NTP technical report on the toxicology studies of cobalt metal (CASRN 7440-48-4) in F344/N rats and B6C3F1/N mice and toxicology and carcinogenesis studies of cobalt metal in f344/NTac rats and B6C3F1/N mice (Inhalation studies)
Exposure to cobalt metal resulted in increased incidences of nonneoplastic lesions of the lung and nose in male and female rats, the testes in the male rats and mice, the adrenal medulla in female rats, and the lung, nose, larynx, and trachea in male and female mice. Synonyms: Cobalt element; super...
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| Format: | eBook |
| Language: | English |
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Research Triangle Park, North Carolina
National Toxicology Program, Public Health Service, U.S. Department of Health and Human Services
December 2014, 2014
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| Series: | NTP TR
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| Online Access: | |
| Collection: | National Center for Biotechnology Information - Collection details see MPG.ReNa |
| Summary: | Exposure to cobalt metal resulted in increased incidences of nonneoplastic lesions of the lung and nose in male and female rats, the testes in the male rats and mice, the adrenal medulla in female rats, and the lung, nose, larynx, and trachea in male and female mice. Synonyms: Cobalt element; super cobalt Trade name: Aquacat Increased incidences of nonneoplastic lesions of the lung occurred in exposed male and female rats and included hemorrhage, acute inflammation, alveolar epi-thelium hyperplasia, histiocytic cellular infiltration of the alveolus, cytoplasmic vacuolization of bronchiolar epithelium, necrosis of the bronchiolar epithelium, and interstitial fibrosis of the alveolar epithelium. Increased incidences of nonneoplastic lesions of the nose occurred in exposed male and female rats and included olfactory epithelium necrosis, olfactory epithelium atrophy, respiratory epithelium necrosis, and respiratory epithelium squamous metaplasia. Tissue concentrations of cobalt increased with increasing exposure concentration in all tissues examined. TWO-WEEK STUDY IN RATS: Groups of five male and five female rats were exposed to cobalt metal particulate aerosol by inhalation at concentrations of 0, 2.5, 5, 10, 20, or 40\smg/m3, 6\shours plus T90 (12\sminutes) per day, 5\sdays per week for 16\sdays. Additional groups of five female rats were exposed to the same concentrations for 16\sdays for tissue burden studies. All rats exposed to 40\smg/m3 and all male and three female rats exposed to 20\smg/m3 died before the end of the study. Mean body weights of males exposed to 10\smg/m3 and of females exposed to 10 or 20\smg/m3 were significantly decreased. Females exposed to 20\smg/m3 lost weight during the study. Exposure-related clinical findings included abnormal breathing, lethargy, and thinness in male rats exposed to 20 or 40\smg/m3 and in females exposed to 40\smg/m3. Dark lungs were observed at necropsy in all rats exposed to 40\smg/m3 and most rats exposed to 20\smg/m3 that died early. There was clear evidence of carcinogenic activity of cobalt metal in female F344/NTac rats based on increased incidences of alveolar/bronchiolar adenoma and carcinoma in the lung, including multiples, and on increased incidences of benign and malignant pheochromocytoma of the adrenal medulla, including bilateral neoplasms. The occurrences of squamous cell neoplasms of the lung (predominantly cystic keratinizing epithelioma), and of mononuclear cell leukemia were considered related to exposure. The occurrences of pancreatic islet carcinoma may have been related to exposure. There was clear evidence of carcinogenic activity of cobalt metal in male and female B6C3F1/N mice based on increased incidences of alveolar/bronchiolar neoplasms of the lung (predominantly carcinoma), including multiple carcinoma. CONCLUSIONS: Under the conditions of these 2-year inhalation studies, there was clear evidence of carcinogenic activity of cobalt metal in male F344/NTac rats based on increased incidences of alveolar/bronchiolar adenoma and carcinoma in the lung, including multiples, and on increased incidences of benign and malignant pheochromocytoma of the adrenal medulla, including bilateral neoplasms (see Explanation of Levels of Evidence of Carcinogenic Activity; a summary of the Peer Review Panel comments and the public discussion on this Technical Report appears in Appendix O). The increased incidences of pancreatic islet adenoma or carcinoma (combined) were considered related to exposure. The occurrences of cystic keratinizing epithelioma of the lung and of renal tubule adenoma or carcinoma (combined) may have been related to exposure. Absolute lung weights of females exposed to 10 or 20\smg/m3 and the relative lung weights of both sexes exposed to 10\smg/m3 and females exposed to 20\smg/m3 were significantly greater than those of the chamber controls. Absolute and relative liver weights of males exposed to 2.5\smg/m3 or greater and absolute liver weights of females exposed to 5\smg/m3 or greater were significantly less than those of the chamber controls. The relative liver weight of 20\smg/m3 females was significantly greater than that of the chamber controls. Absolute kidney weights of males exposed to 10\smg/m3 and females exposed to 20\smg/m3 were significantly less than those of the chamber controls. The absolute testis weight of the 10\smg/m3 group was significantly less than that of the chamber controls. |
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| Physical Description: | 1 PDF file (372 pages) illustrations |