ArticleToxicological sciences : an official journal of the Society of Toxicology2008
Respiratory toxicity of diacetyl in C57BL/6 mice.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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56 citing papers in PubMed, 134 citations in OpenAlex.
- Not Just an Aroma Compound: Expanding Perspectives on Diacetyl in Food Systems and Human Health.Molecules (Basel, Switzerland) · 2026Review
- Hexavalent Chromium Oropharyngeal Aspiration Induced Behavior Effects and Essential Metal Dyshomeostasis in Young Hartley Guinea Pigs.Applied sciences (Basel, Switzerland) · 2026Article
- Diacetyl-induced bronchiolitis obliterans involves ubiquitin C upregulation and fibrosis-related gene activation in rats.Frontiers in pharmacology · 2025Article
- A Review of the Toxicity of Ingredients in e-Cigarettes, Including Those Ingredients Having the FDA's "Generally Recognized as Safe (GRAS)" Regulatory Status for Use in Food.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2024Review
- Toxicity of waterpipe tobacco smoking: the role of flavors, sweeteners, humectants, and charcoal.Toxicological sciences : an official journal of the Society of Toxicology · 2024Review
- Article
- Increased oxidative stress responses in murine macrophages exposed at the air-liquid interface to third- and fourth-generation electronic nicotine delivery system (ENDS) aerosols.Toxicology reports · 2023Article
- IL-17A neutralization fails to attenuate airway remodeling and potentiates a proinflammatory lung microenvironment in diacetyl-exposed rats.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Non-target GC-MS analyses of fecal VOCs in NASH-hepatocellular carcinoma model STAM mice.Scientific reports · 2023Article
- Diacetyl inhalation impairs airway epithelial repair in mice infected with influenza A virus.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Lung Regeneration: Cells, Models, and Mechanisms.Cold Spring Harbor perspectives in biology · 2022Review
- Silymarin constrains diacetyl-prompted oxidative stress and neuroinflammation in rats: involvements of Dyn/GDNF and MAPK signaling pathway.Inflammopharmacology · 2022Article
- Effect ofJournal of food science and technology · 2022Article
- Diacetyl Vapor Inhalation Induces Mixed, Granulocytic Lung Inflammation with Increased CD4Toxics · 2021Article
- Repetitive diacetyl vapor exposure promotes ubiquitin proteasome stress and precedes bronchiolitis obliterans pathology.Archives of toxicology · 2021Article
- An updated overview of e-cigarette impact on human health.Respiratory research · 2021Review
- An Unrecognized Hazard in E-Cigarette Vapor: Preliminary Quantification of Methylglyoxal Formation from Propylene Glycol in E-Cigarettes.International journal of environmental research and public health · 2021Article
- Occupational Bronchiolitis: An Update.Clinics in chest medicine · 2020Review
- The Promise and Peril of Vaping.Current cardiology reports · 2020Review
- The Impact of Device Settings, Use Patterns, and Flavorings on Carbonyl Emissions from Electronic Cigarettes.International journal of environmental research and public health · 2020Article
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4 authors at 3 institutions in 1 country.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.