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Measurement of Libby Amphibole (LA) Elongated Particle Dissolution Rates and Alteration of Size/Shape Distributions in Support of Human Dosimetry Model Development and Relative Potency Determinations
Citation:
MCKEE, J., P. M. COOK, S. H. GAVETT, AND A. M. JARABEK. Measurement of Libby Amphibole (LA) Elongated Particle Dissolution Rates and Alteration of Size/Shape Distributions in Support of Human Dosimetry Model Development and Relative Potency Determinations. Presented at ASTM Johnson Conference, Burlington, VT, July 25 - 29, 2011.
Impact/Purpose:
Dissolution of asbestos fibers in vivo is a key predictor of health effects. Synthetic lung fluid and acid solutions are used to dissolve fiber samples in vitro, which mimics in vivo conditions and predicts biopersistence.
Description:
To maximize the value of toxicological data in development of human health risk assessment models of inhaled elongated mineral particles, improvements in human dosimetry modeling are needed. In order to extend the dosimetry model of deposited fibers (Asgharian et aI., Johnson 2011 abstract) to describe clearance and predict retained dose, characterization of the dissolution rate for Libby amphibole (LA) is required. Additionally, data on physicochemical properties in vitro can provide a rapid way to compare the impacts of chemistry, microstructure, morphology and mineralogy of LA particles on similar data for samples of different types of fibers, including those associated with asbestiform and non-asbestiform amphiboles. This comparative information is critical for understanding differences in dose-response and mode of action at the tissue level over time and ultimately for making inferences regarding the relevance of these assays to human epidemiological data. Following establishment and careful evaluation of laboratory methods and transmission electron microscopy protocols, we are conducting in vitro dissolution studies using two types of solutions to assess potential in vivo impacts on both short term and longer term particle doses. One solution is a synthetic lung lining f1uid (SLF) commonly used for in vitro dissolution studies of manmade and naturally occurring fibrous materials (Zoitos et aI., 1997), which has been shown to correlate well with toxicity and to provide useful kinetic information (Hesterberg et al., 2002). The other is an acid solution (HF/HCL/citric acid) used in previous studies conducted by Dr. Philip Cook (Morton et aI., 1985; Wilson, 2006). Both the SLF and acid in vitro dissolution rates can be calibrated to rates observed in the in vivo intratracheal instillation and inhalation studies. Once calibrated, the in vitro assays can provide a rapid way to compare key dosimetry determinants that play an important role in fiber persistence and durability. Thus, the purpose of these studies was three-fold: (1) to obtain a rate parameter for LA dissolution, an important physical clearance mechanism used in the fiber clearance model; (2) to provide a dataset specifically for LA that can be used to assess its relative biopersistence compared to other types of fibers and to previous studies conducted both in vitro and in vivo; and (3) to provide data for quantitative inference and dosimetric modeling of the proposed intra-tracheal instillation and inhalation studies. (These views do not represent US EPA policy). Session: Session 1, Human Health and Toxicology