OZONE DOSE AND EFFECT IN HUMANS AND RATS - A COMPARISON USING O-18 LABELING AND BRONCHOALVEOLAR LAVAGE

In an effort to improve risk assessments for ozone (O-3) we compared t he incorporation of inhaled oxygen-18-labeled O-3 (O-18(3)) into the l ungs of humans and laboratory rats. Cells and fluids obtainable throug h bronchoalveolar lavage (BAL) were examined after exposure to O-18(3) to determine whether excess O-18 concentrations (presumed to be react ion products of O-18(3)) could be detected and equated to the O-3 dose to the lung. Three O-3 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 corre spondence between dose and effect measurements. Eight human male volun teers 18 to 35 yr of age were exposed to O-18(3) (0.4 ppm for 2 h) wit h 15-min alternating periods of heavy treadmill exercise and rest. Rat s (F344) were exposed identically, except without exercise. O-18(3) wa s generated directly from pure O-18(2). BAL cells and centrifugally se parable surfactant material were freeze-dried and analyzed by mass spe ctrometer for excess O-18. Results showed that the exercising humans h ad four- to fivefold higher O-18 concentrations in all of their BAL co nstituents than did the rats. The humans also had significant increase s in all of the effects markers after 0.4 ppm O-3, whereas the rats di d not. Rats that were exposed to higher concentrations of O-18(3) (2.0 ppm) had levels of O-18 in BAL that were more comparable to but still lower than those of exercising humans. Changes in all of the effects markers in these rats were comparable or higher than in exercising hum ans. Therefore, it appears that O-3 toxicity in resting rats underesti mates effects in exercising humans because rats have a lower than expe cted dose of O-3 to the distal lung. The dose and effect linkage betwe en rats and humans should improve extrapolation of animal toxicity dat a to humans.