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In Vitro Dissolution of Libby Amphibole, Amosite Asbestos, and MMVF Using Acid and Synthetic Lung Fluid Media.
Gavett, S., J. McGee, R. Pescador, D. Hoff, T. Dawson, M. McGee, AND A. Jarabek. In Vitro Dissolution of Libby Amphibole, Amosite Asbestos, and MMVF Using Acid and Synthetic Lung Fluid Media. Society of Toxicology, San Diego, CA, March 22 - 26, 2015.
Toxicity of inhaled fibers is dependent in part on biopersistence due to changes in size distribution after deposition and clearance in the respiratory tract. To model this in vivo behavior, respirable (PM2.5) Libby amphibole (LA) and amosite asbestos, and a reference material glass wool (man-made vitreous fiber; MMVF-11) were subjected to in vitro dissolution. Dissolution tests were conducted with strong acid (HF/HCl/citric acid) or synthetic lung fluid (SLF; EURIMA method, modified Gamble’s salt solution, pH 4.5). Samples were exposed to acid for 30 sec – 60 min, or to SLF by continuous constant flow for 30 or 90 days at 37 °C. TEM analyses showed that up to 10 min acid exposure of LA fibers (representing a chronic exposure in the rat lung) caused no splitting or separation, and little change in size distribution. 30-60 min of LA acid exposure reduced numbers of the smallest particles/fibers, shifting the size distribution to longer fibers with higher aspect ratio. SLF dissolution caused minimal changes in LA fiber size distribution. Amosite and MMVF-11 dissolution data are expected to be substantially similar to historical data from the U.S. EPA fiber database; these data show that similar to LA fibers, UICC amosite had little change in size distribution after acid dissolution up to 10 min, but shifted to longer fibers with higher aspect ratios at 60-120 min exposure. In contrast, acid increased fiberglass and glass microfiber length and aspect ratios as soon as 30 sec after exposure. These data help determine key physicochemical parameters of clearance mechanisms to refine respiratory dosimetry model predictions of retained dose, provide insight into potential pathogenesis, and allow relative potency comparisons with other fiber types. In vitro dissolution provides a rapid way to compare fiber durability and persistence in the respiratory tract. (This abstract does not represent US EPA policy.)
The Libby Action Plan toxicology studies include assessment of fiber dissolution in vitro as a model of in vivo behaviour of fibers. The data generated from this study will help to determine key parameters of the respiratory dosimetry model, and provide a rapid method of assessing fiber durability as a key component of toxicity.
Record Details:Record Type: DOCUMENT (PRESENTATION/SLIDE)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
ENVIRONMENTAL PUBLIC HEALTH DIVISION
CARDIOPULMONARY AND IMMUNOTOXICOLOGY BRANCH