NIOSH Alert: Preventing Lung Disease in Workers Who Use or Make Flavorings

 This Alert describes health effects that may occur because of workplace exposure to some flavorings or their ingredients, gives examples of workplace settings in which illness has occurred, and recommends steps that companies and workers should take to prevent hazardous exposures.

NIOSH has investigated the occurrence of severe lung disease in workers at a microwave popcorn packaging plant. Eight former workers at this plant developed illness characterized by fixed airways obstruction on lung function tests [Akpinar-Elci et al. 2002]. An evaluation of the current workforce at this plant showed an association between exposure to vapors from flavorings used in the production process and decreased lung function [Kreiss et al. 2002a]. Similar fixed obstructive lung disease has also occurred in workers at other plants that use or manufacture flavorings [NIOSH 1986; Lockey et al. 2002]. In animal tests, inhaling vapors from a heated butter flavoring used in microwave popcorn production caused severe injury to airways [Hubbs et al. 2002a].
Medical test results in affected workers (including some lung biopsy results) are consistent with bronchiolitis obliterans, an uncommon lung disease characterized by fixed airways obstruction [Akpinar-Elci et al. 2002]. In bronchiolitis obliterans, inflammation and scarring occur in the smallest airways of the lung and can lead to severe and disabling shortness of breath. The disease has many known causes such as inhalation of certain chemicals, certain bacterial and viral infections, organ transplantation, and reactions to certain medications [King 2000]. Known causes of bronchiolitis obliterans due to occupational or other environmental exposures include gases such as nitrogen oxides (e.g., silo gas), sulfur dioxide, chlorine, ammonia, phosgene, and other irritant gases [King 1998]. Recent NIOSH investigations strongly suggest that some flavoring chemicals can also cause bronchiolitis obliterans in the workplace. (Some workers exposed to flavorings in one of these plants were also found to have occupational asthma.)
The main respiratory symptoms experienced by workers affected by fixed airways obstruction include cough (usually without phlegm) and shortness of breath on exertion. These symptoms typically do not improve when the worker goes home at the end of the workday or on weekends or vacations. The severity of the lung symptoms can range from only a mild cough to severe cough and shortness of breath on exertion. Usually these symptoms are gradual in onset and progressive, but severe symptoms can occur suddenly. Some workers may experience fever, night sweats, and weight loss. Before arriving at a final diagnosis, doctors of affected workers initially thought that the symptoms might be due to asthma, chronic bronchitis, emphysema, pneumonia, or smoking. Severe cases may not respond to medical treatment. Affected workers generally notice a gradual reduction or cessation of cough years after they are no longer exposed to flavoring vapors, but shortness of breath on exertion persists. Several with very severe disease were placed on lung transplant waiting lists. Workers exposed to flavorings may also experience eye, nose, throat, and skin irritation. In some cases, chemical eye burns have required medical treatment.
Medical Evaluation: Medical testing may reveal several of the following findings:- Spirometry, a type of breathing test, most often shows fixed airways obstruction (i.e., difficulty blowing air out fast and no improvement with asthma medications), and sometimes shows restriction (i.e., decreased ability to fully expand the lungs).Lung volumes may show hyperinflation (i.e., too much air in the lungs due to air trapping beyond obstructed airways). Diffusing capacity of the lung (DLCO) is generally normal, especially early in the disease. Chest X-rays are usually normal but may show hyperinflation. High-resolution computerized tomography scans of the chest at full inspiration and expiration may reveal heterogeneous air trapping on the expiratory view as well as haziness and thickened airway walls. Lung biopsies may reveal evidence of constrictive bronchiolitis obliterans (i.e., severe narrowing or complete obstruction of the small airways). An open lung biopsy, such as by thoracoscopy, is more likely to be diagnostic than a transbronchial biopsy. Special processing, staining, and review of multiple tissue sections may be necessary for a diagnosis.
Flavorings are composed of various natural and manmade substances. They may consist of a single substance, but more often they are complex mixtures of several substances. The Flavor and Extract Manufacturers Association evaluates flavoring ingredients to determine whether they are “generally recognized as safe” (GRAS) under the conditions of intended use through food consumption. Though considered safe to eat, ingredients may be harmful to breathe in the forms and concentrations to which food and chemical industry workers may be exposed.
Occupational exposure guidelines have been developed for only a small number of the thousands of ingredients used in flavorings. For example, Occupational Safety and Health Administration (OSHA) permissible exposure limits (PELs) and/or NIOSH recommended exposure limits (RELs) have been established for only 46 (<5%) of the 1,037 flavoring ingredients considered by the flavorings industry to represent potential respiratory hazards due to possible volatility and irritant properties (alpha, beta-unsaturated aldehydes and ketones, aliphatic aldehydes, aliphatic carboxylic acids, aliphatic amines, and aliphatic aromatic thiols and sulfides) [Hallagan 2002] (see Appendix). Material safety data sheets (MSDSs) contain information about known occupational hazards of specific chemicals, but they may not be based on the most up-to-date information in the case of newly recognized occupational health risks.