Non-Neoplastic and Neoplastic Pleural Endpoints Following Fiber Exposure

University of California, San Francisco, San Francisco, California, USA.
Journal of Toxicology and Environmental Health Part B (Impact Factor: 5.15). 05/2011; 14(1-4):153-78. DOI: 10.1080/10937404.2011.556049
Source: PubMed

ABSTRACT Exposure to asbestos fibers is associated with non-neoplastic pleural diseases including plaques, fibrosis, and benign effusions, as well as with diffuse malignant pleural mesothelioma. Translocation and retention of fibers are fundamental processes in understanding the interactions between the dose and dimensions of fibers retained at this anatomic site and the subsequent pathological reactions. The initial interaction of fibers with target cells in the pleura has been studied in cellular models in vitro and in experimental studies in vivo. The proposed biological mechanisms responsible for non-neoplastic and neoplastic pleural diseases and the physical and chemical properties of asbestos fibers relevant to these mechanisms are critically reviewed. Understanding mechanisms of asbestos fiber toxicity may help us anticipate the problems from future exposures both to asbestos and to novel fibrous materials such as nanotubes. Gaps in our understanding have been outlined as guides for future research.

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    • "In vitro, chrysotile was shown to be toxic, caused chromosomal aberrations and preneoplastic transformations [39]; it was reported to be the most potent inflammatory stimulus among all asbestos types [47]. At the same time, there is evidence from epidemiological studies that chrysotile is less efficient in MM induction than the amphiboles [48] [49]. Some epidemiological data favoring chrysotile have been revised at a later date [50]. "
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    ABSTRACT: Asbestos-related health risks have been evaluated on the basis of past experience, when occupational exposures were much higher; while the linear no-threshold (LNT) approach has usually been applied. However, applicability of the LNT dose-response pattern to low levels of asbestos exposure has never been proven. Asbestos-related research has been influenced by vested interests and biases. Furthermore, current evidence does not provide sufficient support for a separate approach to serpentine (chrysotile) and amphibole asbestos by official regulations, the more so as the international trade provides for mixing of different asbestos types. Carcinogenicity and other harmful properties of different asbestos fibers, and of man-made asbestos substitutes, should be tested in large-scale animal experiments. Importantly, researchers must be independent from vested interests. In the meantime, the All Fibers Equal basis for the asbestos-related regulations would be an optimal solution. Current asbestos-related policies are irrational: asbestos production and use are banned by some countries, while others are increasing the manufacturing and exports. The rules and regulations should be internationally coordinated and revised on the basis of scientific knowledge.
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    • "One experimental issue concerns the dissimilarities between the pleural cavities of different species. Despite these differences, much has been learned about the mechanisms of pleural disease, particularly the interactions between fibers and target cells, both in the pleural cavities of laboratory animals and in in vitro studies using both animal and human cells (Broaddus et al. 2011). Non pulmonary effects after asbestos exposure are not well understood. "
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    ABSTRACT: Although asbestos in general is well known to cause a range of neoplastic and non-neoplastic human health effects, not all asbestos fiber types have the same disease-causing potential, and the mode of action (MOA) of specific types of asbestos and related fibers for various health outcomes are not well understood. A workshop was held to discuss the state of the science of the MOA for asbestos-related disease. The objective was to review the range of asbestos-induced health effects (including those at sites remote to the respiratory tract). We sought to identify existing knowledge gaps and define what research is needed to address these gaps and advance asbestos research. Discussions centered on areas of uncertainty in the field, including the ways asbestos is defined and characterized, the role of different fiber characteristics (e.g., length and mineralogy) in disease, and the impact of low-dose exposures on human health. Studying the dosimetry and mode of action of multiple fiber types would enhance our understanding of asbestos-related disease. To better elucidate the MOA of specific asbestos fibers, the risk assessor requires data as to specific characteristics of asbestos in determining fiber toxicity (e.g., surface area, mineral type), which may inform efforts to assess and control exposures and prevent adverse human health outcomes for the diverse range of fiber types. Specific research aims were defined for these topics and for overarching issues to be addressed, including the use of standardized terminology, test materials, and better experimental models to aid in data extrapolation to humans. To resolve these and other issues, participants agreed that diverse scientific disciplines must coordinate to better understand the MOA leading to the various asbestos-related disease end points.
    Environmental Health Perspectives 08/2011; 119(12):1806-10. DOI:10.1289/ehp.1003240 · 7.03 Impact Factor
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    ABSTRACT: Lung carcinomas and pulmonary fibrosis (asbestosis) occur in asbestos workers. Understanding the pathogenesis of these diseases is complicated because of potential confounding factors, such as smoking, which is not a risk factor in mesothelioma. The modes of action (MOA) of various types of asbestos in the development of lung cancers, asbestosis, and mesotheliomas appear to be different. Moreover, asbestos fibers may act differentially at various stages of these diseases, and have different potencies as compared to other naturally occurring and synthetic fibers. This literature review describes patterns of deposition and retention of various types of asbestos and other fibers after inhalation, methods of translocation within the lung, and dissolution of various fiber types in lung compartments and cells in vitro. Comprehensive dose-response studies at fiber concentrations inhaled by humans as well as bivariate size distributions (lengths and widths), types, and sources of fibers are rarely defined in published studies and are needed. Species-specific responses may occur. Mechanistic studies have some of these limitations, but have suggested that changes in gene expression (either fiber-catalyzed directly or by cell elaboration of oxidants), epigenetic changes, and receptor-mediated or other intracellular signaling cascades may play roles in various stages of the development of lung cancers or asbestosis.
    Journal of Toxicology and Environmental Health Part B 05/2011; 14(1-4):76-121. DOI:10.1080/10937404.2011.556047 · 5.15 Impact Factor
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