Review of the U.S. Navy's Exposure Standard for Manufactured Vitreous Fibers (2000) / Chapter Skim
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4 Biopersistence of Vitreous Fibers
4 Biopersistence of Vitreous Fibers
Pages 23-33
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From page 23... ...
Furthermore, the Navy failed to cite many relevant publications, including some that provide important insights into the factors affecting target dose, biological responses to inhaled manufactured v~trous fibers (MVF) , and methods for assessing biopersistence.
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From page 24... ...
fibers that might be of concern for skin irritation, and thoracic fibers that deposit in the lung conductive airways and theoretically might be responsible for bronchitis and bronchogenic cancer in exposed occupational cohorts (Lippmann 1990a,b, 19931. With regard to the Navy's discussion of fiber size in relation to penetration and deposition in lung regions, the subcommittee notes that in adults breathing orally, fibers with aerodynamic diameters of about 10 ,um (physical diameter, about 3.3 Am)
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From page 25... ...
MVF that deposit in intact conducting airways do not appear to cause a significant pathogenic response, because the mucous coating and rapid clearance via the mucociliary escalator prevents interaction between the MVF and the epithelial lining. Airways that are denuded of an epithelial covering, however, because of confounders such as smoking could conceivably be vulnerable; fibers might then persist in a location not normally susceptible to fiber-related pathogenicity.
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From page 26... ...
The half-life of particles and short fibers deposited in the gas-exchange region is 60-90 days in rats, and up to 10 times greater in humans, depending on their clinical condition. Several animal studies have demonstrated that the inflammatory response stimulated by particles and short fibers resolves once exposure ceases and the offending material is removed from the lung (Hesterberg et al.1993; Mast et al.1995a; McConnell et al.1994, 19993.
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From page 27... ...
Therefore, in vitro tests to measure the leaching of specific fiber constituents into the dissolution medium are generally performed at pH values of both 4.5 and 7.4 to simulate the intracellular and extracellular milieus, respectively (Potter and Mattson 19911. Although acellular in vitro techniques measure only dissolution rates of the fibers, in viva methods measure the overall retention of fibers in the lung, including dissolution rates and mechanical clearance.
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From page 28... ...
28 TIC ._ o Cal Em o .
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Initial studies to investigate these phenomena were "add-one" to standard chronic rodent bioassays. In long-term studies, animals (usually rats)
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From page 31... ...
caused only an inflammatory change, MMVF 33 caused a moderate amount of pulmonary and pleural fibrosis and a single mesothelioma, and amosite asbestos caused severe lung and pleural fibrosis and a high incidence of mesotheliomas. ~ WHO fibers are defined as having a length greater than 5.0 ,um, a diameter less than 3.0 ,um, and an aspect ratio equal to or greater than 3:1 (WHO 1985)
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From page 32... ...
Another innovative method that has been used to investigate biopersistence is confocal laser scanning microscopy (CESM) , which allows fibers to be directly visualized in their exact location in the Jung and measured in situ without disturbing the lung by fixation or cutting.
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From page 33... ...
At present, CESM should be viewed as a research too} rather than as a means of assessing biopersistence definitively. CONCLUSIONS The potential hazards posed by a given MVF is directly related to its ability to persist in the lung Tong enough to cause chronic disease.
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