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OZONE DOSE AND EFFECT IN HUMANS AND RATS - A COMPARISON USING OXYGEN-18 LABELING AND BRONCHOALVEOLAR LAVAGE
Citation:
Hatch, G., R. Slade, L. Harris, W. McDonnell, R. Devlin, H. Koren, D. Costa, AND J. McKee. OZONE DOSE AND EFFECT IN HUMANS AND RATS - A COMPARISON USING OXYGEN-18 LABELING AND BRONCHOALVEOLAR LAVAGE. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-95/052, 1994.
Description:
In an effort to improve risk assessments for ozone (03) we have compared the incorporation of inhaled oxygen-18 labeled 03 (1803) in the lungs of humans and laboratory rats. ells and fluids obtainable through bronchoalveolor lovage (BAL) were examined following exposure to 180, to determine whether excess 180 concentrations (presumed to be reaction products of 1803) could be detected and equated to 03 dose to the lung. hree 03 effect measurements (increased BAL protein and neutrophils and decreased BAL macrophages) were also made in subjects or animals exposed in parallel to determine whether there was a correspondence between dose and effect measurements. ight human volunteers (male, age 18-35) were exposed to 180, (0.4 ppm, 2 hr) with 15 min alternating periods of heavy treadmill exercise and rest. ats (F344) were exposed identically, except without exercise. 1803 was generated directly from pure 1802. AL cells and centrifugally separable surfactant material were freeze-dried and analyzed mass spectrometrically for excess 180. esults indicated that the exercising humans had 3.2 to 4.3 fold higher concentrations in all of their BAL constituents than rats. he human subjects also showed significant increases in all of the effects markers after 0.4 ppm 03 while the rats did not. ats which were exposed to higher concentrations (2.0 ppM) of 1803 had levels of 180 in BAL similar to those of exercising humans, and changes in all of the effects markers were also similar to the exercising humans. herefore, it appears that 03 toxicity in resting rats underestimates effects in exercising humans because rats have a lower than expected dose of 03 to the distal lung. he dose and effect linkage between rats and humans should-extrapolation of animal toxicity to humans for purposes of risk assessment.