Coherent Response Models of Ozone Injury in Humans and Rodent Models. D. L. Costa, J. S. Tepper, and J. Highfill, Pulmonary Toxicology Branch, MD-82, Experimental Toxicology Division, NHEERL/USEPA, Research Triangle Park, NC
Exposure concentration, duration, and pulmonary ventilation are factors known to influence the dose of O3 delivered to the lungs. Characterization of the influence of these factors would aid in understanding the mechanisms involved in pulmonary injury and in addressing some of the regulatory concerns surrounding O3 and perhaps other lung toxicants. Ozone-induced alterations in forced vital capacity in 1 sec (FEV1) obtained from humans and rats, and levels of bronchoalveolar lavage fluid protein (BALP) obtained from studies of humans, rats, and guinea pigs were used to compare the utility and generalizability of response models as functions of C and T. The data indicate that the forced vital capacity (FVC) decreases and lavage fluid protein (LFP) increases with O3 exposure, but these changes are not strictly linear with respect to changes in concentration and time. In the rats, the non-invasive measurement, FVC, predicted changes in the invasive measure of LFP and related to the histopathology. It is reasonable to assume that the same holds for humans given the coherence of the models across species. These models may aid in the development of regulations which must address concerns about cumulative toxicity across diverse daily exposure scenarios. (This abstract does not reflect EPA policy.)