PROJECT 3. Physicochemical Parameters of Combustion Generated Atmospheres as Determinants of PM Toxicity.

PI: L.C. Chen; Consultants: R.B. Schlesinger, T. Gordon.

This study examines the hypothesis that the toxicological effects associated with combustion-generated PM depend upon specific physicochemical characteristics of the particles. In this study, cardiopulmonary effects will be measured in healthy and compromised animals exposed by inhalation to laboratory generated particle atmospheres having precisely defined physicochemical characteristics.

A unique furnace system will be used to produce realistic combustion effluent from a mixture of carbon, SO_2, and iron to allow determination of specific components that may be responsible for effects, and assessment of whether any effects follow inhalation of any type of particle. The approaches involve telemetric techniques (heart rate, heart rate variability, blood pressure, and respiratory rates) as well as biochemistry (lung lavage and blood coagulation parameters), lung histopathology, and pulmonary function testing to detect adverse effects of PM on the respiratory and cardiovascular systems. Both healthy and compromised (congestive heart failure) animals (F344 male rats) will be used. Congestive heart failure will be induced by left coronary artery ligation. Animals (n=6/group) will be exposed to either filtered air (control) or combinations of pollutants for 3 hr and the biological endpoints will be evaluated at various time points post exposure. All aerosols will be generated in two size ranges, fine (0.3 µm, initially at 150µg/m³, a value equal to the 24 hr NAAQS for PM10) and ultrafine (0.03 µm, initially at 1.0 x 10⁶ particles/cc). Effects will be compared across the various atmospheres.

The results of this study will allow a determination of whether cardiopulmonary responses to combustion-generated PM are: 1) nonspecific to particle type; or 2) depend upon particle size and/or chemical characteristics of the particles.