Chemistry and toxicology of respirable airborne particulates

Our research has focused on understanding the chemical interactions of combustion generated particulate species. Our goal has been to understand the role of surface chemistry in the biological response to atmospheric particulates. Inhalation of combustion-generated particles has been linked to increases in morbidity and mortality in the human population. Specific information about the mechanisms of toxicity upon respiration is still unknown. A limiting feature in understanding specific interactions of particle surfaces with the lung is the complexity of the combustion-generated particle. Combustion-generated particles are formed in the environment during the combustion of fossil fuels, like diesel fuel and coal. Diesel exhaust particles (DEP) and coal fly ash (CFA) are complex mixtures of organic and inorganic components, so understanding the specific contributions of each component is difficult.; The goal of the research presented in this text was to prepare simplified model systems that realistically mimic a combustion particle surface, that allow for the elucidation of specific mechanisms of particle toxicity could be determined. Inhaled particulates are thought to damage the lung by effecting the production of reactive oxygen species (ROS), including *O2 - and *OH, through the redox cycling of iron on the particle surface. In order to specifically test this hypothesis, mostly carbon-based particles were synthesized, into which iron could be incorporated. In a collaborative effort with the Department of Pathology at the Ohio State University, monocyte-derived macrophages (MDM) were exposed to carbon (C), carbon-iron (C-Fe), carbon-iron/fluorine-aluminosilicate (C-Fe/F-Al-Si), DEP and CFA particles. MDM produce H2O2 upon the phagocytosis of foreign species in a process called the oxidative burst. H2O2 can react with iron on the particle surface to produce *OH. Our results have found a correlation between the ability of the particle surface to catalyze the decomposition of hydrogen peroxide into hydroxyl radicals with increases in TNFalpha release and adhesion molecule production on the surface of cultured endothelial cells.; As mentioned above, combustion-generated particles also have an organic component, which has been linked with increases in inflammation and mutagenicity. Of particular concern are the polycyclic aromatic hydrocarbons (PAH), which are synthesized in the gas-phase during the combustion of fossil fuels. PAH are secondary mutagens, while nitrated PAH are primary mutagens thought to be responsible for much of the mutagenicity of the organic extract of DEP. (Abstract shortened by UMI.)...