[Lung function tests in asbestos workers--effect of asbestos exposure and smoking].
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Asbestosis↗
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[Morphogenesis of granuloma due to asbestos, silica and asbestos-silica combinations].
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Animals↗
NTP Toxicology and Carcinogenesis Studies of Amosite Asbestos (CAS No. 12172-73-5) in F344/N Rats (Feed Studies).
The term "asbestos" has a commercial/industrial derivation limited to naturally occurring fibrous minerals of the serpentine or amphibole series. Chrysotile is the only type of asbestos in the serpentine series, whereas the amphibole series is represented by actinolite, amosite, anthophyllite, crocidolite, and tremolite. The essential characteristic of asbestos minerals is their fibrous nature. Large portions of the population ingest asbestos through consumption of food and water. Asbestos or asbestos-like fibers may gain access to water supplies as a result of mining (Lake Superior), from the presence of natural serpentine or amphibole deposits in watersheds (Seattle, WA, and San Francisco, CA) or, under certain conditions, through the use of asbestos-cement pipes for municipal water supplies. For the latter, erosion of the pipe with release of fibers is associated with the "aggressiveness" of the water, a term representing a mathematical expression of pH, alkalinity, and calcium content. The EPA estimated that 68.5% of water systems in the United States utilize water that is potentially capable of eroding asbestos-cement pipe. Carcinogenesis studies of amosite asbestos alone or in combination with the intestinal carcinogen 1,2-dimethylhydrazine dihydrochloride (DMH) were conducted in male and female rats. Amosite asbestos was administered at a concentration of 1% in pelleted diet for the entire lifetime of the rats, starting with the dams of the study animals. One group of amosite asbestos-exposed rats (amosite preweaning gavage) also received chrysotile asbestos via gavage during lactation. Group sizes varied from 100 to 250. Litter size was the same, but the offspring from mothers exposed to amosite asbestos were smaller at weaning than those from nonexposed mothers and remained smaller throughout their life. The DMH was administered by gavage at a dose of 7.5 mg/kg for males and 15 mg/kg for females every 14 days, starting at 8 weeks of age, for a total of five doses. The administration of DMH did not affect body weight gain either in amosite-exposed or nonexposed animals. The amosite-exposed rats showed enhanced survival compared with that of the nonexposed rats. DMH exposure reduced survival by approximately 1 year, although the survival of the amosite plus DMH groups was slightly greater than that of the DMH group alone. Significant increases in the incidences of C-cell carcinomas of the thyroid gland (untreated control, 11/117; amosite, 50/246, P<0.05; amosite preweaning gavage, 14/100) and of leukemia (38/117; 106/249, P<0.05; 49/100, P<0.01) in male rats were observed in amosite-exposed groups. However, the biologic significance of the C-cell carcinomas in relation to amosite asbestos exposure is discounted because of a lack of significance when C-cell adenomas and carcinomas were combined and because the positive effect was not observed in the amosite preweaning gavage group. The biologic significance of an increased incidence of leukemia is questionable because of a lack of statistical significance in the amosite group when evaluated by life table analysis and because no toxic lesions were observed in the target organs, i.e., gastrointestinal tract and mesothelium. DMH caused a high incidence (62%-74%) of intestinal neoplasia in amosite-exposed and nonexposed groups. Neither an enhanced carcinogenic nor a protective effect was demonstrated by exposure to amosite asbestos. Conclusions: Under the conditions of these feed studies, amosite asbestos was not overtly toxic, did not affect survival, and was not carcinogenic when ingested at a concentration of 1% in the diet by male or female F344/N rats. The cocarcinogenic studies using DMH were considered inadequate because of the high incidence of DMH-induced intestinal neoplasia in both the amosite asbestos-exposed and nonexposed groups. Levels of Evidence of Carcinogenicity: Amosite Asbestos: Male Rats: Negative. Female Rats: Negative. Amosite Asbestos + DMH: Male Rats: Inadequate. Female Rats: Inadequate. Note: Amosite Asbestos was previously tested in Syrmosite Asbestos was previously tested in Syrian Golden Hamsters administered in feed (See TR-249, reported 1983).
Journal Article↗
[Effect of cigarette smoking and/or N-bis(2-hydroxypropyl)nitrosamine (DHPN) on the development of lung and pleural tumors in rats induced by administration of asbestos].
Occupationally induced lung cancer and mesothelioma have long been attributed to asbestos and moreover, several epidemiological studies have indicated a co-carcinogenic effect of cigarette smoking on the incidence of lung cancer in asbestos workers. The aim of the present study was to investigate the co-carcinogenic effects of asbestos and other carcinogens with emphasis placed on determining the effects of cigarette smoking on the incidence of asbestos induced carcinomas. Doses of 15 mg of chrysotile asbestos were administered intratracheally to Wistar rats alone and in conjunction with N-bis(hydroxypropyl)nitrosamine (DHPN) and/or cigarette smoking. DHPN at dose of 1 g/kg/B.W. was injected three times intraperitoneally, and the subject animals were exposed to smoke from 10 cigarettes per day, six days a week, for their entire life span. As a result, lung carcinomas were induced in one out of the 31 rats receiving only asbestos. Lung tumors were induced at a much higher incidence in the groups receiving DHPN alone and in conjunction with asbestos: of the 37 rats treated with DHPN alone 19 (51.4%) developed lung tumors, whereas those receiving asbestos as well showed an incidence of 68.4% (23/38) of carcinomas. The development of lung carcinomas (including adenocarcinomas, epidermoid carcinomas, anaplastic carcinomas, and combined carcinomas) was seen in 8 (21.6%) out of the 37 rats receiving DHPN alone and in 23 (60.5%) out of the 38 rats receiving asbestos as well. The incidence of lung carcinoma was significantly increased in combined treatment with asbestos than DHPN alone. In the group receiving asbestos in combination with cigarette smoke, 4 (13.8%) out of the 29 rats developed lung carcinomas, but these carcinomas were more common than in the group receiving only asbestos. Moreover, in the group administered asbestos, DHPN and smoking combined, lung tumors developed in 18 (62.1%) out of the 29, 15 (51.7%) of which proved to be malignant. Mesothelioma (pleura) was induced in three groups in the following combinations: DHPN plus asbestos, 8/38 (21.1%); smoking plus asbestos, 2/29 (6.9%); and smoking, DHPN and asbestos, 4/29 (13.8%). These tumors were extensively located, that is, on the parietal pleura, visceral pleura, epicardium and diaphragm surface. However, mesothelioma was not induced by asbestos alone nor by DHPN alone. Carcinogenicity of asbestos for pleural tumors was significantly promoted by combined treatment with DHPN to an extent greater than DHPN alone. It should be noted that asbestos plus smoking resulted in a higher incidence of mesothelioma than asbestos alone.(ABSTRACT TRUNCATED AT 400 WORDS)
Adenocarcinoma↗
[Health hazards: asbestos--a review (author's transl)].
The health hazards caused by asbestos are reviewed and some conclusions are drawn. Asbestos and the materials containing a high percentage of asbestos cannot completely be substituted by other materials without dangerous health effects. It is to be expected that the use of asbestos will still increase. An important health hazard has become evident among asbestos insulation workers. But also in other branches the application of asbestos is widespread. It seems to be difficult to find substitutes meeting the same requirements for using like asbestos. Rock-wool and glass fibres are used more and more in exchange for asbestos. Registers for asbestos workers and asbestos working places are established in several countries. The main causes of death induced by asbestos among asbestos workers are asbestosis. mesothelioma and cancer. For the evaluation and assessment of cancer risk due to asbestos epidemiological studies have to be conducted. Even a short period of exposure to low quantities of asbestos fibres proves to be a health hazard causing certain diseases (diffuse pulmonary fibrosis, pleural hyalinosis, pleural calcifications, mesothelioma) after more than 20 years. For avoiding occupational disease hazards among asbestos workers the dust level on the working place has to be lowered to acceptable concentrations (maximal allowable concentrations). The identification of dust sources of asbestos, the application of practice codes for handling of asbestos, the substitution of asbestos by materials without dangerous health effects, and dust control at source are the most effective directions of hygienic practice. The health protection requires annual medical examinations of all persons exposed to airborne concentrations of asbestos.
Adolescent↗
NTP Toxicology and Carcinogenesis Studies of Chrysotile Asbestos (CAS No. 12001-29-5) in F344/N Rats (Feed Studies).
Lifetime toxicology and carcinogenesis studies of short-range (SR) and intermediate-range (IR) fiber length chrysotile asbestos were conducted in groups of 88-250 male and female F344/N rats. Both forms of asbestos were administered at a concentration of 1% in pelleted diet for the lifetime of the rats, starting with the dams of the test animals. Subgroups of 100 male and female IR chrysotile-exposed rats also received 0.47 mg/g IR chrysotile asbestos in water by gavage during lactation (preweaning [PW]). At 9 weeks of age, additional subgroups (125-175) of control and IR chrysotile-exposed rats received 7.5 mg/kg (male) or 15 mg/kg (female) 1,2-dimethylhydrazine dihydrochloride (DMH) by gavage every other week for a total of five doses. When the survival of either the control or test group reached 10%, both groups were killed. Neither type of fiber affected fertility or litter size. The offspring from mothers exposed to SR chrysotile were similar in body weight to the controls at birth but were slightly smaller (13%) at weaning and remained so throughout their lifetimes. Feed consumption and survival were comparable among the SR and IR chrysotile asbestos groups and controls. The DMH-exposed groups showed decreased survival due primarily to the development of lethal neoplasms. The administration of SR chrysotile for the lifetime of exposed male and female rats did not cause any overt toxicity. In addition, no neoplastic or nonneoplastic disease was associated with SR chrysotile exposure. Male and female rats exposed to IR chrysotile asbestos did not show any adverse clinical signs. Benign epithelial neoplasms (adenomatous polyps) were observed in the large intestine of IR chrysotile asbestos male rats (9/250, 3.6%). Although not statistically significant (P=0.08) compared with concurrent controls (0/85), the incidence of these neoplasms was highly significant (P=0.003) when compared with the incidence of epithelial neoplasms (benign and malignant combined) of the large intestine in the pooled male control groups of all the NTP oral asbestos lifetime studies (3/524, 0.6%). The biologic importance of this finding was supported by the observation of lesions of similar morphology in the small intestine or glandular stomach of four additional IR chrysotile male rats and by a low incidence (2/100, 2.0%) of adenomatous polyps in the large intestine of male rats in the IR/PW group. A significant (P<0.05) increase in keratoacanthomas of the skin was observed in male IR (19/250, 7.6%) and IR/PW (8/100, 8.0%) chrysotile-exposed rats compared with the concurrent controls (1/88, 1.1%). The biologic importance of this observation was discounted because the incidence in these groups did not greatly exceed the rate observed in the combined male control groups from all the other NTP oral asbestos studies (19/441, 4.3%). An apparent increase in the incidence of clitoral gland neoplasms in female IR (18/250, 7.2%) and IR/PW (4/100, 4.0%) chrysotile-exposed rats compared with that in the concurrent controls (1/88, 1.1%) was also discounted because of a lack of statistical significance when compared with the pooled female control groups from the other NTP oral asbestos studies (21/441, 4.8%). Rats exposed to DMH and DMH plus IR chrysotile asbestos exhibited neoplasia in those organs known to be targets for DMH (gastrointestinal tract, Zymbal gland, liver, and kidney). There was a significant difference (P<0.05) in the incidence of DMH-induced mixed-cell tumors of the kidney between the DMH alone (13/125, 10%) and DMH plus IR chrysotile asbestos (34/175, 19%) female groups. An increased incidence of thyroid follicular cell tumors was observed in DMH plus IR chrysotile male rats (28/175, 16.0%) compared with the DMH alone group (9/124, 7.3%). The biologic importance of both observations is questionable, since neither organ represents a primary target organ for asbestos and no difference between DMH and DMH plus IR chrysotile was observed for the primary target organs (intestine and mesothelium). An audit of the experimental data was conducteIR chrysotile was observed for the primary target organs (intestine and mesothelium). An audit of the experimental data was conducted for these lifetime carcinogenesis studies of chrysotile asbestos. No data discrepancies were found that influenced the final interpretations. Under the conditions of these lifetime studies, short-range and intermediate-range chrysotile asbestos did not induce overt toxicity and did not affect survival when ingested at a level of 1% in the diet by male and female F344/N rats. There was no evidence of carcinogenicity in male or female rats exposed to SR chrysotile asbestos or in female rats exposed to IR chrysotile asbestos. There was some evidence of carcinogenicity in male rats exposed to IR chrysotile asbestos as indicated by an increased incidence of adenomatous polyps in the large intestine. The cocarcinogenesis studies of 1,2-dimethylhydrazine dihydrochloride and IR chrysotile asbestos were considered inconclusive for determining whether IR chrysotile asbestos had either a tumor-enhancing or protective effect, although an increased incidence of neoplasms was observed in the kidneys of female rats exposed to DMH plus IR chrysotile as compared with those exposed to DMH alone.
Journal Article↗
[Asbestos concentration and fiber size in lungs of the urban residents].
Asbestos fiber concentrations and fiber size distribution in lung tissues of 53 urban residents (males: 34, female: 19) were analyzed by low temperature ashing-analytical transmission electronmicroscopy. The following findings were obtained. 1. Pulmonary asbestos fibers were found in 51 out of 53 patients. The types of asbestos fibers were chrysotile, amosite, crocidolite, actinolite and tremolite. 2. Thirty-six of 53 patients had no history of occupational asbestos exposure, and their geometric mean concentration of asbestos fibers was 1.67 x 10(6) fibers/g dry lung. Most of these asbestos fibers are probably attributable to general environmental contamination. Thirteen patients who had a history of occupational asbestos exposure showed a geometric mean of their pulmonary asbestos concentrations (5.82 x 10(6) fibers/g dry lung) which was significantly higher than that of patients without occupational asbestos exposure (p less than 0.01). 3. The geometric mean concentration of asbestos fiber in males (2.70 x 10(6)) was higher than in females (1.59 x 10(6)), probably due to a difference in the occupational asbestos exposure between males and females. 4. Regardless of the patient's sex, the geometric mean concentration of asbestos fibers in patients without a history of smoking (male: 4.91 x 10(6), female: 1.78 x 10(6)) was higher than that in patients with a smoking history (male: 2.76 x 10(6), female: 1.37 x 10(6)). The difference, however, was not statistically significant, and no correlation was seen between the concentration of asbestos fibers and smoking history. 5. Although most asbestos fiber utilized in Japan is chrysotile, the geometric mean concentration of chrysotile (0.87 x 10(6)) was almost identical to that of amphibole asbestos fiber (0.90 x 10(6)). 6. Of the asbestos fibers observed, 95% of chrysotile and 85% of amphibole asbestos were less than 5 microns in length and 93% of the total asbestos fibers were too small to be visible by light microscopy.
Adult↗
The clinical utility and reliability of asbestos bodies in bronchoalveolar fluid.
Although asbestos bodies are easily identified in bronchoalveolar lavage (BAL) fluid and are thought to be strongly associated with the asbestos body burden in the lung parenchyma, the clinical utility and reliability of this biologic measure of exposure has not been sufficiently studied. To assess the clinical relevance of BAL asbestos bodies we compared this bioassay of exposure to other measures of exposure and also indices of lung disease in asbestos-exposed workers (n = 71). The median concentration of asbestos bodies was 0.8 bodies per ml of BAL fluid (range 0 to 34.3). Seven workers or 9.9% had zero asbestos bodies identified in the BAL fluid. The concentration of BAL asbestos bodies was not associated with the duration of exposure (r = -0.02), the time from first exposure to asbestos (r = 0.12), or the time since last exposure to asbestos (r = 0.05). Moreover, radiographic and physiologic measures of asbestos-induced lung disease were not found to be associated with the concentration of BAL asbestos bodies. In fact, of the seven study subjects with zero BAL asbestos bodies, the mean duration of exposure was 32 yr, and six of these subjects had radiographic evidence of asbestos-induced lung disease. To assess the reliability of measuring BAL asbestos bodies, we performed a second bronchoscopy on 54 subjects and directly compared the concentration of BAL asbestos bodies from both the first and second BAL samples. Within these 54 subjects, the concentration of BAL asbestos bodies was found to be a very reliable measure (r = 0.76; p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
Asbestos↗
Small animals in the study of pathological effects of asbestos.
The main pathological effects attributed to asbestos are carcinogenesis and fibrogenesis. Statistical studies have shown that asbestos workers may expect a higher morbidity not only from cancer of the lung and mesothelioma but also from cancer at other sites. Carcinomas have been reported in animals following the injection of asbestos, but the production of carcinomas by inhaled asbestos is less easy to demonstrate; most examples of experimental carcinogenesis with asbestos have been produced in rats. Rats and man react differently to asbestos in that rats do not produce asbestos bodies. The fibrosis that follows inhalation of asbestos has been frequently described, but studies with specific pathogen free animals have shown that, like the fibrosis that may follow the inhalation of silica dust, gross fibrosis involving the production of abnormal amount of collagen probably requires the intervention of infection as well as asbestos. Because of the difficulties encountered in the direct investigation of carcinogenesis and fibrogenesis resulting from the inhalation of asbestos, attention has been directed to the mechanisms by which the lung is able to protect itself against these fibrous dusts. While non-fibrous dusts and short fibers can be ingested by macrophages and removed via the bronchus, the long fibers that may also reach the alveolar regions may not be removed by this mechanism. The probability that a fiber may reach the alveoli depends largely on the fiber diameter and only to a small extent on the fiber length, so that, for example, fibers 100 mum long may reach the alveoli of a guinea pig. These long fibers may become coated with a ferroprotein derived from hemoglobin to form an asbestos body and, after morphological changes, the asbestos body may be broken up, the fragments ingested by macrophages and dissolved. The lung is thus cleared of asbestos. In the guinea pig lung, consolidated areas from which the asbestos has disappeared shows signs of return to normal. THIS CLEARANCE MECHANISM IS INHIBITED BY OTHER FACTORS: quartz dust may almost completely inhibit asbestos body formation; tobacco smoke has a considerable effect, and even very heavy loads of carbon may act similarly. The normal lung appears able to efficiently eliminate small loads of both nonfibrous and fibrous dust, including the carcinogenic asbestos fibers. The capacity is not unlimited, however, and when the load is heavy there is a much greater probability that fibers will not be detoxicated. In addition, other factors such as silica dust and tobacco smoke may remove the protective mechanism in the lungs.
Animals↗
The effects of long-term ingestion of asbestos on the colon of F344 rats.
Weanling F344 rats, which were fed a diet containing 10% chrysotile (B), were studied over their life-time to determine the effects of ingested asbestos on the colon. Control groups consisted of rats fed a diet containing a 10% nonnutritive cellulose or a standard laboratory rat diet. The pathological findings in the colons of 501 rats (189 on asbestos diet, 197 on fiber control diet, and 115 on standard control diet), are reported here. Epithelial tumors of the colon (eight adenocarcinomas and one adenoma) were found in nine of the rats on study. Four of the tumors were in asbestos-fed rats, two tumors were found in the non-nutritive cellulose controls, and three tumors were found in the standard laboratory rat diet controls. The probability (based on actuarial analysis) of developing adenoma or adenocarcinomas during the 32 months of the study were 7.4% for the asbestos-fed group, 3.5% for the fiber control diet and 4.0% on the standard control diet. In addition, one malignant mesothelioma of the type induced by intraperitoneally administered asbestos was found in the asbestos-fed group. Non-neoplastic lesions of the colon were also evaluated. The cumulative risk for development of any colon-associated lesion (non-neoplastic plus neoplastic lesions) was greatest for asbestos-fed rats (17.9%), compared to 13.6% for those fed the fiber control diet and 8.2% for those fed the standard control diet. The colon tissue levels of adenosine, 3'-5'-cyclic monophosphate (cAMP) were significantly lower in the animals fed asbestos compared to the control diets. Chrysotile fibers were seen by electronmicroscopy (e.m.) in six of ten ashed colon specimens of rats fed the asbestos diet. Although the differences in numbers of tumors between the animals fed asbestos and the controls were not statistically significant at the 5% level, we felt that the combination of observations including 1) evidence of increased probability of asbestos-fed animals to develop colon lesions in general; 2) evidence of a special type of mesothelioma in rats fed asbestos; 3) evidence for a cell regulator defect (lowered cAMP levels) in colon tissues of animals fed asbestos; and 4) evidence for asbestos fiber penetration of the colonic mucosa (e.m. studies) suggest that ingested asbestos is not inert in the colon.
Adenocarcinoma↗
Respiratory health in Turkish asbestos cement workers: the role of environmental exposure.
AIM: Benign and malignant pleural and lung diseases due to environmental asbestos exposure constitute an important health problem in Turkey. The country has widespread natural deposits of asbestos in rural parts of central and eastern regions. Few data exists about the respiratory health effects of occupational asbestos exposure in Turkey. A cross-sectional study was conducted to investigate respiratory health effects of occupational asbestos exposure and the contribution of environmental asbestos exposure. METHODS: Investigations included asbestos dust measurements in the workplace and application of an interviewer-administered questionnaire, a standard posteroanterior chest X-ray and spirometry. Information on birthplace of the workers was obtained in 406 workers and used to identify environmental exposure to asbestos, through a map of geographic locations with known asbestos exposure. RESULTS: Asbestos dust concentration in the ambient air of the work sites (fiber/ml) ranged between 0.2 and 0.76 (mean: 0.25, median: 0.22). Environmental exposure to asbestos was determined in 24.4% of the workers. After the adjustment for age, smoking, occupational asbestos exposure, and potential risk factors environmental asbestos exposure was associated with small irregular opacities grade > or = 1/0 (44.2% vs. 26.6%, P < 0.01), FVC% (97.8 vs. 104.5, P < 0.0001), and FEV1% (92.4 vs. 99.9, P < .0001). Occupational exposure to asbestos was associated with small irregular opacities grade > or = 1/0 (OR: 2.0, 95% CI: 1.3-3.1, per 1 unit increase in the natural logarithm of fiber/ml) and FEV1/FVC% (beta: 1.1, SEM: 0.54; P < 0.05, per 1 unit increase in the natural logarithm of fiber/ml). CONCLUSIONS: Environmental exposure to asbestos could increase the risk of asbestosis and lung function impairment in workers occupationally exposed to asbestos, independent from occupational exposure and smoking.
Adult↗
Exposure and mineralogical correlates of pulmonary fibrosis in chrysotile asbestos workers.
OBJECTIVES: The relation between lifetime cumulative exposure to asbestos, pathological grade of pulmonary fibrosis, and lung burden of asbestos at death, was explored in a necropsy population of former workers in a chrysotile asbestos textile plant in South Carolina. METHODS: Estimates of cumulative, mean, and peak exposures to asbestos were available for 54 workers. Necropsy records and lung tissue samples were obtained from hospital files. Matched control cases were selected from consecutive necropsies performed at the same hospitals. The extent and severity of pulmonary fibrosis was graded on tissue sections. Mineral fibres in lung tissue were characterised by transmission electron microscopy combined with x ray spectroscopy. RESULTS: A significant positive correlation (r = 0.67, P < 0.0001) was found between lifetime cumulative exposure to asbestos and total lung burden of asbestos fibres. This relation was also found for the individual types of asbestos associated with the exposure: chrysotile and tremolite. Pulmonary fibrosis was correlated with both cumulative exposure to asbestos (r = 0.60, P < 0.01) and the concentration of asbestos fibres in the lung (r = 0.62, P < 0.0001). The concentration of tremolite fibres in the lung provided a better estimate of lung fibrosis than did the concentration of chrysotile. Asbestosis was usually present in asbestos textile workers with more than 20 fibre-years cumulative exposure. The lengths and aspect ratios of chrysotile asbestos, but not amphibole asbestos, were greater in the lungs of asbestos fibre workers than in the control population. Textile workers with lung cancer had significantly greater cumulative exposures and fibrosis scores than workers without lung cancer. CONCLUSIONS: Both cumulative exposure to asbestos and lung fibre burden are strongly correlated with severity of asbestosis. The data also support the hypothesis that the high prevalence of asbestosis and lung cancer in this population resulted from exposure to long fibres of chrysotile asbestos in the workplace.
Asbestos, Serpentine↗
Multicentric study on malignant pleural mesothelioma and non-occupational exposure to asbestos.
Insufficient evidence exists on the risk of pleural mesothelioma from non-occupational exposure to asbestos. A population-based case-control study was carried out in six areas from Italy, Spain and Switzerland. Information was collected for 215 new histologically confirmed cases and 448 controls. A panel of industrial hygienists assessed asbestos exposure separately for occupational, domestic and environmental sources. Classification of domestic and environmental exposure was based on a complete residential history, presence and use of asbestos at home, asbestos industrial activities in the surrounding area, and their distance from the dwelling. In 53 cases and 232 controls without evidence of occupational exposure to asbestos, moderate or high probability of domestic exposure was associated with an increased risk adjusted by age and sex: odds ratio (OR) 4.81, 95% confidence interval (CI) 1.8-13.1. This corresponds to three situations: cleaning asbestos-contaminated clothes, handling asbestos material and presence of asbestos material susceptible to damage. The estimated OR for high probability of environmental exposure (living within 2000 m of asbestos mines, asbestos cement plants, asbestos textiles, shipyards, or brakes factories) was 11.5 (95% CI 3.5-38.2). Living between 2000 and 5000 m from asbestos industries or within 500 m of industries using asbestos could also be associated with an increased risk. A dose-response pattern appeared with intensity of both sources of exposure. It is suggested that low-dose exposure to asbestos at home or in the general environment carries a measurable risk of malignant pleural mesothelioma.
Adult↗
Mesothelioma: risk apportionment among asbestos exposure sources.
The mesothelioma epidemic in the United States, which peaked during the 2000-2004 period, can be traced to high-level asbestos exposures experienced by males in occupational settings prior to the full recognition of the disease-causing potential of asbestos and the establishment of enforceable asbestos exposure limits by the Occupational Safety and Health Administration (OSHA) in 1971. Many individuals diagnosed with mesothelioma where asbestos has been identified as a contributing cause of the disease have filed claims seeking compensation from asbestos settlement trusts or through the court system. An individual with mesothelioma typically has been exposed to asbestos in more than one setting and from more than one asbestos product. Apportioning risk for mesothelioma among contributing factors is an ongoing problem faced by occupational disease compensation boards, juries, parties responsible for paying damages, and currently by the U.S. Senate in its efforts to formulate a bill establishing an asbestos settlement trust. In this article we address the following question: If an individual with mesothelioma where asbestos has been identified as a contributing cause were to be compensated for his or her disease, how should that compensation be apportioned among those responsible for the asbestos exposures? For the purposes of apportionment, we assume that asbestos is the only cause of mesothelioma and that every asbestos exposure contributes, albeit differentially, to the risk. We use an extension of the mesothelioma risk model initially proposed in the early 1980s to quantify the contribution to risk of each exposure as a percentage of the total risk. The percentage for each specific discrete asbestos exposure depends on the start and end dates, the intensity, and the asbestos fiber type for the exposure. We provide justification for the use of the mesothelioma risk model for apportioning risk and discuss how to assess uncertainty associated with its application.
Asbestos↗
Asbestos directly increases lung epithelial permeability.
Asbestos causes the fibrotic lung disease asbestosis, but the biologic basis for this is unknown. Lung epithelial dysfunction including increased permeability is hypothesized to contribute to lung scarring in other forms of pulmonary fibrosis. Lung epithelial permeability is increased in both animals and humans exposed to asbestos. It is not known whether the increased epithelial permeability results from direct effects of asbestos or occurs as a result of the inflammatory reaction to asbestos fibers. To address this question we used a cultured human lung epithelial model, and we measured the direct effect of asbestos on lung epithelial barrier integrity as measured by mannitol permeability. We exposed the monolayer to chryogenically ground, respirable-sized chrysotile asbestos particles. This chrysotile asbestos caused a dose- and time-dependent increase in mannitol permeability across the epithelial monolayer. Increased mannitol permeability occurred both in the presence and in the absence of serum, was not due to cytotoxicity as measured by lactate dehydrogenase release, and was not associated with altered actin cytoskeleton at the light microscopic level. Permeability to 70 kDa neutral dextran also increased after asbestos exposure; however, the absolute permeability to dextran was less than mannitol permeability. Neither latex beads nor tantalum caused any change in permeability, suggesting that our findings are not explained by nonspecific effects of particles. Increased permeability did not reverse in the continued presence of asbestos and persisted even after removing the asbestos. Finally, surface-bound iron did not appear to be necessary for this effect because neither chelating iron with deferoxamine nor iron-loading the asbestos altered the effect on mannitol permeability. These results show that asbestos has direct effects on lung epithelial permeability. Together with the recent observation that asbestos directly increases epithelial fibrinolytic activity, our results suggest a novel mechanism for asbestos-induced lung injury.
Asbestos↗
Asbestos-induced lung inflammation and epithelial cell proliferation are altered in myeloperoxidase-null mice.
Asbestos fibers are carcinogens causing oxidative stress and inflammation, but the sources and ramifications of oxidant production by asbestos are poorly understood. Here, we show that inhaled chrysotile asbestos fibers cause increased myeloperoxidase activity in bronchoalveolar lavage fluids (BALF) and myeloperoxidase immunoreactivity in epithelial cells lining distal bronchioles and alveolar ducts, sites of initial lung deposition of asbestos fibers. In comparison with sham mice, asbestos-exposed myeloperoxidase-null (MPO-/-) and normal (MPO+/+) mice exhibited comparable increases in polymorphonuclear leukocytes, predominately neutrophils, in BALF after 9 days of asbestos inhalation. Differential cell counts on BALF revealed decreased proportions of macrophages and increased lymphocytes in all mice exposed to asbestos, but numbers were decreased overall in asbestos-exposed myeloperoxidase-null versus normal mice. Asbestos-associated lung inflammation in myeloperoxidase-null mice was reduced (P < or = 0.05) in comparison with normal asbestos-exposed mice at 9 days. Decreased lung inflammation in asbestos-exposed myeloperoxidase-null mice at 9 days was accompanied by increases (P < or = 0.05) in Ki-67- and cyclin D1-positive immunoreactive cells, markers of cell cycle reentry, in the distal bronchiolar epithelium. Asbestos-induced epithelial cell proliferation in myeloperoxidase-null mice at 30 days was comparable to that found at 9 days. In contrast, inflammation and epithelial cell proliferation in asbestos-exposed normal mice increased over time. These results support the hypothesis that myeloperoxidase status modulates early asbestos-induced oxidative stress, epithelial cell proliferation, and inflammation.
Animals↗
Quality control analysis of the potential for asbestos contamination during tissue processing in pathology laboratories.
CONTEXT: Various quality assurance procedures are applied in pathology and analytical microscopy laboratories to ensure accurate results. OBJECTIVE: To assess the potential of cross-contamination of tissue with asbestos fibers and asbestos bodies during the fixation and washing process. DESIGN: Lung tissue from 10 patients with potential asbestos-related disease was evaluated. Samples of fixative, water, and lung tissue from each case were evaluated by light and analytical transmission electron microscopy for asbestos bodies and uncoated asbestos fibers. RESULTS: The lung samples tested contained a range of asbestos bodies and uncoated asbestos fibers. One wash water sample contained one asbestos body. No asbestos bodies or uncoated asbestos fibers were found in any other water or fixative samples. CONCLUSIONS: The absence of uncoated asbestos fibers in wash water or fixative samples argues that the fixation process stabilizes asbestos fibers within tissue and the protocol used in this pathology laboratory protects against cross-contamination of tissue. The finding of one asbestos body in one water sample further supports the efficiency of the protective controls used in the testing methods, since this asbestos body was in the external solution that was being discarded before tissue sampling occurred.
Aged↗
Relation between lung asbestos fibre burden and exposure indices based on job history.
Lung asbestos burden was compared with exposure indices derived from job history interviews in 42 male subjects originating from the Montréal Case-Control Study project, 12 of whom had documented asbestos exposed job histories. Job interview data consisting of a chronological timetable of job histories were translated into detailed exposure indices by an expert group of hygienists and chemists. Total and individual asbestos fibre type concentrations were quantified by transmission electron microscopy with fibre identification by energy dispersive chi ray spectrometry after deparaffinisation of tissue blocks and low temperature plasma ashing. Geometric mean or median asbestos content was higher in subjects with an asbestos exposed job history than those without for retained dose of amosite, total commercial amphiboles, and total asbestos fibre. Except for crocidolite fibre diameter, which was significantly less in the lungs of exposed workers, no consistent differences were found in measurements of fibre dimension for any fibre type. Subgroups of subjects exposed to silica, metals, or smokers and non-smokers without significant occupational exposure showed varying patterns of lung asbestos fibre type deficit compared with the asbestos exposed subgroup. There was an overall trend for higher lung asbestos content proportional to higher exposure indices for asbestos representing concentration, frequency, and reliability. These exposure indices as well as duration of exposure (in years) were independent predictors of total asbestos content in regression analyses when combined in a model with age. Stepwise regression indicated that exposure concentration was the most important variable, explaining 32% of the total variation in total asbestos content. Smoking, whether expressed in ever or never smoked dichotomy or in smoked-years, had no relation to lung asbestos content in this model.
Adult↗