[Size distribution of amphibole fibres from lung and pleural tissues sampled from mesothelioma cases due to environmental exposure]. / Caratterizzazione dimensionale di fibre anfiboliche nel polmone e nella pleura di casi di mesotelioma da esposizione ambientale.

BACKGROUND: It has been suggested that malignant mesothelioma might be mainly or only connected with the action of short and ultrathin fibres. On the basis of this hypothesis fibres less than 5 microm long and 0.2-0.1 microm thick would enter the pulmonary-pleura barrier and reach the parietal pleura thus inducing mesothelioma. The hypothesis raised a stimulating scientific discussion. OBJECTIVES: The aim of this communication is to report the initial results obtained comparing the size of amphibole fibres from healthy lung tissue with those from pleural tissue sampled from subjects whose death cause of death was mesothelioma. METHODS: Four mesothelioma cases due to environmental exposure were studied; the fibres were categorized by scanning electron microscopy; for every fibre, length and diameter were measured and the mineral type was defined by its chemical composition determined by X-ray microanalysis. RESULTS: The most important characteristics of the detected fibres were: the average length offibres from the lung and pleural tissues taken from the same subject did not difer, in all cases, by more than 10-12%; 95% offibres found in the lung tissues of all subjects had a length greater than 5 microm; 98% of fibres found in the pleural tissues had a length greater than 5 microm; the average diameter of the fibres found in the pleural tissues was 70% of the diameter of the fibres from the lung tissues. CONCLUSIONS: The experimental data obtained in this study confirm the correlation between malignant mesothelioma and the presence in the lung and pleural tissues of fibres with a length greater, even much greater, than 4-5 microm; thus the hypothesis that the chief factors inducing mesothelioma are the "ultrashort" and "ultrathin" fibres appears rather weak.

Mesothelioma and asbestos.

The current state of knowledge concerning mesothelioma risk estimates is reviewed. Estimates of the risk of mesothelioma exist for the commercial asbestos fiber types chrysotile, amosite and crocidolite. Data also exist on which to assess risks for winchite (sodic tremolite) and anthophyllite asbestos. Uncertainty in estimates is primarily related to limitations in measurements of exposure. Differences in the dimensions of the various fiber types and of the same fiber types at different stages of processing add a further complication. Never-the-less, in practical terms, crocidolite presents the highest asbestos related mesothelioma risk. The risk associated with sodic tremolite (winchite) appears to be similar. In chrysotile miners and millers, the mesothelioma risk has been linked with exposure to asbestiform tremolite. Exposure to chrysotile in a pure form seems likely to present a very low if any risk of mesothelioma. While the majority of mesothelial tumors result from exposure to the asbestos minerals, there are other well established and suspected etiological agents. While a practical threshold seems to exist for exposure to chrysotile, it is unlikely to exist for the amphibole asbestos minerals, especially for crocidolite. To date there is no indication of an increased risk of mesothelioma resulting from non-commercial fiber exposure in the taconite industry.

Exposure to airborne amphibole structures and health risks: Libby, Montana.

Libby, Montana is the site of a large vermiculite deposit that was mined between 1920 and 1990 to extract vermiculite for commercial applications such as insulation, gardening products, and construction materials. The Libby vermiculite deposit also contains amphibole minerals including tremolite, actinolite, richterite, and winchite. Historically, Libby mine workers experienced high exposures to amphibole structures, and, as a group, have experienced the health consequences of those occupational exposures. It has been suggested that Libby residents also have been and continue to be exposed to amphibole structures released during the vermiculite mining operations and therefore are at increased risk for disease. The Agency for Toxic Substance and Disease Registry (ATSDR) conducted two epidemiological-type studies of residents living in Libby and the surrounding areas to assess these risks. The Environmental Protection Agency (EPA) collected and analyzed exposure data in Libby and used those data to project risks of asbestos-associated disease for Libby residents. The EPA has placed the Libby Asbestos Site, which includes the mine and the town of Libby, on its National Priority List of hazardous waste sites in need of clean up. This article presents a review of the exposure studies conducted in Libby and an analysis of health risks based on the data collected in those studies. Libby mine workers have experienced elevated levels of asbestos-associated disease as a consequence of their occupational exposures to amphibole structures. Libby residents' exposures typically are substantially lower than mine workers' historical exposures, and the health risk projections for residents are, accordingly, substantially lower.

An overview of the risk of lung cancer in relation to exposure to asbestos and of taconite miners.

Exposure-response relationships between the relative risk of lung cancer and quantitative measures of exposure to asbestos are available from a number of epidemiological studies. Meta-analyses of these relationships have been published by Lash et al. (1997) [Lash, T.L., Crouch, E.A.C., Green, L.C., 1997. A meta-analysis of the relation between cumulative exposure to asbestos and relative risk of lung cancer. Occup. Environ. Med. 54, 254-263] and Hodgson and Darnton (2000) [Hodgson, J.T., Darnton, A., 2000. The quantitative risks of mesothelioma and lung cancer in relation to asbestos exposure. Ann. Occup. Hyg. 44, 565-601]. In this paper, the risks derived in these meta-analyses have been compared. Lash et al., concentrated on process and found that the risk of lung cancer increased as the asbestos is refined by processing. Hodgson and Darnton concentrated on fibre type and found that the risk was highest for exposure to amphibole asbestos (crocidolite and amosite), lowest for chrysotile and intermediate for mixed exposure. Some of the differences between the conclusions from the two meta-analyses are a consequence of the choice of studies included. The range of asbestos types included in the studies in the analysis of Hodgson and Darnton was wider than that in Lash et al., enabling differences between fibre types to be analyzed more readily. There are situations where occupational exposure to chrysotile asbestos has shown no detectable increase in risk of lung cancer. Taconite miners have shown no increased risk of mortality due to lung cancer.

South African experience with asbestos related environmental mesothelioma: is asbestos fiber type important?

South Africa (SA), a country in which all three commercially important asbestos minerals have been mined and milled, has retained proven cases of mesothelioma linked with environmental exposure to asbestos. This study illustrates the importance of fiber type in the occurrence of environmental mesothelioma. Four studies have reviewed the source of occupational or environmental asbestos exposure in 504 histologically proven cases of mesothelioma in South Africa. One hundred and eighteen cases (23%) were thought to be related to environmental exposure to asbestos. In the vast majority of these cases, exposure was linked to crocidolite mining activities in the Northern Cape Province. Two cases were thought to have occurred in relation to amosite and Transvaal crocidolite exposure in the Limpopo Province. In the balance of cases there was some uncertainty. No cases were reported with exposure to South African chrysotile. Consequently, in the vast majority of cases of mesothelioma, environmental exposure to asbestos occurred in the Northern Cape Province, in proximity to mines, mills and dumps where crocidolite was processed. Crocidolite appears to be far more mesotheliomagenic than amosite, and chrysotile has not been implicated in the disease. This is true for both occupationally and environmentally exposed individuals.

Assessment of the pathogenic potential of asbestiform vs. nonasbestiform particulates (cleavage fragments) in in vitro (cell or organ culture) models and bioassays.

Asbestos fibers are highly fibrous silicate fibers that are distinguished by having a large aspect (length to diameter) ratio and are crystallized in an asbestiform habit that causes them to separate into very thin fibers or fibrils. These fibers are distinct from nonasbestiform cleavage fragments and may appear as thick, short fibers which break along cleavage planes without the high strength and flexibility of asbestiform fibers. Since cleavage fragments of respirable dimensions have generally proven nonpathogenic in animal studies, little data exists on assessing well-characterized preparations of cleavage fragments in in vitro models. The available studies show that cleavage fragments are less bioreactive and cytotoxic than asbestiform fibers.

Risk assessment due to environmental exposures to fibrous particulates associated with taconite ore.

In the early 1970s, it became a concern that exposure to the mineral fibers associated taconite ore processed in Silver Bay, Minnesota would cause asbestos-related disease including gastrointestinal cancer. At that time data gaps existed which have now been significantly reduced by further research. To further our understanding of the types of airborne fibers in Silver Bay we undertook a geological survey of their source the Peter Mitchell Pit, and found that there are no primary asbestos minerals at a detectable level. However we identified two non-asbestos types of fibrous minerals in very limited geological locales. Air sampling useful for risk assessment was done to determine the type, concentrations and size distribution of the population of airborne fibers around Silver Bay. Approximately 80% of the airborne fibers have elemental compositions consistent with cummingtonite-grunerite and the remaining 20% have elemental compositions in the tremolite-actinolite series. The mean airborne concentration of both fiber types is less than 0.00014 fibers per milliliter that is within the background level reported by the World Health Organization. We calculate the risk of asbestos-related mesothelioma and lung cancer using a variety of different pessimistic assumptions. (i) that all the non-asbestos fibers are as potent as asbestos fibers used in the EPA-IRIS listing for asbestos; with a calculated risk of asbestos-related cancer for environmental exposure at Silver Bay of 1 excess cancer in 28,500 lifetimes (or 35 excess cancers per 1,000,000 lifetimes) and secondly that taconite associated fibers are as potent as chrysotile the least potent form of asbestos. The calculated risk is less than 0.77 excess cancer case in 1,000,000 lifetimes. Finally, we briefly review the epidemiology studies of grunerite asbestos (amosite) focusing on the exposure conditions associated with increased risk of human mesothelioma.

The So-called Short-Fiber Controversy: Literature Review and Critical Analysis.

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.

An introduction to the short-term toxicology of respirable industrial fibres.

Fibrous materials, exemplified by asbestos, that release respirable fibres are in common use and there is considerable knowledge regarding the toxicology of these common fibres. Newer materials or those that are under development, such as synthetic organic fibres and carbon nanotubes may have a different toxicology paradigms. The existing paradigm for silicate fibres suggests that respirable fibre types vary in their ability to cause lung disease and that this can be understood on the basis of the length of the fibres and their biopersistence in the lungs. Because fibres are regulated on a fibre number basis and the hazard is understood on the basis of the number of long fibres, in fibre testing the dose should always be expressed as fibre number, not mass and the length and diameter distribution need to be known. Short-term biological tests are likely to produce false positives in the case of long non-biopersistent fibres, because whilst they may have effects in vitro, they do not persist long enough in the lungs for sufficient dose to build up and produce effects in vivo. The biopersistence of fibres is therefore a key factor that needs to be known in order to interpret short-term tests that may claim to predict fibre pathogenicity.

No effect or no information? Comments on a nested case-control study of lung cancer among European rock and slag wool production workers.

The author considers the validity of a recent study of lung cancer among European rock and slag wool workers. The study failed to demonstrate an association between lung cancer and exposure to man-made vitreous fibers and also did not manage to demonstrate a relationship between lung cancer and asbestos exposure, an odd finding that casts doubt on its validity. This article deals with bias towards the null and other aspects of the reviewed study that may explain its failure to demonstrate an effect of asbestos, concluding that the study does not add to knowledge about a possible carcinogenic effect of rock and slag wool fibers, the apparent null results simply being non-informative because of the study's poor ability to detect existing associations.

Relationships between ferruginous bodies and uncoated asbestos fibers in lung tissue.

Tissue was obtained from two American groups. The tissue was defined by ferruginous body levels of either < or = 1000 or > 1000 ferruginous bodies/g dry weight, and tissue was evaluated by light microscopy and analyzed by analytical transmission electron microscopy. Tissue was bleach digested, and uncoated asbestos fibers were classified with respect to type and size. In addition, some ferruginous body cores were analyzed. There was a wide range of uncoated fibers associated with each ferruginous body. A relationship was found between amosite fibers and ferruginous bodies. Other asbestos types were not associated significantly with the development of ferruginous bodies. Uncoated crocidolite fibers were not detected in these samples; this result further emphasizes the under-appreciated exposure of Americans to amosite. The levels of ferruginous bodies in both groups suggest exposures above those expected in the general population. Uncoated chrysotile levels were below the ranges reported previously for some general populations. The data suggest that there is a wide variation in the ratio of uncoated to coated fibers and that the amphibole in the United States is more likely to be amosite than crocidolite.

Lung mineral fibers of former miners and millers from Thetford-Mines and asbestos regions: a comparative study of fiber concentration and dimension.

Fiber dimension and concentration may vary substantially between two necropsy populations of former chrysotile miners and millers of Thetford-Mines and Asbestos regions. This possibility could explain, at least in part, the higher incidence of respiratory diseases among workers from Thetford-Mines than among workers from the Asbestos region. The authors used a transmission electron microscope, equipped with an x-ray energy-dispersive spectrometer, to analyze lung mineral fibers of 86 subjects from the two mining regions and to classify fiber sizes into three categories. The most consistent difference was the higher concentration of tremolite in lung tissues of workers from Thetford-Mines, compared with workers from the Asbestos region. Amosite and crocidolite were also detected in lung tissues of several workers from the Asbestos region. No consistent and biologically important difference was found for fiber dimension; therefore, fiber dimension does not seem to be a factor that accounts for the difference in incidence of respiratory diseases between the two groups. The greater incidence of respiratory diseases among workers of Thetford-Mines can be explained by the fact that they had greater exposure to fibers than did workers at the Asbestos region. Among the mineral fibers studied, retention of tremolite fibers was most apparent.

[Refractory ceramic fibers, kinds, health effects after exposure, TLVs]. / Ogniotrwale wlókna ceramiczne, rodzaje, skutki zdrowotne ekspozycji, NDS.

Ceramic fibres are amorphous or crystalline synthetic mineral fibres which are characterised by refractory properties (i.c. stability in temperature above 1000 degrees C). In general, ceramic fibres are produced from aluminium oxide, silicon oxide and other metal oxides and less frequently from non-oxide materials such as silicon carbide, silicon nitride and boron nitride. In Poland, the production of ceramic fibres was begun in the Refractory Materials Plant, Skawina, during mid-eighties. The production capacity accounts for about 600 tons annually. It is estimated that approximately 3000 persons are exposed to the effect of ceramic fibres in Poland. During the production of ceramic fibres, concentrations of respiral fibres in the air at work places range from 0.07 to 0.27 f/cm3; during the manufacture of ceramic fibre products from 0.23 to 0.71 f/cm3 and during the application of ceramic fibre products from 0.07 to 1.67 f/cm3. As published data depict, fibres longer than 5 microns are most common in the work environment, and the proportion of fibres with diameters below 1 micron accounts for 40-50%. Bearing in mind the present situation in Poland, namely combined exposure to asbestos (during removal of worn out heat-insulating materials) and ceramic fibres (during installation of new insulation), as well as in view of own investigations and literature data which evidence a strong carcinogenic effect of certain fibres, the following MAC values have been adopted: Dusts of refractory ceramic fibres: total dust-2 mg/m3; respirable fibres-1 f/cm3 (L > 5 microns; D < 3 microns; L: D < 3:1) Dusts of reflactory ceramic fibres mixed with asbestos: total dust-1 mg/m3; respirable fibres-1 f/m3. Dusts of refractory ceramic fibres mixed with other man-made mineral fibres (MMMF): total dust-2 mg/m3; respirable fibres-1 f/m3. According to the IARC, ceramic fibres have been included into group 2B-suspected human carcinogen.

[Health effects of artificial mineral fibers]. / Effets sur la santé des fibres minérales artificielles.

Data from mortality studies in cohorts of workers employed in the production of man-made mineral fibres, where levels of exposure were generally low, show an excess of mortality by lung cancer, although the role of the fibres themselves remains unclear in this excess. Standardized mortality ratio for lung cancer was lower in glass-wool production workers than in rock-slag-wool workers. Preliminary data for refractory ceramic fibres-exposed workers suggest the occurrence of benign pleural diseases and obstructive functional defects. Attention should be paid to levels of exposure to various man-made mineral fibres encountered by end-users commonly exposed to peaks of fibre concentrations higher than production workers.

Classification of man-made vitreous fibers: Comments on the revaluation by an IARC working group.

In 2001, an IARC working group revaluated the carcinogenic risks of man-made vitreous fibers (MMVF). Compared with the IARC evaluation in 1987, the overall evaluations of insulation glass wool, rock (stone) wool, and slag wool were changed from Group 2B to Group 3. These changes ensued from an alteration in the evidence for cancer in humans and in experimental animals: Instead of "sufficient," the evidence for cancer in experimental animals is now looked upon as "limited" if there is a carcinogenic response after intraperitoneal injection but not after recently conducted inhalation experiments. For these studies, it is argued that they did properly address the technological limitations of earlier inhalation experiments. For Maxim and McConnell [Maxim L.D., McConnell E.E., 2001. Interspecies comparisons of the toxicity of asbestos and synthetic vitreous fibers: a weight-of-the-evidence approach. Regul. Toxicol. Pharmacol. 33, 319-342], well-conducted inhalation studies are very sensitive and rats may be more sensitive than humans in detecting the carcinogenic potential of MMVF. However, their arguments are highly questionable. The explanations of the IARC working group for preferring the newer inhalation studies are not sufficiently supported by the published data. Having in mind the higher sensitivity of humans compared to rats after inhalation of asbestos, more emphasis should have been given to the carcinogenic response after intraperitoneal injection.

Comparison of measures of exposure to asbestos in former crocidolite workers from Wittenoom Gorge, W. Australia.

Determinations of exposure-response relationships between crocidolite and the major asbestos-related diseases in the Wittenoom cohort have previously depended on the validity of estimates of airborne exposure to asbestos. This work aims to validate the airborne exposure measurements by obtaining measurements of the concentrations of uncoated crocidolite fibers and asbestos bodies retained in the lungs of individual workers, and to estimate the half-life of crocidolite fibers in the lungs. Samples of lung tissue, excluding tumor, of all former Wittenoom workers known to have died in Western Australia (WA) were sought from teaching hospitals, pathology departments, and the Coroner's pathologist. The lung specimens were processed using Pooley's method with TEM for counts of fibers of all types and using Smith and Naylor's method with conventional light microscopy for asbestos bodies (AB). Multiple linear regression was utilized to examine the associations between crocidolite concentrations in the lung and duration of employment at Wittenoom, time since last employed at Wittenoom, nature of job, estimated average fiber concentration at the worksite, and estimated cumulative crocidolite exposure (CCE) in fiber-years/ml for each subject. Lung tissue from 90 cases was processed and there was good agreement between counts of crocidolite fibers, asbestos bodies, and CCE. Correlations were 0.77 for AB and fibers, 0.54 for AB and CCE, and 0.58 for CCE and fibers, after log transformation. The half-life of crocidolite fibers in the lung was estimated at 92 months (95% CI 55-277 months). Previous estimates of airborne exposure to Wittenoom crocidolite have been reasonably reliable. The relatively simple technique of light microscopy for counting ABs in lung tissue also provides a useful and reliable indication of the level of past occupational exposure to crocidolite in subjects whose exposure has been only to crocidolite. The half-life of crocidolite fibers in the lungs of former Wittenoom workers is about 7-8 years.

Potential significance of airborne fiber dimensions measured in the U.S. refractory ceramic fiber manufacturing industry.

BACKGROUND: To determine dimensions of airborne fibers in the U.S. refractory ceramic fiber (RCF) manufacturing industry, fibers collected through personal air sampling for employees at RCF manufacturing and processing operations have been measured. METHODS: Data were derived from transmission electron microscopy analyses of 118 air samples collected over a 20-year period. RESULTS: Characteristics of sized fibers include: diameter measurements of <60; 0.19 to 1.0 micron, m of which 75% are less than 0.6 micron and length ranging from < 0.6 to > 20 micron, with 68% of fibers between 2.4 and 20 micron. CONCLUSIONS: Exposures in RCF manufacturing include airborne fibers with dimensions (diameter < 0.1-0.4 micron, length < 10 micron) historically associated with biological effects in pleural tissues. Air sampling data and a review of studies relating fiber size to pleural effects in animals and humans support the belief that information on fiber dimensions is essential for studies with synthetic vitreous fibers.