Respiratory Toxicity of Diacetyl in C57Bl/6 Mice
Open Access
- 27 January 2008
- journal article
- research article
- Published by Oxford University Press (OUP) in Toxicological Sciences
- Vol. 103 (1), 169-180
- https://doi.org/10.1093/toxsci/kfn016
Abstract
Diacetyl, a component of artificial butter flavoring, is a potential etiological agent of obliterative bronchiolitis (OB); however, the toxic dose and mechanisms of toxicity remain controversial. We evaluated the respiratory toxicity of diacetyl in a murine model using several exposure profiles relevant to workplace conditions at microwave popcorn packaging plants. Male C57Bl/6 mice were exposed to inhaled diacetyl across several concentrations and duration profiles, or by direct oropharyngeal aspiration. Effects of diacetyl on the respiratory tract were evaluated by histopathology and BALF analyses. Subacute exposure to 200 or 400 ppm diacetyl for 5 days caused deaths, necrotizing rhinitis, necrotizing laryngitis and bronchitis. Reducing the exposure to 1 h/day (100, 200, 400 ppm) for 4 weeks resulted in less nasal and laryngeal toxicity, but led to peribronchial and peribronchiolar lymphocytic inflammation. A similar pattern was observed with intermittent high-dose exposures at 1200 ppm (15 min, twice a day, 4 weeks). Subchronic exposures to 100 ppm (6 h/day, 12 weeks) caused moderate nasal injury, and peribronchial lymphocytic inflammation accompanied by epithelial atrophy, denudation, and regeneration. Treatment with 400 mg/kg by oropharyngeal aspiration to bypass the nose caused foci of fibrohistiocytic proliferation with little or no inflammation at the junction of the terminal bronchiole and alveolar duct. Depending on the route and duration of exposure, diacetyl causes significant epithelial injury, peribronchial lymphocytic inflammation, or fibrohistiocytic lesions in the terminal bronchioles. Collectively these results indicate that clinically relevant diacetyl exposures result in a pattern of injury that replicates features of human OB.Keywords
This publication has 27 references indexed in Scilit:
- Popcorn worker's lung: In vitro exposure to diacetyl, an ingredient in microwave popcorn butter flavoring, increases reactivity to methacholineToxicology and Applied Pharmacology, 2006
- Evaluation of Flavorings-Related Lung Disease Risk at Six Microwave Popcorn PlantsJournal of Occupational and Environmental Medicine, 2006
- Necrosis of Nasal and Airway Epithelium in Rats Inhaling Vapors of Artificial Butter FlavoringToxicology and Applied Pharmacology, 2002
- INHALATION TOXICITY STUDIES OF THE α,β-UNSATURATED KETONES: Ethyl Vinyl KetoneInhalation Toxicology, 2001
- INHALATION TOXICITY STUDIES OF THE a,ß-UNSATURATED KETONES:2-Cyclohexene-1-OneInhalation Toxicology, 2001
- Airflow, Gas Deposition, and Lesion Distribution in the Nasal PassagesEnvironmental Health Perspectives, 1990
- Effects of low levels of NO2 on terminal bronchiolar cells and its relative toxicity compared to O3Toxicology and Applied Pharmacology, 1988
- Pathology of toxic responses to the RD50 concentration of chlorine gas in the nasal passages of rats and miceToxicology and Applied Pharmacology, 1983
- Bronchiolitis Obliterans From a Burning AutomobileSouthern Medical Journal, 1980
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976