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Relationship: 1838
Title
Airway epithelial injury leads to Increase, Inflammation
Upstream event
Downstream event
Key Event Relationship Overview
AOPs Referencing Relationship
AOP Name | Adjacency | Weight of Evidence | Quantitative Understanding | Point of Contact | Author Status | OECD Status |
---|---|---|---|---|---|---|
α-diketone-induced bronchiolitis obliterans | adjacent | Not Specified | Not Specified | Agnes Aggy (send email) | Under development: Not open for comment. Do not cite |
Taxonomic Applicability
Sex Applicability
Life Stage Applicability
Key Event Relationship Description
Damage of the airway epithelium leads to inflammatory reactions.
Evidence Collection Strategy
Evidence Supporting this KER
Biological Plausibility
Inflammation is a biological response to harmful stimuli, including cell damage. Therefore, damage to airway epithelium will initiate inflammatory reactions.
Empirical Evidence
Moderately damaged epithelium can regenerate itself after exposure cessation and the inflammatory reaction, initiated by the release of various inflammatory cytokines (Anderson et al. 2010), will be of limited duration. However, severely damaged epithelium is unable to recover, probably due to the depletion of progenitor cells required to regenerate the epithelium (McGraw et al. 2017). This leads to sustained inflammation. The inability of epithelium regeneration and the resulting chronic inflammation might explain the threshold for the manifestation of negative health effects typically observed after α-diketone inhalation.
Uncertainties and Inconsistencies
It is clear that inflammatory reactions occur after exposure to α-diketones. The exact role of inflammation in the ultimate development of bronchiolitis obliterans remains unclear.
Known modulating factors
Quantitative Understanding of the Linkage
Response-response Relationship
Time-scale
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
References
Anderson, S.E., Jackson, L.G., Franko, J., Wells, J.R., 2010. Evaluation of dicarbonyls generated in a simulated indoor air environment using an in vitro exposure system. Toxicol. Sci. 115, 453–461.
McGraw, M. D., Rioux, J. S., Garlick, R. B., Rancourt, R. C., White, C. W., & Veress, L. A. (2017). Impaired proliferation and differentiation of the conducting airway epithelium associated with bronchiolitis obliterans after sulfur mustard inhalation injury in rats. Toxicological Sciences, 157(2), 399–409. https://doi.org/10.1093/toxsci/kfx057