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Key Event Title
Fibroproliferative airway lesions
|Level of Biological Organization|
Key Event Components
Key Event Overview
AOPs Including This Key Event
Key Event Description
Repeated exposure to α-diketones might result in the loss of the regenerative capacity of the airway epithelium, e.g. due to insufficient residual stem cells. Sustained loss of the epithelial cells might lead to damage to the underlying basement membrane and exposure of the lamina propria. Fibroblast in the lamina propria are activated and start to proliferate and elaborate collagen matrix. Cytokines and growth factors released by epithelial cells and infiltrated neutrophils may promote the migration and proliferation of fibroblasts into the airway lumen. The initially fibromyxoid tissue is gradually replaced by mature connective tissue that is rich in collagen (rats, Flake & Morgan 2017).
How It Is Measured or Detected
Fibroproliferative airway lesions can be observed in biopsies of α-diketone exposed laboratory animals in a dose dependent manner using various tissue stainings of histological specimen. (rats, Morgan et al. 2016, Flake & Morgan 2017)
Domain of Applicability
Flake, G. P., & Morgan, D. L. (2017). Pathology of diacetyl and 2,3-pentanedione airway lesions in a rat model of obliterative bronchiolitis. Toxicology, 388, 40–47. https://doi.org/10.1016/j.tox.2016.10.013
Morgan, D. L., Jokinen, M. P., Johnson, C. L., Price, H. C., Gwinn, W. M., Bousquet, R. W., & Flake, G. P. (2016). Chemical Reactivity and Respiratory Toxicity of the alpha-Diketone Flavoring Agents: 2,3-Butanedione, 2,3-Pentanedione, and 2,3-Hexanedione. Toxicologic Pathology, 44(5), 763–783. https://doi.org/10.1177/0192623316638962