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Biomarkers of Dose and Effect of inhaled ozone in resting versus exercising human subjects: comparison with resting rats
Citation:
Hatch, G., J. Mckee, James Brown, W. McDonnell, E. Seal, J. Soukup, R. Slade, K. Crissman, AND R. Devlin. Biomarkers of Dose and Effect of inhaled ozone in resting versus exercising human subjects: comparison with resting rats. Biomarker Insights. Libertas Academica Ltd, North Harbour, New Zealand, 8:53-67, (2013).
Impact/Purpose:
This paper provides data for extrapolating between exercise levels in humans and between humans and rats. It reports dose and effect at the cellular level of the lung alveoli after exposure to ozone.
Description:
Background: Human controlled exposure studies have generally focused on subjects exposed to ozone (O3) while exercising while exposures in rats have been done at rest. 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 and resting rats. Methods: We measured O3 dose as the concentration of 18O in cells and extracellular material of nasal, bronchial and bronchoalveolar lavage fluid (BALF) 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 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 BALF supernatant protein, LDH, IL-6 and antioxidant substances) 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 and toxicity that were observed previously in exercising subjects were greatly reduced or non-observable in O3 exposed resting subjects. Resting rats and resting humans have similar alveolar O3 dose. Disclaimer The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.
