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Flavorings-Related Lung Disease

In 2000, NIOSH conducted an investigation of exposures at a microwave popcorn manufacturing plant in Missouri. Public health officials contacted NIOSH because a cluster of former employees of the facility had developed a rare lung disease called bronchiolitis obliterans. The majority of employees diagnosed with bronchiolitis obliterans had been exposed to mixtures of butter flavoring chemicals. Evaluations of employees working in the plant revealed high rates of both respiratory symptoms and abnormal lung function.1 The investigation concluded that there was "a risk for occupational lung disease in workers with inhalation exposure to butter flavoring chemicals".2

Manufacturing Plant

Investigations of other workplaces have also shown that employees that use or manufacture certain flavorings have developed similar health problems. Because many of the cases have been associated with popcorn manufacturing plants, the term "popcorn lung" has often been used to describe the respiratory symptoms and fixed obstructive lung disease seen in these employees. Although much of the research and attention has been focused on butter flavorings, employees who are involved in the use or manufacture of other types of flavorings may also be at risk.2

Flavorings can be either natural or manmade. Some are simple and made up of only one ingredient but others are complex mixtures of several substances. Employees may be exposed to flavorings in the form of vapors, dusts, or sprays.2 There are many different types of flavorings and most have not been tested for respiratory toxicity. The Food and Drug Administration (FDA) regulates food additives for safety when eaten, but it does not require testing by other routes of occupational exposure, such as inhalation. Research continues to determine if certain components or combinations of flavorings are associated with pulmonary disease. Consumers are not believed to be at risk from preparing or eating microwave popcorn products.3

There are currently no specific standards for occupational exposure to butter-flavoring or the chemical diacetyl. However, OSHA standards regulating all workplaces offer protection to workers exposed to these substances.

References

1 Kreiss K. et al. "Clinical bronchiolitis obliterans in workers at a microwave-popcorn plant". New England Journal of Medicine 347.5(2002): 330-330.

2 Gilster-Mary Lee Corporation, Jasper, Missouri National Institute for Occupational Safety and Health (NIOSH) Health Hazard Evaluation Report [4 MB PDF, 175 pages]. HETA 2000-0401-299, (2006, January).

3 Limiting Job Exposures to Food Flavorings, Flavoring Ingredients, is Recommended in New Alert. US Department of Health and Human Services (DHHS), National Institute for Occupational Safety and Health (NIOSH) Update, (2004, January 15).

OSHA Standards

This section highlights OSHA standards and directives (instructions for compliance officers) related to occupational exposure to butter-flavoring or the chemical diacetyl.

Section 5(a)(1) of the OSH Act, often referred to as the General Duty Clause, requires employers to "furnish to each of his employees employment and a place of employment which are free from recognized hazards that are causing or are likely to cause death or serious physical harm to his employees". Section 5(a)(2) requires employers to "comply with occupational safety and health standards promulgated under this Act".

Note: Twenty-five states, Puerto Rico and the Virgin Islands have OSHA-approved State Plans and have adopted their own standards and enforcement policies. For the most part, these States adopt standards that are identical to Federal OSHA. However, some States have adopted different standards applicable to this topic or may have different enforcement policies.

General Industry (29 CFR 1910)

Directives

  • National Emphasis Program - Microwave Popcorn Processing Plants. DIR 11-01 (CPL 03), (2011, January 18). Similar to the expired 2007 NEP, CPL 03-00-005, and described policies and procedures for implementing an emphasis program to identify and reduce or eliminate exposures to butter-flavoring chemicals - such as diacetyl and chemical substitutes - used in microwave popcorn manufacturing facilities.

  • National Emphasis Program - Facilities that Manufacture Food Flavorings Containing Diacetyl. CPL 03-00-011, (2009, October 30). Describes policies and procedures for implementing an emphasis program to identify and reduce or eliminate hazards associated with exposures to flavoring chemicals in any facility that manufactures food flavorings containing diacetyl. This instruction is available on the public page.

  • National Emphasis Program - Microwave Popcorn Processing Plants. CPL 03-00-005, (2007, July 27) (Expired as of July 27, 2008). Described policies and procedures for implementing an emphasis program to identify and reduce or eliminate exposure to butter-flavoring chemicals - such as diacetyl - used in microwave popcorn manufacturing facilities.

  • Search all available directives.

Health Effects

What are the health effects of flavorings-related lung disease?

Exposure to certain airborne flavorings is associated with higher rates of respiratory symptoms such as cough, fatigue, and difficulty breathing with exertion or exercise. Studies have shown an association with occupational exposure to certain flavorings and the development of lung disease characterized by fixed airways obstruction. Some employees exposed to these flavorings have developed permanent lung damage including a rare disease called bronchiolitis obliterans.1,2

How is flavorings-related lung disease diagnosed?

Individuals with flavorings-related lung disease may have respiratory symptoms and/or abnormal spirometry findings of fixed airways obstruction. Spirometry is a test that evaluates lung function. Fixed airways obstruction is diagnosed when the person tested has difficulty blowing air out of the lungs (obstruction) and this difficulty does not improve with asthma medication, indicating a fixed obstruction.

Employees exposed to certain airborne flavorings may complain of respiratory symptoms such as cough, fatigue, and difficulty breathing with exertion. These symptoms may vary in range from mild to severe. Usually symptoms progress gradually, but in some cases severe symptoms can occur suddenly. The symptoms usually do not get better when employees leave the workplace or go on vacation.1

What is the treatment for flavorings-related lung disease?

Employers and employees need to make sure that healthcare providers are aware of potential airborne exposures to flavorings in the workplace. The finding of fixed airways obstruction in an exposed employee, especially in a symptomatic individual, should be investigated for possible occupational lung disease, including bronchiolitis obliterans.

Healthcare providers should advise employees about workplace exposures that may possibly aggravate or worsen existing lung disease. Recommendations and options for restricting employee exposure should be discussed.1

Affected employees may notice a gradual improvement in their cough after they are removed from the flavoring exposure, but this may take years. Unfortunately, the shortness of breath with exertion often persists even after the cough has improved.

Patients with severe lung disease including bronchiolitis obliterans are usually treated with steroid medication, although most have not experienced significant improvement of their illness with this treatment. Patients with severe disease may require a lung transplant.

Can exposure to flavorings cause any other adverse health effects?

Employees may experience eye, nose, throat, and skin irritation after occupational exposure to certain flavorings. Chemical eye burns have also been noted. Additionally, there is some evidence that occupational asthma may be associated with workplace exposure to certain flavorings.1

What is bronchiolitis obliterans?

Bronchiolitis obliterans is a very rare lung disease that occurs when the smallest airways of the lung become inflamed and scarred, resulting in thickening and narrowing (obstruction) of the airways. This obstruction interferes with ventilation, the movement of air in the lungs.3

Normal Lung

Normal lung

(Photo courtesy of Uniformed Services University of the Health Sciences)


Small airway with obstruction in bronchiolitis obliterans


Small airway with obstruction
in bronchiolitis obliterans

(Photo used with permission from European Respiratory Society Journals 4)


Spirometry Test

How is bronchiolitis obliterans diagnosed?

There are several diagnostic tools available to diagnose bronchiolitis obliterans. Spirometry is a test that evaluates lung function. Patients with bronchiolitis obliterans often have spirometry findings of fixed airways obstruction. Some patients also show restriction on spirometry which means that the lungs have decreased ability to expand.

Additional tests include chest x-rays which are often normal, but may show hyperinflation (too much air trapped in the lungs). Another imaging test, high resolution computerized tomography scans (CT or CAT scans) may also show airtrapping and thickening of the airway walls. If a biopsy or tissue sample of the lungs is performed, narrowing or complete obstruction of the small airways may be seen when the tissue is examined with a microscope.1,2,3

What causes bronchiolitis obliterans?

Storage Tanks

Bronchiolitis obliterans has been diagnosed in employees with occupational exposures to certain flavorings or certain irritant gasses such as ammonia, chlorine or sulfur dioxide. People who have had organ transplants or who have connective tissue disorders such as rheumatoid arthritis and lupus can develop bronchiolitis obliterans. Some respiratory infections caused by viruses/bacteria and certain medications are also associated with the development of bronchiolitis obliterans. Although many diseases or occupational exposures are associated with bronchiolitis obliterans, it is actually a rare disease.1,2,3

References

1 Preventing Lung Disease in Workers Who Use or Make Flavorings. US Department of Health and Human Services (DHHS), National Institute for Occupational Safety and Health (NIOSH) Publication No. 2004-110, (2003, December).

2 Kreiss, K., et al. "Clinical bronchiolitis obliterans in workers at a microwave-popcorn plant". New England Journal of Medicine 347.5(2002): 330-338.

3 Lazarus, S. Murray & Nadel's Textbook of Respiratory Medicine. "Chapter 41: Disorders of Intrathoracic Airways." 4th ed. Saunders: Philadelphia, (2005): 1295-1310.

4 Akpinar-Elci M., et al. "Bronchiolitis obliterans syndrome in popcorn production plant workers". European Respiratory Journal 24(2004): 298-302.

Diacetyl

Diacetyl (also called 2,3-butanedione), is a chemical that has been used to impart a butter-like flavor to food products, including popcorn. This chemical has been used as a marker of exposure to flavoring vapors in investigations evaluating lung disease in microwave popcorn manufacturing facilities.1 Acetoin (also called acetyl methyl carbinol), 2,3-pentanedione, 2,3 hexanedione and 2,3 heptanedione are all structurally related to diacetyl and have been suggested as possible substitutes for diacetyl.

Animal studies of exposure to butter flavoring vapors, including diacetyl, have shown airway injury in rats after acute inhalation of these flavorings.1,2 These studies demonstrated that butter flavoring vapors are capable of causing severe airway injury in laboratory animals, but the causal relationship between diacetyl exposure and development of bronchiolitis obliterans has not been firmly established. Research continues on diacetyl and other flavoring chemicals to evaluate the relationship of exposure to butter flavorings and adverse health effects, including lung disease.

References

1 Fixed Obstructive Lung Disease in Workers at a Microwave Popcorn Factory --- Missouri, 2000--2002. Centers for Disease Control and Prevention (CDC), Morbidity and Mortality Weekly Report (MMWR) 51(16);345-7, (2002, April 26).

2 Hubbs A., et al. "Necrosis of Nasal and Airway Epithelium in Rats Inhaling Vapors of Artificial Butter Flavoring". Toxicology and Applied Pharmacology 185(2002): 128-135.

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