Diacetyl and 2,3-pentanedione exposures associated with cigarette smoking: implications for risk assessment of food and flavoring workers

Crit Rev Toxicol. 2014 May;44(5):420-35. doi: 10.3109/10408444.2014.882292. Epub 2014 Mar 17.


Diacetyl and 2,3-pentanedione inhalation have been suggested as causes of severe respiratory disease, including bronchiolitis obliterans, in food/flavoring manufacturing workers. Both compounds are present in many food items, tobacco, and other consumer products, but estimates of exposures associated with the use of these goods are scant. A study was conducted to characterize exposures to diacetyl and 2,3-pentanedione associated with cigarette smoking. The yields (μg/cigarette) of diacetyl and 2,3-pentanedione in mainstream (MS) cigarette smoke were evaluated for six tobacco products under three smoking regimens (ISO, Massachusetts Department of Public Health, and Health Canada Intense) using a standard smoking machine. Mean diacetyl concentrations in MS smoke ranged from 250 to 361 ppm for all tobacco products and smoking regimens, and mean cumulative exposures associated with 1 pack-year ranged from 1.1 to 1.9 ppm-years. Mean 2,3-pentanedione concentrations in MS smoke ranged from 32.2 to 50.1 ppm, and mean cumulative exposures associated with 1 pack-year ranged from 0.14 to 0.26 ppm-years. We found that diacetyl and 2,3-pentanedione exposures from cigarette smoking far exceed occupational exposures for most food/flavoring workers who smoke. This suggests that previous claims of a significant exposure-response relationship between diacetyl inhalation and respiratory disease in food/flavoring workers were confounded, because none of the investigations considered or quantified the non-occupational diacetyl exposure from cigarette smoke, yet all of the cohorts evaluated had considerable smoking histories. Further, because smoking has not been shown to be a risk factor for bronchiolitis obliterans, our findings are inconsistent with claims that diacetyl and/or 2,3-pentanedione exposure are risk factors for this disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Bronchiolitis Obliterans / etiology
  • Bronchiolitis Obliterans / pathology
  • Canada
  • Diacetyl / toxicity*
  • Disease Models, Animal
  • Evaluation Studies as Topic
  • Flavoring Agents / adverse effects
  • Food-Processing Industry*
  • Humans
  • Inhalation Exposure / adverse effects*
  • Occupational Exposure / adverse effects*
  • Pentanones / toxicity*
  • Risk Assessment
  • Smoking / adverse effects*


  • Flavoring Agents
  • Pentanones
  • Diacetyl
  • 2,3-pentanedione