Interspecies differences in time course of pulmonary toxicity following repeated exposure to ozone.
To compare the extent and time course of pulmonary injury and repair in 3 rodent species, rats, mice and guinea pigs were continuously exposed for 3, 7, 28, and 56 days to 400 and 800 microg O3/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 time points by histology, electron microscopy, morphometry, and biochemistry. In all 3 species a concentration-related centriacinar inflammation occurred, with a maximum after 3 days of exposure. The number of alveolar macrophages and the pulmonary cell density in the centriacinar region increased progressively until 56 days of exposure, with the guinea pig the most sensitive species. Only the mouse displayed a concentration and exposure-time dependent hypertrophy of bronchiolar epithelium. After 56 days of exposure to 800 microg O3/m(3) in the rat and the guinea pig, giant lamellar bodies in type II cells were present. Exposures for 3 and 7 days at near ambient ozone concentrations (400 microg O3/m(3)) resulted in significantly elevated lung enzyme activities in the mouse, and in significant histological and morphometric changes in all 3 species. In rat and guinea pigs exposures for 56 days resulted in alveolar duct fibrosis. The highest biochemical response and the slowest recovery from ozone exposure were seen in the mouse. Histology, morphometry, and biochemistry revealed a total recovery from a 28-day exposure period in rats after 28 days, while in guinea pigs the ductular septa were still thickened and in mice all enzyme activities were still elevated in comparison with control values. In conclusion, the response of mice to ozone was evaluated as most severe, followed by those of guinea pigs and least in rats.
Dormans
J A
JA
Laboratory for Pathology and Immunobiology, National Institute of Public Health and the Environment, P.O. Box 1, 3720 BA, Bilthoven, The Netherlands. j.dormans@rivm.nl.
van Bree
L
L
Boere
A J
AJ
Marra
M
M
Rombout
P J
PJ
D000280:Administration, Inhalation; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000648:ultrastructure; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects / Q000648:ultrastructure; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006168:Guinea Pigs; D019570:Inhalation Exposure; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010126:Ozone / Q000008:administration & dosage / Q000633:toxicity*; D011009:Pneumoconiosis / Q000209:etiology* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D013047:Specific Pathogen-Free Organisms
D010126:Ozone; D007770:L-Lactate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase