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Dose and effect of inhaled ozone in resting versus exercising human subjects: comparison with resting rats
Hatch, G., J. Mckee, J. Brown, B. McDonnell, E. Seal, J. Soukup, R. Slade, K. Crissman, AND R. Devlin. Dose and effect of inhaled ozone in resting versus exercising human subjects: comparison with resting rats. Presented at Society of Toxicology, March 10 - 13, 2013.
This abstract describes research that enables extrapolation of lung alveolar ozone dose between different physical exercise levels in humans and between resting humans and resting rats.
Dose and effect of inhaled ozone in resting versus exercising human subjects: comparison with resting rats Authors: Gary E. Hatch, John McKee, James Brown, Bill McDonnell, Elston Seal, Joleen Soukup, Ralph Slade, Kay Crissman and Robert Devlin, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711 Background: Human controlled exposure studies have generally focused on subjects exposed to ozone (O3) while exercising. We exposed resting subjects to labeled O3 (18O3, 0.4 ppm, for 2 hr) and compared O3 dose and effects with our previously published study of exercising subjects. Methods: We measured O3 dose as the concentration of 18O in cells and extracellular material of nasal, bronchial and bronchoalveolar lavage fluid (BALF) immediately post exposure and related these measurements to O3 effects on inflammation, epithelial permeability and phagocytosis in the same fluids and to breathing parameters measured during the 18O3 exposure. A parallel study of resting subjects examined FEV1 changes during and immediately following a 2 hr exposure to 0.18, 0.25, 0.3 and 0.4 ppm O3. Results: Subjects exposed while resting had 18O concentrations in BALF and nasal lavage that were proportional to the amount of air breathed during exposure. Significant but small changes were observed in BALF total cells and neutrophils and in BALF cell phagocytosis following resting O3, however, most indicators of O3 effects that were observable in exercising subjects (including increased BALF supernatant protein, lactate dehydrogenase, interleukin-6 and low molecular weight antioxidants) were not observed in resting subjects. The 18O incorporation into BALF of resting humans was similar to that of similarly exposed resting F344 rats. FEV1 changes in resting human subjects showed a much attenuated response compared to exercising subjects. Conclusion: Quantitative measures of alveolar O3 dose a