Toxicology and Carcinogenesis Studies of Ozone and Ozone 4-(N-Nitrosomethylamino)-1-(3-Pyridyl)-1-Butanone in Fischer-344/N Rats
| Autor: | Rick Hmley, Robert C. Sills, Joseph K. Haseman, Gary A. Boorman, Thomas J. Goehl, Sondra L. Grumbein, Joseph H. Roycroft, Billy J. Chou, Ron Herbert, P. W. Mellick |
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| Rok vydání: | 1994 |
| Předmět: |
Male
Lung Neoplasms Nitrosamines Ozone Carcinogenicity Tests 040301 veterinary sciences Respiratory System Toxicology medicine.disease_cause 030226 pharmacology & pharmacy Pathology and Forensic Medicine 0403 veterinary science 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Administration Inhalation Toxicity Tests medicine Animals Molecular Biology Carcinogen Inhalation exposure Cocarcinogenesis Lung Inhalation 04 agricultural and veterinary sciences Cell Biology 4-N-Nitrosomethylamino-1-3-Pyridyl-1-Butanone Rats Inbred F344 Rats medicine.anatomical_structure chemistry Toxicity Carcinogens Female Carcinogenesis |
| Zdroj: | Toxicologic Pathology. 22:545-554 |
| ISSN: | 1533-1601 0192-6233 |
| DOI: | 10.1177/019262339402200510 |
| Popis: | The purpose of this study was to evaluate the toxicity and potential carcinogenicity or cocarcinogenicity of ozone exposure in rats. Fischer-344/N (F-344/N) rats were exposed 6 hr/day, 5 days/wk, to 0, 0.12, 0.5, or 1.0 ppm ozone by inhalation for 2-yr and lifetime exposures. The cocarcinogenicity study included subcutaneous administration of 0, 0.1, or 1.0 mg/kg body weight of 4-( N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK) and inhalation of 0 or 0.5 ppm ozone to male rats. NNK was administered by subcutaneous injections 3 times per week for the first 20 wk with ozone inhalation exposure. The ozone inhalation exposure was for 2 yr (104 wk), including the first 20 wk of NNK treatment and continuing for 84 wk after the last NNK injection. Ozone exposure caused a concentration-related increase in inflammation of the centriacinar region of the lung. There was also increased fibrosis and an extension of the bronchiolar epithelium in these centriacinar regions to involve the proximal alveoli. There was no increased incidence of neoplasms at any site, including the lung, that was associated with ozone exposure. Rats administered 1.0 mg/kg body weight NNK alone had an increased incidence of bronchiolar/alveolar neoplasms, but this effect was not enhanced by ozone exposure. Ozone exposure for 2 yr and lifetime was associated with site-specific toxic alterations in the nasal passage and lung similar to those previously described for short-term exposures. While there was significant attenuation of the pulmonary lesions as compared to short-term exposures, lesions persisted in the lifetime study and there was evidence of a mild progressive fibrosis. We conclude that under the conditions of these studies: (a) ozone exposure is not carcinogenic to either male or female F-344/N rats, (b) ozone does not enhance the incidence of pulmonary neoplasms in F-344/N rats exposed to a known pulmonary carcinogen (NNK), and (c) mild site-specific toxic lesions characteristic of ozone exposure persist in the nasal passage and lung throughout the lifetime of the rat with continued ozone exposure. |
| Databáze: | OpenAIRE |
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