P. Sébastien

Mesothelioma and asbestos fiber type: evidence from lung tissue analyses

Lung tissue samples from 78 cases from autopsy of mesothelioma in Canada, 1980 through 1984, and from matched referents were examined by optical and analytical transmission electron microscopic study. Concentrations of amosite, crocidolite, and tremolite fibers, and of typical asbestos bodies discriminated sharply between cases and referents. The distributions of chrysotile and anthophyllite/talc fibers and of all other natural and man‐made inorganic fibers (≥8 μm) in the two series were quite similar. Relative risk was related to the concentration of long (≥8 μm) amphibole fibers with no additional information provided by shorter fibers. The proportion of long fibers was much higher for amphiboles than chrysotile and, except for chrysotile, systematically higher in cases than referents. Amphibole asbestos fibers could explain most mesothelioma cases in Canada and other inorganic fibers, including chrysotile, very few. Fibrous tremolite, contaminant of many industrial minerals including chrysotile, probably explained most cases in the Quebec mining region and perhaps 20% elsewhere.

Cohort study of mortality of vermiculite miners exposed to tremolite.

A cohort of 406 men employed before 1963 for at least one year in a vermiculite mine in Montana was followed up until July 1983. The vermiculite ore as fed to the mill contained 4-6% of amphibole fibre in the tremolite series. Vital status was established in all but one of the 406 and death certificates were obtained and coded for 163 of the 165 men who died. Compared with white men in the United States, the cohort experienced excess mortality from all causes (SMR 1.17), respiratory cancer (SMR 2.45), non-malignant respiratory disease (SMR 2.55), and accidents (SMR 2.14). Four deaths were from malignant mesothelioma (proportional mortality 2.4%). Compared with Montana death rates, the SMR for respiratory cancer was somewhat higher (3.03). Man-year analyses of respiratory cancer and estimated cumulative exposure gave a relation that did not depart significantly from linearity. The results of this and case-referent analyses indicate an increased risk of mortality from respiratory cancer in this cohort of about 1% for each fibre year of exposure. In relation to estimated exposure the mortality experienced by the cohort from both lung cancer and mesothelial tumours was higher than in chrysotile mining.

Respiratory cancer in chrysotile textile and mining industries: exposure inferences from lung analysis.

In an attempt to explain the much greater risk of respiratory cancer at the same cumulative exposure in asbestos textile workers in Charleston, South Carolina, than in Quebec miners and millers, both exposed to chrysotile from the same source, 161 lung tissue samples taken at necropsy from dead cohort members were analysed by transmission electron microscopy. Altogether 1828 chrysotile and 3270 tremolite fibres were identified; in both cohorts tremolite predominated and fibre dimensions were closely similar. Lung fibre concentrations were analysed statistically (a) in 32 paired subjects matched for duration of employment and time from last employment to death and (b) in 136 subjects stratified by the same time variables. Both analyses indicated that the Quebec/Charleston ratios for chrysotile fibre concentration in lung tissue were even higher than the corresponding ratios of estimated exposure intensity (mpcf). After allowance for the fact that regression analyses suggested that the proportion of tremolite in dust was probably 2.5 times higher in Thetford Mines, Quebec, than in Charleston, the results from both matched pair and stratification analyses of tremolite fibre concentrations in lung were almost the same as for chrysotile. It is concluded that neither fibre dimensional differences nor errors in estimation of exposure can explain the higher risks of lung cancer observed in asbestos textile workers. The possible co-carcinogenic role of mineral oil used in the past in asbestos textile plants to control dust provides an alternative hypothesis deserving consideration.

Mesothelioma in Quebec chrysotile miners and millers: Epidemiology and aetiology

In a cohort of some 11,000 men born 1891-1920 and employed in the Quebec chrysotile production industry, including a small asbestos products factory, of 9780 men who survived into 1936, 8009 are known to have died before 1993, 38 probably from mesothelioma--33 in miners and millers and five in factory workers. Among the 5041 miners and millers at Thetford Mines, there had been 4125 deaths from all causes, including 25 (0.61%) from mesothelioma, a rate of 33.7 per 100,000 subject-years; the corresponding figures for the 4031 men at Asbestos were eight out of 3331 (0.24%, or 13.2 per 100,000 subject-years). At the factory in Asbestos, where all 708 employees were potentially exposed to crocidolite and/or amosite, there were 553 deaths, of which five (0.90%) were due to mesothelioma; the rate of 46.2 per 100,000 subject-years was 3.5 times higher than among the local miners and millers. Six of the 33 cases in miners and millers were in men employed from 2 to 5 years and who might have been exposed to asbestos elsewhere; otherwise, the 22 cases at Thetford were in men employed 20 years or more and the five at Asbestos for at least 30 years. The cases at Thetford were more common in miners than in millers, whereas those at. Asbestos were all in millers. Within Thetford Mines, case-referent analyses showed a substantially increased risk associated with years of employment in a circumscribed group of five mines (Area A), but not in a peripherally distributed group of ten mines (Area B); nor was the risk related to years employed at Asbestos, either at the mine and mill or at the factory. There was no indication that risks were affected by the level of dust exposure. A similar pattern in the prevalence of pleural calcification had been observed at Thetford Mines in the 1970s. These geographical differences, both within the Thetford region and between it and Asbestos, suggest that the explanation is mineralogical. Lung tissue analyses showed that the concentration of tremolite fibres was much higher in Area A than in Area B, a finding compatible with geological knowledge of the region. These findings, probably related to the far greater biopersistence of amphibole fibres than chrysotile, have important implications in the control of asbestos related disease and for wider aspects of fibre toxicology.

Radiological survey of past and present vermiculite miners exposed to tremolite

Chest radiographs taken by a standard technique were obtained from 173 current employees (164 men, 9 women) of a vermiculite mine in Montana, from 80 of 110 past employees resident within 200 miles, and from 47 men from the same area without known exposure to dust. In 43 of the 80 and 24 of the 47 an earlier chest x ray film was retrieved from the hospital archives. All 367 films were assessed blind and independently by three experienced readers using the ILO 1980 classification. Median radiographic assessment scores were analysed in relation to estimated cumulative exposure to the amphibole fibres that contaminate the vermiculite. Logistic regression analyses showed independent effects of age, smoking, and exposure on the prevalence of small opacities and of age and probably of exposure on pleural thickening. Overall, the data suggest that by retirement age the increase in prevalence of small opacities (greater than or equal to 1/0) lies between 5% and 10% per 100 f/ml years. This gradient may be somewhat steeper than for chrysotile miners and millers, but not much so.

Health of vermiculite miners exposed to trace amounts of fibrous tremolite.

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.

EFFECTS OF NONFIBROUS PARTICLES ON CERAMIC FIBER (RCF1) TOXICITY IN RATS

In previous investigations a reference test sample of prepared ceramic fibers called RCF1 induced lung tumors in a 2-yr inhalation study in rats. It was hypothesized that nonfibrous particles in RCF1 may have played a significant role. The objective of the present study was to compare lung retention and biological effects of another sample of ceramic fibers, called RCF1a, to the original RCF1. The main difference between these 2 samples was the content of nonfibrous particles: 25% of the mass of RCF1 versus 2% for RCF1a. These nonfibrous particles were chemically identical to the fibers. Female Wistar rats were exposed 6 h/day, 5 days/wk for 3 wk to either RCF1a or RCF1 fiber aerosol at a concentration of about 125 fibers (> 20 µm long)/ml. Because of differences in the nonfibrous particle contents, the average gravimetric aerosol concentration differed between the two samples (RCF1, 51.2 mg/m 3; RCF1a, 25.8 mg/m 3) . The post-treatment observation period was 12 mo. Biological effects measured include the clearance function of alveolar macrophages (clearance of fibers and tracer particles), and inflammation and its persistence during the recovery period. Alveolar clearance of tracer particles (46 Sc 2 O 3) was barely retarded after RCF1a exposure (80 days clearance half time compared to 60 days in controls). After RCF1 exposure, however, a severe retardation of clearance was observed (1200 vs. 66 days). In both groups, differential cell counts on pulmonary lavage showed a significant increase of polymorphonuclear leukocytes (PMNs) (about 15%) and lymphocytes 3 days after the end of exposure. The PMN influx persisted longer after exposure to RCF1 than RCF1a. The conclusion of the study is that the particle fraction of RCF1 significantly enhanced any adverse effects. This clearly demonstrates the importance of the physical characteristics of the test material for the degree of toxic effects to be expected. The presence of nonfibrous particulates can enhance the effects on the lung of a mixture of fibrous and nonfibrous particulates following exposure.In previous investigations a reference test sample of prepared ceramic fibers called RCF1 induced lung tumors in a 2-yr inhalation study in rats. It was hypothesized that nonfibrous particles in RCF1 may have played a significant role. The objective of the present study was to compare lung retention and biological effects of another sample of ceramic fibers, called RCF1a, to the original RCF1. The main difference between these 2 samples was the content of nonfibrous particles: 25% of the mass of RCF1 versus 2% for RCF1a. These nonfibrous particles were chemically identical to the fibers. Female Wistar rats were exposed 6 h/day, 5 days/wk for 3 wk to either RCF1a or RCF1 fiber aerosol at a concentration of about 125 fibers (>20 microm long)/ml. Because of differences in the nonfibrous particle contents, the average gravimetric aerosol concentration differed between the two samples (RCF1, 51.2 mg/m(3); RCF1a, 25.8 mg/m(3)). The posttreatment observation period was 12 mo. Biological effects measured include the clearance function of alveolar macrophages (clearance of fibers and tracer particles), and inflammation and its persistence during the recovery period. Alveolar clearance of tracer particles ((46)Sc(2)O(3)) was barely retarded after RCF1a exposure (80 days clearance half-time compared to 60 days in controls). After RCF1 exposure, however, a severe retardation of clearance was observed (1200 vs. 66 days). In both groups, differential cell counts on pulmonary lavage showed a significant increase of polymorphonuclear leukocytes (PMNs) (about 15%) and lymphocytes 3 days after the end of exposure. The PMN influx persisted longer after exposure to RCF1 than RCF1a. The conclusion of the study is that the particle fraction of RCF1 significantly enhanced any adverse effects. This clearly demonstrates the importance of the physical characteristics of the test material for the degree of toxic effects to be expected. The presence of nonfibrous particulates can enhance the effects on the lung of a mixture of fibrous and nonfibrous particulates following exposure.

Asbestos Fiber Type and Length in Lungs of Chrysotile Textile and Production Workers: Fibers Longer than 18 μm

Excess lung cancer risk for a cohort of chrysotile textile plant workers was many times the risk observed in a cohort of chrysotile miners/millers. The latter had greater exposure to chrysotile/tremolite. A previous lung burden study confirmed this excess exposure in miners/millers and showed little difference in fiber length. Selection of too short a fiber length cut-off (5 µm or more) in the previous study could have masked differences in lung-retained fiber length. In this follow-up, we counted only those intrapulmonary fibers exceeding 18 µm in length. Lung fiber concentration and dimension were assessed by transmission electron microscopy (TEM) and energy-dispersive x-ray spectrometry (EDS) for autopsy samples from 64 textile workers and 43 chrysotile miners and millers. These long fibers were significantly more concentrated in the lungs of chrysotile miners and millers, consistent with their greater exposure. However, when only these longest fibers were compared, there was a somewhat greater mean and median intrapulmonary fiber length for chrysotile textile workers (mean fiber length, all fiber types combined, 25.2 ± 10.2 µm vs. 22.9 ± 6.6 µm in miners/millers, < .001; medians 21.6 vs. 20, p < .05). Despite their lesser apparent lung cancer risk, chrysotile, tremolite, total amphibole, and total long fiber asbestos concentrations were all highest in the lungs of miners/millers. Twenty-two of 64 textile workers had lung content of crocidolite and/or amosite (32.5% of 508). These amosite/crocidolite fibers were present in the lungs of workers who ceased employment prior to the first use of such fibers recorded in this industry. The results suggest that (I) asbestos fiber length differences cannot explain the difference in lung cancer risk excess and slope between cohorts and (2) the experience of textile workers should not be used to assess risk of lung cancer in miners, cement workers, and friction product workers, regardless of fiber type.

Morphology and surface characteristics of particulates from silicon carbide industries

Faced with the lack of a correlation between health effects and exposures to known air contaminants in silicon carbide plants, an attempt was made to better characterize particles from these working environments with the use of electron microscopy with energy dispersive x-ray analysis and selected area electron diffraction, x-ray photoelectron spectroscopy and scanning Auger spectroscopy. The occurrence of SiC fibers was confirmed. SiC particulates were shown to be covered largely by silicon dioxide islets, heterogeneously distributed at the surfaces. These findings are discussed briefly in relation to the hypothesis on the toxicity of fibers and to the Altree-Williams and Sprogis risk function.

Particle Contamination in Experimental Fiber Preparations.

Abstract Two samples of refractory ceramic fibers (RCF1 and RCF1a) were tested in rats exposed by inhalation for 3 wk and followed thereafter for 12 mo. RCF1 and RCFIa have similar fiber chemistry but differ in the fiber size distributions and the contents of nonfibrous particles (2% for RCFIa, 25% for RCFli. For both test samples the target aerosol concentration was 130 fibers/ml > 20 µm but the RCF1 aerosol contained more short fibers (less than 20 µm long) and more nonfibrous particles. Radioactive tracer measurements carried out during a period of 90 days after exposure demonstrated an almost complete abolition of alveolar clearance in RCFI-exposed animals. With RCFIa the half-time of46Sc2O3 particles was 80 days, compared to 60 days for controls (not statistically different). Biochemical and cytological analyses were carried out in bronchoalveolar lavage at days 3, 17, 31, 94, and 365 postexposure. They revealed a more important and more persistent inflammation in RCFI-exposed animals compared to RCFIa. These observations show that the biological activity of synthetic vitreous fibers (SVFs) assessed by inhalation experiments depends not only on the chemical composition of the fiber type but also on the physical characteristics of the test sample. They are in line with results of previous studies and support the hypothesis of a synergistic effect between fibrous and nonfibrous particles. They raise questions about the interpretation of the so called RCC experiments in which the several SVFs samples tested were not prepared using the same method and differed in their physical characteristics. In particular, these differences existed especially between the RCF and MMV F samples.