Long-term toxicity studies of ozone in F344/N rats and B6C3F1 mice

Toxicology Letters
G A BoormanR A Herbert

Abstract

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 cocarcinogenicity study (male rats only) included the subcutaneous administration of 0, 0.1 or 1.0 mg/kg/body wt. of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) for the first 20 weeks along with inhalation 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 increased incidence of lung neoplasms. In the cocarcinogenicity study, ozone 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 neoplasms from the ozone-exposed mice.

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Citations

Nov 20, 2009·Cell Biology and Toxicology·Romain HacquemandGerard Brand
Oct 1, 1996·Risk Analysis : an Official Publication of the Society for Risk Analysis·B N AmesM K Shigenaga
Jun 11, 1999·Environmental Research·E BermúdezM G Mustafa
Mar 16, 2005·Experimental Lung Research·Anna Maciag, Lucy M Anderson

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