This application will provide definitive experimental evidence that the physicochemical properties governing capture of chemical agents by airborne particles and release into lung physiological fluids and cells are determinants of exposure to lung tissue. This hypothesis is based on the assumption that chemical agents absorbed on the surfaces of particles can cause adverse biological effects only when released from the surface by any physical or chemical process. The capture of gas phase molecules by carbon blacks and silica particles will be quantified dynamically by gas solid chromatography. The physicochemical release of these molecules into biological media will be quantified using liquid solid chromatography (HPLC) with synthetic alveolar lung fluid and zwitterionic micelles as the mobile phases. Enthalpies of adsorption and desorption will be used to predict the physical bioavailability of the adsorbate. Pulmonary macrophage phagocytosis may contribute to the release of adsorbed molecules by biochemical processes. The metabolic contribution to release will be quantified using rat alveolar macrophage in a standard phagocytic assay which determines the number of particles phagocytized by the macrophage as a function of the particle surface physical chemistry. The quantification of the phagocytic potential of macrophage which have ingested either particles, particle-sorbate complexes and sorbates alone will be used to demonstrate the relationship between metabolic release and viability of the respiratory defense system. The in vitro model will be validated with nose-only inhalation studies currently under investigation in which rats are exposed to acrolein or formaldehyde with or without concurrent exposure to respirable carbon black particles.
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