Abstract  To obtain complete establishment of all fatal cases of primary malignant mesothelioma (PMM) known to pathologists in Canada from 1960 to 1975 and in the United States (US) for 1972, data derived from published and unpublished surveys were consolidated and examined. Consideration was given to the epidemiologic interpretation and to etiologic factors. The results were discussed in regard to sex, age, and tumor site; incidence by age, sex, and geographic region; probability of occupational exposure to asbestos (1332214) for patients and referents; home exposure of patients and referents to the dusty clothing of asbestos workers; neighborhood exposure of patients and referents without occupational or domestic exposure; correlation of tumor site and occupation for patients and referents; exposure of patients and referents to dust from fiberglass (14808607), cement, rubber, copper (7440508), nickel (7440020), and wood; and cigarette smoking habits of patients and referents. Of the 395 male cases reported to the end of 1972, 78 and 22 percent were pleural and peritoneal, respectively; 61 and 39 percent of the female cases were pleural and peritoneal, respectively. Incidences of accepted cases of PMM differed little in three regions of Canada; rates for males in the US were highest in the Pacific and Mid Atlantic regions. The highest relative risk (RR), 46.0, was found in males employed in insulation, followed by asbestos production and manufacturing and the heating trades other than insulation, with RR values of 6.1 and 4.4, respectively. Eight subjects, but no referents, had been exposed at home to the dusty clothing of an asbestos worker. Excluding persons with occupational or domestic exposure, one US case had lived within 20 miles of a chrysotile (12001295) mine. Over half of male cases with pleural or peritoneal PMM had been employed in one of the five occupational groups having recognized association with PMM. Exposure to other dusts and cigarette smoking habits appeared not to be etiologic factors.

Abstract  Three parallel cohort studies of asbestos factory workers were undertaken to investigate the effects of mineral fibre type and industrial process on malignant mesothelioma, respiratory cancer, and asbestosis. This report describes the mortality of a cohort of 2543 men, defined as all those employed for at least a month from 1938 to 1958 in a textile plant in South Carolina in which chrysotile was the only type of asbestos used. Of these, 863 men (34%) had died before 31 December 1977, one from malignant mesothelioma. Twenty one deaths were ascribed to asbestosis and 66 to cancer of the lung. Compared with the number expected from South Carolina, there was an excess of 30 deaths from respiratory cancer (ICD 160-164) in men 20 or more years after first employment (SMR 199.5). In men employed five years or more, no SMRs for this category rose above 300. Individual exposures were estimated (in mpcf X years) from recorded environmental measurements. Life table analyses and "log-rank" (case-control) analyses both showed a steep linear exposure-response that was some 50-fold greater at similar accumulated dust exposures than in Canadian chrysotile mining and milling. These findings agree closely with those from another study in this plant and confirm that mesothelioma is rarely associated with chrysotile exposure. Cigarette smoking habits did not greatly differ between the textile workers and the Canadian miners and millers. The far greater risk of lung cancer in the textile industry, if not attributable to other identified cocarcinogens, may be related to major differences in the size distribution of fibres in the submicroscopic range which are not detected by the usual fibre or particle counting procedures.

Abstract  Asbestos materials are now infrequently used in new ship construction. However, significant amounts were used in vessels constructed before 1975. As a consequence, for the next 30 or more years, the potential for asbestos exposure in the repair of such vessels will remain. We studied 286 workers who were 30 or more years from onset of employment in ship repair work. Eighty-six percent had radiological evidence of asbestosis, and five instances of previously undiagnosed lung cancer were found. This suggests that unless industrial hygiene precautions are taken in the future repair of vessels that have been built with asbestos, we will add additional decades to the legacy we already face as the result of uncontrolled shipyard exposures of the past.

Abstract  In 72 experiments, durable minerals in the form of particles on respirable size and of wide chemical and structural varieties, were implanted in the pleurae of outbred female Osborne- Mendel rats for periods of more than 1 year. The incidence of induced malignant mesenchymal neoplasms correlated well with the dimensional distribution of the particles. The probability of pleural sarcoma correlated best with a number of fibers that measured 0.25 micro or less in diameter and more than 8 micrometer in length, but relatively high correlations were also noted with fibers in other size categories having diameters up to 1.5 micrometer and lengths greater than 4 micrometer. Morphologic observations indicated that short fibers and large-diameter fibers were inactivated by phagocytosis and that negligible phagocytosis of long, thin fibers occurred. The wide variety of compounds used in these experiments suggested that the carcinogenicity of fibers depended on dimension and durability rather than on physicochemical properties.

Abstract  A 30-year follow-up study of the mortality of 500 women employed in manufacturing gas masks during the second world war showed a pronounced excess of deaths from mesothelioma and lung cancer. Although these women were subject only to short periods of exposure, greater excesses were found for those exposed for between one and five years than for those exposed for under one year. Even in the latter group, however, five deaths from lung cancer and four deaths from mesothelioma were recorded compared with 1.5 deaths and 0.1 deaths expected (p approximately equal to 0.02). An excess of deaths from cancer of the ovary was also found, and this appeared to be related to exposure to asbestos.

Abstract  N/A.

Abstract  Long-term inhalation and intraperitoneal injection studies were undertaken with laboratory rats treated with a specially prepared short-fibre sample of Canadian chrysotile asbestos. This was compared, at an equal mass dose, to dust generated from the same chrysotile batch so as to contain the highest possible number of long fibres. The long-fibre cloud contained roughly five times more fibres greater than 5 micron in length as seen by phase contrast optical microscopy (PCOM). For increasing lengths, the ratio between the dust clouds increased progressively, reaching over 80: 1 for fibres greater than 30 microns in length. Rats treated with long-fibre chrysotile developed six times more advanced interstitial fibrosis (asbestosis) than animals treated with short-fibre chrysotile and three times more pulmonary tumours. At the end of the 12-month dusting period, three times more short chrysotile than long had been retained in the rat lung tissues. During the following 6 months, however, the short-fibre chrysotile was removed from the lungs much more rapidly than the long. Following intraperitoneal injection at a mass dose of 25mg of dust, both long and short chrysotile produced mesotheliomas in more than 90% of rats. At a dose level of 2.5mg of dust, the short-fibre chrysotile produced mesotheliomas in only one-third as many rats as the long-fibre dust which still produced mesotheliomas in more than 90% of animals injected. At a dose level of 0.25mg of dust, the short-fibre chrysotile produced no mesotheliomas while the long-fibre chrysotile still produced these tumours in 66% of rats. In the two highest doses, where short-fibre chrysotile produced mesotheliomas, the mean tumour induction period was significantly longer than for tumours produced by long chrysotile.

Abstract  Human exposure to fibers in occupational and nonoccupational environments has been a health concern for nearly a century. In this review, selected results from the literature are presented to highlight the availability, limitations, and interpretive difficulties associated with the past and current human fiber exposure data sets. In the traditionally defined asbestos fibers, large amounts of the data available suffer from the diversity of sample collection and analysis methods. Two simple generalizations suggest that occupational exposures are several orders of magnitude higher than that of environmental exposures; and currently extant data and the current routine measurement practices present significant difficulties in the consistent interpretation of the data with respect to health effects. The data on the human exposures to man-made vitreous fibers are much more complete than the data on asbestos exposure, while exposure data on other man-made fibrous materials are lacking. The human exposure data to many minerals which, at times, exist in fibrous habit, are very scanty, and in view of the biological activity of some of these fibers, this lack may be of significant concern.

Abstract  Opportunities for genital exposure to talc were assessed in 215 white females with epithelial ovarian cancers and in 215 control women from the general population matched by age, race, and residence. Ninety-two (42.8%) cases regularly used talc either as a dusting powder on the perineum or on sanitary napkins compared with 61 (28.4%) controls. Adjusted for parity and menopausal status, this difference yielded a relative risk of 1.92 (P less than 0.003) for ovarian cancer associated with these practices. Women who had regularly engaged in both practices had an adjusted relative risk of 3.28 (P less than 0.001) compared to women with neither exposure. This provides some support for an association between talc and ovarian cancer hypothesized because of the similarity of ovarian cancer to mesotheliomas and the chemical relation of talc to asbestos, a known cause of mesotheliomas. The authors also investigated opportunities for potential talc exposure from rubber products such as condoms or diaphragms or from pelvic surgery. No significant differences were noted between cases and controls in these exposures, although the intensity of talc exposure from these sources was likely affected by variables not assessed in this study.

Abstract  The relationship between the development of mesothelioma and occupational asbestos (1332214) exposure was investigated. A total of 162 hospitals serving 6.5 million people in Pennsylvania reported mesotheliomas diagnosed between 1958 and 1963. There were 34 mesotheliomas of the pleura and 8 of the peritoneum. Of the 15 cases in which lung tissue could be examined, 7 contained asbestos bodies. Of the 42 cases of mesothelioma, 10 had definite occupational exposure to asbestos, 3 were family contacts of asbestos workers, 8 lived in the immediate vicinity of asbestos factories, 6 were clustered around an insulation factory, and 21 had little or no asbestos exposure. Workers exposed to asbestos included makers of acoustic tile and linoleum, plaster and textile workers, and makers of asbestos insulation. The attack rate for mesothelioma was low, and a long latent period existed between exposure and onset of disease. The authors conclude that asbestos may be a causative or trigger agent for malignant mesothelioma in some cases.

Abstract  Background: Exposure to chrysotile dust has been associated with the development of mesothelioma and recent studies have implicated contaminating tremolite fibers as the likely etiological factor. Tremolite also contaminates talc, the most common non-asbestos mineral fiber in our control cases. Methods: We examined 312 cases of mesothelioma for which fiber burden analyses of lung parenchyma had been performed by means of scanning electron microscopy to determine the content of tremolite, non-commercial amphiboles, talc and chrysotile. The vast majority of these patients were exposed to dust from products containing asbestos. Results: Tremolite was identified in 166 of 312 cases (53%) and was increased above background levels in 81 cases (26%). Fibrous talc was identified in 193 cases (62%) and correlated strongly with the tremolite content (P < 0.0001). Chrysotile was identified in only 32 cases (10%), but still correlated strongly with the tremolite content (P < 0.0001). Talc levels explained less of the tremolite deviance for cases with an increased tremolite level than for cases with a normal range tremolite level (22 versus 42%). In 14 cases (4.5%) non-commercial amphibole fibers (tremolite, actinolite and/or anthophyllite) were the only fiber types found above background. Conclusions: We conclude that tremolite in lung tissue samples from mesothelioma victims derives from both talc and chrysotile and that tremolite accounts for a considerable fraction of the excess fiber burden in end-users of asbestos products.

Abstract  A study of the occupational histories of 52 females with malignant mesothelioma and certain of their relatives, carried out to measure the risk of this disorder attributable to indirect asbestos exposure, showed that a significantly greater number of husbands and fathers of cases than of controls worked in asbestos-related industries, and the relative risk for this factor was 10. The frequency of parental cancer, especially gastrointestinal malignancy, was also significantly greater for cases than for their controls. This raises the possibility of a genetic predisposition to malignant mesothelioma.

Abstract  This review assesses the contribution of occupational asbestos exposure to the occurrence of mesothelioma and lung cancer in Europe. Available information on national asbestos consumption, proportions of the population exposed, and exposure levels is summarized. Population-based studies from various European regions on occupational asbestos exposure, mesothelioma, and lung cancer are reviewed. Asbestos consumption in 1994 ranged, per capita, between 0. 004 kg in northern Europe and 2.4 kg in the former Soviet Union. Population surveys from northern Europe indicate that 15 to 30% of the male (and a few percent of the female) population has ever had occupational exposure to asbestos, mainly in construction (75% in Finland) or in shipyards. Studies on mesothelioma combining occupational history with biologic exposure indices indicate occupational asbestos exposure in 62 to 85% of the cases. Population attributable risks for lung cancer among males range between 2 and 50% for definite asbestos exposure. After exclusion of the most extreme values because of methodologic aspects, most of the remaining estimates are within the range of 10 to 20%. Estimates of women are lower. Extrapolation of the results to national figures would decrease the estimates. Norwegian estimates indicate that one-third of expected asbestos-related lung cancers might be avoided if former asbestos workers quit smoking. The combination of a current high asbestos consumption per capita, high exposure levels, and high underlying lung cancer rates in Central Europe and the former Soviet Union suggests that the lung cancers will arise from the smoking-asbestos interaction should be a major concern.

Abstract  To investigate translocation of asbestos fibers, tissue samples from 13 North American insulators were examined, using electron microscopy. Of the two major types of asbestos, chrysotile and amosite, chrysotile was found to be much more active in the translocation than amosite, being the fiber mainly detected in mesotheliomas and hyaline plaques.

Abstract  The Office of Drinking Water, Environmental Protection Agency, has prepared a Drinking Water Criteria Document on Asbestos. This Criteria Document is an extensive literature review of the following topics: physical and chemical properties of asbestos; toxicokinetics and human exposure to asbestos; health effects of asbestos in humans and animals; mechanisms of toxicity of asbestos; and quantification of toxicological effects of asbestos. (Author 's abstract)

Abstract  The National Institute for Occupational Safety and Health (NIOSH) has determined that exposure to asbestos fibers causes cancer and asbestosis in humans and recommends that exposures be reduced to the lowest feasible concentration. As the federal agency responsible for conducting research and making recommendations for the prevention of worker injury and illness, NIOSH has undertaken a reappraisal of how to ensure optimal protection of workers from exposure to asbestos fibers and other elongate mineral particles (EMPs). As a first step in this effort, NIOSH convened an internal work group to develop a framework for future scientific research and policy development. This State of the Science and Roadmap for Scientific Research (herein referred to as the Roadmap), clarifies NIOSH's REL, summarizes NIOSH's understanding of occupational exposure and toxicity issues concerning asbestos fibers and other EMPs, and identifies key issues which need to be resolved to allow NIOSH to update its REL. In 1990, NIOSH reviewed the available information on EMPs from the nonasbestiform analogs of the asbestos minerals. The epidemiological evidence was considered inconclusive, and the toxicological evidence was interpreted to mean that carcinogenic potential depends on a mineral particle's length and width and neither chemical composition nor mineralogical origin are critical factors in determining a mineral particle's carcinogenic potential. NIOSH also considered the lack of routine analytical methods to accurately and consistently distinguish between asbestos fibers and nonasbestiform EMPs in air samples. As a result of the review, NIOSH revised its REL at that time, retaining the 0.1 f/cm3 limit but explicitly encompassing EMPs from the nonasbestiform analogs of the asbestos minerals as a precautionary measure. Uncertainty remains concerning the adverse health effects that may be caused by nonasbestiform EMPs encompassed by NIOSH since 1990 in the REL for asbestos, and the Roadmap does not change NIOSH's REL. In the Roadmap, NIOSH makes clear that such nonasbestiform minerals are not "asbestos" or "asbestos minerals," and no longer refers to particles from the nonasbestiform analogs of the asbestos minerals as "asbestos fibers." However, particles that meet the specified dimensional criteria remain countable under the REL for the reasons stated above, even if they are derived from the nonasbestiform analogs of the asbestos minerals. NIOSH's intent is to reduce existing scientific uncertainties, to resolve current policy controversies, and to update its REL. To help accomplish these goals, the Roadmap proposes that interdisciplinary research address the following three strategic goals: (1) develop a broader and clearer understanding of the important determinants of toxicity for EMPs; (2) develop information on occupational exposures to various EMPs and health risks associated with such exposures; and (3) develop improved sampling and analytical methods for asbestos fibers and other EMPs. The results of the research programs are intended to provide a sound scientific foundation for development of future recommendations that provide optimal health protection. Originally published in March 2011, the Roadmap was revised in April 2011 to (1) correct an erroneous statement that NIOSH adopted the designation of asbestos as a "Potential Occupational Carcinogen" § in the 1970s; (2) more clearly indicate that NIOSH has determined that exposure to asbestos fibers causes cancer and asbestosis in humans; and (3) provide an updated discussion of the potency of chrysotile for causing mesothelioma.

Abstract  PURPOSE OF REVIEW: The vermiculite ore formerly mined in Libby, Montana, contains asbestiform amphibole fibers of winchite, richterite, and tremolite asbestos. Because of the public health impact of widespread occupational and nonoccupational exposure to amphiboles in Libby vermiculite, numerous related studies have been published in recent years. Here we review current research related to this issue. RECENT FINDINGS: Excess morbidity and mortality classically associated with asbestos exposure have been well documented among persons exposed to Libby vermiculite. Excess morbidity and mortality have likewise been documented among persons with only nonoccupational exposure. A strong exposure-response relationship exists for many malignant and nonmalignant outcomes and the most common outcome, pleural plaques, may occur at low lifetime cumulative exposures. SUMMARY: The public health situation related to Libby, Montana, has led to huge investments in public health actions and research. The resulting studies have added much to the body of knowledge concerning health effects of exposures to Libby amphibole fibers specifically and asbestos exposure in general.

Abstract  The differences between chrysotile asbestos, a serpentine mineral, and amphibole asbestos have been debated extensively. Many studies have shown that chrysotile is cleared from the lung more rapidly than amphibole. In order to quantify the comparative clearance of chrysotile and the amphibole asbestos tremolite, both fibers were evaluated in an inhalation biopersistence study that followed the European Commission recommended guidelines. In addition, the histopathological response in the lung was evaluated following the short-term exposure. This article presents the results of this study through 90 days after cessation of exposure. Following the termination of the study, a subsequent article will provide the complete results through 12 mo after cessation of exposure. In order to quantify the dynamics and rate by which these fibers are removed from the lung, the biopersistence of a sample of commercial grade chrysotile from the Coalinga mine in New Idria, CA, of the type Calidria RG144 and of a long-fiber tremolite were studied. For synthetic vitreous fibers, the biopersistence of the fibers longer than 20 microm has been found to be directly related to their potential to cause disease. This study was designed to determine lung clearance (biopersistence) and the histopathological response. As the long fibers have been shown to have the greatest potential for pathogenicity, the aerosol generation technique was designed to maximize the number of long respirable fibers. The chrysotile samples were specifically chosen to have 200 fibers/cm3 longer than 20 microm in length present in the exposure aerosol. These longer fibers were found to be largely composed of multiple shorter fibrils. The tremolite samples were chosen to have 100 fibers/cm3 longer than 20 microm in length present in the exposure aerosol. Calidria chrysotile fibers clear from the lung more rapidly (T1/2, fibers L > 20 microm = 7 h) than any other commercial fiber tested including synthetic vitreous fibers. With such rapidly clearing fibers, the 5-day exposure would not be expected to result in any pathological change in the lung, and the lungs of animals that inhaled Calidria chrysotile showed no sign of inflammation or pathology and were no different than the lungs of those animals that breathed filtered air. Following this 5-day exposure to tremolite, the tremolite fibers once deposited in the lung parenchyma do not clear and almost immediately result in inflammation and a pathological response in the lung. At the first time point examined, 1 day after cessation of exposure, inflammation was observed and granulomas were already formed. By 14 days postexposure these microgranulomas had turned fibrotic, and by 90 days postexposure the severity of the collagen deposits had increased and interstitial fibrosis was observed in one of the rats. These findings provide an important basis for substantiating both kinetically and pathologically the differences between chrysotile and the amphibole tremolite. As Calidria chrysotile has been certified to have no tremolite fiber, the results of the current study together with the results from toxicological and epidemiological studies indicate that this fiber is not associated with lung disease

Abstract  BACKGROUND: Mesothelioma is significant as an indicator of asbestos exposure, as a continuing major cause of death in those exposed, and as a risk following lesser exposures. One such exposure is living in the household of an asbestos worker, and coming into contact with fibers brought home on his/her body, clothing, etc.

METHODS: Law firms throughout the US known for their pursuit of asbestos claims were polled for mesothelioma claims brought on behalf of family members of identifiable asbestos-exposed workers. Cases with any occupational, environmental, or other possible exposure were not included.

RESULTS: This study reports 32 household-exposure mesothelioma cases, diagnosed since 1990. Relationships were wife (15), daughter (11), son (3), sister-in law (1), niece (1), and boarder (1). Occupations of the workers included shipyard (13), insulator (7), and other (12). Of the 27 pleural cases, 13 were epithelial, 5 fibrous, 3 biphasic, and 6 not specified; of the 5 peritoneal cases, 4 were epithelial and 1 fibrous. Latency was greater than 40 years in 27 cases; 6 cases were 40-49 years of age and 17 were 60 or older.

CONCLUSIONS: Records from law firms were a useful source of information. Mesothelioma resulting from household exposure is a continuing problem. It is more likely to present in the elderly, after latencies of >40 years.

Abstract  In former mine workers of Libby, MT, exposure to amphibole-containing vermiculite was linked to increased rates of asbestosis, lung cancer, and mesothelioma. Although many studies showed adverse effects following exposure to Libby amphibole (LA; a mixture of winchite, richterite, and tremolite), little is known regarding the relative toxicity of LA compared to regulated asbestos, or regarding the risks associated with acute high-dose exposures relative to repeated low-dose exposures. In this study, pulmonary function, inflammation, and pathology were assessed after single or multiple intratracheal (IT) exposures of LA or a well-characterized amosite (AM) control fiber with equivalent fiber characteristics. Male F344 rats were exposed to an equivalent total mass dose (0.15, 0.5, 1.5, or 5 mg/rat) of LA or AM administered either as a single IT instillation, or as multiple IT instillations given every other week over a 13-wk period, and necropsied up to 20 mo after the initial IT. When comparing the two fiber types, in both studies LA resulted in greater acute neutrophilic inflammation and cellular toxicity than equal doses of AM, but long-term histopathological changes were approximately equivalent between fibers, suggesting that LA is at least as toxic as AM. In addition, although no dose-response relationship was discerned, mesothelioma or lung carcinomas were found after exposure to low and high dose levels of LA or AM in both studies. Conversely, when comparing studies, an equal mass dose given over multiple exposures instead of a single bolus resulted in greater chronic pathological changes in lung at lower doses, despite the initially weaker acute inflammatory response. Overall, these results suggest that there is a possibility of greater long-term pathological changes with repeated lower LA dose exposures, which more accurately simulates chronic environmental exposures.

Abstract  We report a family with domestic exposure to asbestos and diagnosis of multiple cancers, including eight pleural malignant mesotheliomas and several other lung or pleural tumors. DNA sequence analysis revealed no evidence for an inherited mutation of BAP1. Sequence analysis of other potentially relevant genes, including TP53, CDKN2A, and BARD1, also revealed no mutation. DNA microarray analysis of tissue from two mesotheliomas revealed multiple genomic imbalances, including consistent losses of overlapping segments in 2q, 6q, 9p, 14q, 15q, and 22q, but no losses of chromosome 3 harboring the BAP1 locus. However, the results of immunohistochemical analysis demonstrated loss of nuclear BAP1 staining in three of six mesotheliomas tested, suggesting that somatic alterations of BAP1 occurred in a subset of tumors from this family. Since mesothelioma could be confirmed in only a single generation, domestic exposure to asbestos may be the predominant cause of mesothelioma in this family. Given the existence of unspecified malignant pleural tumors and lung cancers in a prior generation, we discuss the possibility that some other tumor susceptibility or modifier gene(s) may contribute to the high incidence of mesothelioma in this family. Because the incidence of mesothelioma in this family is higher than that expected even in workers heavily exposed to asbestos, we conclude that both asbestos exposure and genetic factors have played a role in the high rate of mesothelioma and potentially other pleural or lung cancers seen in this family. 

Abstract  CONTEXT: Numerous articles in the scientific literature indicate that pathogenic fibers with respect to asbestos-related diseases are those that exceed 5 μm in length. Nonetheless, some authors have expressed concerns regarding pathogenicity of shorter fibers.

OBJECTIVE: To review the scientific evidence regarding pathogenicity (or lack thereof) of fibers less than or equal to 5 μm in length, with particular attention to publications indicating that such fibers might be hazardous.

DATA SOURCES: The scientific literature was reviewed for experimental animal studies and human studies that address the role of fiber size in causation of disease. Sources included original studies, as well as review articles related to the topic.

CONCLUSIONS: Experimental animal studies involving inhalation of fibers have demonstrated that fibers greater than 5 μm in length are associated with both pulmonary fibrosis (ie, asbestosis) and malignancies (carcinoma of the lung and mesothelioma). There is no convincing evidence for a pathogenic effect for fibers that are 5 μm or less in length. Fiber analyses of human lung tissue samples provide further support for pathogenicity of long fibers, particularly the more biopersistent amphibole fibers. Similar observations have been reported for nonasbestos mineral fibers. Concerns expressed by some authors (eg, the greater abundance of short fibers) do not alter these conclusions. Similarly, in vitro studies demonstrating biological activity of short fibers do not override inhalational studies of whole animals or the epidemiological findings in humans.