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Projections of cancer risks attributable to future exposure to asbestos.

To assess the maximum possible impact of further government regulation of asbestos exposure, projections were made of the use of asbestos in nine product categories for the years 1985-2000. A life table risk assessment model was then developed to estimate the excess cases of cancer and lost person-years of life likely to occur among those occupationally and nonoccupationally exposed to the nine asbestos product categories manufactured in 1985-2000. These estimates were made under the assumption that government regulation remains at its 1985 level. Use of asbestos in the nine product categories was predicted to decline in all cases except for friction products. The risk assessment results show that, although the cancer risks from future exposure to asbestos are significantly less than those from past exposures, in the absence of more stringent regulations, a health risk remains.

Actuarial Analysis↗

Case study 1: asbestos--the TLV approach.

A review of the control of carcinogenic exposures using the TLV approach presents a prospect of limited effectiveness. With asbestos, as with any carcinogen, no threshold is known below which no health effect may be manifest. At best, we have only limited dose-response information at levels much above those of practical concern. In the case of asbestos, current exposures can only be described crudely at any level of exposure, and health effects are only known for past high, but ill-defined, exposures. Limited information exists on the effects of synergistic interactions with other materials. The current U.S. TLV, based on data concerned with occurrence of asbestosis, has not been evaluated with regard to possible effectiveness in the prevention of asbestos cancer. Yet cancer is the heart of the asbestos-hazard problem. Finally, enforcement of the existing TLV, especially for asbestos has been limited, frequently absent, and often ineffective. Workers are exposed in many situations to levels much above the current standard. As discouraging as this picture may seem, a TLV can be useful for stimulating the development and application of engineering-control procedures. The application of these procedures, however, must be specified and mandated in future standards to lower worker exposures to the minimum commensurate with existing technology. As technology is developed that makes lower exposure levels possible in a large part of the industry, TLVs should be reduced to take advantage of that technology.

Air Pollutants, Occupational↗

Asbestos exposure: factors associated with excess cancer and respiratory disease mortality.

A cohort of 1075 men who completed their working lifetimes with an asbestos company, worked at a facility in the United States, and retired with a company pension during the period 1941--67 was updated for deaths through 1973. The average length of employment was 25 years, and all had been exposed to asbestos dust. Respiratory cancer and pneumoconiosis-pulmonary fibrosis mortalities were examined in relation to cumulative dust exposure and to other factors after taking into account cumulative dust exposure. Men who worked in the production of asbestos cement pipe exhibited a higher risk of respiratory cancer, as did men with some crocidolite asbestos exposure. Because these two groups overlap, we could not be certain that crocidolite asbestos was responsible for the increased risk. Men working in general plant maintenance displayed a striking lack of deaths due to pneumoconiosis-pulmonary fibrosis, as compared with production workers and with maintenance personnel assigned to specific departments. Five mesothelioma deaths were observed at age 65 and over. Three of these deaths occurred during the period 1970--3.

Aged↗

Analysis of asbestos fibers in lung parenchyma, pleural plaques, and mesothelioma tissues of North American insulation workers.

Asbestos fibers and ferruginous bodies (FBs) in lung parenchyma, lung cancer tissues, pleural plaques, and pleural and peritoneal mesothelioma tissues from 13 North American insulation workers were analyzed and quantified using an analytical transmission electron microscope and a polarized microscope. Diseases from which these workers suffered included asbestosis, lung cancer, and mesothelioma. They had been occupationally exposed to materials containing chrysotile and amosite; their pathological diagnoses, occupational and cigarette smoking histories, and clinical summaries have been reported. Large numbers of FBs were found in the lungs and small numbers found in extrapulmonary sites. Most of the FBs had cores of amosite fibers. In all instances, lung parenchyma and lung cancer tissues showed chrysotile and amosite fibers in high concentrations (63.1 x 10(6) and 150.2 x 10(6) fibers/g dry tissue as mean values, respectively). Crocidolite fibers were seen in seven of the 13 cases, but in much smaller numbers. Other amphiboles were rarely found. In pleural plaques and in pleural and peritoneal mesothelioma tissues, amosite fibers were markedly fewer in number, whereas chrysotile fibers were seen in similar numbers as in the lungs. No significant differences in the size distribution of asbestos fibers were seen in the different sites. However, the mean widths of chrysotile fibers were thinner than those of amosite fibers. These results strongly suggest that translocation of inhaled asbestos fibers from the lung to other tissues, such as the pleura and the peritoneum, occurs frequently, and that chrysotile may be more actively translocated from the lung, compared to amosite or amphibole asbestos. The likelihood of translocation seems to be strongly related to the thinness of the fibers. Translocated chrysotile fibers may play an important role in the induction of either malignant mesothelioma and/or hyaline plaques, since the asbestos fibers detected in both these sites were mainly chrysotile.

Adult↗

The clinical relevance of asbestos-induced pleural fibrosis.

Asbestos-induced pleural fibrosis is the most common radiographic abnormality among asbestos-exposed persons. Circumscribed pleural plaques and diffuse pleural thickening account for more than 90% of the asbestos-induced chest wall abnormalities, and their prevalence is expected to increase for the next 15 to 20 years. Several investigators have recently found that pleural plaques and diffuse pleural thickening independently contribute to the development of restrictive lung function. The work presented in this paper indicates that asbestos-induced pleural fibrosis is also associated with evidence of interstitial lung abnormalities, even among those with normal parenchyma on chest X-ray film. These parenchymal abnormalities include an increased percentage of lymphocytes on bronchoalveolar lavage and an increase in the interstitial changes observed on high-resolution chest computerized tomography (HRCT) scan. However, neither a lymphocytic alveolitis nor an interstitial parenchymal fibrosis influenced the relationship between pleural fibrosis and restrictive lung function. We conclude that asbestos-induced pleural disease contributes to the development of restrictive lung function and identify a group of exposed individuals who are at excess risk of asbestosis.

Asbestos↗

Mesothelioma among employees with likely contact with in-place asbestos-containing building materials.

The occurrence of mesothelioma is a sentinel event in occupational and environmental disease. A mesothelioma surveillance system was established utilizing existing computerized Wisconsin vital statistics data maintained since 1959 and a Cancer Reporting System (CRS) established in 1978. Review of the death certificate listing of usual occupation and industry from 487 mesothelioma deaths in Wisconsin from 1959 to 1989 led to the investigation of 41 persons with likely exposure to inplace asbestos-containing building materials (ACBM): 12 school teachers, 10 school maintenance employees, 7 public building maintenance workers, 5 private building maintenance workers, and 7 commercial and factory workers performing maintenance activities. For 10 (34%) of the 29 maintenance workers the only source of asbestos exposure identified was their maintenance work. For five (17%) histories indicated some prior employment in occupations and industries with probable asbestos exposures. Opportunities for indirect occupational exposure were identified for ten who had been employed in the residential construction industry. One maintenance worker was exposed to asbestos in the household and another had neighborhood exposure. For 9 (75%) of the school teachers, the only identifiable potential source of asbestos exposure was derived from in-place ACBM in schools. One teacher had spent a season in the merchant marine aboard an iron ore-hauling ship and 2 had worked in the residential construction industry. Two of the teachers were sisters, and in two instances, two teachers had taught in the same school facility. We conclude that individuals occupationally exposed to in-place ACBM are at risk for the subsequent development of mesothelioma.

Adult↗

Study of the secular trend in asbestos bodies in lungs in London 1936-66.

Thick sections (30mu unstained) cut from blocks of lung tissue from 100 consecutive necropsies for the years 1936, 1946, 1956, and 1966 at the Archway Hospital, London, have been searched for asbestos bodies. The incidence rose progressively-0, 3, 14, and 20% respectively. The rise was not explained by the increasing age of death in the later years or by the likely effects of changes in the areas within London in which the deaths occurred. There was no similar increase in the incidence of other bodies in the lungs which might be mistaken for asbestos bodies. The rising incidence is shown to fit reasonably with a model based on the hypothesis that the risk of inhaling asbestos increases in relation to the cumulative total of asbestos imported into the country from 1910 onwards. The rising incidence does not fit a model in which the risk depends simply on the current level of asbestos imports.

Adult↗

Antagonistic activity of poly (4-vinylpyridine-N-oxide) to the inhibition of viral interferon induction by asbestos fibres.

The depressive activity of both serpentine (Canadian and Rhodesian chrysotiles) and amphibole (amosite, crocidolite, and anthophyllite) asbestos fibres on interferon induction by influenza virus was significantly diminished or abolished completely when either asbestos fibres or LLC-MK2 cell monolayers were pretreated with poly(4-vinylpyridine-N-oxide). Maximal antagonistic activity of the polymer was time and concentration dependent. Pretreating asbestos fibres with the polymer was more rapid and effective in encouraging viral interferon synthesis than pretreating cell monolayers. Virus multiplication in the presence of asbestos fibre-treated cell monolayers attained a twofold higher level than that noted in normal cell monolayers or those containing polymer-pretreated asbestos fibres. These findings were related to the suppression of interferon production.

Asbestos↗

Histological types of malignant mesothelioma and asbestos exposure.

The Los Angeles County Cancer Surveillance Program abstracts hospital pathology records on almost all cases of cancer occurring in the county. Those cases of pleural and peritoneal mesothelioma that occurred between 1972 and 1978 were identified. Occupational histories were obtained from interviews, and the histopathology of the tumours was reviewed by a member of a mesothelioma reference panel who was unaware of the exposure histories. The relation of asbestos exposure to the three histological types of mesothelioma (epithelial, mesenchymal, and mixed) was studied among the 29 cases for whom occupational histories were available and who were also considered to have histopathology consistent with mesothelioma. The proportion of cases exposed to asbestos was high for both the epithelial (11/17, 65%) and mixed histological types (6/11, 55%). The single case of mesothelioma classified as a mesenchymal type was also exposed to asbestos. Cases who had worked in shipyards were represented in each of the three groups. In cases who had worked in asbestos production and manufacture an exclusively epithelial type of tumour was observed. In cases who had worked as insulators or in heating trades the histological type was predominantly (3/4) mixed. These data do not support the hypothesis that any specific histological type of mesothelioma is especially related to asbestos exposure.

Asbestos↗

Serum type III procollagen peptide in asbestos workers: an early indicator of pulmonary fibrosis.

Serum type III procollagen peptide (PIIIP) concentrations were determined in 36 male workers exposed to asbestos fibres in the production of asbestos cement items and in 13 healthy male controls. Mean (SD) PIIIP serum concentrations were 9.3 (1.5) ng/ml (range 7-12) in the controls and 13.7 (3.5)ng/ml (range 7.5-20) in the asbestos workers; the difference was statistically significant (p less than 0.01). The exposed workers were subdivided according to presence or absence of radiological signs of asbestosis and intensity and duration of exposure. PIIIP serum values of workers with asbestos related interstitial fibrosis were the highest of the groups at 14.6 (2.3) ng/ml. In workers with heavy exposure the PIIIP values were significantly related to duration of exposure (r = 0.95; p less than 0.01). PIIIP serum values may be a useful index for the early diagnosis of asbestos induced pulmonary fibrosis and its use should be considered as part of the biological monitoring of exposed workers.

Adolescent↗

Incidence of cancer and mortality among employees in the asbestos cement industry in Denmark.

In a cohort study of the incidence of cancer and mortality among 7996 men and 584 women employed in the Danish asbestos cement industry between 1928 and 1984 over 99% were traced. Chrysotile asbestos was the only fibre type used until 1946, when amosite and (in 1952) crocidolite were also introduced. Chrysotile constituted 89%, amosite 10%, and crocidolite 1% of the asbestos used. During the first 25 years of manufacture the exposure levels were high, especially in areas where the asbestos was handled dry. Measurements from 1948 indicate that the fibre levels may have ranged from 100 to 1600 times over the present Danish threshold limit value of 0.5 fibre/ml. In 1973 more than 41% of personal samples were higher than 2 f/ml. About 76% of the workforce left the factory within five years of starting employment. A total of 1346 deaths and 612 cases of cancer were observed in the cohort between 1943 and 1984. Among employed men the overall mortality (O/E 1.18; 95% CI 1.12-1.25), cancer mortality (O/E 1.32; 95% CI 1.19-1.46), and overall incidence of cancer (O/E 1.22; 95% CI 1.12-1.32) were significantly increased compared with all Danish men. This was not so among employed women. For men, significant excess risks were found for cancer of the lung (O/E 1.80; 95% CI 1.54-2.10), pleura (O/E 5.46; 95% CI 2.62-10.05), mediastinum (O/E 5.00; 95% CI 1.01-14.61), stomach (O/E 1.43; 95% CI 1.03-1.93), and other male genital organs (O/E 3.03; 95% CI 1.11-6.60). The mortality was significantly increased for men for non-malignant pulmonary diseases (O/E 1.63; 95% CI 1.33-1.98). Among the group of asbestos cement workers with first employment 1928-40 an excess risk of laryngeal cancer was found (O/E 5.50;95% CI 1.77-12.82). A total of 12 cases of pleural and one of peritoneal mesotheliomas was observed when the original notification forms were reviewed for all patients with cancer in the cohort.

Asbestos↗

Effect of smoking on pleural thickening in asbestos workers.

It is well known that an interaction exists between smoking and exposure to asbestos in the occurrence of lung cancer, whereas occurrence of malignant mesothelioma has not been related to smoking. In the case of pleural thickening related to asbestos, there is a disagreement in previous studies as to the effect of smoking. This could be because the diagnosis of pleural changes has a subjective element. Taking this into account, in the present work the maximum width of the pleura was used as an index of pleural changes. Study subjects were 134 asbestos workers of a brake manufacturing company who had received medical checks in 1978 and in 1990. The maximum width of the pleura on the chest x ray films of the workers was measured by two examiners who did not know the year of examination or smoking state of the worker. A general linear model was applied to analyse the effects of smoking, the year of examination, age, and duration of exposure to asbestos. The difference between maximum widths measured in 1978 and 1990 suggested chronological progression. The increase in width during the 12 years, however, did not differ significantly between smokers and nonsmokers. This suggests that smoking does not significantly increase pleural thickening in asbestos workers.

Aged↗

Genetic polymorphism for glutathione-S-transferase mu in asbestos cement workers.

OBJECTIVE: To investigate whether a lack of glutathione-S-transferase mu (GSTM1) activity was related to an increased risk for adverse outcome after asbestos exposure. METHODS: A study was made of 78 male former asbestos cement workers, with retrospective cohort data on exposure, radiographical findings, and lung function. Venous blood samples were obtained for the analysis of GSTM1 polymorphism by the polymerase chain reaction technique. Chest x ray films were classified according to the International Labour Organisation (ILO) 1980 classification. Vital capacity (VC) and forced expiratory volume during 1 s (FEV1) were determined. Individual estimates of asbestos exposure were calculated, and expressed as duration of exposure, average exposure intensity, and cumulative dose. Data on smoking were obtained from interviews. RESULTS: The lung function in the study group was reduced, compared with reference equations. 23% of the workers had small opacities > or = 1/0, 29% circumscribed pleural thickenings, 14% diffuse thickenings, and 12% obliterated costophrenic angles. 54% of the workers were GSTM1 deficient. They were comparable with the other workers in age, follow up time (median 30 years), and duration of exposure (median 18 years), but had a slightly higher cumulated dose (median 18 v 10 fibre-years) than the others. Neither in radiographical changes nor lung function variables were there any differences between the different GSTM1 groups. The findings were similar when smoking habits and estimated asbestos exposure were taken into account. CONCLUSIONS: We could not show that lack of GSTM1 activity was related to an increased risk for radiographical or lung function changes in a group of asbestos cement workers, followed up for a long period after the end of exposure.

Aged↗

Decline in annual lung function in workers exposed to asbestos with and without pre-existing fibrotic changes on chest radiography.

OBJECTIVES: To examine whether or not workers with pre-existing mild pulmonary fibrosis have accelerated decline in forced expiratory volume in one second (FEV1) or forced vital capacity (FVC), under low level exposure to chrysotile asbestos. METHODS: All male workers in two asbestos manufacturing factories were followed up annually for six years to compare their declines in FEV1 and FVC. The values of FEV1 and FVC were divided by the square of the person's height to adjust for body size differences (FEV1/Ht2 and FVC/Ht2, respectively). Annual change was calculated for each subject as a slope of the simple linear regression with FEV1/Ht2 or FVC/Ht2 regressed according to age. Analysis was conducted on 242 middle aged workers who had normal routine spirometry values, normal chest radiographs or mild pneumoconiosis up to 1/2 grade, without changes either in smoking habit or severity of pneumoconiosis during the study period, and with acceptable spirograms in three or more surveys. The occupational environment, in terms of chrysotile asbestos, had been well controlled below the threshold limit value of Japan at that time--namely, 2 fibres/micromilligrams. RESULTS-There was no significant effect from the interaction between pre-existing mild pulmonary fibrosis and low level of exposure to chrysotile asbestos on the accelerated annual decline of FEV1/Ht2, or FVC/Ht2. Fibrosis significantly contributed to annual changes in FEV1/Ht2, even after adjustment for mean FEV1 and smoking. The point estimate of the contribution was - 4.9 ml/m2/y. No significant independent contribution of exposure was found in decline of either FEV1/Ht2 or FVC/Ht2. CONCLUSIONS: Pre-existing pulmonary fibrosis is an independent risk factor for accelerated annual decline of FEV1, even when mild and stable. Additional decline due to exposure to chrysotile asbestos is less probable if it is well controlled under the current threshold limit value.

Adult↗

Pleural mesothelioma in Sweden: an analysis of the incidence according to the use of asbestos.

OBJECTIVE: To investigate if the preventive measures taken to reduce the occupational exposure to asbestos have resulted in a decreased incidence of pleural mesothelioma in Sweden. METHODS: The incidence of pleural mesothelioma between 1958 and 1995 for birth cohorts born between 1885 and 1964 was investigated. The cases of pleural mesothelioma were identified through the Swedish Cancer Register. RESULTS: In 1995, around 80 cases of pleural mesothelioma could be attributed to occupational exposure to asbestos. There is an increasing incidence in more recent birth cohorts in men. The incidence was considerably higher in the male cohort born between 1935 and 1944 than in men born earlier. CONCLUSIONS: The annual incidence of pleural mesothelioma attributable to occupational exposure to asbestos is today larger than all fatal occupational accidents in Sweden. The first asbestos regulation was adopted in 1964 and in the mid 1970s imports of raw asbestos decreased drastically. Yet there is no obvious indication that the preventive measures have decreased the risk of pleural mesothelioma. The long latency indicates that the effects of preventive measures in the 1970s could first be evaluated around 2005.

Adult↗

Asbestos related diseases from environmental exposure to crocidolite in Da-yao, China. I. Review of exposure and epidemiological data.

BACKGROUND: Scattered patches of crocidolite, one form of asbestos, were found in the surface soil in the rural county of Da-yao in southwestern China. In 1983, researchers from the West China University of Medical Sciences (WCUMS) discovered that residents of two villages in Da-yao had hyperendemic pleural plaques and excessive numbers of pleural mesotheliomas. AIMS: To review and summarise epidemiological studies, along with other relevant data, and to discuss the potential contribution to environmental risk assessment. METHODS: This report is based on a review of several clinical/epidemiological studies conducted by WCUMS researchers since 1984, which included one cross sectional medical examination survey, one clinical/pathological analysis of 46 cases of mesothelioma, and three retrospective cohort mortality studies. Additional information acquired from reviewing original data first hand during a personal visit along with an interview of medical specialists from Da-yao County Hospital was also incorporated. RESULTS: The prevalence of pleural plaque was 20% among peasants in Da-yao over 40 years of age in the cross sectional survey. The average number of mesothelioma cases was 6.6 per year in the 1984-95 period and 22 per year in the 1996-99 period, in a population of 68 000. For those mesothelioma cases that were histology confirmed, there were 3.8 cases/year in the first period and 9 cases/year in the second. Of the 2175 peasants in this survey, 16 had asbestosis. Lung cancer deaths were significantly increased in all three cohort studies. The annual mortality rate for mesothelioma was 85 per million, 178 per million, and 365 per million for the three cohort studies, respectively. The higher exposed peasants had a fivefold increased mesothelioma mortality compared to their lower exposed counterparts. There were no cases of mesothelioma in the comparison groups where no crocidolite was known to exist in the environment. In the third cohort study, almost one of five cancer deaths (22%) was from mesothelioma. The ratio of lung cancer to mesothelioma deaths was low for all three studies (1.3, 3.0, and 1.2, respectively). CONCLUSIONS: The observation of numerous mesothelioma cases at Da-yao was a unique finding, due mainly to their lifetime exposure to crocidolite asbestos. The finding of cases dying at a younger age and the relatively high ratio of mesothelioma cases to lung cancer could also be another unique result of lifetime environmental exposure to crocidolite asbestos. Although the commercial use of crocidolite has been officially banned since 1984, the incidence of mesothelioma has continued to show a steady increase, particularly among peasants. Since the latency of mesothelioma is approximately 30-40 years, the ban had little effect in the 1990s. The increased awareness and changes in diagnosis over time may also contribute to the increase. Furthermore, exposure to asbestos stoves and walls continued. The government implemented reduction of these exposures. However, from a public health standpoint, the most important issue is the complete avoidance of further exposure to asbestos.

Asbestos, Crocidolite↗

Two dimensional protein patterns of bronchoalveolar lavage fluid from non-smokers, smokers, and subjects exposed to asbestos.

BACKGROUND: Bronchoalveolar lavage (BAL) fluid contains a large number of proteins which comprise a potential resource for studying respiratory effects due to occupational and environmental exposures. A study was undertaken to compare protein patterns of BAL fluid from non-smokers, smokers, and subjects exposed to asbestos. METHODS: BAL fluid samples were analysed with two dimensional gel electrophoresis (2-DE). The separated proteins were detected, quantified, and pattern-matched between different individuals with a computerised imaging system designed for evaluations of 2-DE patterns. RESULTS: About 200 different protein spots were detected in each sample of BAL fluid. As is the case with blood plasma, the BAL fluid samples contained large amounts of albumin, transferrin, and immunoglobulins. Higher levels of basic proteins were found in smokers than in non-smokers, while subjects exposed to asbestos had increased amounts of several high molecular weight proteins as well as basic proteins. Lower levels of albumin and higher levels of immunoglobulins were found in smokers than in non-smokers, while higher levels of transferrin were found in asbestos exposed subjects than in unexposed subjects. Moreover, in the group exposed to asbestos differences were found between patients with pleuritis and patients with pleural plaque, and one protein spot was found only in two patients with progressive pleural disease. CONCLUSION: These results suggest that both smokers and asbestos exposed subjects have significant changes in their airway protein expression compared with non-smokers and unexposed subjects. It is inferred that analysis of protein patterns in the BAL fluid with 2-DE may be used to detect and characterise, at a molecular level, respiratory effects due to occupational and environmental exposures.

Adult↗

Cigarette smoke increases amosite asbestos fiber binding to the surface of tracheal epithelial cells.

Binding of asbestos fibers to the cell surface appears to be important in the initiation of intracellular signaling events as well as in initiation of particle uptake by the cell. We have previously shown that cigarette smoke increases the uptake of asbestos fibers by tracheal epithelial cells in explant culture. Whether smoke acts by increasing surface binding of fibers is not known. In this study, we exposed rat tracheal explants to air or cigarette smoke and then to a suspension of amosite asbestos. Explants were harvested after 1 or 24 h of dust exposure and washed by repeated dips in culture medium to remove loosely bound fibers, and the number of fibers adhering to the apical cell surfaces was determined by scanning electron microscopy. Smoke-exposed explants retained significantly more surface fibers than air-exposed explants. After four washes, binding levels were similar at 1 and 24 h. The smoke effect was still present when incubations were carried out at 4 degrees C, but binding was decreased approximately 25%. Preincubation of the asbestos fibers with iron chloride to increase surface iron increased fiber binding in both air- and smoke-exposed explants, whereas preincubation of the fibers with the iron chelator deferoxamine decreased binding after air exposure and completely eliminated the smoke effect. Inclusion of mannitol or catalase in the medium or preincubation of the explants with GSH produced decreases in binding of 10-25% in air-exposed explants and generally greater decreases in smoke-exposed explants. We conclude that 1) amosite binding is a very rapid process that does not require active cellular metabolism, 2) cigarette smoke increases adhesion of fibers to the epithelial surfaces, and 3) iron on the asbestos fiber appears to play an important role in binding, probably through an active oxygen species-mediated process.

Animals↗