Interspecies differences in time course of pulmonary toxicity following repeated exposure to ozone

To compare the extent and rime course of pulmonary injury and repair in 3 r odent species, rats, mice and guinea pigs were continuously exposed for 3, 7, 28, and 56 days to 400 and 800 mu g O-3/m(3) (0.2 and 0.4 ppm). Recovery from 28 days of exposure was studied at 3, 7, and 28 days after exposure. Pulmonary injury and repair was studied at various rime points by histology , electron microscopy, morphometry, and biochemistry. In ail 3 species a co ncentration-related centriacinar inflammation occurred, with a maximum afte r 3 days of exposure. The number of alveolar macrophages and the pulmonary cell density in the centriacinar region increased progressively until 56 da ys of exposure, with the guinea pig the most sensitive species. Only the mo use displayed a concentration and exposure-time dependent hypertrophy of br onchiolar epithelium. After 56 days of exposure to 800 mu g O-3/m(3) in the rat and the guinea pig, giant lamellar bodies in type II cells were presen t. Exposures for 3 and 7 days at near ambient ozone concentrations (400 mu g O-3/m(3)) resulted in significantly elevated lung enzyme activities in th e mouse, and in significant histological and morphometric changes in ail 3 species. in rat and guinea pigs exposures for 56 days resulted in alveolar duct fibrosis. The highest biochemical response and the slowest recovery fr om ozone exposure were seen in the mouse. Histology, morphometry, and bioch emistry revealed a total recovery from a 28-day exposure period in rats alt er 28 days, while in guinea pigs the ductular septa were still thickened an d in mice all enzyme activities were still elevated in comparison with cont rol valuer. In conclusion, the response of mice to ozone was evaluated as m ost severe, followed by those of guinea pigs and least in rats.