EFFECTS OF REPEATED EXPOSURES OF GERIATRIC RATS TO OZONE AND PARTICLE-CONTAINING ATMOSPHERES: AN ANALYSIS OF BRONCHOALVEOLAR LAVAG E AND PLASMA PROTEINS

Abstract

Inhalation of ozone (O3) and airborne particles less than 10 m (PM-10) in mass median aerodynamic diameter (MMAD) is associated with adverse health effects in sensitive human populations, and pulmonary injury in laboratory animals. In order to simulate environmental exposures of sensitive individuals, such as the elderly, geriatric rats were exposed to O and particulate mixtures. This pilot study determined whether the pul3 monary effects of higher O3 concentrations reported in earlier studies are also seen after repeated exposures to lower O3 concentration used in this study, whether the O3 effects are modified by PM-10 components, and whether plasma biomarkers can be developed as noninvasive tests of pulmonary injury. Male Fischer 344 rats, 22-24 mo old, were exposed 4 h/ day, 3 days/wk for 4 wk to (a) purified air, (b) O3 (0.2 ppm), (c) low-level mixture of carbon (C, 50 g/ m3) plus ammonium bisulfate (ABS, 70 g/m3) plus O3, and (d) high-level mixture of C (100 g/m3) plus ABS (140 g/m3) plus O3. Twenty-four hours after the last exposure, groups of rats were prepared for measurement of protein and albumin concentrations in bronchoalveolar lavage (BAL) as markers of airways permeability, and blood was drawn for analysis of plasma immunoreactive prolyl 4-hydroxylase and fibronectin. Exposures to O3 and O3 /particle mixtures did not produce a consistent, significant change in the BAL markers of permeability. Nonsignificant changes represented individual animal variations. On the other hand, a significant increase in plasma fibronectin was observed in the group exposed to O3, but not in the rats exposed to O3/particle combinations. Such an effect was not observed for plasma immunoreactive prolyl 4- hydroxylase. The inability of low-level O3 and O3/particle combinations to produce intra pulmonary effects suggests potential utility of plasma biomarkers for the evaluation of pulmonary toxicity. These results also suggest modification of O3 effects upon its combination with PM-10.