Flavorings-Related Lung Disease

Exposures to Flavoring Chemicals

How and Where Exposures May Occur

In general, flavoring chemicals are very volatile, so they evaporate into the air from their liquid or solid form and can be easily inhaled. They can also be inhaled in the form of a powder if airborne dust is created in the production process. Many of these chemicals are highly irritating to the eyes, respiratory tract, and skin. At flavoring and microwave popcorn production plants where workers developed severe lung disease, workers routinely handled or were exposed to open vessels containing flavorings or their chemical ingredients. In a sense, such plants are large kitchens where workers mix several chemical ingredients in large pots or other containers to produce various products. The application of heat in the production process can increase the amount of flavoring chemicals that get into the air. In addition to microwave popcorn and flavorings plants, other food industries with potential exposure to butter flavoring chemicals include snack foods (e.g. chips, pretzels), commercial and retail bakeries (e.g. cakes, cookies, bread), retail baking mix production, margarine and other vegetable oil-based cooking products, butter and other diary products, and candy manufacturers. Use of butter-flavored cooking oil products to prepare meals in restaurants may also lead to worker exposures. While exposures in the flavoring industry and in microwave popcorn production have caused severe lung disease in some workers, the degree of risk to workers from exposures in other settings is currently unknown.

What are Flavorings?

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, and the lack of health data for many of the component materials, identifying the relative contributions of individual substances to causing flavoring-induced lung disease is a difficult 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

Diacetyl is a chemical that was found to be a prominent volatile constituent in butter flavoring and 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, NIOSH's initial studies in a total of 6 microwave popcorn plants were not able to definitely determine if diacetyl exposure contributed to lung disease or was a marker for other hazardous substances that contributed 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 of lung function 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 of butter flavorings and heated soybean oil 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.

Subsequent studies have helped to clarify the role of diacetyl. Toxicology studies have shown that vapors from heated butter flavorings can cause damage to airways in animals (Hubbs et al, 2002). Studies in both rats and mice demonstrate that the cells lining airways can be damaged by inhaling diacetyl vapors as a single agent exposure in both acute and subchronic studies (Hubbs et al, 2008; Morgan et al, 2008). In mice, aspiration of diacetyl alone caused a pattern of injury that replicates some of the features of human obliterative bronchiolitis (Morgan et al, 2008). These findings support the hypothesis that diacetyl vapors are an inhalation hazard in the workplace. Also, a recent study from the Netherlands shows that chemical workers in a plant that manufactured diacetyl developed the same type 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 in the Dutch chemical workers, alone or in combination - diacetyl, acetoin, and acetaldehyde. Overall, current evidence points to diacetyl as one agent that can cause flavorings-related lung disease. Other flavoring ingredients may also play a role.

Measuring Exposures

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 some hazardous flavorings, as it has been an 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 engineering controls, improved work practices, and respiratory protection, to reduce or eliminate exposures NIOSH researchers developed and published an analytical method to measure diacetyl in the workplace (Pendergrass 2004). Recent investigations indicate this method is adversely affected by humidity, resulting in an underestimation of true concentrations. A NIOSH project is underway to investigate these factors and determine the extent of this phenomenon. 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.

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