Experimental asbestos carcinogenesis

Laboratory rodents were exposed to one of three mineralogical types of asbestos dust, amosite, crocidolite, or chrysotile. Inhalation exposures were accomplished in chambers where ballmilled specimens of these dusts were disseminated for 4 hours daily, 4 days weekly, at a mean atmospheric concentration of about 48 mg/m³. Additional animals were injected with these dusts intratracheally, intrapleurally, or intraperitoneally. Histopathologic studies showed a fibrotic reaction in all species to all three types of dusts, with amosite provoking the strongest such response especially in guinea pigs. Two pulmonary cancers were produced in rats exposed to the inhalation of crocidolite. Local injection into the pleural or peritoneal cavities caused 5 mesotheliomas in rats after chrysotile treatment and 6 mesotheliomas in rats and rabbits after crocidolite treatment. Guinea pigs and hamsters developed no tumors in this experiment, and with the dose used, there were no tumors in any species in the amosite group.     

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.     

Asbestos as reference material for fibre-induced cancer

The objective of this paper is to review published data on the carcinogenicity of asbestos fibres with regard to the elucidation of a potential risk originating from exposure to man-made vitreous fibres (MMVF). Steps in the comparison of the two fibre classes are characterization of the fibres, pulmonary deposition, biodurability and biopersistence and a review of the cancer risk from asbestos fibres after inhalation in rats and humans. Various dust samples of chrysotile, crocidolite, and amosite were used as reference materials in studies with experimental animals. These fibres are normally thinner and shorter than MMVF. These differences in dimensions cause differences in the deposition in the airways. In addition, significant dissimilarities exist in the deposition pattern between rats and humans. Data from biopersistence studies show that focusing only on fibres longer than 20 wm and using weighted half-time for a characterization of risk may be misleading. Inhalation experiments with rats need fibre exposure concentrations over 100 times higher to match the lung cancer risk of asbestos workers, and about 1000 times higher to reach the same mesothelioma risk. Also, the striking difference between the low lung burden of amphibole fibres of asbestos workers with mesothelioma and the more than 1000 times higher lung burden of rats with a low mesothelioma risk demonstrates the low sensitivity of the inhalation test model for the carcinogenic potency even of crocidolite fibres. It can be concluded that the rat inhalation model is also not sensitive enough to predict the cancer risk of other fibre types for humans.     

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.     

Malignant pleural mesothelioma in parts of Japan in relationship to asbestos exposure

Malignant pleural mesothelioma is induced by asbestos exposure. Many reports have described this situation in America and European countries, but a few have been published in Japan. In this study malignant pleural mesothelioma cases in hospitals located in an area facing the Seto Inland Sea were evaluated. A total of 106 patients were examined with 100 patients having had occupational exposure to asbestos and 6 patients without such histories of asbestos exposure. Ninety seven were male and 9 were female. Ages ranged from 41 to 87 yr with mean of 64.8+/-5.3 yr. Thirty seven cases showed epithelial type of tumor, 25 biphasic type and 15 showed sarcomatous. The remaining 23 cases had insufficient evidence for typing the tumor. The mean survival rate for all cases was 9.2+/-11.6 months. Fifty-one patients had occupational histories of shipyard work, 16 patients worked in asbestos cement piping, and the remainder were employed in miscellaneous jobs related asbestos exposure. The duration of asbestos exposure ranged up to 20 yr or longer with the mean of 17.2+/-8.9 yr and the average latent period for the occurrence of malignant pleural mesothelioma was more than 31 yr with the mean of 37.0+/-13.3 yr. Quantification of asbestos bodies in the lungs indicated a high concentration in most patients and the major types of asbestos fibers were crocidolite and amosite. Six cases appeared after exposure to chrysotile. These results indicated that ninety four percent of malignant pleural mesothelioma appeared due to the exposure to asbestos including crocidolite and amosite. The remainder may be blamed on exposure to chrysotile.     

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.     

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.     

Mortality of workers manufacturing friction materials using asbestos

A mortality (1942-80) study was carried out on 13460 workers of a factory producing friction materials. The only type of asbestos used was chrysotile, except during two well-defined periods before 1945 when crocidolite was used, and over 99% of the population was traced. Compared with national death rates there were no detectable excesses of deaths due to lung cancer, gastrointestinal cancer, or other cancers; 11 deaths were due to pleural mesothelioma. A case-control study was carried out on deaths due to mesothelioma; this showed that eight workers had been exposed to crocidolite and another was possibly exposed intermittently to crocidolite. The other two had been employed for most of their working lives outside the factory, and their mesotheliomas could not be definitely attributed to exposure to chrysotile. Limiting the study to cases and controls who had exposure to 5 fibres/ml of chrysotile asbestos it was found that five of the six cases compared with two of the 10 controls had also been exposed to crocidolite. The probability (1:36) of this occurring were there no association with crocidolite is most unlikely. A case-control study was also carried out on deaths due to lung cancer and gastrointestinal cancer to investigate the dose-response relationships between these tumours and exposure to chrysotile. Measured and estimated fibre concentrations were available for the different jobs over the period of the study. No dose-response relationships were observed, but the exposures were low with only 5% of men accumulating 100 fibre-years/ml. The experience at this factory over a 40-year period showed that chrysotile asbestos was processed with no detectable excess mortality.     

Mortality of workers manufacturing friction materials using asbestos.

A mortality (1942-80) study was carried out on 13460 workers of a factory producing friction materials. The only type of asbestos used was chrysotile, except during two well-defined periods before 1945 when crocidolite was used, and over 99% of the population was traced. Compared with national death rates there were no detectable excesses of deaths due to lung cancer, gastrointestinal cancer, or other cancers; 11 deaths were due to pleural mesothelioma. A case-control study was carried out on deaths due to mesothelioma; this showed that eight workers had been exposed to crocidolite and another was possibly exposed intermittently to crocidolite. The other two had been employed for most of their working lives outside the factory, and their mesotheliomas could not be definitely attributed to exposure to chrysotile. Limiting the study to cases and controls who had exposure to 5 fibres/ml of chrysotile asbestos it was found that five of the six cases compared with two of the 10 controls had also been exposed to crocidolite. The probability (1:36) of this occurring were there no association with crocidolite is most unlikely. A case-control study was also carried out on deaths due to lung cancer and gastrointestinal cancer to investigate the dose-response relationships between these tumours and exposure to chrysotile. Measured and estimated fibre concentrations were available for the different jobs over the period of the study. No dose-response relationships were observed, but the exposures were low with only 5% of men accumulating 100 fibre-years/ml. The experience at this factory over a 40-year period showed that chrysotile asbestos was processed with no detectable excess mortality.     

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.     

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 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.     

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).     

Asbestosis in Experimental Animals

Previous animal experiments with asbestos dusts have been almost entirely confined to chrysotile asbestos. It was, therefore, decided to investigate the effects of mill dusts from the three types of asbestos that are produced commercially in South Africa, namely chrysotile, amosite, and crocidolite. Chrysotile and amosite samples were relatively pure while in contrast the crocidolite dust was found to consist mainly of ironstone and silica and contained less than 10% of asbestos fibre. Guinea-pigs, Vervet monkeys, and rabbits were exposed to these dusts. The results were assessed on histological criteria. It was found that, in all three species of animals, the amosite dust produced more marked lesions than the chrysotile and that these lesions occurred at an earlier period. It was not possible to compare these lesions with those caused by the crocidolite dust, owing to its impure nature. It was noted, however, that this dust caused severe lesions in guinea-pigs and monkeys and that the animals in this group succumbed more readily to respiratory infections.     

Clinical study of asbestos-related lung cancer

We analyzed the characteristics of 120 patients of primary lung cancer supposed to be induced by exposure to asbestos. Most of 120 patients were male and the age ranged from 47 to 87 years with a median of 70 years. No particular tendency was observed in the histological types of the lung cancer in 120 patients. Forty of the 120 patients were heavy smokers. When the occupational history was analyzed, most of the patients had been exposed to asbestos in former Japanese naval shipyard, commercial shipyards, construction industry and ironworks. The term of asbestos exposure was 2 to 60 years with a median 27 years. Lung cancers appeared after 15 to 69 years with a median 43 years from the initial exposure to asbestos. Lung cancer was accompanied by asbestosis in 35 patients and by pleural plaques in 77. Twenty-two patients had both asbestosis and pleural plaques. The number of asbestos bodies per 5 g wet lung tissue for 72 patients whose lung tissues obtained from autopsy or surgery was more than 150 bodies which meant the number of occupational asbestos exposure. As for the kinds of asbestos fibers of 32 patients, 14 patients exposed to crocidolite, 10 patients to amosite and 8 patients to chrysotile.     

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.     

The mortality of amphibole miners in South Africa, 1946-80.

A cohort was established in 1981 of all 7317 white male employees in the amosite and crocidolite mines in South Africa whose names had appeared in the personnel records (initiated between 1945 and 1955) of the major companies. Some of the men had been employed as early as 1925, but only 8% had had more than 10 years of service. Three subcohorts were defined: 3212 men whose only exposure to asbestos was to amosite; 3430 exposed to crocidolite; and 675 to both amphiboles. No deaths or losses to view occurred before 1946, and 5925 men (81%) were known to be alive at the end of 1980. Losses to view numbered 167 (2%), and there had been 1225 deaths (17%), an excess of 331 over the number of deaths expected on the basis of the mortality of all white South African males. The fibre related excesses were of mesothelioma, lung cancer, and other respiratory diseases, but there were other excesses perhaps mainly related to socioeconomic factors including lifestyle. When cause of death was determined according to "best evidence" (after study of clinical, radiological, biopsy, and necropsy reports in conjunction with the death certificate), there were 30 deaths due to mesothelioma (22 pleural, six peritoneal, two other) and 65 due to cancer of trachea, bronchus, and lung. Various analyses of these deaths showed that crocidolite had higher toxicity than amosite for lung cancer and this was most pronounced for mesothelioma; there can now be no question that crocidolite is far more dangerous than amosite at least in so far as mesothelioma is concerned. Nevertheless, crocidolite induced mesothelioma appeared only in men who had been exposed for long periods, at least 12 months, but on average about 15 years.     

The mortality of amphibole miners in South Africa, 1946-80.

A cohort was established in 1981 of all 7317 white male employees in the amosite and crocidolite mines in South Africa whose names had appeared in the personnel records (initiated between 1945 and 1955) of the major companies. Some of the men had been employed as early as 1925, but only 8% had had more than 10 years of service. Three subcohorts were defined: 3212 men whose only exposure to asbestos was to amosite; 3430 exposed to crocidolite; and 675 to both amphiboles. No deaths or losses to view occurred before 1946, and 5925 men (81%) were known to be alive at the end of 1980. Losses to view numbered 167 (2%), and there had been 1225 deaths (17%), an excess of 331 over the number of deaths expected on the basis of the mortality of all white South African males. The fibre related excesses were of mesothelioma, lung cancer, and other respiratory diseases, but there were other excesses perhaps mainly related to socioeconomic factors including lifestyle. When cause of death was determined according to "best evidence" (after study of clinical, radiological, biopsy, and necropsy reports in conjunction with the death certificate), there were 30 deaths due to mesothelioma (22 pleural, six peritoneal, two other) and 65 due to cancer of trachea, bronchus, and lung. Various analyses of these deaths showed that crocidolite had higher toxicity than amosite for lung cancer and this was most pronounced for mesothelioma; there can now be no question that crocidolite is far more dangerous than amosite at least in so far as mesothelioma is concerned. Nevertheless, crocidolite induced mesothelioma appeared only in men who had been exposed for long periods, at least 12 months, but on average about 15 years.