Editor’s note:   A serious lung disease diagnosed in a Colorado man was linked to excessive exposure to microwave popcorn flavor vapor, according to news reports suggesting that acetyl-loaded popcorn flavor may not only affect popcorn workers, but consumers as well.   The man has been eating popcorn twice a day for more than ten years.   Here is some background information for those who want to know some details about the disease, cited from the Centers for Disease Control and Prevention.

Flavorings-Related Lung Disease

This Topic Page provides a resource for findings and recommendations by the National Institute for Occupational Safety and Health (NIOSH) to reduce the risk of severe obstructive lung disease (bronchiolitis obliterans) associated with occupational exposures to flavorings.

Background

In August 2000, the Missouri Department of Health and Senior Services requested technical assistance from NIOSH in an investigation of bronchiolitis obliterans in former workers of a microwave popcorn plant in Jasper, Missouri. Bronchiolitis obliterans is a serious lung disease that is irreversible. The Missouri request led to intensive NIOSH research performed in collaboration with the microwave popcorn industry and flavorings manufacturers. The findings from that research provided a basis for a 2004 NIOSH Alert, " Preventing Lung Disease in Workers Who Use or Make Flavorings ." In addition to the full Alert in English, a Summary Sheet from the Alert is available in Spanish (en Español) . Although much remains unknown regarding the toxicity of flavoring-related chemicals, employers and workers can take steps to address working conditions and work practices that place workers at risk.

Symptoms

The main respiratory symptoms experienced by workers affected by bronchiolitis obliterans include cough (usually without phlegm) and shortness of breath on exertion. The severity of the lung symptoms can range from only a mild cough to severe cough 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. 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.

Medical testing may reveal several of the following findings:

• Spirometry, a type of breathing test
• often shows fixed airways obstruction (i.e., difficulty blowing air out fast and no improvement with asthma medications)
• 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

Treatment

Workers should be promptly referred for further medical evaluation if they have persistent cough; persistent shortness of breath on exertion; frequent or persistent symptoms of eye, nose, throat, or skin irritation; abnormal lung function on spirometry testing; or accelerated decline in lung function. Physicians should advise workers about any suspected or confirmed medical condition that may be caused or aggravated by work exposures, about recommendations for further evaluation and treatment, and specifically about any recommended restriction of the worker’s exposure (including removal from the workplace) or use of personal protective equipment. 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.

Exposures

Flavorings are often complex mixtures of natural and manmade substances. The Food and Drug Administration evaluates flavoring ingredients to determine whether they are "generally recognized as safe" (GRAS) to be eaten. Even if they are safe to eat, these ingredients might still be harmful to breathe in the forms and amounts to which food and chemical industry workers may be exposed. Given the complexity of flavorings mixtures, identifying the relative contributions of individual substances to causing flavoring-induced lung disease is an important challenge. As noted in the NIOSH Alert, Preventing Lung Disease in Workers Who Use or Make Flavorings , the flavorings industry has estimated that over a thousand flavoring ingredients have the potential to be 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).

Diacetyl is a chemical that was found to be the predominant ketone in butter flavoring and in air at the microwave popcorn plant initially investigated by NIOSH. Diacetyl is also known as 2,3-butanedione or by its Chemical Abstracts Service (CAS) number, 431-03-08. Workers in microwave popcorn manufacturing are exposed to many materials besides diacetyl. Thus, the studies that NIOSH has performed in a total of 6 microwave popcorn plants cannot, in themselves, determine if diacetyl exposure contributes to lung disease or is a marker for other hazardous substances that contribute to disease. Still, NIOSH studies in the initial plant documented a relationship between cumulative exposure to diacetyl vapor over time and having abnormal lung function as measured by a test called spirometry. Also, higher cumulative exposure to diacetyl in this plant was associated with having a lower level of forced expiratory volume in 1 second (FEV1), an important measure of lung function. Across all six microwave popcorn plants studied by NIOSH, working as a mixer was associated with higher exposure to diacetyl vapor than working in other areas of the plants. People who had ever worked as mixers had more chest symptoms and poorer lung function as measured by lower FEV1 than people who had never worked as mixers. People who had worked as mixers for more than 12 months had more shortness of breath with exertion and lower FEV1 than people who had worked as mixers for less than 12 months.

Toxicology studies show that vapors from heated butter flavorings cause damage to airways in animals (Hubbs et al, 2002). Preliminary studies show similar damage after exposure to diacetyl alone (Hubbs et al, 2004). In addition, a recent study from the Netherlands shows that chemical workers in a plant manufacturing diacetyl developed the same types of lung disease as microwave popcorn workers (Van Rooy et al, 2007). These chemical workers had less complicated exposures than microwave popcorn workers. Three major exposures were thought to possibly play roles in causing lung disease, alone or in combination – diacetyl, acetoin, and acetaldehyde. Overall, current evidence points to diacetyl as one agent causing flavorings-induced lung disease. Other flavoring ingredients may also play a role.

In view of the above, measurement of diacetyl exposures is likely to be helpful in preventing flavorings-induced lung disease, even though flavorings exposures are often more complex. Diacetyl may serve as a marker or surrogate for mixed exposures to hazardous flavorings, as it has been a prominent ingredient in flavorings mixtures where disease has been observed. In addition, as already noted, preliminary studies suggest that diacetyl has toxic properties as a single component that are similar to the effects of exposure to a butter flavoring mixture.

Thus, measuring diacetyl exposures may help to identify hazards.  Furthermore, these measurements can guide corrective actions, such as respiratory protection and engineering controls, to reduce or eliminate exposures.

Analytical Method for Diacetyl Measurement

n 2004, NIOSH researchers developed and published an analytical method to measure diacetyl in the workplace (Pendergrass 2004). Recent investigations suggest that this method might be affected by relative humidity. Preliminary data suggest that high humidity levels may result in an underestimation of true concentrations. A laboratory special measurements project is underway to investigate these factors and determine whether, and at what relative humidity levels this phenomenon may occur. NIOSH is working to validate a new method for the measurement of diacetyl in the workplace. As new information becomes available, it will be shared with the public and our stakeholders will be notified. For additional information about ongoing evaluation of sampling and analytical methodology, contact NIOSH at 1-800-35-NIOSH (1-800-356-4674).

Control

In order of preference, according to standard occupational health practices, NIOSH recommends that employers minimize occupational exposures to flavorings or flavoring ingredients by:

• Substituting a material or materials that may be less hazardous, after carefully evaluating potential substitutes
• Using engineering controls such as closed systems, isolation, or ventilation
• Instituting administrative controls such as housekeeping and work practices
• Educating employers and employees to raise their awareness of potential hazards and controls
• Using personal protective equipment where needed as an adjunct to primary engineering or administrative controls
• Monitoring occupational exposures and the status of workers health, tracking potential symptoms or cases, and reporting such symptoms or cases to NIOSH and state health departments

NIOSH does not have authority under the Occupational Safety and Health Act to issue regulations. For information on the Occupational Safety and Health Administration's (OSHA) current policy on regulatory protection for workers exposed to flavorings, see the relevant OSHA web page at http://www.osha.gov/SLTC/flavoringlung/standards.html