Asbestos fiber analysis in 27 malignant mesothelioma cases.

The asbestos body counts per 5 gm wet lung tissue in 27 (23 pleural and 4 peritoneal) malignant mesothelioma cases derived from 19 autopsy and 8 surgical cases were, according to our own criteria, low level exposure in 13 cases (48.2%), moderate level exposure in 2 cases (7.4%), and high level exposure in 12 cases (44.4%). In our previous study on 235 consecutive autopsy cases, the low level exposure was considered to be environmental, the moderate level was secondary or blue collar, and the high level was occupational. In the present study, about half of the cases examined (44.4%, high level exposure) are closely related to some occupational asbestos exposure and the other half (48.2%) to environmental exposure. The type and size of asbestos fibers from the 12 cases of high level exposure were analyzed and the characteristics were compared with those of cases of low level exposure without lung cancer or mesothelioma. Most fibers analyzed (98%) were longer than 5 microns and thicker than 0.10 micron by our counting rules. In the control group, predominant fibers were tremolite or actinolite. In all the 11 pleural mesothelioma cases, the content of amosite fibers was significantly higher than in the controls. In one case of peritoneal mesothelioma, incipient asbestosis was found and the predominant fibers were crocidolite. It is suggested that the presence of amosite and crocidolite is linked to mesothelioma. The mean lengths of amosite and crocidolite, as detected by our resolution capabilities, were 36.0 and 20.9 microns, and the mean diameters were 0.51 and 0.27 micron, respectively. Both amosite and crocidolite fibers had high aspect ratios (94.2 and 115.4).     

Comparison of fibre types and size distributions in lung tissues of paraoccupational and occupational cases of malignant mesothelioma.

The results of analysis of mineral fibres in lung tissues from 10 paraoccupational cases of malignant mesothelioma were compared with analysis obtained from seven cases of malignant mesotheliomas that had developed in gas mask workers. Nine of the paraoccupational cases were considered to have developed their tumours because of exposure to asbestos on their husbands' working clothes and one cancer developed in the daughter of a man who had died of asbestosis. The gas mask workers had direct exposure to asbestos while working in a factory that produced military gas masks. The results of mineral fibre analysis in the paraoccupational cases were variable; six showed high crocidolite concentrations, seven raised amosite concentrations and two normal concentrations of all types of asbestos fibre measured. Chrysotile was raised in one case but crocidolite and amosite were also increased. The gas mask workers showed a consistent pattern with high crocidolite concentrations and normal or low concentrations of chrysotile and amosite. Fibre lengths for chrysotile were similar in both groups and predominantly less than 5 microns. Crocidolite fibres tended to be longer in the gas mask workers than in the paraoccupational group and longer than chrysotile in both groups. Amosite fibres tended to be more variable in width than those of chrysotile or crocidolite.     

Comparison of fibre types and size distributions in lung tissues of paraoccupational and occupational cases of malignant mesothelioma

The results of analysis of mineral fibres in lung tissues from 10 paraoccupational cases of malignant mesothelioma were compared with analysis obtained from seven cases of malignant mesotheliomas that had developed in gas mask workers. Nine of the paraoccupational cases were considered to have developed their tumours because of exposure to asbestos on their husbands' working clothes and one cancer developed in the daughter of a man who had died of asbestosis. The gas mask workers had direct exposure to asbestos while working in a factory that produced military gas masks. The results of mineral fibre analysis in the paraoccupational cases were variable; six showed high crocidolite concentrations, seven raised amosite concentrations and two normal concentrations of all types of asbestos fibre measured. Chrysotile was raised in one case but crocidolite and amosite were also increased. The gas mask workers showed a consistent pattern with high crocidolite concentrations and normal or low concentrations of chrysotile and amosite. Fibre lengths for chrysotile were similar in both groups and predominantly less than 5 microns. Crocidolite fibres tended to be longer in the gas mask workers than in the paraoccupational group and longer than chrysotile in both groups. Amosite fibres tended to be more variable in width than those of chrysotile or crocidolite.     

Inhalation carcinogenesis from various forms of asbestos

Rats, rabbits, guinea pigs, gerbils, and mice were exposed to the inhalation of chrysotile, crocidolite, or amosite for 2 years. Mean atmospheric concentrations were 47.9–50.2 mg/m³, but only 0.08–1.82% of the dusts retained fibrous morphology during the dissemination procedure which involved hammer milling. Trace contamination especially by chromium and nickel was also increased. Light microscopic fiber counts per ml chamber air were 54 (chrysotile), 1105 (crocidolite), and 864 (amosite). A fibrogenic response to these dusts was observed in all five animal species, the severity corresponding to the extent of exposure (with reaction to chrysotile frequently very slight). Gerbils developed frequent alveolar proteinosis. Mice developed spontaneous papillary carcinomas in the lungs. Disregarding the latter species, carcinogenic response to asbestos inhalation was restricted to rats and occurred in all three exposure groups. There were 2 lung cancers and 1 pleural mesothelioma after chrysotile inhalation; 4 lung cancers after crocidolite inhalation; and 1 lung cancer and 2 pleural mesotheliomas after amosite inhalation. These cases constituted 7–9% incidence of malignancy among rats with adequate survival record. Hypotheses of asbestos carcinogenesis are reviewed and it is suggested that different etiologic principles may be involved in the causation of lung cancer and of pleural mesothelioma.     

The quantitative risks of mesothelioma and lung cancer in relation to asbestos exposure

Mortality reports on asbestos exposed cohorts which gave information on exposure levels from which (as a minimum) a cohort average cumulative exposure could be estimated were reviewed. At exposure levels seen in occupational cohorts it is concluded that the exposure specific risk of mesothelioma from the three principal commercial asbestos types is broadly in the ratio 1:100:500 for chrysotile, amosite and crocidolite respectively. For lung cancer the conclusions are less clear cut. Cohorts exposed only to crocidolite or amosite record similar exposure specific risk levels (around 5% excess lung cancer per f/ml.yr); but chrysotile exposed cohorts show a less consistent picture, with a clear discrepancy between the mortality experience of a cohort of xhrysotile textile workers in Carolina and the Quebec miners cohort. Taking account of the excess risk recorded by cohorts with mixed fibre exposures (generally<1%), the Carolina experience looks uptypically high. It is suggested that a best estimate lung cancer risk for chrysotile alone would be 0.1%, with a highest reasonable estimate of 0.5%. The risk differential between chrysotile and the two amphibole fibres for lunc cancer is thus between 1:10 and 1:50.Examination of the inter-study dose response relationship for the amphibole fibres suggests a non-linear relationship for all three cancer endpoints (pleural and peritoneal mesotheliomas, and lung cancer). The peritoneal mesothelioma risk is proportional to the square of cumulative exposure, lung cancer risk lies between a linear and square relationship and pleural mesothelioma seems to rise less than linearly with cumulative dose. Although these non-linear relationships provide a best fit ot the data, statistical and other uncertainties mean that a linear relationship remains arguable for pleural and lung tumours (but not or peritoneal tumours).Based on these considerations, and a discussion fo the associated uncertainties, a series of quantified risk summary statements for different elvels of cumulative exposure are presented.     

Fibre type and concentration in the lungs of workers in an asbestos cement factory.

The predominant asbestos fibre type used in the production of asbestos cement is chrysotile. The use of asbestos in relation to fibre type in a Norwegian asbestos cement plant during 1942-80 was 91.7% chrysotile, 3.1% amosite, 4.1% crocidolite, and 1.1% anthophyllite respectively. Electron microscopy and x ray microanalysis of lung tissue samples of asbestos cement workers who had died of malignant pleural mesothelioma or bronchogenic carcinoma showed a completely inverse ratio with regard to fibre type. The percentage of chrysotile asbestos in lung tissue varied between 0% and 9% whereas the corresponding numbers for the amphiboles were 76% and 99%. These differences are discussed with respect to the behaviour of different fibre types in the human body and to the occurrence of malignant mesothelioma in this asbestos cement factory.     

Fibre type and concentration in the lungs of workers in an asbestos cement factory

The predominant asbestos fibre type used in the production of asbestos cement is chrysotile. The use of asbestos in relation to fibre type in a Norwegian asbestos cement plant during 1942-80 was 91.7% chrysotile, 3.1% amosite, 4.1% crocidolite, and 1.1% anthophyllite respectively. Electron microscopy and x ray microanalysis of lung tissue samples of asbestos cement workers who had died of malignant pleural mesothelioma or bronchogenic carcinoma showed a completely inverse ratio with regard to fibre type. The percentage of chrysotile asbestos in lung tissue varied between 0% and 9% whereas the corresponding numbers for the amphiboles were 76% and 99%. These differences are discussed with respect to the behaviour of different fibre types in the human body and to the occurrence of malignant mesothelioma in this asbestos cement factory.     

Asbestos-related disease associated with exposure to asbestiform tremolite

Tremolite is nearly ubiquitous and represents the most common amphibole fiber in the lungs of urbanites. Tremolite asbestos is not mined or used commercially but is a frequent contaminant of chrysotile asbestos, vermiculite, and talc. Therefore, individuals exposed to these materials or to end-products containing these materials may be exposed to tremolite. We have had the opportunity to do asbestos body counts and mineral fiber analysis on pulmonary tissue from five mesothelioma cases and two asbestosis cases with pulmonary tremolite burdens greater than background levels. There were no uncoated amosite or crocidolite fibers detected in any of these cases. Three patients were occupationally exposed to chrysotile asbestos; two patients had environmental exposures (one to vermiculite and one to chrysotile and talc) and one was a household contact of a shipyard worker. The tremolite burdens for the asbestosis cases were one to two orders of magnitude greater than those for the mesothelioma cases. Our study confirms the relationship between tremolite exposure and the development of asbestos-associated diseases. Furthermore, the finding of relatively modest elevations of tremolite content in some of our mesothelioma cases suggests that, at least for some susceptible individuals, moderate exposures to tremolite-contaminated dust can produce malignant pleural mesothelioma.     

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.     

Asbestos-related lung cancer and mesothelioma in Japan

In Japan, crocidolite had been used for asbestos cement pipe and spraying, and amosite had been used for building board and spraying. These two types of asbestos had stopped to use in Japan in the late 1970s. An extreme increase in imported asbestos (all 3 commercial types) was observed between 1960 and 1974. In 1960, 77,000 tons of asbestos were imported, and reached the peak as 352,316 tons in 1974. This extreme rise of asbestos imports corresponds with the recent rapid increase in mortality of malignant pleural mesothelioma. Between 1995 and 1999, an estimated mean annual death from pleural mesothelioma was about 500. The annual number of compensated occupational respiratory cancers due to asbestos exposure has also been increasing. Up to the end of March 2000, 162 cases with malignant mesothelioma and 197 cases with lung cancer were compensated. As for lung cancer, epidemiological studies are scanty in Japan. Limited environmental data of the working places in asbestos textile factories suggests that heavy asbestos exposure in the past made deaths from respiratory diseases. Less asbestos exposure will enable exposed workers to survive enough to reach cancer age. Even now smoking rate among males in Japan are over 50%. So lung cancer deaths caused by the interaction between smoking and asbestos exposure will be continuing.     

The incidence of malignant mesothelioma (1977-1996) and asbestos exposure in the population of an area neighboring Lake Iseo, northern Italy

The study was stimulated by the occurrence of malignant mesotheliomas among the workers of two adjacent factories located in Sarnico, near Lake Iseo (province of Brescia, northern Italy), one of which manufactured crocidolite and chrysotile ropes and gaskets until 1993. The aim of the study was: identification of malignant mesotheliomas occurring between 1977 and 1996 among the residents of 11 villages, which constituted the recruitment area of the work-force; estimation of the incidence of malignant pleural mesothelioma; collection of working histories of all cases to evaluate previous exposure to asbestos and radiation therapy. 21 cases of mesothelioma were detected (20 pleural, 1 peritoneal; 9 among males), and 20 were supported by histopathologic diagnosis. The incidence (x 100,000 person-years, standard: European population) was 2.5 (0.7-4.2) and 2.8 (1.2-4.3) among males and females, respectively, corresponding to a three-fold increase among males and a more than ten fold increase among women in comparison with the incidence reported by the Lombardy Cancer Registry. No cases had been exposed to radiation therapy, whereas all cases had been occupationally exposed to asbestos. Occupational exposure to asbestos had occurred in work on the production of crocidolite and chrysotile ropes and gaskets (6 males); in work in a textile factory producing cotton garments that was adjacent to and polluted by the former, where, in addition, chrysotile blankets were used for fireproofing in the weaving area and pipes were insulated using amosite-containing materials (10 cases, 6 among females); 5 cases occurred among women working in silk factories, where asbestos exposure was possible because of the presence of pipes insulated with asbestos and because women were handling temperature-controlled trays insulted with asbestos. In conclusion, the study demonstrated that the occurrence of mesothelioma was higher among females than males in the study area and that all cases of mesotheliomas had been occupationally exposed to asbestos.     

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.     

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.     

Evaluation of the pleural malignant mesothelioma patients with the relation of asbestos exposure

There has been a recent increase in the number of patients with malignant mesothelioma in parts of Japan where Naval shipyards were located during World War II. This can be attributed to asbestos exposure during work in the shipyard. We have studied eight patients who were seen between 1984 and 1986 in Kure Kyosai Hospital. All had a history of asbestos exposure, seven in a Naval shipyard. In these seven cases, the latent period between exposure and the appearance of mesothelioma was 43-49 years. Quantification of asbestos bodies in the lung indicated a high concentration in all patients, giving further weight to the concept that asbestos is an etiologic factor in the genesis of mesothelioma. The major types of asbestos fibers were crocidolite and amosite. The study of structural features of these two types may provide a clue to the pathogenesis of the disease.     

Risk of developing mesothelioma due to neighborhood exposure to asbestos]

Routes of asbestos exposure consist of occupational and non-occupational exposures, and furthermore the latter is classified as para-occupational, neighborhood or true general environmental exposure. Consequently, in order to evaluate health risk caused by neighborhood exposure to asbestos, it is necessary to exclude risk due to the other exposure routes from overall risk. We reviewed epidemiological studies on the relationship between neighborhood asbestos exposure and risk of mesothelioma. In studies on a crocidolite mine in South Africa and a chrysotile mine in Canada, occupational exposure was not excluded. In studies on a crocidolite mine in Australia and an asbestos manufacturing factory in U.S.A., risk caused by non-occupational exposure was evaluated, but the risk was not classified as para-occupational and neighborhood exposures. In a study on an asbestos cement factory in Italy, first, occupational and para-occupational exposures were excluded, and next, the incidence rate of mesothelioma in neighborhood residents was calculated, so that risk caused by neighborhood exposure could be evaluated. In case-control studies in Italy, South Africa, three European countries and the U.K., risks caused by occupational, para-occupational and neighborhood exposures were evaluated separately. As a whole, relative risk (RR) of neighborhood exposure in crocidolite and amosite mines was about 10 to 30 and RR in major asbestos factories was about 5 to 20. On the other hand, statistically significant RR of neighborhood exposure was not observed in chrysotile mines and some asbestos facilities.     

Characterization of asbestos fibers in lungs and mesotheliomatous tissues of baboons following long-term inhalation

Changes in the dimensions of inhaled asbestos fibers in the lung and translocation of intrapulmonary asbestos fibers into mesothelial tissues were investigated in 17 baboons (5 exposed to amosite, 4 to chrysotile, 5 to crocidolite, and 3 unexposed). The animals received different cumulative doses of asbestos by inhalation, followed by varying recovery periods (0–69 months). All asbestos types induced pulmonary asbestosis with severity directly related to the cumulative dose. There were a larger number of asbestos bodies in the lung of the amphibole-exposed animals than in those exposed to chrysotile. A tissue burden study, using transmission electron microscopy on 25-μm paraffin sections, ashed in a low-temperature asher, was performed. Intrapulmonary amosite fibers were shorter in geometric mean length compared with a standard amosite sample (UICC) (3.3 μm). In explanation, it was considered that long fibers might not be able to reach the lower respiratory tract and/or long fibers might be fragmented into shorter fibers. Further, in the amosite-exposed group, the mean length of intrapulmonary fibers increased with the extension of recovery period, suggesting that shorter fibers had been cleared from the lung. The chrysotile standard sample (UICC) had a shorter geometric mean length (1.1 μm) than amosite. The mean length of intrapulmonary chrysotile did not noticeably change with the extension of inhalation and recovery periods; however, the mean width decreased with the extension of these periods. This finding strongly suggested that separation of thick chrysotile fibers had occurred in the lung. The crocidolite standard sample (Transvaal) had a shorter geometric mean length (1.4 μm) than amosite. The mean length of intrapulmonary crocidolite fibers increased with the extension of inhalation and recovery periods, suggesting that shorter fibers had been cleared from the lung during both the inhalation and recovery periods. There was no specific tendency of size distribution among four distinct interstitial locations (peribronchiolar, alveolar septal, subpleural, and interlobular connective tissue) within the same lung exposed to either amosite, chrysotile or crocidolite. In four animals, malignant mesothelioma developed in the pleura (2 amosite and 1 UICC crocidolite) and the peritoneum (1 UICC crocidolite). Asbestos fibers were found in the mesotheliomas. Their size distribution in mesotheliomatous tissue and lung was not significantly different in two animals, but the fibers were shorter and thinner in another two. The presence of fibers in the neoplasms was confirmed, and translocation of fibers from the lung into the pleura or the peritoneum was strongly suggested. © 1993 Wiley-Liss, Inc.     

Airborne fibre concentrations and lung burden compared to the tumour response in rats and humans exposed to asbestos

The excess risk of tumours exposed to asbestos were previously compared with the results of rat inhalation experiments. It could be demonstrated that humans at the workplace suffer from a tumour risk at fibre concentrations which are 300 times lower than those needed in the rat inhalation model to produce the same risk. However, the estimation of human risk was based on the study of workers at a chrysotile textile factory, whereas animal experimental results were related to exposure to amphiboles. Since for this comparison the risk of cancer due to exposure to amosite or crocidolite fibres at the workplace is of interest, quantitative exposure-response relationships for lung cancer and mesothelioma for the white workforce of South African amosite and crocidolite mines were discussed. On comparing the risk of lung cancer in this study with the risk of lung cancer for chrysotile textile workers, it can be concluded, that the risk of lung cancer and mesothelioma from crocidolite and amosite was higher than in the chrysotile textile factory.It could be also demonstrated, on the basis of a study of the lung burden of mesothelioma cases and of controls, that a significantly increased odds ratio of about 5 was established at amphibole concentrations of between 0.1 and 0.2 f μg⁻¹ dry lung (WHO fibres longer than 5 μm from TEM analysis). On the other hand, carcinogenic response was observed at a fibre concentration 6000 times higher in animal inhalation experiments with crocidolite asbestos (SEM analysis of WHO fibres). As a result of these findings, it has been concluded that inhalation studies in rats are not sufficiently sensitive for the detection of hazards and risks to humans exposed to man-made fibres.     

Pulmonary mineral fibers after occupational and environmental exposure to asbestos in the Russian chrysotile industry

BACKGROUND: As an indicator of occupational, domestic, and environmental exposure, the level and type of asbestos fibers were determined from lung tissue samples of workers and residents who resided in the area of the world's largest asbestos mine at Asbest, Russia. METHODS: Electron microscopy was used to analyze and measure the concentration of asbestos fibers in a series of 47 autopsies at the Asbest Town Hospital. Work histories were obtained from pathology reports and employment records. RESULTS: In 24 chrysotile miners, millers, and product manufacturers, the pulmonary concentrations of retained fibers (over 1 microm in length) were 0. 8-50.6 million f/g for chrysotile, and < 0.1-1.9 million f/g for amphiboles (tremolite and anthophyllite). The concentrations were lower in 23 persons without any known occupational contact with asbestos; 0.1-14.6 million f/g for chrysotile, and < 0.1-0.7 million f/g for amphiboles. On average, 90% of all inorganic fibers were chrysotile, and 5% tremolite/anthophyllite. No amosite or crocidolite fibers were detected in any of the samples. CONCLUSIONS: The mean and range of pulmonary chrysotile concentrations were about the same as reported previously from the Canadian mining and milling industry. In the Russian samples, the mean concentration of tremolite fibers were less by at least one order of magnitude. Occupational contact was the most important source of asbestos exposure.     

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.