Findings published in the Journal of Agricultural and Food Chemistry are amongst the first to propose a mechanism between diacetyl and the lung disease bronchiolitis obliterans syndrome (BOS), diagnosed in a number of workers at US popcorn manufacturing plants in 2007.
Following those initial reports some of the largest US popcorn makers, including Pop Weaver and ConAgra, removed diacetyl from popcorn flavoring. The ingredient is also often used in flavorings for snacks, sweets and frozen foods.
Researchers from RTI International and the National Institute of Environmental Health Sciences (NIEHS), both located in the Research Triangle Park, North Carolina, now report that their new study is the first to structurally characterize the formation of links between diacetyl and the amino acid arginine-containing compounds in cell membranes.
“The synthesis and characterization of this diacetyl-arginine complex has important implications for investigating the mechanism(s) of diacetyl-mediated lung disease,” wrote the researchers in the Journal of Agricultural and Food Chemistry.
“Currently, the mechanism(s) of diacetyl toxicity is (are) unknown; however, the results of this study suggest that injury to the airway epithelium may involve alteration of cellular proteins containing arginine, including those on cell membranes,” they added.
Historical context
Industry concerns about diacetyl, an ingredient with GRAS (generally recognized as safe) status from the Food and Drug Administration (FDA) as a direct food ingredient (although this is reportedly under review), were initially raised after researcher from the Netherlands linked the industrial use of diacetyl with the debilitating lung disease.
The team, from the Universiteit Utrecht's department of environmental epidemiology examined a population of workers at an unnamed chemical plant that produced diacetyl, and found a cluster of previously undiagnosed bronchiolitis obliterans syndrome (BOS) cases.
While the researchers said they were unable to rule out contributions of other chemicals to the development of BOS, the study significantly narrows the field of suspects to diacetyl and the components and byproducts of its manufacturing process.
BOS leads to inflammation and obstruction of the lungs through rapid thickening or scarring of the small airways. The disease is irreversible, progressive and can cause death, with the only possible treatment available being a lung transplant.
Biological plausibility
For the new study the North Carolina-based scientists examined the effects of diacetyl on N-R-acetylarginine (AcArg), selected as a model compound for “potential reactions with arginine-containing peptides and proteins as a prelude to determining the chemical basis for potential immunological effects”, explained the researchers.
Results showed that diacetyl did indeed react with the arginine-containing compound, with some conversion under acidic conditions (pH2) and greater conversion at neutral pH (pH 7).
“Studies are underway to utilize this new information to investigate the immune response to membrane proteins and enzymes altered by diacetyl reaction with arginyl residues,” added the researchers.
Source: Journal of Agricultural and Food Chemistry
Published online ahead of print, ASAP Article, doi: 10.1021/jf103251w
“Reaction of the Butter Flavorant Diacetyl (2,3-Butanedione) with N-r-Acetylarginine: A Model for Epitope Formation with Pulmonary Proteins in the Etiology of Obliterative Bronchiolitis”
Authors: J.M. Mathews, S.L.Watson, R.W. Snyder, J.P. Burgess, D.L. Morgan