NTP technical report on the toxicology and carcinogenesis studies of 2,3-Butanedione (CASRN 431-03-8) in Wistar Han [Crl:WI (Han)] rats and B6C3F1/N mice (Inhalation studies)
THREE-MONTH STUDY IN RATS: Groups of 10\smale and 10\sfemale rats were exposed to 2,3-butanedione vapor by whole body inhalation at concentrations of 0, 6.25, 12.5, 25, 50, or 100\sppm, 6\shours plus T90 (10\sminutes) per day, 5\sdays per week for 14\sweeks. Additional groups of 10\smale and 10\sfem...
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| Format: | eBook |
| Language: | English |
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Research Triangle Park, , North Carolina, USA
National Toxicology Program, Public Health Service, U.S. Department of Health and Human Services
2018, August 2018
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| Series: | Technical report
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| Online Access: | |
| Collection: | National Center for Biotechnology Information - Collection details see MPG.ReNa |
| Summary: | THREE-MONTH STUDY IN RATS: Groups of 10\smale and 10\sfemale rats were exposed to 2,3-butanedione vapor by whole body inhalation at concentrations of 0, 6.25, 12.5, 25, 50, or 100\sppm, 6\shours plus T90 (10\sminutes) per day, 5\sdays per week for 14\sweeks. Additional groups of 10\smale and 10\sfemale rats were exposed to the same concentrations for 23\sdays for clinical pathology analyses. Two male rats in the 100\sppm group died before the end of the study. All other rats survived to the end of the study. The mean body weights of 100\sppm males and females were significantly less than those of the chamber control groups. Clinical observations, noted only in the 50 and 100\sppm groups, included abnormal breathing, sneezing, and lethargy. On day\s23 and at study termination, neutrophil counts were significantly increased in 100\sppm females and were consistent with the inflammation observed in the respiratory tract. In the trachea, necrosis and regeneration occurred in the epithelium of males and females and hyperplasia occurred in the epithelium of females. In the lung, significantly increased incidences of nonneoplastic lesions only occurred in the 100\sppm groups of males and females and included hyperplasia and regeneration of the bronchus epithelium and bronchiole epithelium hyperplasia; in addition, the incidences of histiocyte cellular infiltration and bronchus epithelium necrosis were significantly increased in 100\sppm males, and the incidence of atypical hyperplasia of the bronchus epithelium was significantly increased in 100\sppm females. CONCLUSIONS: Under the conditions of these 2-year inhalation studies, there was some evidence of carcinogenic activity of 2,3-butanedione in male Wistar Han rats based on the combined incidences of squamous cell papilloma and squamous cell carcinoma of the nose. There was some evidence of carcinogenic activity of 2,3-butanedione in female Wistar Han rats based on the incidences of squamous cell carcinoma of the nose (see Explanation of Levels of Evidence of Carcinogenic Activity; see a summary of the Peer Review Panel comments and the public discussion on this Technical Report in Appendix K). There was no evidence of carcinogenic activity of 2,3-butanedione in male B6C3F1/N mice exposed to 12.5, 25, or 50\sppm. There was equivocal evidence of carcinogenic activity of 2,3-butanedione in female B6C3F1/N mice based on the occurrences of adenocarcinoma of the nose. Exposure to 2,3-butanedione resulted in increased incidences of nonneoplastic lesions of the nose, larynx, trachea, lung, and eye in male and female rats and mice. Synonyms: Biacetyl; butane-2,3-dione; butanedione; diacetyl; dimethylglyoxal Trade name: NSC 8750 Significant increases in the erythron occurred most consistently in the 100\sppm male and female groups on day\s23 and at study termination. These erythron increases were consistent with dehydration or a secondary erythrocytosis. 2,3-Butanedione exposure resulted in a significant increase of nonneoplastic lesions in the respiratory tract of male and female rats, primarily in the 50 and 100\sppm groups. The highest number of lesions occurred in the nose and included suppurative inflammation; necrosis, regeneration, squamous metaplasia and hyperplasia of the respiratory epithelium; necrosis, degeneration, and respiratory metaplasia of the olfactory epithelium; atrophy of the turbinate; and hyperplasia of the lymphoid tissue. In the larynx, lesions included respiratory epithelium squamous metaplasia and squamous epithelium hyperplasia in males and females and epithelium necrosis and chronic active inflammation in females. |
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| Physical Description: | 1 PDF file (various pagings) illustrations |