Malignant mesothelioma and duration of asbestos exposure: Correlation with tissue mineral fibre content

Among 441 cases of malignant mesothelioma in the author's files, there were 324 for whom reliable information was available regarding the duration of exposure to asbestos. Included were 298 pleural and 26 peritoneal mesotheliomas. The mean duration of exposure to asbestos was 23 ± 14 years for all cases, and was not different for the pleural and peritoneal groups. Lung tissue was available for analysis of mineral fibre content in 94 cases. Linear regression analysis showed a significant correlation between duration of exposure and asbestos bodies per gramme of wet lung as determined by light microscopy, and between duration of exposure and total uncoated fibres (5 μm or greater in length) as well as commercial amphibole fibres per gramme as determined by scanning electron microscopy (P < 0.05). Individuals with direct exposures had on average higher asbestos contents than patients with indirect exposures. Furthermore, for each duration of exposure, shipyard workers had on average higher asbestos contents than non-shipyard workers (P < 0.05). Mesotheliomas are associated with a wide range of durations of exposure to asbestos and pulmonary asbestos burdens, and there is a rough correlation between duration of exposure and pulmonary commercial amphibole content.     

Pleural plaques and exposure to mineral fibres in a male urban necropsy population.

OBJECTIVES--The study aimed to evaluate the risk of pleural plaques according to the degree of past exposure to asbestos, type of amphibole asbestos, and smoking, as well as to estimate the aetiologic fraction of asbestos as a cause of plaques among urban men. METHODS--The occurrence and extent of pleural plaques were recorded at necropsies of 288 urban men aged 33 to 69 years. The pulmonary concentration of asbestos and other mineral fibres was analysed with scanning electron microscopy. The probability of past exposure was estimated from the last occupation. RESULTS--Pleural plaques were detected in 58% of the cases and their frequency increased with age, probability of past occupational exposure to asbestos, pulmonary concentration of asbestos fibres, and smoking. The risk of both moderate and widespread plaques was raised among asbestos exposed cases, and the risk estimates were higher for widespread plaques than for moderate plaques. The age adjusted risk was higher for high concentrations of crocidolite/amosite fibres than for anthophyllite fibres. The aetiologic fraction of pulmonary concentration of asbestos fibres exceeding 0.1 million fibres/g was 43% for widespread plaques and 24% for all plaques. The median pulmonary concentrations of asbestos fibres were about threefold greater among cases with widespread plaques than among those without plaques. No increased risk of pleural plaques was associated with raised total concentrations of non-asbestos fibres. CONCLUSION--The occurrence of pleural plaques correlated closely with past exposure to asbestos. The risk was dependent on the intensity of exposure. Due to methodological difficulties in detecting past exposures to chrysotile and such low exposures that may still pose a risk of plaques, the aetiologic fractions calculated in the study probably underestimate the role of asbestos.     

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.     

Assessment of asbestos exposure, mortality study, and health intervention in workers formerly exposed to asbestos in a small factory making drying machines for textile finishing and the paper mill industry in Pistoia, Italy

BACKGROUND AND OBJECTIVES: Three malignant pleural mesotheliomas occurred among workers of a small factory that manufactured drying machines for the textile and paper mill industries using asbestos cement (crocidolite, amosite and chrysotile) as insulating panels. The Occupational Medicine Unit of the Local Health Unit of Pistoia, Italy, carried out an intervention programme in the plant in order to 1) assess past asbestos exposure via analysis of the fibre content of samples from drying machines, and of dust samples collected in the factory. Information on the characteristics of occupational exposure was also collected; 2) investigate cancer mortality by means of a mortality study of the employees and, 3) carry out a health intervention programme in workers formally exposed to asbestos in the past. METHODS: Samples from the drying machines and dust samples collected in the factory were analysed using X-ray diffractometric methods. Information on the characteristics of occupational exposure were collected by interviewing plant workers. Two-hundred and fifty employees who had worked in the factory between 1962 and 2000 were included in the mortality study. Follow-up was performed from 1962 to 2002. Health intervention in workers exposed to asbestos in the past involved general practitioners and occupational physicians (first level medical examinations); pneumologists and radiologists (second level medical examinations) of the local health unit. RESULTS: Asbestos fibres were found both in samples from drying machines and in dust samples collected in the factory. Interviews with workers showed that asbestos exposure varied considerably. The SMR for mesothelioma and lung cancer in 234 male workers were 37.0 (95%CI: 4.47-130.0), and 1.29 (95%CI: 0.26-3.78), respectively, based on mortality rates for Tuscany region. Sixty-two workers underwent first level medical examinations; 57 second level examinations. Chronic obstructive lung disease was found in 3 workers; restrictive lung disease was found in 3 employees, one of whom had pleural plaques. CONCLUSIONS: Further investigation is needed in order to identify unknown asbestos exposures in small metal engineering factories.     

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.     

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.     

Pleural malignant mesothelioma and non-occupational exposure to asbestos in Casale Monferrato, Italy.

OBJECTIVES--To assess and quantify the occurrence of pleural malignant mesotheliomas in people who neither experienced occupational exposure to asbestos nor were married to (or known to live with) workers exposed to asbestos in the workplace. The study was conducted in the area of the local health authority of Casale Monferrato, in north western Italy, where a large factory that produced asbestos cement was active up to 1985. No other major activities related to asbestos have ever been present in the area. METHODS--A retrospective survey covering the period 1980 to 1991 identified 126 incident pleural malignant mesotheliomas histologically diagnosed among residents in the local health authority (population at the 1981 census 98,000). Submission of 83 of 95 cases diagnosed during 1980-9 for revision by a panel of five expert pathologists led to the exclusion of 21. The 31 cases diagnosed in 1990-1 were not submitted for revision. For 64 of the 105 retained cases, information derived from different sources (rosters of the employees in the asbestos cement factory dated back to 1907, list of their spouses, clinical records) did not suggest occupational or paraoccupational exposure to asbestos. RESULTS--Incidence excludes cases for which there was some suggestion of occupational or paraoccupational exposure to asbestos. Incidence of histologically confirmed malignant mesothelioma among residents in the local health authority (annual x 100,000; age adjusted) was 4.2 in men and 2.3 in women (based on 26 and 18 cases respectively). In both sexes, rates in 1985-9 were higher than in the previous quinquennium. Corresponding estimates for 1990-1 (based on unrevised diagnoses) suggest similar rates in men and women. CONCLUSION--Rate ratios which are four to six times those measured by conventional Italian cancer registries can hardly be totally explained by bias produced by lack of recognition of occupational or paraoccupational exposure. The problem of proving this type of negative data is common to other circumstances of alleged cancer clusters of environmental (non occupational) origin.     

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.     

Urinary fibres in occupational exposure to asbestos

Urine samples from 10 workers from an asbestos cement factory and from a control group of 10 workers from a foundry, were obtained; drastic precautions were taken to avoid contamination. Each urinary mineral fibre was sized and identified by transmission electron microscopy. Results show that contamination problems encountered by other authors have been overcome and that the workers exposed to chrysotile appear to excrete more chrysotile fibres, but that this difference is not statistically significant. Possibly only a few of the exposed workers are significantly exposed to asbestos, the overall exposure level being very low. The degradability of chrysotile fibres in biological fluids or the retention of fibres in some organ could explain the lack of apparent correlation between exposure and urinary concentration. Unexpectedly high concentrations of crocidolite fibres of unknown origin were detected in both groups of workers.     

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.     

Mesotheliomas among Italians,returned to the home country,who worked when migrant at a cement-asbestos factory in Switzerland

OBJECTIVES: To report the occurrence of mesotheliomas in Italy among subjects who worked, when migrant, at a cement-asbestos factory in Niederurnen, Switzerland, and had resettled to the home country. METHODS: Information about the disease and on the working history of subjects was collected by regional mesothelioma registries. Only cases diagnosed by means of histo-pathological examinations have been considered here. RESULTS: 15 mesotheliomas (13 pleural, 2 perithoneal; 12 among males, 3 among females) have been identified among Italians, who had worked at the factory. None of them had other occupational exposure to asbestos. The majority was living in the Veneto Region (North East of Italy), and in Puglia (Southern Italy). CONCLUSIONS: Exposure to asbestos at this factory has already caused an important number of occupational cancers among the employees, a large fraction being constituted of migrants. In order to avoid under-estimation of risks and to allow compensation, diseases which occur among foreign workers returned to their home country should be evaluated. Migration for work is at the genesis of asbestos-related mesotheliomas now occurring in Italy.     

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.     

Pleural malignant mesothelioma in Tuscany, Italy (1970-1988): II. Identification of occupational exposure to asbestos.

Following the finding of an unexpected cluster of mesotheliomas in textile workers, a surveillance system of malignant mesotheliomas was implemented in the region of Tuscany, Italy. This article reports on the investigation of 124 cases of mesothelioma diagnosed and reviewed by the Institutes of Morbid Anatomy and Histopathology at the Universities of Florence, Pisa, and Siena between 1970 and 1988. A complete occupational and asbestos exposure history was assessed through a semi-structured questionnaire directly administered to resident cases of Tuscany or, if deceased, to their closest living relatives, for a total of 100 interviews. The hypothesis of past occupational asbestos exposure was verified and documented. Seventy-two cases have been classified as occupationally exposed to asbestos; four were classified in the category of "possible domestic" exposure to asbestos. For two others, the role of other risk factors was stressed, and for 22 cases, either no asbestos exposure was found or the available data were not adequate to define it. The present study allowed identification of some unknown or scarcely known occupational asbestos exposures in the study area.     

Further follow-up study of workers from an asbestos cement factory.

A further follow-up traced 1970 workers employed at an asbestos cement factory for at least six months between 1936 and 1977. At the beginning of this period some crocidolite was used in the factory but by the end of 1936 chrysotile had become the only type of asbestos in use. Only 378 women were employed during the period concerned, and of the 30 who had died, none had a cause of death that is generally associated with exposure to asbestos. The mortality experience of the men was examined separately for all workers, all workers alive after 15 or more years after first exposure, and a smaller group of workers who were employed in 1935-6 and may have been exposed to crocidolite. In none of the three groups was there an appreciably raised standardised mortality ratio (SMR) for the causes of death investigated. These were: all causes, all neoplasms, cancers of the lung and pleura, and cancers of the gastrointestinal tract. An excess of lung cancers noted in the first follow-up study in 1964 was not found in this study. Two pleural mesotheliomas were identified but in both cases the men had worked at the factory before 1936 and therefore had been exposed to crocidolite. No cancers of the larynx were found.     

Mineral fibre analysis and routes of exposure to asbestos in the development of mesothelioma in an English region

OBJECTIVES: To compare the concentrations of inorganic fibres in the lungs in cases of mesothelioma and controls: to determine whether concentrations of retained asbestos fibres differ with the different exposures identified from interview; and to investigate the existence of a cut off point in concentrations of asbestos fibres that indicates occupational exposure. METHODS: Case-control study; 147 confirmed cases of mesothelioma and 122 controls identified from deaths occurring in four districts of Yorkshire between 1979 and 1991. Surviving relatives were interviewed to determine lifetime exposure history to asbestos. Mineral fibre analysis was carried out on lung tissue from postmortem examinations. RESULTS: Odds on high concentrations of retained asbestos fibres were greater in cases than controls. After excluding subjects with occupational and paraoccupational exposure, the odds on high concentrations were still greater in cases than controls, but only significantly so for amphiboles. There was only a weak relation between probability of occupational exposure to asbestos and concentrations of retained asbestos fibres, and no significant difference in fibre concentrations was found between subjects who had been exposed to asbestos through different routes: these comparisons were only based on small groups. There was considerable overlap in concentrations of retained asbestos fibres between cases and controls with and without histories of occupational exposure. CONCLUSIONS: The study has confirmed previous results of higher concentrations of asbestos fibres in cases than controls, and has shown that this is still found in subjects with little evidence of occupational and para-occupational exposure. The overlap in concentrations of retained asbestos for different groups of subjects did not suggest a clear cut of value.

 

     

Asbestos-related mesothelioma: factors discriminating between pleural and peritoneal sites.

Up to the end of 1980, 144 confirmed cases of mesothelioma were identified among employees of an organisation using asbestos in manufacturing and insulation. The primary site was peritoneal in 74 cases, pleural in 66, and undetermined in four. All employees had been exposed to amphibole asbestos, and evidence from different factories confirmed the predominant role of crocidolite in the production of mesothelioma. The ratio of pleural to peritoneal sites showed a continuous change when related to the year of first exposure, varying from 5:1 pleural to peritoneal before 1921 to 1:3 after 1950. The strong temporal relationship appeared to reflect progressive dust suppression, including the non-fibrous dusts present in insulation materials and perhaps also the degree to which the fibres had been opened. Other predisposing factors were related to the degree of individual exposure, the peritoneal site being associated preferentially with longer and heavier exposures.     

Fibre distribution in the lungs and pleura of subjects with asbestos related diffuse pleural fibrosis.

The lungs from 13 cases of diffuse pleural fibrosis associated with a history of exposure to asbestos were examined. Samples were taken from the visceral pleura and central and subpleural zones of the lungs for histopathological and mineralogical studies. The fibre type, size, and number were estimated for each of these regions by transmission electron microscopy and energy dispersive x ray analysis. Amphibole fibre counts were raised when compared with a non-occupationally exposed group and matched those seen in cases of pleural plaques, mild asbestosis, and mesothelioma. A wide case to case variation of distribution was seen. No significant difference was apparent between central and subpleural zones, whereas low asbestos counts were found in the pleura; these were mainly short chrysotile fibres. Within the lungs more (45%) of the longer (greater than 4 microns) and thinner (less than 0.25 micron) amphibole fibres were retained in keeping with other studies implicating such fibre profiles in the pathogenesis of asbestos related disease.     

Asbestos-related mesothelioma: factors discriminating between pleural and peritoneal sites

Up to the end of 1980, 144 confirmed cases of mesothelioma were identified among employees of an organisation using asbestos in manufacturing and insulation. The primary site was peritoneal in 74 cases, pleural in 66, and undetermined in four. All employees had been exposed to amphibole asbestos, and evidence from different factories confirmed the predominant role of crocidolite in the production of mesothelioma. The ratio of pleural to peritoneal sites showed a continuous change when related to the year of first exposure, varying from 5:1 pleural to peritoneal before 1921 to 1:3 after 1950. The strong temporal relationship appeared to reflect progressive dust suppression, including the non-fibrous dusts present in insulation materials and perhaps also the degree to which the fibres had been opened. Other predisposing factors were related to the degree of individual exposure, the peritoneal site being associated preferentially with longer and heavier exposures.