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Measurement of Elongated Particle Dissolution Rates and Consequent Size/Shape Distribution Alterations in Support of Relative Potency Determinations and Human Dosimetry Model Development
Citation:
COOK, P. M., J. SWINTEK, T. DAWSON, AND M. ETTERSON. Measurement of Elongated Particle Dissolution Rates and Consequent Size/Shape Distribution Alterations in Support of Relative Potency Determinations and Human Dosimetry Model Development. Presented at American Society for Testing and Materials, Burlington, VT, July 25 - 29, 2011.
Impact/Purpose:
To document research results.
Description:
Clearance of inhaled bio-persistent elongated particles (EPs) from the lungs and their associated translocation to pleural and other extra-pulmonary tissues involves a number of inter-related and coincidental physicochemical and physiological processes. These can result in EP dissolution, splitting/separation, comminution, and associated impacts on particokinetics. Depending on an EP’s structure, chemistry,,and initial point of deposition in the lungs, the collective contributions of each of these processes to resultant EP persistence and relative potency will be different. Despite the complexity of these in vivo dose realities, exhaustive analyses of compatible rat pleural dose-mesothelioma response data show clearly that dose characterizations based on TEM analyses of short term acid leached test samples consistently provide better predictions of dose-response than the unleached sample dose TEM data. Acid leaching (HF/HCL/citric acid mixture), used in previous studies conducted by P.M. Cook, provides a rapid bio-durability assay for EPs. This convenient model focuses on particle propensity for transformation through dissolution but is not a direct model for much slower lung fluid or other tissue/cell residence associated particle changes in vivo. However, comparisons of the acid treatment results for the same samples after residence for up to two years in rat lungs or five months in rat pleural membranes reveal consistent outcomes for EP size and shape distributions and EP number and surface area concentrations when adjusted for apparent EP clearance rates.