Pathology of diacetyl and 2,3-pentanedione airway lesions in a rat model of obliterative bronchiolitis

Abstract

Inhalation of diacetyl vapors by workers has been associated with obliterative bronchiolitis (OB), a poorly understood fibroproliferative disease of the small airways. Significant insights into the pathogenesis of OB have been obtained through the use of a rat model. Inhalation exposure of rats to diacetyl or 2,3-pentanedione, a related flavoring agent, can cause severe injury to the airway epithelium and underlying basement membrane. Repeated exposure to diacetyl or 2,3-pentanedione leads to aberrant repair, fibroproliferation and partial to complete occlusion of the airway lumen. Fibroproliferative lesions in rat airways were found to include both intraluminal polyps and circumferential intramural lesions. Intraluminal polyps have been observed to form secondary attachments spanning the airway lumen causing increasing obstruction. These airway lesions in rats are accompanied by inflammation in the form of peribronchial and perivascular infiltrates of lymphocytes, eosinophils and neutrophils. Diacety-linduced OB lesions in the rat are similar to OB lesions in humans and provide a good model for studying the pathogenesis of this disease.

Inflammatory and Oxidative Responses Induced by Exposure to Commonly Used e-Cigarette Flavoring Chemicals and Flavored e-Liquids without Nicotine

“…Obliterative bronchiolitis (bronchiolitis obliterans) is a disease caused by exposure to butter flavoring chemicals (diacetyl, 2, 3-pentanedione). Chronic inhalation of these chemicals causes airway epithelium injury ultimately resulting in the formation of pro-fibrotic lesions (Morgan et al, 2012 ; Flake and Morgan, 2017 ; Wallace, 2017 ). Chocolate flavoring chemical, 2.5-dimerthylpyrazine has shown to alter cystic fibrosis transmembrane conductance regulator (CFTR) expression, which could have adverse effects in immune mechanisms, such as mucociliary clearance, dampening the epithelial defense against inhaled particulates and pathogens (Sherwood and Boitano, 2016 ).…”

Mechanisms of toxicity and biomarkers of flavoring and flavor enhancing chemicals in emerging tobacco and non-tobacco products

“…2,3-pentanedione or acetyl propionyl (a popular replacement for diacetyl) is also an α-diketone, chemically and structurally very similar to diacetyl (Day et al, 2011; Flake and Morgan, 2017). 2,3-pentanedione and acetoin (another popular diacetyl replacement) were detected in e-cigarette aerosol at concentrations up to 64 and 529 μg/e-cigarette (Allen et al, 2016).…”

Volatile organic contamination analysis in packaged foods

“…Furthermore, this same functional group has the capacity to form advanced glycation end products, or proteins (i.e.-arginine) that bind to sugar molecules (i.e.-glucose), specifically its electron-attracting carbonyl groups inherent to the structure (Figure 1.1) (Anders, 2017;. 2,3-pentanedione has been reported to be even more reactive than diacetyl Flake et al, 2016;. Acetoin (3-hydroxy-2-butanone) is a structurally similar compound to diacetyl, and is often included in may butter flavor formulations.…”

“…Numerous studies have linked this disease to inhalative exposure to ketone-type flavoring compounds, such as diacetyl Fedan et al, 2006;Flake and Morgan, 2016;. One study claims microwave popcorn could pose a significant health risk to consumers .…”

“…Repeated inhalative exposures to 2,3-pentanedione have been shown to cause fibrosis of intra-pulmonary airways in rats, demonstrating symptoms similar to BO in humans . Several studies have linked this disease to exposure to ketonetype flavoring compounds such as diacetyl Flake and Morgan (2016). And other studies claim microwave popcorn could pose a significant health risk to consumers.…”