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1.
Toxicol Sci ; 74(2): 287-96, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12773761

ABSTRACT

Vanadium pentoxide (V2O5) is a slightly soluble compound found in airborne particle emissions from metallurgical works and oil and coal burning. Because the carcinogenic potential of V2O5 was not known, F344/N rats and B6C3F1 mice (N=50/sex/species) were exposed to V2O5 at concentrations of 0, 0.5 (rats only), 1, 2, or 4 (mice only) mg/m3, by whole-body inhalation for 2 years. The survival and body weights of rats were minimally affected by exposure to V2O5. The survival and body weights of male mice exposed to 4 mg/m3 and body weights of all exposed groups of female mice were lower than the controls. Alveolar/bronchiolar (A/B) neoplasms occurred in male rats exposed to 0.5 and 2 mg/m3 at incidences exceeding the National Toxicology Program (NTP) historical control ranges. A marginal increase in A/B neoplasms was also observed in female rats exposed to 0.5 mg/m3. Increases in chronic inflammation, interstitial fibrosis, and alveolar and bronchiolar hyperplasia/metaplasia and squamous metaplasia were observed in exposed male and female rats. A/B neoplasms were significantly increased in all groups of exposed mice. As with rats, increases in chronic inflammation, interstitial fibrosis, and alveolar and bronchiolar epithelial hyperplasia were observed in mice exposed to V2O5. Thus, V2O5 exposure was a pulmonary carcinogen in male rats and male and female mice. The marginal tumor response in the lungs of female rats could not be attributed conclusively to exposure to V2O5. These responses were noted at and slightly above the OSHA permissible occupational exposure limit of 0.5 mg/m3 (dust) (National Institute for Occupational Safety and Health, NIOSH Pocket Guide to Chemical Hazards, U.S. Department of Health and Human Services, Washington, DC, 1997, p. 328).


Subject(s)
Adenoma/chemically induced , Carcinogens/toxicity , Carcinoma/chemically induced , Lung Neoplasms/chemically induced , Neoplasms, Experimental/chemically induced , Vanadium Compounds/toxicity , Adenoma/pathology , Administration, Inhalation , Animals , Body Weight/drug effects , Carcinogenicity Tests , Carcinogens/administration & dosage , Carcinoma/pathology , Female , Longevity/drug effects , Lung Neoplasms/pathology , Male , Mice , Mice, Inbred Strains , Rats , Rats, Inbred F344 , Respiratory System/drug effects , Respiratory System/pathology , Vanadium Compounds/administration & dosage
2.
Toxicol Sci ; 71(2): 198-206, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12563105

ABSTRACT

Citral, a widely used natural ingredient, is added to foods and cosmetics as a flavoring and fragrance agent. Male and female F344/N rats and B6C3F1 mice were exposed to microencapsulated citral in the feed for 14 weeks or two years. All studies included untreated and vehicle control groups. In the 14-week studies, rats and mice were given diets containing 3,900, 7,800, 15,600, or 31,300 ppm citral. In rats, food consumption was reduced in the two highest dose groups. In mice an apparent increase in food consumption was observed, but was due to mice scattering the feed. Body weights of all treated animals were less than controls. All rats and four male mice were killed moribund in the high dose groups. In rats, forestomach and kidney lesions were observed. At the higher doses, lesions observed in the bone marrow, testes, and thymus in rats and in the ovary in mice were considered related to inanition and resultant moribundity. In the two-year studies, rats were exposed to 1,000, 2,000, or 4,000 ppm citral. Body weights were reduced in the 4,000 ppm rats. Mice were exposed to 500, 1,000, or 2,000 ppm citral. Body weights in the 1,000 and 2,000 ppm groups were reduced. No neoplasms were attributed to citral in rats or mice. Malignant lymphoma occurred with a positive trend and was significantly greater than controls in female mice in the 2,000 ppm group. However, the incidences were within the NTP historical control range and could not be clearly related to citral administration.


Subject(s)
Carcinogenicity Tests , Carcinogens/toxicity , Flavoring Agents/toxicity , Monoterpenes/toxicity , Neoplasms, Experimental/etiology , Acyclic Monoterpenes , Administration, Oral , Animals , Body Weight/drug effects , Carcinogens/administration & dosage , Diet , Dose-Response Relationship, Drug , Drug Compounding , Female , Flavoring Agents/administration & dosage , Kidney/drug effects , Kidney/pathology , Male , Mice , Mice, Inbred Strains , Monoterpenes/administration & dosage , Neoplasms, Experimental/pathology , Rats , Rats, Inbred F344 , Stomach/drug effects , Stomach/pathology
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