2-YEAR AND LIFETIME TOXICITY AND CARCINOGENICITY STUDIES OF OZONE IN B6C3F1 MICE

To evaluate the toxicity and carcinogenic potential of long-term expos ure to ozone, B6C3F1 mice were exposed by whole-body inhalation to 0, 0.12, 0.5, or 1.0 ppm and 0, 0.5, or 1.0 ppm ozone for 24 or 30 mo (li fetime), respectively. The incidence of alveolar/bronchiolar adenomas and carcinomas (combined) increased (p < 0.05) in female mice exposed to 1.0 ppm for 24 or 30 mo and marginally increased (p > 0.05) in male mice exposed to concentrations of 0.5 or 1.0 ppm. An increased incide nce of nonneoplastic lesions were observed in the nasal cavities and i n the centriacinar region of the lung of mice exposed to 0.5 or 1.0 pp m for 24 and 30 mo. Nasal cavity lesions were mild and included hyalin e degeneration, hyperplasia, squamous metaplasia, fibrosis and suppura tive inflammation of the transitional and respiratory epithelium of th e lateral wall, and atrophy of the olfactory epithelium. Lung lesions included replacement of the epithelium of the alveolar ducts and adjac ent alveolar septa with epithelium similar to that normally found in t erminal bronchioles (metaplasia) and associated alveolar histiocytosis . Based on the results of these studies, we conclude that inhalation e xposure of B6C3F1 mice to ozone for 24 or 30 mo (a) is carcinogenic in female B6C3F1 mice exposed to 1.0 ppm of ozone based on an increased incidence of alveolar/bronchiolar adenoma or carcinoma and (b) results in mild, site-specific, nonneoplastic lesions in the nasal cavity and centriacinar lung of male and female mice exposed to 0.5 or 1.0 ppm o f ozone for 2 yrs, which persist with continued exposure to 30 mo. It is uncertain whether or not the marginal increase (p > 0.05) of alveol ar/bronchiolar neoplasms in male B6C3F1 mice resulted from exposure to ozone.