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NIOSH Respiratory Diseases Research Program

Evidence Package for the National Academies' Review 2006-2007

NIOSH Programs > Respiratory Diseases > Evidence Package > 4. Airways Diseases > 4.2 Obstructive Airways Disease

4.2d) Prevention and Reduction of Flavorings-Induced Bronchiolitis Obliterans

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RDRP was requested by the Missouri Department of Health in May, 2000, to perform an HHE (HETA # 2000-0401-2991 Gilster-Mary Lee Corp. Jasper, Missouri; A4-49). A cluster of eight bronchiolitis obliterans cases was identified among individuals working in the same small microwave buttered popcorn production plant in the period between 1993 and 2000.

Findings from the initial RDRP investigation implicating butter flavoring chemicals in the etiology of bronchiolitis obliterans, and subsequent informal communications between RDRP and other researchers have led to the realization that workers in flavorings production plants are also at risk for bronchiolitis obliterans. There are approximately 4,000 production workers in the microwave popcorn and flavoring manufacturing industries; approximately 150,000 workers at food production companies may also face some risk for developing this potentially severe and irreversible disease from inhalation exposures to flavoring chemicals.


RDRP investigators adopted a three-pronged approach to conducting research to prevent flavoring-related occupational lung disease in flavoring and food manufacturing industries. Medical epidemiologists addressed the objective of determining the exposure that was causing the bronchiolitis obliterans; they did this in part by identifying process related risk. Laboratory based toxicologists turned their attention to the objective of identifying the active ingredient or most prevalent component of the mixture. Industrial hygienists and engineers focused on the third objective of determining how the exposures could be mitigated. The solution to the third part was found in the implementation of control technology, with air sampling by industrial hygienists to determine the effectiveness of controls and medical surveillance to determine the diminution of health effects.

RDRP scientists developed sampling methods to assess workplace exposure to butter flavoring chemicals such as diacetyl, the predominant volatile butter flavoring chemical in the air at the index microwave popcorn plant. In 2001, RDRP investigators began to assess exposures and the occurrence of respiratory disease in workers at five other microwave popcorn plants. They also conducted medical and environmental surveys at the index microwave popcorn plant every four to six months from 2000 through 2003 to assess exposures to flavoring chemicals and worker lung function after the implementation of engineering controls. These studies revealed that microwave popcorn production workers were at risk throughout the industry and that workers were likely at risk from peak exposures to butter flavoring chemicals due to open handling of butter flavorings, even when ventilation maintained low average exposures. To their recommendations that companies isolate the production process and implement general dilution and local exhaust ventilation and mandatory respirator use for workers that handled flavorings, RDRP investigators added a recommendation to reengineer production to a closed process (i.e. no handling of flavorings in open containers or open tanks).

To obtain additional supporting evidence for the potential toxicity of butter flavoring chemicals on the respiratory tract, RDRP investigators conducted animal inhalation toxicology studies utilizing diacetyl and a butter flavoring used at the index microwave popcorn plant. Rats exposed to intact butter flavoring developed severe injury to their airways epithelium. Rats exposed to diacetyl alone also developed airways epithelial injury. RDRP investigators concluded that diacetyl alone could cause airways damage. However, other butter flavoring ingredients might also contribute to airways toxicity, alone or in combination with diacetyl.

RDRP investigators performed laboratory analyses of emissions from bulk butter flavoring samples collected at six microwave popcorn plants in order to assess exposure potential from liquid and paste flavorings and different powder formulations. In general, liquids and pastes had higher emissions of chemicals in the form of vapors than did powders. RDRP investigators also studied the potential for generation of respirable dust during manual handling of different powdered butter flavorings. This work led RDRP to recommend that microwave popcorn companies consider substitution of liquid and paste flavorings with powder flavorings that have low emissions of volatile chemicals and that generate little airborne dust when handled.

In order to begin to assess the potential for flavoring-related occupational lung disease in other food production industries, RDRP investigators performed walkthrough surveys at a beverage manufacturing plant, a flavored coffee plant, and a packaged oil plant. RDRP investigators made presentations at meetings of the Flavor and Extract Manufacturers Association to inform member companies of the identification of occupational lung disease risk from inhalation exposures to butter flavoring chemicals in microwave popcorn plants and to seek partnerships with member companies to work with RDRP to assess worker risk in flavorings manufacturing plants. Recently, efforts to study flavorings manufacturing plants have borne fruit through requests for technical assistance from California-OSHA.

Outputs and Transfer

After each walkthrough or medical/environmental survey at a plant, RDRP investigators provided plant-specific summary findings and control recommendations (e.g. ventilation, process isolation, work practices, personal protective equipment) to management and workers in the form of interim or final letters/reports. RDRP investigators made three presentations at popcorn and flavoring trade association meetings in 2001 and 2002 to provide member companies with information on flavoring-related occupational lung disease risk and prevention strategies. RDRP investigators provided updated research findings and recommendations (e.g. reengineer to a closed process; implement medical monitoring of potentially exposed workers) to representatives of microwave popcorn and butter flavoring companies at a RDRP-sponsored workshop in November 2003 (A4-73).

RDRP investigators also developed and published a “NIOSH Alert: Preventing Lung Disease in Workers Who Use or Make Flavorings (A4-74) containing information on occupational lung disease in microwave popcorn and flavoring plant workers and strategies to minimize risk to workers. RDRP sent the NIOSH Alert to 6,607 U.S. companies that might utilize butter flavorings in the production of various food products (e.g. cookies, candy) or that manufactured flavorings (10 phone calls and two e-mail requests were documented). Due to popular demand, the Alert recently underwent a second printing. Also, the summary sheet from the Alert has been disseminated in Spanish ( (A4-75).

RDRP hosted a workshop in 2001 for physician researchers and public health professionals to present and discuss the findings from the investigation at the index microwave popcorn plant (A4-76). RDRP investigators presented research findings at 20 local, national, and international scientific and technical meetings from 2000 through 2005. RDRP investigators published 14 articles on the medical, epidemiologic, environmental, animal toxicology, and laboratory studies in peer-reviewed scientific journals from 2002 through 2006 (A4-77), four of which are cited here (16-19, A4-78A4-79, A4-80, A4-81).

RDRP scientists and other staff produced a comprehensive and informative “Flavorings-Related Lung Disease” Topic page, which has recently been posted to the NIOSH Web site (

Intermediate Outcomes

Microwave popcorn manufacturers implemented RDRP recommendations concerning engineering controls that were designed to reduce workplace exposures. In follow-up visits to four microwave popcorn plants, RDRP investigators have confirmed that companies have followed their prevention recommendations with regard to engineering controls, respiratory protection programs, and medical surveillance. At the index plant, exposures to butter flavoring chemicals declined two to three orders of magnitude after implementation of engineering controls.

Further confirmation that the microwave popcorn manufacturers used RDRP recommendations to good effect is the observation that three companies are actively pursuing ways to re-engineer the production process to further decrease exposure potential.

There is also an increased awareness of potential occupational lung disease risk from inhalation exposure to flavoring chemicals. The Flavor and Extract Manufacturers Association developed and published a guidance document for both member and non-member companies that included information on RDRP investigations, work practices and exposures that may pose risk to flavoring workers, and recommendations to minimize worker risk. This trade association has made this document freely accessible on its Web site.

In addition, at least two flavoring manufacturers have revised their material safety data sheets to reflect the findings and recommendations of RDRP investigators with regard to the potential inhalation toxicity of flavoring chemicals. This not only reflects awareness on the part of the manufacturers but also raises awareness with others, including workers who are at risk of exposure.

Similarly, OSHA Region Seven published recommendations for microwave popcorn companies to minimize worker risk from exposures to butter flavoring chemicals (these were based on RDRP recommendations for the index plant). In addition, the Cal-OSHA working with the flavoring industry to develop a study protocol in order to evaluate California flavoring plants.

Since 2001, RDRP has received 10 to 20 inquiries from U.S. and international physicians and public health investigators regarding flavoring-related occupational lung disease risk. As a result, RDRP has learned of additional affected workers at four flavoring plants and one diacetyl plant. Local investigators have evaluated diacetyl manufacturing facilities in Canada and The Netherlands.

Progress Towards End Outcomes

Preliminary evidence suggests that RDRP research findings could lead to significant end outcomes. Occupational lung disease risk for microwave popcorn production workers has likely decreased. Approximately 80 to 90 percent of workers in the industry are now likely at minimal risk due to isolation of the area(s) where butter flavorings are handled. A small percentage (10 to 20 percent) of workers is still at potential risk and requires respiratory protection due to open handling of flavorings. Since 2003, RDRP investigators have received no reports that workers in microwave popcorn plants have developed butter flavoring-related lung disease after exposure controls and medical monitoring were implemented by companies.

What’s Ahead

RDRP investigators will pursue evaluations of flavoring-related occupational lung disease risk in flavorings manufacturing plants and in food industries other than microwave popcorn as such opportunities arise. As part of the efforts to develop a plan for investigation of risk factors for flavoring-related lung disease in flavoring plant workers, RDRP investigators have met with the Flavoring and Extract Manufacturers Association, California OSHA, and the California State Health Department regarding evaluations of plants in that state. RDRP investigators are exploring ways to learn more about the settings in which workers may be at risk. These efforts include development of a worker case registry, as well as communication strategies to alert physicians to the possibility that workers exposed to flavoring chemicals at work may develop lung disease and to request that they contact RDRP investigators if they identify affected workers. RDRP investigators plan additional animal toxicology studies to further characterize the respiratory toxicity of butter flavoring chemicals. In response to a technical assistance request from California-OSHA and the California-Department of Health Services, RDRP investigators will be working to evaluate exposures in California flavoring manufacturing plants and develop control technologies tailored to the needs of flavoring manufacturing. RDRP investigators are also developing a longer-term research program in this area.

Intermediate Goal and Objectives Moving Forward

The RDRP intermediate goal is to prevent and reduce flavorings-induced bronchiolitis obliterans. Objectives that have been set are to:

  • Prevent additional cases of occupational lung disease in flavoring manufacturing workers
  • Identify which other food production industries besides microwave popcorn might have workers at risk
  • Continue to work with industry, OSHA, and state health departments to create opportunities for field investigations through agency technical assistance requests, management or labor HHE requests, and RDRP proposals for industry-wide studies
  • Characterize the work environment and lung function of workers in flavoring plants
  • Develop and investigate the effectiveness of various control technology approaches in flavoring plants
  • Work with the flavoring industry to identify flavoring users
  • Inform physicians of the potential for occupational flavoring exposures to cause lung disease