seven with mesothelioma) exposed to chrysotile asbestos and small amounts of amphiboles, has been studied by transmission electron microscopy, together with lung tissue from 96 controls. The exposed workers with mesothelioma had a significantly higher total content of asbestos fibre in the lungs than those without mesothelioma, who in turn, had higher concentrations than the controls (medians 189, 50, and 29 x 10(6) fibres/g (f/g]. Chrysotile was the major type of fibre. The differences were most pronounced for the amphibole fibres (62, 4.7, and 0.15 f/g), especially crocidolite (54, 1.8 and less than 0.001 f/g), but were evident also for tremolite (2.9, less than 0.001, and less than 0.001 f/g) and anthophyllite (1.7, less than 0.001, and less than 0.001 f/g). For amosite, there was no statistically significant difference between lungs from workers with and without mesothelioma; the lungs of workers had, however, higher concentrations than the controls. Strong correlations were found between duration of exposure and content of amphibole fibres in the lungs. Asbestos bodies, counted by light microscopy, were significantly correlated with the amphibole but not with the chrysotile contents. Fibrosis was correlated with the tremolite but not the chrysotile content in lungs from both exposed workers and controls. Overall, similar results were obtained using fibre counts and estimates of mass.

Topics: Adult; Aged; Aged, 80 and over; Asbestos; Asbestos, Amphibole; Asbestos, Serpentine; Construction Materials; Humans; Lung; Mesothelioma; Middle Aged; Occupational Diseases; Pulmonary Fibrosis; Silicic Acid; Silicon Dioxide

Environmental exposure to asbestos, as observed in Anatolia (Turkey), usually results in pleural pathology (plaques and mesothelioma). We report the case of a 50-year old woman who, until the age of 50, had lived in Eregli, central Anatolia, a region where inhalation of environmental asbestos is responsible for a high prevalence of pleural diseases. Radiology showed diffuse interstitial pneumonia without pleural involvement. Bronchoalveolar lavage brought back asbestos bodies (AB) in concentrations of 4,250 per millilitre. All were made of tremolite, a non-commercial variety of asbestos. The patient's family was investigated by chest radiography and search for AB in sputum. The husband, who came from the same town as his wife and had been exposed until the age of 45, had the classical response with bilateral pleural thickening but no parenchymal abnormalities; 2 AB were found in his sputum. The 3 sons, exposed for 10, 13 and 20 years respectively, had normal radiograms and no AB in their sputum, except for the older (3 AB) who had been exposed for 20 years. These cases illustrate the importance of environmental exposure to asbestos which may produce lesions similar to those observed in industrial exposure. Only mineralogical examinations can determine whether the asbestos is environmental or industrial.

Topics: Asbestos; Asbestos, Amphibole; Bronchoalveolar Lavage Fluid; Environmental Exposure; Female; Humans; Middle Aged; Pedigree; Pulmonary Fibrosis; Silicic Acid; Tomography, X-Ray Computed; Turkey

Health status is often measured in epidemiologic studies on an ordinal scale, but data of this type are generally reduced for analysis to a single dichotomy. Several statistical models have been developed to make full use of information in ordinal response data, but have not been much used in analyzing epidemiologic studies. The authors discuss two of these statistical models--the cumulative odds model and the continuation ratio model. They may be interpreted in terms of odds ratios, can account for confounding variables, have clear and testable assumptions, and have parameters that may be estimated and hypotheses that may be tested using available statistical packages. However, calculations of asymptotic relative efficiency and results of simulations showed that simple logistic regression applied to dichotomized responses can in some realistic situations have more than 75% of the efficiency of ordinal regression models, but only if the ordinal scale is collapsed into a dichotomy close to the optimal point. The application of the proposed models to data from a study of chest x-rays of workers exposed to mineral fibers confirmed that they are easy to use and interpret, but gave results quite similar to those obtained using simple logistic regression after dichotomizing outcome in the conventional way.

Topics: Asbestos, Amphibole; Epidemiologic Methods; Humans; Models, Theoretical; Occupational Diseases; Pulmonary Fibrosis; Regression Analysis; Silicic Acid; Statistics as Topic

A small cohort of 194 men with low exposure to fibrous tremolite (mean 0.75 f/ml y) in the mining and milling of vermiculite in South Carolina experienced 51 deaths 15 years or more from first employment. The SMR (all causes) was 1.17 reflecting excess deaths from circulatory disease. There were four deaths from lung cancer and 3.31 expected (SMR 1.21, 95% CI 0.33-3.09). Three of the four deaths were in the lowest exposure category (less than 1 f/ml y); no death was attributed to mesothelioma or pneumoconiosis. These findings contrast with those in Montana where the vermiculite ore was heavily contaminated with fibrous tremolite. A radiographic survey of 86 current and recent South Carolina employees found four with small parenchymal opacities (greater than or equal to 1/0) and seven with pleural thickening. These proportions were not higher than in a non-exposed group and much lower than had been observed in Montana. Examination of sputum from 76 current employees showed that only two specimens contained typical ferruginous bodies, confirming low cumulative fibre exposure. Any possible adverse effects of work with vermiculite, minimally contaminated with fibrous or non-fibrous tremolite, were thus beyond the limits of detection in this workforce.

Topics: Aluminum Silicates; Asbestos, Amphibole; Canada; Cohort Studies; Humans; Lung Neoplasms; Mesothelioma; Mining; Occupational Diseases; Pulmonary Fibrosis; Silicic Acid; Silicon Dioxide

Evidence on the mechanism by which inhaled mineral fibres lead to pulmonary fibrosis has not been forthcoming. As with silica, a biphasic cell culture system was required to distinguish phagocytosis from collagen formation. Synthesis of total protein and collagen by rat fibroblasts was estimated by incorporation of labelled proline after treatment with the medium from rat peritoneal macrophages that had been cultured in the presence of different types of mineral fibre. The influence of fibre length was also examined. All the main varieties of asbestos reacted with macrophages to produce or release a fibrogenic factor. However, chrysotile and the longer amosite fibres evoked the response only after prolonging the period of incubation with macrophages, presumably by permitting more complete phagocytosis of curled or longer fibres. Short amosite fibres proved to be more active than longer ones and under certain conditions were as potent as quartz. Fibrous glass also possessed stimulatory properties and again a sample having a short length gave a stronger response than a long one. Collagen formation by asbestos thus appears to be mediated by a macrophage factor, so operating in a manner similar to that previously demonstrated for quartz. The conventional view that short fibres are comparatively insignificant in asbestos fibrogenesis cannot, on the present evidence, be sustained. Furthermore, it should not be assumed than man-made mineral fibres of respirable diameter are innocuous or that short ones can be ignored.

Topics: Animals; Asbestos; Asbestos, Amphibole; Cells, Cultured; Collagen; Culture Media; Fibroblasts; Glass; Macrophages; Phagocytosis; Proline; Protein Biosynthesis; Pulmonary Fibrosis; Rats; Silicic Acid