Skip to main content
SpringerLink
Log in

Diacetyl-Induced Lung Disease

  • Review Article
  • Published:
Toxicological Reviews

Abstract

Diacetyl is a diketone flavouring agent that is commonly employed for buttery taste as well as other purposes. Industrial exposure to flavouring agents, particularly diacetyl, has recently been associated with bronchiolitis obliterans, a severe respiratory illness producing fibrosis and obstruction of the small airways. This has been most commonly reported in the microwave popcorn production industry, but it has occurred elsewhere. In addition to bronchiolitis obliterans, spirometry abnormalities (fixed airflow obstruction) and respiratory symptoms have been associated with exposure. A direct effect on the respiratory epithelium with the disorganised fibrotic repair appears most likely as the underlying mechanism. Current data suggest that diacetyl is the agent responsible, although it is possible that diacetyl is simply a marker for another causative agent.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Table I

Similar content being viewed by others

Notes

  1. The predominance of neutrophilic (rather than lymphocytic) response in laboratory animals is consistent with the lack of response to corticosteroid therapy in humans.

References

  1. Parmet AJ, Von Essen S. Rapidly progressive, fixed airway obstructive disease in popcorn workers: a new occupational pulmonary illness? J Occup Environ Med 2002; 44(3): 216–8

    Article  PubMed  CAS  Google Scholar 

  2. Kreiss K, Gomaa A, Kullman G, et al. Clinical bronchiolitis obliterans in workers at a microwave-popcorn plant. N Engl J Med 2002; 347(5): 330–8

    Article  PubMed  Google Scholar 

  3. Lockey J, McKay R, Barth E, et al. Bronchiolitis obliterans in the food flavoring manufacturing industry. Am J Respir Crit Care Med 2002; 165: A461

    Google Scholar 

  4. The Flavor and Extracts Manufacturers Association of the United States. Respiratory health and safety in the flavor manufacturing workplace [online]. Available from URL: http://www.femaflavor.org/html/public/RespiratoryRpt.pdf [Accessed 2006 May 15]

  5. McConnell R, Hartle R. Cincinnati (OH): Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health, 1986. Report no. 85-171-1710

  6. Harrison R, Gelb A, Harber P. Food flavoring workers with bronchiolitis obliterans following exposure to diacetyl, California [online]. Available from URL: http://www.capanet.org/pdfs/BO_cases_%20final_5_16_06.pdf [Accessed 2006 May 15]

  7. Centers for Disease Control and Prevention. Fixed obstructive lung disease in workers at a microwave popcorn factory–Missouri, 2000–2002. MMWR Morb Mortal Wkly Rep 2002; 51(16): 345–7

    Google Scholar 

  8. Centers for Disease Control and Prevention. Fixed obstructive lung disease in workers at a microwave popcorn factory–Missouri, 2000–2002. JAMA 2002; 287(22): 2939–40

    Article  Google Scholar 

  9. National Institute for Occupational Safety and Health. HETA 2002-0408-2915, Agrilink Foods Popcorn Plant, Ridgway, Illinois, NIOSH Health Hazard Evaluation Report. Cincinnati (OH): Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health, 2003 Oct. Report no. 2002-0408-2915

    Google Scholar 

  10. National Institute for Occupational Safety and Health. HETA # 2000-0401-2991, Gilster-Mary Lee Corporation, Jasper, Missouri, NIOSH Health Hazard Evaluation Report. Cincinnati (OH): Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health, 2006 Jan. Report no. 2000-0401-2991

    Google Scholar 

  11. Kanwal R, Kullman G. ConAgra Snack foods. Marion, Ohio, NIOSH Health Hazard Evaluation Report. Cincinnati (OH): Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health, 2004. Report no. 2003-0112-2949

    Google Scholar 

  12. Kanwal R, Boylstein R, Piacitelli C. American Pop Corn Co., Sioux City, Iowa, NIOSH Health Hazard Evaluation Report. Cincinnati (OH): Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health, 2004. Report no. 2001-0474-2943

    Google Scholar 

  13. US Occupational Safety and Health Administration. Chemical sampling information: diacetyl [online]. Available from URL: http://www.osha.gov/dts/chemi-calsampling/data/CH_231710.html [Accessed 2006 Aug 23]

  14. US Occupational Safety and Health Administration. Diacetyl [online]. Available from URL: http://www.osha.gov/dts/sltc/methods/partial/t-pv2118t-pv2118.html [Accessed 2006 Aug 23]

  15. Bartowsky EJ, Henschke PA. The ‘buttery’ attribute of wine-diacetyl-desirability, spoilage and beyond. Int J Food Microbiol 2004; 96(3): 235–52

    Article  PubMed  CAS  Google Scholar 

  16. Pripis-Nicolau L, de Revel G, Bertrand A, et al. Formation of flavor components by the reaction of amino acid and carbonyl compounds in mild conditions. J Agric Food Chem 2000; 48(9): 3761–6

    Article  PubMed  CAS  Google Scholar 

  17. Suomalainen H, Ronkainen P. Mechanism of diacetyl formation in yeast fermentation. Nature 1968; 220(5169): 792–3

    Article  PubMed  CAS  Google Scholar 

  18. Birkenhauer JM, Oliver JD. Use of diacetyl to reduce the load of Vibrio vulnificus in the Eastern oyster, Crassostrea virginica. J Food Prot 2003; 66(1): 38–43

    PubMed  CAS  Google Scholar 

  19. Chan A, Allen R. Bronchiolitis obliterans: an update. Curr Opin Pulm Med 2004; 10(2): 133–41

    Article  PubMed  Google Scholar 

  20. Lynch DA. Imaging of small airways diseases. Clin Chest Med 1993; 14(4): 623–34

    PubMed  CAS  Google Scholar 

  21. Trulock EP. Lung transplantation. Am J Respir Crit Care Med 1997; 155(3): 789–818

    PubMed  CAS  Google Scholar 

  22. Akpinar-Elci M, Stemple KJ, Enright PL, et al. Induced sputum evaluation in microwave popcorn production workers. Chest 2005; 128(2): 991–7

    Article  PubMed  Google Scholar 

  23. Akpinar-Elci M, Travis WD, Lynch DA, et al. Bronchiolitis obliterans syndrome in popcorn production plant workers. Eur Respir J 2004; 24(2): 298–302

    Article  PubMed  CAS  Google Scholar 

  24. BASF Aktiengesellscheft. Study on the acute inhalation toxicity LC50 of diacetyl FCC as a vapor in rats 4 hour exposure. Ludwigshafen: BASF, 1993

    Google Scholar 

  25. Hubbs AF, Battelli LA, Goldsmith WT, et al. Necrosis of nasal and airway epithelium in rats inhaling vapors of artificial butter flavoring. Toxicol Appl Pharmacol 2002; 185(2): 128–35

    Article  PubMed  CAS  Google Scholar 

  26. Fedan JS, Dowdy JA, Fedan KB, et al. Popcorn worker’s lung: in vitro exposure to diacetyl, an ingredient in microwave popcorn butter flavoring, increases reactivity to methacholine. Toxicol Appl Pharmacol 2006; 215(1): 17–22

    Article  PubMed  CAS  Google Scholar 

  27. Riordan JF. Arginyl residues and anion binding sites in proteins. Mol Cell Biochem 1979; 26(2): 71–92

    Article  PubMed  CAS  Google Scholar 

  28. National Institute for Occupational Safety and Health. Disease reporting [online]. Available from URL: http://www.cdc.gov/niosh/topics/flavorings/#diseasereporting [Accessed 2006 Dec 4]

  29. Kullman G, Boylstein R, Jones W, et al. Characterization of respiratory exposures at a microwave popcorn plant with cases of bronchiolitis obliterans. J Occup Environ Hyg 2005; 2(3): 169–78

    Article  PubMed  CAS  Google Scholar 

  30. Boylstein R, Piacitelli C, Grote A, et al. Diacetyl emissions and airborne dust from butter flavorings used in microwave popcorn production. J Occup Environ Hyg 2006; 3(10): 530–5

    Article  PubMed  CAS  Google Scholar 

  31. Pendergrass SM. Method development for the determination of diacetyl and acetoin at a microwave popcorn plant. Environ Sci Technol 2004; 38(3): 858–61

    Article  PubMed  CAS  Google Scholar 

  32. Kanwal R, Kullman G, Piacitelli C, et al. Evaluation of flavorings-related lung disease risk at six microwave popcorn plants. J Occup Environ Med 2006; 48(2): 149–57

    Article  PubMed  CAS  Google Scholar 

  33. Smith RL, Cohen SM, Doull J, et al. Criteria for the safety evaluation of flavoring substances. The Expert Panel of the Flavor and Extract Manufacturers Association. Food Chem Toxicol 2005; 43(8): 1141–77

    Article  PubMed  CAS  Google Scholar 

  34. Hansen TH, Hoffa JP. Petition for an OSHA emergency temporary standard for diacetyl [online letter]. Available from URL: http://www.worksafe.org/images/contentEdit/docs/2006-07-26_UFCW-IBT_diacetly_Petition%5B4pps%5D.pdf [Accessed 2006 Aug 23 9]

Download references

Acknowledgements

The authors thank Noe Sanchez and Yanjapriya Kunasaleen for assistance in preparing the manuscript. The authors also thank Drs Allen Parmet, Matthew Sies, Arthur Gelb and Richard Lubman for their advice. In particular, the authors acknowledge the insight provided by our patients with diacetyl-induced bronchiolitis obliterans.

Supported in part by the Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health grant for the UCLA Occupational Medicine Residency. UCLA has an educational affiliation agreement with CAL-OSHA. Dr Harber has spoken with attorneys for his patients.

Author information

Authors and Affiliations

  1. Division of Occupational and Environmental Medicine, Department of Family Medicine, David Geffen School of Medicine at UCLA, 10880 Wilshire Boulevard, Suite 1800, Los Angeles, California, 90024, USA

    Philip Harber, Kaochoy Saechao & Catherine Boomus

Authors
  1. Philip Harber
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kaochoy Saechao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Catherine Boomus
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Philip Harber.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Harber, P., Saechao, K. & Boomus, C. Diacetyl-Induced Lung Disease. Toxicol Rev 25, 261–272 (2006). https://doi.org/10.2165/00139709-200625040-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00139709-200625040-00006

Keywords

Search

Navigation