The authors response to letters re: "Clinical Bronchiolitis Obliterans in Workers at a Microwave-Popcorn Plant." (N Engl J Med 2002 Aug; 347(5)330-338). We used diacetyl as an index of exposure to volatile organic chemicals in the popcorn plant because it was the predominant one found in plant air. However, identification of the causal agent or agents in the flavoring will rely on studies in animals in which individual constituents are tested; such studies are now under way. Diacetyl is a leading candidate for investigation of potential respiratory toxicity because alpha-dicarbonyl compounds react with functionally reactive arginine residues in proteins and with guanine and inhibit superoxide dismutase and glutathione reductase, which are involved in protection from oxidative stress. In addition to Dr. Ezrailson's concern about the properties of a derivative diepoxide, diacetyl itself has been nominated for studies by the National Toxicology Program (NTP) because of widespread human exposure, limited evidence of mutagenicity, and relations to carcinogens and mutagens in terms of structure and activity, as well as because diacetyl is representative of aliphatic alpha-diketones. We did not detect 1,3-butadiene-2,3-diol or 1,2;3,4-diepoxybutane- 2,3-diol in any samples collected by thermal desorption tubes and analyzed with gas chromatography-mass spectrometry. However, we agree with Dr. Ezrailson that diacetyl would be present in equilibriuin with its tautomers, as governed by the equilibrium constants for the conversions. Since diacetyl occurs naturally in butter and during the manufacture of alcoholic beverages, any proposed ban of diacetyl in food products raises issues of practicality. As noted by Taubert and colleagues, other agents within the workplace may contribute to the clinical bronchiolitis obliterans seen in this workforce. Indeed, necrosis of the respiratory epithelium in the mainstem bronchus was more severe in rats exposed to butter-flavoring vapors than in rats exposed to diacetyl alone at a similar diacetyl concentration (unpublished data). We did not measure tannins. Workers managing the grain bins, presumably with greater exposure to organic dust, were in the low-risk group; mixers, who had almost no active contact with com or its dusts, had the highest historical risk of fixed airway obstruction. The role of respirable salt dust in the airway damage found in microwave-popcorn production workers remains unclear. However, our observation that the same syndrome occurs in flavoring-production workers without exposure to grains or salt makes these agents less likely to be causal contributors.
Airway-obstruction; Occupational-exposure; Organic-compounds; Lung-disease; Respiratory-irritants; Air-sampling; Air-quality-monitoring; Chronic-exposure; Respirable-dust; Respiratory-system-disorders; Pulmonary-system-disorders; Food-processing-workers; Food-processing-industry; Food-processing; Food-additives; Toxic-effects
National Institute for Occupational Safety and Health, Division of Respiratory Disease Studies, MS H-2800, 1095 Willowdale Road, Morgantown, WV 26505