LONG-TERM TOXICITY STUDIES OF OZONE IN F344 N RATS AND B6C3F1 MICE/

The toxicity and carcinogenicity of ozone was evaluated in Fischer 344 /N rats and B6C3F1 mice exposed to 0, 0.12 (2 years only), 0.5 or 1.0 ppm ozone by inhalation for 2-year and lifetime exposures. A 2-year co carcinogenicity study (male rats only) included the subcutaneous admin istration of 0, 0.1 or 1.0 mg/kg/body wt. of -(N-methyl-N-nitrosamino) -1-(3-pyridyl)-1-butanone (NNK) for the first 20 weeks along with inha lation exposure to 0 or 0.5 ppm ozone followed by additional 84 weeks of ozone exposure alone. Ozone exposure in rats did not cause an incre ased incidence of lung neoplasms. In the cocarcinogenicity study? ozon e exposure did not have an additive carcinogenic effect. Lifetime and 2-year ozone exposure was associated with a marginal increase in lung tumors in male B6C3F1 mice and a more pronounced increase in females. Unique mutations in the K-ras gene were found in the mouse lung neopla sms from the ozone-exposed mice.