Flavorings-Related Lung Disease: a Brief Review and New Mechanistic Data

Introduction:
This text provides an in-depth analysis of the association between diacetyl and flavorings-related lung disease in workers. It also discusses the pulmonary toxicity of diacetyl and related a-dicarbonyl compounds in experimental studies and provides new experimental data on the toxicity of the structurally related 3-carbon a-dicarbonyl compound methylglyoxal and the toxicity of inhaled mixtures containing diacetyl.

Key Points:

* Diacetyl is a butter flavoring that occurs naturally in foods and drinks. It has been classified as Generally Recognized as Safe for the conditions of intended use as an additive to food.
* The discovery of diacetyl toxicity is the story of how researchers from multiple disciplines can work together to identify new hazards and protect workers.
* Diacetyl and related a-dicarbonyl compounds are reactive compounds that interact with cellular constituents, especially proteins, through both well-established chemical reactions and potentially in some ways that are currently incompletely elucidated.
* Endogenous a-dicarbonyl compounds, such as glyoxal, methylglyoxal, and 3-deoxyglucosone, are believed to be produced during glucose degradation and glycation reactions.
* Occupational exposures to diacetyl and the associated lung disease were first described in the food production industry, with subsequent investigations identifying additional a-dicarbonyl compounds that were present during food production.
* Diacetyl and 2,3-pentanedione each cause airway fibrosis in rodents, while in vitro studies document the susceptibility of the human respiratory epithelium to diacetyl-induced damage.
* The fundamental lesion of bronchiolitis obliterans is fibrosis (scarring) of bronchioles that reduces the size of the airway lumen and obstructs airflow.
* The airway epithelial toxicity of diacetyl and 2,3-pentanedione is well-documented in vitro and in vivo, with repeated inhalation exposure causing necrosis of airway epithelium and damage to the underlying basement membrane.

Main Message:
The text emphasizes the importance of identifying and addressing workplace hazards, particularly those related to diacetyl and a-dicarbonyl compounds. It highlights the significance of interdisciplinary collaboration in identifying new hazards and protecting workers, as well as the need for ongoing research to better understand the mechanisms of toxicity and potential health effects associated with exposure to these compounds. Employers and regulatory agencies must take appropriate measures to control exposures and protect the health of workers in affected industries.

hubbs, ann F., Kathleen Kreiss, Kristin J. Cummings, Kara L. Fluharty, Ryan O’Connell, allison Cole, Tiana M. Dodd, et al. “Flavorings-Related Lung Disease: a Brief Review and New Mechanistic Data.” Toxicologic Pathology 47, no. 8 (December 2019): 1012–26. https://doi.org/10.1177/0192623319879906.