Tremolite and mesothelioma

BACKGROUND: Exposure to chrysotile dust has been associated with the development of mesothelioma and recent studies have implicated contaminating tremolite fibers as the likely etiological factor. Tremolite also contaminates talc, the most common non-asbestos mineral fiber in our control cases. METHODS: We examined 312 cases of mesothelioma for which fiber burden analyses of lung parenchyma had been performed by means of scanning electron microscopy to determine the content of tremolite, non-commercial amphiboles, talc and chrysotile. The vast majority of these patients were exposed to dust from products containing asbestos. RESULTS: Tremolite was identified in 166 of 312 cases (53%) and was increased above background levels in 81 cases (26%). Fibrous talc was identified in 193 cases (62%) and correlated strongly with the tremolite content (P < 0.0001). Chrysotile was identified in only 32 cases (10%), but still correlated strongly with the tremolite content (P < 0.0001). Talc levels explained less of the tremolite deviance for cases with an increased tremolite level than for cases with a normal range tremolite level (22 versus 42%). In 14 cases (4.5%) non-commercial amphibole fibers (tremolite, actinolite and/or anthophyllite) were the only fiber types found above background. CONCLUSIONS: We conclude that tremolite in lung tissue samples from mesothelioma victims derives from both talc and chrysotile and that tremolite accounts for a considerable fraction of the excess fiber burden in end-users of asbestos products.     

Fibers in lung tissues of mesothelioma cases among miners and millers of the township of asbestos,quebec

Twenty cases of mesothelioma among miners of the township of Asbestos, Quebec, Canada, have been reported. To further explore the mineral characteristics of various fibrous material, we studied the fibrous inorganic content of postmortem lung tissues of 12 of 20 available cases. In each case, we measured concentrations of chrysotile, amosite, crocidolite, tremolite, talc-anthophyllite, and other fibrous minerals. The average diameter, length, and length-to-diameter ratio of each type of fiber were also calculated. For total fibers > 5 μm, we found > 1,000 asbestos fibers per mg tissue (f/mg) in all cases; tremolite was above 1,000 f/mg in 8 cases, chrysotile in 6 cases, crocidolite in 4 cases, and talc anthophyllite in 5 cases. Among cases with asbestos fibers, the tremolite count was highest in 7 cases, chrysotile in 3 cases, and crocidolite in 2 cases. The geometric mean concentrations of fibers ? 5 μm were in the following decreasing order: tremolite > crocidolite > chrysotile > other fibers > talc-anthophyllite > amosite. For total fibers < 5 μm, we found > 1,000 fibers per mg tissue (f/mg) in all cases; tremolite was above 1,000 f/mg in 12 cases, chrysotile in 8 cases, crocidolite in 7 cases, and talc-anthophyllite in 6 cases. Tremolite was highest in 8 cases, chrysotile in 2 cases, and crocidolite and amosite in 2 cases. The geometric mean concentrations of fibers < 5 μm were in the following decreasing order: tremolite > other fibers > chrysotile > crocidolite > talc-anthophyllite > amosite. We conclude, on the basis of the lung burden analyses of 12 mesothelioma cases from the Asbestos township of Quebec, that the imported amphibole (crocidolite and amosite) were the dominant fibers retained in the lung tissue in 2/12 cases. In 10/12 cases, fibers from the mine site (chrysotile and tremolite) were found at highest counts; tremolite was clearly the highest in 6, chrysotile in 2, and 2 cases had about the same counts for tremolite and chrysotile. If a relation of fiber burden-causality of mesothelioma is accepted, mesothelioma would be likely caused by amphibole contamination of the plant in 2/12 cases and by the mineral fibers (tremolite and chrysotile) from the mine site in the 10 other cases.     

An examination of the fibrous mineral content of asbestos lung tissue from the Canadian chrysotile mining industry.

An examination of postmortem lung tissue from 20 cases of diagnosed asbestosis from the Canadian chrysotile mining industry has shown that fibrous minerals other than chrysotile were present in many of the cases. Tremolite fiber was found in 11 of the cases, often in large amounts, and crocidolite and amosite fibers were found in 2 of the cases. Fibers corresponding to talc and anthophyllite were found in 3 cases. In 4 of the cases, fibers were not detected. Amphibole and other fibers were found to be present in larger numbers than chrysotile in 7 of the cases. No attempt has been made to relate the results to occupation and location where the exposures may have occurred. It is possible, however, that fibrous minerals other than chrysotile are active in the incidence of asbestosis in the Canadian chrysotile mining industry.     

Retention of asbestos fibres in lungs of workers with asbestosis, asbestosis and lung cancer, and mesothelioma in Asbestos township.

OBJECTIVE: To conduct a mineralogical study on the particles retained in the necropsied lungs of a homogenous group of asbestos miners and millers from Asbestos township (and a local reference population) and to consider the hypothesis that there is a difference in size between fibres retained in the lungs of patients with asbestosis with and without lung cancer. METHODS: Samples of lung tissue were obtained from 38 patients with asbestosis without lung cancer, 25 with asbestosis and lung cancer, and 12 with mesothelioma, from necropsied Quebec chrysotile miners and millers from Asbestos township. Fibre concentrations in the lungs of these patients were compared with those in tissue from necropsies carried out on a local reference population: men who had died of either accidental death or acute myocardial infarction between 1990 and 1992. 23 were born before 1940 and 26 after 1940. RESULTS: Geometric mean (GM) concentrations were higher in cases than in the controls for chrysotile fibres 5 to 10 microns long in patients with asbestosis with or without lung cancer; for tremolite fibres 5 to 10 microns long in all patients; for crocidolite, talc, or anthophyllite fibres 5 to 10 microns long in patients with mesothelioma; for chrysotile and tremolite fibres > or = 10 microns long in patients with asbestosis; and crocidolite, talc, or anthophyllite fibres > or = 10 microns long in patients with mesothelioma. However, median concentrations of each type of fibre in the lungs did not show any significant differences between the three disease groups. Average length to diameter ratios of the fibres were calculated to be larger in patients with asbestosis and lung cancer than in those without lung cancer for crocidolite fibres > or = 10 microns long, for chrysotile, amosite, and tremolite fibres 5 to 10 microns long, and for chrysotile and crocidolite fibres < 5 microns long. However, there was no statistical difference in the median length to diameter ratios for any type of fibres across the disease groups when they were calculated in each patient. Cumulative smoking index (pack-years) was higher in the group with asbestosis and lung cancer but was not statistically different from the two other disease groups. CONCLUSION: Lung cancers occurred in workers with asbestosis from Asbestos township who had an equal concentration of retained fibres but a tendency to a higher length to diameter ratio of amphiboles. These workers had a 29% higher average cumulative smoking index.     

Occupational asbestos exposure and predictable asbestos-related diseases in India

BACKGROUND: India imports nearly 100,000 metric tons of asbestos per year, and small-scale asbestos (chrysotile and tremolite) mining and milling contributes nearly 5%-10% of the total national usage. The industry is relatively young, having started in the 1950s and 1960s. METHODS: Surveys of asbestos-exposed workers have identified significant occupational exposures, early pleural and parenchymal changes on chest radiograph, and decrements in lung function. RESULTS AND CONCLUSIONS: Based on knowledge of past and current exposures to asbestos in industry, we can predict a future occurrence of clinical asbestos-related diseases-pleural changes, pulmonary fibrosis, bronchogenic carcinoma, and diffuse malignant mesothelioma. These cases of asbestos related disease are expected to occur in asbestos exposed workers from mining, milling, and manufacturing as well as in those with secondary exposures to asbestos-containing materials, including construction and maintenance workers, users of asbestos-containing consumer products, and the occupants of asbestos-containing buildings.     

Exposure to brake dust and malignant mesothelioma: a study of 10 cases with mineral fiber analyses

OBJECTIVES: A large number of workers in the USA are exposed to chrysotile asbestos through brake repair, yet only a few cases of malignant mesothelioma (MM) have been described in this population. Epidemiologic and industrial hygiene studies have failed to demonstrate an increased risk of MM in brake workers. We present our experience of MM in individuals whose only known asbestos exposure was to brake dust and correlate these findings with lung asbestos fiber burdens. METHODS: Consultation files of one of the authors were reviewed for cases of MM in which brake dust was the only known asbestos exposure. Lung fiber analyses were performed using scanning electron microscopy (SEM) in all cases for which formalin-fixed or paraffin-embedded lung tissue was available. RESULTS: Ten cases of MM in brake dust-exposed individuals were males aged 51-73 yr. Nine cases arose in the pleura and one in the peritoneum. Although the median lung asbestos body count (19 AB/g) is at our upper limit of normal (range 0-20 AB/g), half of the cases had levels within our normal range. In every case with elevated asbestos fiber levels by SEM, excess commercial amphibole fibers were also detected. Elevated levels of chrysotile and non-commercial amphibole fibers were detected only in cases that also had increased commercial amphibole fibers. CONCLUSIONS: Brake dust contains exceedingly low levels of respirable chrysotile, much of which consists of short fibers subject to rapid pulmonary clearance. Elevated lung levels of commercial amphiboles in some brake workers suggest that unrecognized exposure to these fibers plays a critical role in the development of MM.     

Quantitative analysis of asbestos burden in women with mesothelioma

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Asbestos bodies and the diagnosis of asbestosis in chrysotile workers

It has been suggested that because chrysotile asbestos forms asbestos bodies poorly, use of the traditional histologic requirements (diffuse interstitial fibrosis plus asbestos bodies) for the diagnosis of asbestosis, may lead to an underdiagnosis of this condition in workers exposed only to chrysotile. We examined lungs from 25 chrysotile miners with diffuse interstitial fibrosis. Asbestos bodies were found easily in histologic section using hematoxylin and eosin stains in all cases. Mineralogic analysis of four cases showed that 46 of 72 (64%) bodies isolated and examined contained chrysotile cores, and 21 of 72 (29%) bodies contained cores of the amphiboles tremolite and actinolite. By contrast, tremolite and actinolite constituted the majority of uncoated fibers in these cases. The mean length for bodies formed on chrysotile was 35 micron, and for bodies formed on tremolite or actinolite, 36 micron. We conclude that (1) the usual histologic criteria for the diagnosis of asbestos are applicable to chrysotile-exposed workers; (2) in workers with occupational chrysotile exposure, bodies form readily on this mineral; and (3) asbestos bodies in these lungs reflect the presence of long asbestos fibers.     

Exposure and mineralogical correlates of pulmonary fibrosis in chrysotile asbestos workers.

OBJECTIVES: The relation between lifetime cumulative exposure to asbestos, pathological grade of pulmonary fibrosis, and lung burden of asbestos at death, was explored in a necropsy population of former workers in a chrysotile asbestos textile plant in South Carolina. METHODS: Estimates of cumulative, mean, and peak exposures to asbestos were available for 54 workers. Necropsy records and lung tissue samples were obtained from hospital files. Matched control cases were selected from consecutive necropsies performed at the same hospitals. The extent and severity of pulmonary fibrosis was graded on tissue sections. Mineral fibres in lung tissue were characterised by transmission electron microscopy combined with x ray spectroscopy. RESULTS: A significant positive correlation (r = 0.67, P < 0.0001) was found between lifetime cumulative exposure to asbestos and total lung burden of asbestos fibres. This relation was also found for the individual types of asbestos associated with the exposure: chrysotile and tremolite. Pulmonary fibrosis was correlated with both cumulative exposure to asbestos (r = 0.60, P < 0.01) and the concentration of asbestos fibres in the lung (r = 0.62, P < 0.0001). The concentration of tremolite fibres in the lung provided a better estimate of lung fibrosis than did the concentration of chrysotile. Asbestosis was usually present in asbestos textile workers with more than 20 fibre-years cumulative exposure. The lengths and aspect ratios of chrysotile asbestos, but not amphibole asbestos, were greater in the lungs of asbestos fibre workers than in the control population. Textile workers with lung cancer had significantly greater cumulative exposures and fibrosis scores than workers without lung cancer. CONCLUSIONS: Both cumulative exposure to asbestos and lung fibre burden are strongly correlated with severity of asbestosis. The data also support the hypothesis that the high prevalence of asbestosis and lung cancer in this population resulted from exposure to long fibres of chrysotile asbestos in the workplace.     

Epidemiology of occupational asbestos-related diseases in China

In 1950s and 60s, asbestosis had been a major health hazard for asbestos exposed workers. In the late 1970s, lung cancers with or without asbestosis were found among asbestos workers. All cohort studies on asbestos workers and on chrysotile miners in China showed excess deaths from lung cancer. In a large scale of cohort study on asbestos workers, a synergistic effect was found between cigarette smoking and asbestos exposure in the production of lung cancer. There have been not so many cases of malignant mesotheliomas reported, so far. In the cohort of chrysotile miners, 4 cases of pleural mesothelioma were observed. In the large scale of cohort study on asbestos workers in 9 factories using only chrysotile only one case of pleural mesothelioma was detected for 10 years' observation. In another 2 cohort studies, 2 cases of peritoneal mesotheliomas were found, one in Shanghai asbestos factory where a small amount of crocidolite had been used in 1960s, and one in Anqing asbestos factory that was located near tremolite mine. Further study is needed especially for the relationship between exposure to Chinese chrysotile and malignant mesotheliomas.     

Correlation between fibre content of the lung and disease in east London asbestos factory workers

The lungs from 36 past workers at an east London asbestos factory who had died from asbestos related disease were compared with lung tissue from 56 matched control patients being operated on in east London for carcinoma of the lung, correlating the severity of asbestosis and the presence of pulmonary carcinoma or mesothelioma of the pleura or peritoneum with an asbestos exposure index and type and amount of mineral fibre in the lungs. Asbestosis was associated with far heavier fibre burdens than mesothelioma. There was also a striking difference in the degree of asbestosis between the subjects with mesothelioma and those with carcinoma of the lung, the asbestosis being more severe in the latter. A further finding was that crocidolite and amosite were strongly associated with asbestosis, carcinoma of the lung complicating asbestosis, and mesothelioma, whereas no such correlation was evident with chrysotile or mullite. It is suggested that more emphasis should be placed on the biological differences between amphibole and serpentine asbestos fibre.     

Electron microscopy analysis of mineral fibers in human lung tissue.

In the present study, lung samples from 126 autopsied cases were examined to determine the content of mineral fibers using analytical transmission electron microscopy (ATEM). The cases were divided into four groups (22 lungs of persons exposed to ambient environmental pollution, 32 cases of mesothelioma, 38 cases of primary lung cancer, and 34 asbestosis cases, 13 of these with additional pleural plaques). Fibers were counted, measured, and mineralogically identified using a combination of X-ray microanalysis and electron diffraction of the non-oriented fiber. Concentration of fibrous particles (defined as particles above 1 micron in length with roughly parallel long sides and an aspect ratio of 5:1 and greater) was calculated as fibers 10(6)/g dry lung weight. The concentration of chrysotile was found to be similar throughout the groups except for two cases in the asbestosis group with comparably high numbers of chrysotile. However, a remarkable difference for amphiboles could be observed between the groups. Asbestos bodies were mostly found in the asbestosis group. There was a rather good correlation between numbers of amphibole fibers and asbestos bodies, with an average ratio of 10:1. For comparison purposes between occupationally exposed/non-exposed individuals, a transition was found in the concentration range of 3-10(7) asbestos fibers/g dried lung weight.     

Correlation between fibre content of the lung and disease in east London asbestos factory workers.

The lungs from 36 past workers at an east London asbestos factory who had died from asbestos related disease were compared with lung tissue from 56 matched control patients being operated on in east London for carcinoma of the lung, correlating the severity of asbestosis and the presence of pulmonary carcinoma or mesothelioma of the pleura or peritoneum with an asbestos exposure index and type and amount of mineral fibre in the lungs. Asbestosis was associated with far heavier fibre burdens than mesothelioma. There was also a striking difference in the degree of asbestosis between the subjects with mesothelioma and those with carcinoma of the lung, the asbestosis being more severe in the latter. A further finding was that crocidolite and amosite were strongly associated with asbestosis, carcinoma of the lung complicating asbestosis, and mesothelioma, whereas no such correlation was evident with chrysotile or mullite. It is suggested that more emphasis should be placed on the biological differences between amphibole and serpentine asbestos fibre.     

Ferruginous body counts in sputum as an index of past exposure to mineral fibres.

Previous work by our group among vermiculite miners exposed to fibrous tremolite demonstrated that asbestos body counts in sputum closely reflected intensity and duration of past exposure. In the present project sputum samples from nearly 600 volunteers from 11 cohorts of workers exposed to asbestos and other mineral fibres were found to contain much lower numbers of asbestos bodies than had been observed in vermiculite workers and these counts did not reliably reflect past levels of exposure. No evidence was found that occupational exposure to man-made mineral fibres led to any ferruginous body formation. Asbestos body counts appeared to differentiate between mesothelioma cases and controls and between levels of radiological asbestosis, but in both comparisons, based on small numbers, the power of discrimination was low. Substantial variation was found both in asbestos body and in macrophage counts in daily sampling of vermiculite workers but it was not sufficient to invalidate comparison between groups for epidemiological study. In individual subjects, however, little reliance can be put on results from a single sputum sample, particularly if negative.     

Malignant mesothelioma caused by childhood exposure to long-fiber low aspect ratio tremolite

A 41-year-old man was found to have a malignant mesothelioma of the pleura. During childhood in Corsica, he had been exposed at home to chrysotile ore from the Canari mine. Analysis of lung mineral content revealed background levels of chrysotile but an elevated level of tremolite and actinolite asbestos. The latter had a geometric mean length of 3.7 μm, a value considerably longer than we have found for tremolite and actinolite from Quebec chrysotile miners but roughly the same as the mean length of amosite and crocidolite in workers with occupational amphibole exposure. No tremolite or actinolite fibers of length greater than 8 μm microns and width less than 0.25 μm were observed. The mean aspect ratio of the tremolite and actinolite fibers was 7, a value similar to that found in chrysotile miners with mesothelioma but considerably less than the mean aspect ratio of amosite and crocidolite from those with occupational expsoure. These data suggest that long-fiber tremolite is a potential mesothelial carcinogen in humans, and that fiber length is more important than fiber aspect ratio in this regard.     

Vermiculite, respiratory disease, and asbestos exposure in Libby, Montana: update of a cohort mortality study

BACKGROUND: Vermiculite from the mine near Libby, Montana, is contaminated with tremolite asbestos and other amphibole fibers (winchite and richterite). Asbestos-contaminated Libby vermiculite was used in loose-fill attic insulation that remains in millions of homes in the United States, Canada, and other countries. OBJECTIVE: This report describes asbestos-related occupational respiratory disease mortality among workers who mined, milled, and processed the Libby vermiculite. METHODS: This historical cohort mortality study uses life table analysis methods to compare the age-adjusted mortality experience through 2001 of 1,672 Libby workers to that of white men in the U.S. population. RESULTS: Libby workers were significantly more likely to die from asbestosis [standardized mortality ratio (SMR) = 165.8; 95% confidence interval (CI), 103.9-251.1], lung cancer (SMR = 1.7; 95% CI, 1.4-2.1), cancer of the pleura (SMR = 23.3; 95% CI, 6.3-59.5), and mesothelioma. Mortality from asbestosis and lung cancer increased with increasing duration and cumulative exposure to airborne tremolite asbestos and other amphibole fibers. CONCLUSIONS: The observed dose-related increases in asbestosis and lung cancer mortality highlight the need for better understanding and control of exposures that may occur when homeowners or construction workers (including plumbers, cable installers, electricians, telephone repair personnel, and insulators) disturb loose-fill attic insulation made with asbestos-contaminated vermiculite from Libby, Montana.     

Fiber size and number in workers exposed to processed chrysotile asbestos, chrysotile miners, and the general population

We analyzed chrysotile and chrysotile-associated amphibole (largely tremolite) asbestos fibers in 21 workers exposed to various types of processed (milled) chrysotile ore, 20 long-term chrysotile miners, and 20 members of the general population (controls). Significantly greater amounts of both chrysotile and tremolite were found in processed-ore workers and miners than in controls. On average, the mean fiber lengths and aspect ratios for the mining and processed-ore-exposed workers were similar and were significantly greater than the values seen in the controls; within the processed-ore group, there was a marked variation in these parameters, and some workers appeared to be exposed to fairly long, thin fibers. It was found empirically that the fiber size data, and to a lesser extent the concentration data, could be used to classify workers accurately into those with processed-ore exposure and controls. We conclude that fiber sizes in the lungs of processed-ore-exposed workers are similar to those of chrysotile miners and are considerably longer than those found in the general population; some processed-ore workers have longer fibers which might be responsible for higher disease incidences in certain working groups; tremolite accompanies chrysotile in a variable proportion of workers exposed to processed chrysotile products and might be important in the genesis of mesothelioma in such workers; and mineralogic analysis will usually detect exposure even when chrysotile has largely disappeared from lung tissue.     

Epidemiology of malignant mesothelioma--an outline

In the 1960s and 1970s, well designed case-referent studies put beyond doubt that exposure to airborne asbestos fibres was a cause of malignant mesothelioma. Some 35 cohort mortality studies in a large variety of industries during the 20-year period, 1974-1994, showed a wide range of outcomes, but in general that the risk was higher in exposures which included amphiboles rather than chrysotile alone. Real progress began, however, with discoveries along several lines: the link between pleural changes and mineralogy, the concept and importance of biopersistence, the developments in counting and typing mineral fibres in lung tissue, and data on amphibole mining in South Africa and Australia for comparison with that on chrysotile in Canada and Italy. This led to the recognition of the potential contamination in North America of chrysotile with tremolite. A survey in Canada in 1980-1988 and other surveys demonstrated that crocidolite, amosite, and tremolite could explain almost all cases of mesothelioma. Effective confirmation of this was finally achieved with data on vermiculite miners in Libby, Montana, in the years 1983-1999, where exposure was to tremolite-actinolite and/or other amphibole fibres alone.     

Lung asbestos burden in shipyard and construction workers with mesothelioma: comparison with burdens in subjects with asbestosis or lung cancer

Although mesothelioma is generally considered to be caused by asbestos, epidemiologic studies indicate that some cases have another cause. In order to determine whether pulmonary asbestos burden can be used to define asbestos-related mesotheliomas, asbestos burden was quantified in 27 shipyard or construction workers with diffuse malignant mesothelioma of the pleura or peritoneum and a history of asbestos exposure. Their burden was significantly greater than the burden found in 19 unexposed men (P less than 0.001). The burdens were also compared to those of previously reported subjects with asbestosis or lung cancer. The median concentration for total amphibole fibers (2.7 million/g dry lung) in subjects with mesothelioma did not differ significantly from our previously reported median values for 14 subjects with asbestosis (1.3 million/g dry lung) or for 60 asbestos workers with lung cancer (1.3 million/g dry lung). Fiber size distribution for amosite, the most prevalent fiber type, was similar in all three subject groups. Fifteen of 25 (60%) subjects with mesothelioma had mild asbestosis. Asbestos body (AB) concentrations were greater than or equal to 1900/g dry lung, and total amphibole fiber concentrations were greater than or equal to 390,000/g dry lung. Counts of ABs greater than or equal to 0.5/cm2 in histologic sections always signified both of these concentrations in extracts. Thus, histologic sections showing greater than or equal to 0.5 ABs/cm2 or extracts containing asbestos body or amphibole fiber concentrations of at least 1900 or 390,000/g dry lung, respectively, will confirm an asbestos-related mesothelioma.     

Inferences on the kinetics of asbestos deposition and clearance among chrysotile miners and millers

BACKGROUND: The health effects of asbestos are intimately related to the fate of inhaled fibers in the lungs. The kinetics of asbestos fibers have been studied primarily in rodents. The objective of this study was to explore the application of these kinetic models to human autopsy data. METHODS: We analyzed the asbestos fiber content of the lungs of 72 Quebec chrysotile miners and millers and 49 control subjects using analytical transmission electron microscopy. Statistical methods included standard multivariate linear regression and locally weighted regression methods. RESULTS: The lung burdens of asbestos bodies and chrysotile and tremolite fibers were correlated, as were the concentrations of short, medium, and long fibers of each asbestos variety. There were significant associations between the duration of occupational exposure and the burdens of chrysotile and tremolite. The concentration of chrysotile decreased with the time since last exposure but the concentration of tremolite did not. The clearance rate varied inversely with the length of chrysotile fibers. For fibers greater than 10 mu in length the clearance half-time was estimated to be 8 years. CONCLUSIONS: The patterns in our data are compatible with both of the hypotheses suggested from rodent experiments; the existence of a long-term sequestration compartment and overload of clearance mechanisms in this compartment.