NTP Research Report on Respiratory Tract Toxicity of the Flavoring Agent 2,3-Hexanedione in Mice Exposed by Inhalation: Research Report 10 [Internet]

2,3-Hexanedione is a 6-carbon α-diketone flavoring agent that is a potential replacement for 2,3-butanedione. 2,3-Butanedione inhalation has been associated with obliterative bronchiolitis in workers. The inhalation toxicity data for 2,3-hexanedione are limited to one study conducted in rats. In this study, we provide additional data on the respiratory toxicity of 2,3-hexanedione in male and female B6C3F1 mice. Mice (six per group) were exposed (whole body) to 0, 100, 150, or 200 ppm 2,3-hexanedione 6 hours/day, 5 days/week for 2 weeks plus 2 days (12 exposure days total). Animals were euthanized the morning after the last exposure and respiratory tract tissues collected for histopathological evaluation. All mice survived to the end of the study. Body weights of female mice exposed to 150 and 200 ppm 2,3-hexanedione were significantly less than controls, and relative lung weights were significantly greater following exposure to 100, 150, and 200 ppm. Squamous metaplasia was the most prevalent lesion observed in the nasal cavity, larynx, and trachea of exposed male and female mice. 2,3-Hexanedione caused atypical hyperplasia of the bronchial respiratory epithelium in male and female mice exposed to 200 ppm 2,3-hexanedione. 2,3-Hexanedione exposure did not cause airway fibrosis or obliterative bronchiolitis in mice.