Analysis of asbestos bodies in BAL from subjects with particular exposures

Four patients with asbestos-related diseases and with unusual exposures underwent bronchoalveolar lavage (BAL) for mineralogical analysis. Asbestos bodies (AB) were counted by light microscopy and analyzed by transmission electron microscopy and X-ray energy spectrometry. AB's were found in all cases, after a mean delay from the end of exposure of 27.7 years. Analysis of the core fibers indicated the type of alveolar asbestos burden and was compared with the previous exposures: —Pleural plaques due to household exposure to amosite and crocidolite. —Pleural plaques due to occult occupational exposure to crocidolite in a coal miner. —Asbestosis due to environmental exposure to tremolite in Turkey. —Asbestosis, pleural plaques, and peritoneal mesothelioma due to a short, intense exposure to crocidolite. AB counting in BAL and identification of the central fibers by analytical electron microscopy is a useful, non-invasive and reliable method to evaluate the alveolar retention of bio-persistent fibers and to relate them to specific exposures. Am. J. Ind. Med. 31:699–704, 1997. © 1997 Wiley-Liss, Inc.     

Tumor incidence was not related to the thickness of visceral pleural in female Syrian hamsters intratracheally administered amphibole asbestos or manmade fibers.

Histological observations were performed on female Syrian hamsters 2 years after the intratracheal administration of amphibole asbestos, amosite, and crocidolite to evaluate the tumorigenicity of six types of fine manmade fibers (reported previously). A mesothelioma and a lung tumor were induced in 20 animals administered amosite, but no tumors were found in the crocidolite group. Because this incidence is not higher than that of manmade fibers, such as basic magnesium sulfate fiber [9 tumor-bearing hamsters in 20 hamsters (9/20)], metaphosphate fiber (5/20), calcium sulfate fiber (3/20), and fiberglass (2/20), it is suggested that some types of manmade fibers have a greater ability than asbestos to induce tumors. Moreover, as a specific observation in manmade fiber groups, tumors were induced at intracelial organs rather than at the pleural cavity. On the other hand, the average thickness of visceral pleura was higher in all asbestos and manmade fiber groups than in the control (2.9 microns), for instance, 36.95 microns in potassium titanate fiber group, 15.90 microns crocidolite group, 13.00 microns basic magnesium sulfate fiber group, and 10.45 microns in the rockwool group. Although both pleural thickening and mesothelioma are known as peculiar lesions in asbestos-exposed people, it might also be suggested that these lesions could be induced by different mechanisms from the result that there was no relation between the pleural thickening and mesothelioma incidence in hamsters.     

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

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

Malignant mesothelioma caused by childhood exposure to long-fiber low aspect ratio tremolite

A 41-year-old man was found to have a malignant mesothelioma of the pleura. During childhood in Corsica, he had been exposed at home to chrysotile ore from the Canari mine. Analysis of lung mineral content revealed background levels of chrysotile but an elevated level of tremolite and actinolite asbestos. The latter had a geometric mean length of 3.7 μm, a value considerably longer than we have found for tremolite and actinolite from Quebec chrysotile miners but roughly the same as the mean length of amosite and crocidolite in workers with occupational amphibole exposure. No tremolite or actinolite fibers of length greater than 8 μm microns and width less than 0.25 μm were observed. The mean aspect ratio of the tremolite and actinolite fibers was 7, a value similar to that found in chrysotile miners with mesothelioma but considerably less than the mean aspect ratio of amosite and crocidolite from those with occupational expsoure. These data suggest that long-fiber tremolite is a potential mesothelial carcinogen in humans, and that fiber length is more important than fiber aspect ratio in this regard.     

Fibers in lung tissues of mesothelioma cases among miners and millers of the township of asbestos,quebec

Twenty cases of mesothelioma among miners of the township of Asbestos, Quebec, Canada, have been reported. To further explore the mineral characteristics of various fibrous material, we studied the fibrous inorganic content of postmortem lung tissues of 12 of 20 available cases. In each case, we measured concentrations of chrysotile, amosite, crocidolite, tremolite, talc-anthophyllite, and other fibrous minerals. The average diameter, length, and length-to-diameter ratio of each type of fiber were also calculated. For total fibers > 5 μm, we found > 1,000 asbestos fibers per mg tissue (f/mg) in all cases; tremolite was above 1,000 f/mg in 8 cases, chrysotile in 6 cases, crocidolite in 4 cases, and talc anthophyllite in 5 cases. Among cases with asbestos fibers, the tremolite count was highest in 7 cases, chrysotile in 3 cases, and crocidolite in 2 cases. The geometric mean concentrations of fibers ? 5 μm were in the following decreasing order: tremolite > crocidolite > chrysotile > other fibers > talc-anthophyllite > amosite. For total fibers < 5 μm, we found > 1,000 fibers per mg tissue (f/mg) in all cases; tremolite was above 1,000 f/mg in 12 cases, chrysotile in 8 cases, crocidolite in 7 cases, and talc-anthophyllite in 6 cases. Tremolite was highest in 8 cases, chrysotile in 2 cases, and crocidolite and amosite in 2 cases. The geometric mean concentrations of fibers < 5 μm were in the following decreasing order: tremolite > other fibers > chrysotile > crocidolite > talc-anthophyllite > amosite. We conclude, on the basis of the lung burden analyses of 12 mesothelioma cases from the Asbestos township of Quebec, that the imported amphibole (crocidolite and amosite) were the dominant fibers retained in the lung tissue in 2/12 cases. In 10/12 cases, fibers from the mine site (chrysotile and tremolite) were found at highest counts; tremolite was clearly the highest in 6, chrysotile in 2, and 2 cases had about the same counts for tremolite and chrysotile. If a relation of fiber burden-causality of mesothelioma is accepted, mesothelioma would be likely caused by amphibole contamination of the plant in 2/12 cases and by the mineral fibers (tremolite and chrysotile) from the mine site in the 10 other cases.     

Fibrous minerals in the lungs of mesothelioma patients: comparison between data on SEM, TEM, and personal interview information.

To determine and compare the fiber types and size distributions in the lung tissue of mesothelioma patients in Finland, samples from 29 patients with known work history were analyzed with transmission electron microscopy (TEM) and X-ray microanalysis. Compared with the earlier results using scanning electron microscopy (SEM), the fiber concentrations were about three times as high and ranged from 0.1 million to 5,200 million fibers per gram of dry tissue. In 15 patients (52%), crocidolite/amosite were the dominating fiber types, representing more than 70% of all fibers. Anthophyllite asbestos was the most prevalent fiber type in eight patients (28%), and it was found in the samples of 13 patients (45%). One-half of the anthophyllite fibers were longer than 5 microns, whereas other fiber types were somewhat smaller.     

Malignant mesothelioma induced in baboons by inhalation of amosite asbestos

Ten out of 12 South African baboons (Papio ursinus) survived exposure to amosite asbestos dust for periods ranging from 242 days to 898 days at an aerosol level ranging between 1,100 and 1,200 fibers per milliliter. After exposure, they were kept under observation until they died; the total residence time of amosite varied from 1.2–10.2 years. All underwent detailed postmortem necropsy examinations. All baboons had asbestosis. Five of the baboons developed malignant diffuse mesothelioma; three peritoneal, and two pleural with peritoneal invasion. These results indicate that amosite is highly carcinogenic. Since it is difficult to accomplish follow-up of persons exposed to amosite asbestos because of the geographic location of the amosite mines and mills in South Africa (a majority of the workers being migrant laborers from countries bordering on the Transvaal), it is therefore probable that cases of peritoneal mesothelioma have been missed. If human beings are likely to react to amosite as do baboons, epidemiological follow-up should include identification of abdominal as well as thoracic neoplasms. © 1993 Wiley-Liss, Inc.     

Inhalation carcinogenesis from various forms of asbestos

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

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.     

Diffuse malignant pleural mesothelioma in an urban hospital: clinical spectrum and trend in incidence over time

This retrospective analysis reviews the clinical experience of a major urban referral hospital with diffuse malignant pleural mesothelioma during the 14-year period from 1973 through 1986. Seventy-five cases of definite or equivocal mesothelioma were identified. There were four cases of primary malignant peritoneal mesothelioma, seven cases of benign fibrous mesothelioma, and 64 cases of diffuse malignant pleural mesothelioma. In 43 cases (67%) of diffuse malignant pleural mesothelioma, there was historic evidence of asbestos exposure. In 21 cases (33%), there was no known history of asbestos exposure. An increase in annual incidence of diffuse malignant pleural mesothelioma was observed over the study period, from three cases in 1973 to ten cases in 1986. Despite greater awareness of this disease, the diagnosis remains a difficult one to establish given the nonspecific symptoms, signs and radiographic appearance, variable histologic appearance, and poor diagnostic sensitivity and specificity of thoracentesis and closed pleural biopsy. Thoracotomy, thoracoscopy, and CT-guided needle biopsies gave higher yields and are the diagnostic measures of choice when diffuse malignant pleural mesothelioma is suspected.     

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.     

Asbestos-related disease associated with exposure to asbestiform tremolite

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

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

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

Carcinoma of the colon in asbestos-exposed workers: analysis of asbestos content in colon tissue.

Epidemiological studies have indicated an increased incidence of carcinoma of the colon in asbestos workers. The present study evaluated the colon tissue asbestos burden, by light and electron microscopic analytic techniques, in patients with a history of occupational asbestos exposure and colon cancer. Asbestos fibers and/or asbestos bodies were present in colon tissue from 14 of 44 (31.8%) asbestos workers with colon carcinoma (range 142,199 to 15,231, 543 fibers/g/wet weight, mean 2,517,823). Chrysotile was identified in 9 patients and amosite in 3 patients. Both amosite and chrysotile were found in the colonic wall in one individual. Other forms of asbestos (e.g., crocidolite, tremolite, or anthophyllite) were not found. Asbestos fibers and asbestos bodies were not found in colon tissue from 20 control patients (colon carcinoma and no asbestos exposure). Asbestos fibers frequently enter and reside in the wall of the colon and are often intimately associated with tumor tissue at the site of colon carcinoma in workers with asbestos exposure and colon carcinoma.     

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

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

Asbestos-related lung cancer and mesothelioma in Japan

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

Amosite mesothelioma in a cohort of asbestos workers

A cohort of 820 asbestos workers with a short duration of exposure to amosite between 1941 and 1945 was followed. These men were alive five years after starting work and were observed until 1988. Seventeen cases of malignant mesothelioma (eight pleural, nine peritoneal) were found. The mean age at the onset of exposure was 33 years for men with pleural mesothelioma and 30 years for those with peritoneal mesothelioma. Chest pain was the main symptom in pleural mesothelioma and abdominal pain in peritoneal mesothelioma. Open lung biopsy was the most useful diagnostic approach for pleural mesothelioma, whereas for peritoneal mesothelioma it was exploratory laparotomy. Pleural patients died of pulmonary insufficiency, and peritoneal patients of wasting and inanition. In both groups the death certificate diagnosis was less accurate than the clinical diagnosis at death. The mean survival was 12.5 months from first symptom to death for the pleural group and 5.4 months for the peritoneal group.     

Asbestos bodies in lung tissue following exposure to crocidolite

A series of 206 necropsies in Western Australia (WA) have had routine counts made of asbestos bodies in samples of lung tissue using conventional light microscopy. Thirty-two cases had worked in the asbestos industry at Wittenoom, WA and (log) counts of asbestos bodies in their lung tissue correlated well with estimates of their (log) cumulative airborne exposure to crocidolite fibers (r = 0.60). There was no association between the number of asbestos bodies and time since exposure to asbestos ceased. In subjects without known exposure to asbestos, there was a weak but nonsignificant increase in number of asbestos bodies with increasing age, with 26% of cases having no asbestos bodies present. It is concluded that the relatively simple technique of light microscopy for counting of asbestos bodies in lung tissue provides a reliable indication of the level of past occupational exposure to crocidolite in subjects whose exposure has been only to crocidolite. This could be extremely useful in follow-up studies of cohorts that lack reliable measures of airborne exposure to crocidolite asbestos.     

Asbestos and Peritoneal Mesothelioma among College-educated Men

Abstract

The proportion of peritoneal mesotheliomas among all mesotheliomas has been decreasing, leading some to suggest that peritoneal mesothelioma occurs only after high levels of exposure to asbestos. To investigate the relationship between asbestos exposure and the development of peritoneal mesothelioma, a case–control study examined 40 cases of primary peritoneal mesothelioma from a single institution. This series differed from previous reports in that 75% of the cases and controls had attended college. Results show an odds ratio of 6.6 for asbestos exposure among this group of primary peritoneal mesothelioma cases with relatively slight asbestos exposures.     

Cancer in ex‐asbestos cement workers in Israel, 1953–1992

A cohort of 3,057 male workers employed in an asbestos‐cement plant using 90% chrysotile‐10% crocidolite, located in Northern Israel, was followed from 1953–1992 for incidence and mortality from cancer. In the years 1978–1992, the cohort had an elevated risk for all malignant neoplasms combined (n > 153, SIR > 117, ns), lung cancer (n > 28, SIR > 135, ns), mesothelioma (n > 21; SIR >5000, p > .0001), unspecified pleural cancer (n > 5; SIR > 278 , P > .0001), and liver cancer (n > 7, SIR 290, ns). Risks for colo‐rectal (n > 19; SIR > 79, ns), bladder (n = 12, SIR 69) and renal cancers (n > 5, SIR 104) were less than expected. Risk for mesothelioma showed a sharp risk gradient with duration of exposure, increasing from 1 per 625 for those employed less than 2 years to 1 per 4.5 workers employed over 30 years. The ratio of mesothelioma to excess lung cancer cases was 2.9 to 1, or 3.6 to 1, if pleural cases of unspecified origin were included; the pleura to peritoneum ratio of verified mesothelioma cases was 20 to 1. This atypically high ratio of mesothelioma to excess lung cancer cases is suggested to be the combined result of high past asbestos exposures in the workers and their low prior risk for lung cancer, and possibly, relatively early smoking cessation in relation to asbestos exposure. Am. J. Ind. Med. 35:1–8, 1999. © 1999 Wiley‐Liss, Inc.