Effect of cumulative exposure on nasal response to ozone.

To assess the potential health risks associated with exposure to low levels of ozone, it is essential to know if the ozone-induced responses are dependent on cumulative exposures or on the peak concentrations. To answer this question female F344/N rats, 11-13 weeks of age, were exposed to a matrix of equal concentration x time values that included exposures to 0, 0.12, 0.24, and 0.48 ppm ozone for 3, 6, 12, or 24 hr. the response of the nasal epithelium was measured as induced DNA synthesis determined by the uptake of bromodeoxyuridine (a thymidine analog) into epithelial cells lining the nasal anterior maxilloturbinates. No increased DNA synthesis was observed in rats exposed to 0.12 ppm ozone for any of the time periods. For exposures higher than 0.12 ppm ozone, the response of the nasal epithelium was similar for equal cumulative exposures. The responses, however, were not linearly related to the cumulative (concentration x time) exposures. It appeared that some mitigating factor was present which decreased the responses at the higher cumulative exposures. No frank toxicity or cellular necrosis was observed, indicating that sublethal cell damage was sufficient to induce DNA synthesis. A simple mathematical model was developed to describe the relationship between ozone exposure and the induction of DNA synthesis in the nasal epithelium. The model predicted that the threshold concentration of ozone for inducing DNA synthesis in the nasal epithelium was 0.1 +/- 0.1 ppm. For one measure of ozone toxicity (induced DNA synthesis) at a sensitive site in the respiratory tract (maxilloturbinates), the effects of ozone were dependent on cumulative exposures at concentrations > 0.12 ppm and within the time and concentration ranges used in this study.