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HCDE 333 E Toxicology Report Group 5

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Diacetyl

Anna Margot Fretheim

Deeqa Mohamed Yunis

Michael James Chen

Xiaoqiong Huang


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Contents

Chapter 1: Executive Summary 3

Chapter 2: Introduction 4

The Nature of Diacetyl and Its Use 4

Environmental Sources 5

Health Effects of Exposure 5

Regulations 5

Chapter 3: Environmental Sources 7

Flavorings and Food 7

Alcohol 10

Mosquito Repellent 10

Other Uses 11

Chapter 4: H ealth E ffects 12

Eye, Nose, and Skin 12

Lungs 13

Chapter 5: References 17


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1. Executive Summary

Diacetyl is a chemical compound that is produced both naturally and industrially. At room temperature, it is a green-yellow liquid with a pronounced buttery odor. Diacetyl is widely used in the production of food flavorings and food products, alcoholic beverages, and mosquito repellent. Despite the growing concern toward occupational exposure, the Occupational Safety and Health Administration (OSHA) has yet to establish a permissible exposure limit (PEL) for diacetyl.

Diacetyl inhalation and dermal contact are most prevalent in flavor and food manufacturing facilities that use diacetyl as an ingredient. Most notably this has been seen in the microwavea popcorn industry, where diacetyl is used as an artificial butter flavoring, and in chemical production factories that produce diacetyl. Certain jobs and tasks within popcorn and chemical manufacturing plants incur greater exposure to diacetyl than others.

Exposure to diacetyl remains largely unregulated in the occupational setting. While larger manufacturing operations implement exposure prevention measures, small and medium-sized operations fail to do so. Several microwave popcorn companies have switched to butter flavoring that does not contain diacetyl. Occupational exposure to diacetyl can be greatly reduced with proper workplace control measures.

Diacetyl inhalation has been strongly linked to the deterioration of lung function and development of the rare disease bronchiolitis obliterans in chemical production and microwave popcorn plants, deemed popularly as ‘popcorn worker’s lung’. Treatment for this disease ultimately requires lung transplantation. Dermal exposure to Diacetyl also poses a health threat, and has been linked to the occurrence of rashes and skin irritation. Little research has analyzed the effects of ingestion.

While negative health effects have been confirmed in chemical production and microwave popcorn factory employees exposed to diacetyl, determining direct causality has been difficult. Currently available research focuses on chemical production and microwave popcorn plants, and little to no research has been done on diacetyl exposure in other occupational settings. Most studies are focused on respiratory health effects, ignoring skin, eye, and other health consequences. Finally, there has been a lack of research examining health threats to the general public.


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2. Introduction

This report explores the currently available data on the exposure and health effects of diacetyl. Although relatively few toxicological studies have been conducted to determine environmental exposure to diacetyl and its potential adverse health effects, there is evidence that the compound can pose a danger to human health.

The Nature of Diacetyl and Its Use

Diacetyl is a compound that exists naturally as a fermentation byproduct and artificially as a synthesized chemical (OSHA, 2011). It is also referred to in scientific literature as butanedione, 2,3-butanedione, and biacetyl (DefendingScience, 2012). Diacetyl is an -diketone with a molecular formula of C4H6O2 and a molecular weight of 86.09 g/mol (OSHA, 2011). Diacetyl has a boiling point of 88 ⁰C and a melting point of -2 ⁰C (DefendingScience, 2012). At room temperature, it exists as a green-yellow liquid with a pronounced buttery odor (Elan Chemical Company, 2007). The structural formula of diacetyl is shown below:

(Elan Chemical Company, 2007)

Diacetyl can be prepared industrially by converting methyl ethyl ketone to an isonitro compound, and subsequently hydrolyzing it with hydrochloric acid (Elan Chemical Company, 2007). It is also obtained via extraction from dairy products. (Elan Chemical Company, 2007). Diacetyl is produced naturally during bacterial fermentation of glucose and as a byproduct of lactic acid bacteria (Elan Chemical Company, 2007). As a result, diacetyl is present in naturally and artificially fermented foods and drinks, including cheese and beer.

Because of its wide use in the food and drink industry, large amounts of diacetyl are produced each year. Between 10,000 and 500,000 pounds were produced in 1986, 1990, 1994, 1998, and 2002 (Elan Chemical Company, 2007).


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Environmental Sources

Diacetyl occurs naturally in numerous food products. Because it contributes a buttery flavor or scent to foods and beverages it is widely manufactured as a food additive (WA L&I, n.d.). Food products to which diacetyl-containing flavoring is often added include microwave popcorn with butter flavoring, candies, and baked goods (DefendingScience.org, 2012). In addition, diacetyl is a common component of artificial butter flavorings used in home cooking (Elan Chemical Company, 2007). Diacetyl is commonly added to beer, and is an ingredient in mosquito repellents.

High levels of exposure to diacetyl occur in chemical production plants and microwave popcorn factories. Workers at these establishments are exposed to diacetyl vapors, droplets, and dust (SCOEL, 2010). The general public is also at risk of diacetyl exposure through the heating and consumption of foods and drinks containing diacetyl. The public is also exposed through the use of mosquito repellents.

H ealth E ffects of Exposure

There is growing concern in the scientific community that diacetyl poses a hazard to human health. The populations considered most at risk from adverse health effects are employees at chemical production companies that produce diacetyl and microwavable popcorn manufacturers due to their constant exposure to butter flavoring vapors (Integrated Laboratory Systems, 2007). Currently, it is not suspected that the general public is at a significant risk from the consumption of food products containing diacetyl (Integrated Laboratory Systems, 2007). However, diacetyl is being investigated for potential respiratory effects because it has been strongly linked to the occurrence of bronchiolitis obliterans in microwave popcorn factory workers (Integrated Laboratory Systems, 2007).

Regulations

OSHA has not set a PEL for diacetyl (Martyny et al., 2008). However, OSHA has recommended that exposure prevention methods be taken by workers that are exposed to diacetyl to reduce the risk of potential health effects (Martyny et al., 2008).

In partnership with OSHA, the California Department of Industrial Relations (DIR) implemented a new standard of diacetyl exposure prevention measures. These regulations, described in section 5197 of the California Code of Regulations, went into effect December 2, 2012, and remain the “only state-OSHA plan to have such a standard” (California Becomes First State to Set Safety Guidelines for Diacetyl, 2010). The new standard requires employers to regulate and provide safety measures in facilities using diacetyl at certain concentrations throughout the state of California (California Becomes First State to Set Safety Guidelines for Diacetyl, 2010).


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The rest of this report will cover the possible environmental sources of diacetyl, as well as the suspected adverse health effects of diacetyl exposure.


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3. Environmental Sources

Diacetyl is found in a wide variety of food products as a synthetic flavor additive and as a byproduct of natural processes (Stohler, 2009). In addition, diacetyl is the active ingredient in some mosquito repellents and a natural and artificial component of alcoholic beverages. Production for commercial use can occur through several ways, including fermentation, extraction from dairy products, and chemical synthesis (Stohler, 2009). It is within manufacturing facilities which use diacetyl-containing products that the risk for exposure is greatest.

The bulk of scientific studies on diacetyl exposure have been conducted on microwave popcorn facilities, where the chemical is used to add a butter flavor, and chemical production plants that produce diacetyl. Studies on non-occupational exposure have yet to be done. Due to the fact that diacetyl is likely readily metabolized and excreted upon ingestion, studies have mainly focused on inhalational exposure pathways (SCOEL, 2010). Dermal contact is also of interest, but has been less frequently studied.

F lavorings and Food

Diacetyl is widely used in food flavorings to “provide a dairy, butter, or ripe taste” (Stohler, 2009). Most notably, it has been used to confer microwave popcorn with a buttery flavor (Stohler, 2009). Its use in microwave popcorn typically involves the combination of a diacetyl containing flavoring with oils and various other ingredients. This mixture is subsequently combined with popcorn kernels and added to a microwaveable bag (Stohler, 2009). In addition, diacetyl is “commonly used in the production of margarine and butter-flavored oils and cooking sprays, in retail and commercial bakeries, the production of some snack foods (particularly those with cheese flavoring), and in many confectioneries” (Stohler, 2009). Diacetyl also occurs naturally in several food products, including beer, dairy products, coffee, honey, and fruits (WA L&I, n.d.). Currently, diacetyl is being produced for commercial use on a large scale. The Flavor and Extract Manufacturers Association estimates that 228,000 pounds of diacetyl are used in the U.S. for the manufacture of flavoring every year (Stohler, 2009). A total of 139 flavoring manufacturing establishments have been identified by OSHA, with an estimated 8,972 employees producing diacetyl containing flavorings (Stohler, 2009). Employees within butter flavoring and microwave popcorn plants are at high risk for exposure to diacetyl (Kanwal et al., 2006). They may be exposed to diacetyl vapors, droplets, or dust on a regular basis (SCOEL, 2010). Microwave popcorn plant workers may experience particularly high diacetyl exposure compared to other diacetyl-utilizing food production plants due to the high diacetyl concentrations used for microwave popcorn (SCOEL, 2010). Employees that mix butter


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flavoring before it is added to popcorn kernels are at particularly high risk for diacetyl exposure. Butter flavoring is mixed in designated mixing rooms kept at temperatures of 51-54 ⁰C (Integrated Laboratory Systems, 2007). Butter flavoring can be in liquid, paste, or powder form and is poured by hand into 400- to 800-gallon tanks containing heated soybean oil (Integrated Laboratory Systems, 2007). On average, mixers spend 1-1.5 hours a day performing these operations (Integrated Laboratory Systems, 2007). Combining butter flavoring with heated oil leads to high exposure levels compared to other activities (Martyny et al., 2008). Depending on the popcorn plant, mixture tanks frequently have loose-fitting or absent lids (Integrated Laboratory Systems, 2007). Any time the lids are removed, or if there are no lids at all, vapors are released that expose mixers to diacetyl and other volatilized compounds (Integrated Laboratory Systems, 2007). One 2006 study evaluated six popcorn plants and found only one mixer that used an appropriate respirator that contained organic vapor cartridges (Kanwal et al., 2006). After mixing, the flavoring mixture is piped to packaging lines and automatically added to popcorn kernel-containing microwaveable bags. Bags are subsequently sealed, labeled, and enclosed in plastic wrap (SCOEL, 2010). In some plants, the packaging lines are located near the mixing tanks; this significantly increases packaging workers’ risk of exposure to flavoring fumes (Integrated Laboratory Systems, 2007). The severity of occupational exposure to diacetyl has sparked a number of investigations of the nation’s largest popcorn manufacturing facilities. The National Institute for Occupational Safety and Health (NIOSH) investigated several microwave popcorn plants to determine the exposure to diacetyl from butter flavoring. It was found that the average full shift air levels of diacetyl in mixing areas and production areas near mixing tanks ranged from 0.2 to 38 ppm (Kanwal et al., 2006). In packaging areas isolated from mixing tanks, concentrations were found to be 0.03 ppm or less (Kanwal et al., 2006). The relationship between proximity to mixing tanks and concentrations of diacetyl is an important factor in diacetyl exposure. Microwave popcorn quality control workers are also at high risk for diacetyl exposure. On average, quality control workers microwave up to 100 bags of popcorn per work shift to check product quality, and are exposed to flavoring vapors when the bags are opened (Integrated Laboratory Systems, 2007). One study published in 2007 found that in a chemical production plant, levels of diacetyl ranged from 1.8 to 351 mg/m3 (van Rooy, 2007). Operators were found to have the highest exposure to diacetyl. The activity that exposed operators to the highest levels of diacetyl was discharging diacetyl into containers, with exposure levels ranging from 3 to 396 mg/m3 (van Rooy, 2007). The study found that maintenance workers were also likely to be exposed to high levels of diacetyl (van Rooy, 2007). Transport, health and safety, management, and research and development personnel were unlikely to be exposed to high levels.


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Exposure to factory workers can be varied since commercial use of diacetyl in food flavorings happens on a wide variety of scales. Flavor companies can be categorized as small, medium, or large-sized operations primarily using liquid or powder-based ingredients. In a study done by the National and Jewish Medical Center in 2008, “few of the small to medium-sized flavor companies... had pre-existing exposure monitoring or respiratory protection programs in place at the time of our initial industrial hygiene consultation” (Martyny et al., 2008). It remains uncertain if these companies have since implemented protection programs to benefit their factory workers who may be receiving high doses of diacetyl. Investigations of flavor-manufacturing plants in which workers have been diagnosed with respiratory diseases have shown an overall lack of proper exposure control methods (Gelb and Harber, 2007). Many lack local exhaust ventilation and respirator use, with employees often using dust masks that are inadequate for proper protection from diacetyl (Gelb and Harber, 2007). There have been a number of cases where factory workers mixing ingredients with diacetyl ended up suffering from fixed obstructive lung diseases and bronchiolitis obliterans (Stohler, 2009). Treatment for these diseases is limited, and ultimately requires organ transplantation. Bronchiolitis obliterans, in particular, is the “primary cause of death following a lung or heart-lung transplant” (Bronchiolitis Obliterans: Treatment, n.d.). Motivated by the threat of workers’ compensation and the possible adverse health effects of diacetyl, some food product and flavoring manufacturers are searching for alternative flavoring chemicals (Stohler, 2009). ConAgra Foods, maker of Act II and Orville Redenbacher’s microwave popcorn brands, successfully switched to a non-diacetyl butter flavoring in 2007 (ConAgra Foods, 2007). Diacetyl is not a necessary component in many flavorings and can be substituted with other chemicals, including acetoin, diacetyl trimer, and a sulfite adduct of diacetyl (Stohler, 2009). One drawback to the use of these chemicals is that diacetyl trimer and the sulfite adduct of diacetyl are converted to diacetyl during food preparation, exposing consumers through home heating and ingestion (Stohler, 2009). In addition to workers in flavoring factories and food manufacturing plants, restaurant workers may also be exposed to diacetyl on a frequent basis. A 2009 investigation conducted by the United States Department of Labor stated that “when food preparation facilities and restaurants heat food and other products containing butter-flavored margarines, oils, cooking sprays, and butter, food preparation employees may be exposed to diacetyl” (Stohler, 2009). While OSHA has not established a PEL for diacetyl (Martyny et al., 2008), OSHA strongly recommends that flavor manufacturers implement diacetyl exposure prevention measures (New Building Requirements Stress Durability in Green Building, 2011).


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Several microwave popcorn plants have successfully lowered average diacetyl air concentrations through the implementation of recommended exposure controls (SCOEL, 2010). A plant in Missouri that employed control measures reduced average mixing room concentrations from 38 ppm in 2001 to 0.46 ppm in 2003 (SCOEL, 2010). Although there are limited studies on the exposure to diacetyl people experience at home through cooking using diacetyl-containing food products, there is presumably inhalation exposure from heating of the products and ingestion exposure through consumption. We recommend that scientific studies should be conducted on exposure through the at-home use of diacetyl-containing food products. Alcohol

Diactyl naturally occurs in alcohol. During fermentation diacetyl is present as an indirect byproduct of yeast valine synthesis. At low concentrations, diacetyl gives a feeling of slipperiness to the alcoholic beverage. As the concentration of diacetyl increases, it contributes a buttery flavor. It is acceptable or even desirable to contain low, or in some cases, moderate levels of diacetyl in some styles of beer. However, for other styles of beer, connoisseurs consider the addition or presence of diacetyl to be a flaw. As a result, workers at beer manufacturer facilities are likely to be exposed to diacetyl during processing where diacetyl is used as an ingredient. This exposure is predominately through inhalation. It is also not uncommon for customers to be exposed to diacetyl through ingestion of these styles of beer in which diacetyl is present. Again, it should be noted that scientific evidence on the adverse health effects through ingestion is limited. Mosquito Repellent Diacetyl is commonly used in mosquito repellent to distract the carbon dioxide sensors of fruit flies (Discovery of Natural Odors Could Help Develop Mosquito Repellents, n.d.). This suggests that use of mosquito repellent serves as another environmental source of diacetyl. When people spray mosquito repellent on their skin to fend off mosquitoes, they are at risk for diacetyl exposure through dermal contact and inhalation. Mosquito repellent is not considered as a major pathway of diacetyl exposure. Nonetheless, it is possible that the presence of diacetyl in mosquito repellent could pose an extra risk due to the threat of global warming. As the earth continues to become warmer, mosquitoes will become more prevalent in previously temperate regions of the United States (Reiter, 2001). An increase in the mosquito population in these regions could potentially increase people’s use of mosquito repellent, and thus increase their dermal and respiratory exposure to diacetyl.


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Other Uses Diacetyl has been reported to be used in fruit and floral fragrances, such as in magnolia and geranium scents that are added to scented candles (Lone Star, 2003). From this it can be inferred that workers at candle manufacturing plants and consumers that use scented candles are at risk for diacetyl exposure. It has also been reported that diacetyl has anti-bacterial properties, and as a result may be used as a preservative (Bibek, 2004).


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4. Health E ffects A variety of studies have been conducted to explore the link between diacetyl exposure and negative health effects for workers in chemical production and microwave popcorn plants. These have included clinical case studies of former workers who were diagnosed with severe respiratory illness, cross-sectional epidemiological studies among current workers, explorative exposure studies, and animal exposure studies (van Rooy et al., 2007). Diacetyl has been linked to a wide array of health effects. OSHA states that diacetyl exposure can lead to respiratory, skin, and eye irritation (OSHA, 2007). Its list of potential symptoms includes persistent cough, wheezing, dyspnea, and severe skin rashes (OSHA, 2007). The most severe observed health effect from diacetyl exposure has been bronchiolitis obliterans, a severe, irreversible lung disease (OSHA, 2007). No permissible exposure limit (PEL) or immediately dangerous to life or health (IDLH) concentrations of diacetyl have been established. One 2003 study found that one rat out of four died after a 6-hour exposure to vapors from heated popcorn flavoring that contained 285 ppm diacetyl. However, the same study found that six rats exposed to 203 ppm and 352 ppm diacetyl survived (Hubbs et al., 2003). Oral LD50 levels of diacetyl in rats have been estimated to be between 3,000 and 3,400 mg/kg, and dermal LD50 levels have been estimated to be near 5,000 mg/kg in rabbits (SCOEL, 2010). Eye, Nose, and Skin Diacetyl exposure has been linked to eye irritation. In 2005, a healthy male worked with large amounts of diacetyl-containing butter flavoring for several hours over the period of a day (SCOEL, 2010). At the end of his shift, he had sore and reddened eyes with a sticky conjunctival secretion. After several days of treatment with steroid and antihistamine, his symptoms resolved (SCOEL, 2010). Workers in popcorn manufacturing plants have been known to experience eye and nasal irritation (SCOEL, 2010). Studies conducted on rabbits showed diacetyl exposure led to severe eye and skin irritation (SCOEL, 2010). A NIOSH study conducted on rats found that levels of 203-371 ppm caused necrosuppurative rhinitis, affecting all four levels of the nose (Hubbs et al., 2002). Necrosis and inflammation was principally localized to the nasopharyngeal duct in the two posterior levels (Hubbs et al., 2002). Diacetyl exposure has been linked to skin irritation. One study found that workers in a microwave popcorn plant suffered skin irritation symptoms that declined when the production process was isolated and ventilated (Kanwal et al., 2011). A 2004 study that examined eight microwave popcorn plant workers found that the workers reported


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experiencing rashes and other skin problems after starting work at the plant (Akpinar-Elci et al., 2004). One study examined eight workers that were experiencing health symptoms after working in a microwave popcorn plant (Kreiss et al., 2002). Researchers conducted environmental surveys and medical examinations of workers employed at the plant to determine the extent of exposures and illness. Air samples showed diacetyl was the major compound present in the factory (Kreiss et al., 2002). Workers in the popcorn production area had higher rates of rashes and other skin problems than workers in other areas (Kreiss et al., 2002). It can be inferred that workers in microwave popcorn plants that work in the popcorn production area are at higher risk for adverse health effects than workers in other areas of the plant. A 2003 NIOSH report on workers who use or make flavorings – including diacetyl – advises workers exposed to diacetyl to promptly seek medical evaluation if they experience skin or eye irritation (NIOSH, 2004). Lungs At high concentrations (> 30 ppm), diacetyl is an irritant that affects the respiratory system. Exposure to diacetyl at even greater concentrations (> 190 ppm) results in necrosis of the air epithelium (Kreiss et al., 2007). Recent NIOSH investigations strongly suggest a correlation between flavoring chemicals such as diacetyl and development of bronchiolitis obliterans in the workplace (CDC, 2007). Flavor manufacturing and microwave popcorn manufacturing workers have been reported to acquire the lung disease bronchiolitis obliterans after being exposed to butter flavoring vapors (Hubbs et al., 2002). The first reported case of bronchiolitis obliterans in a flavor manufacturing worker who had handled diacetyl was brought to the attention of the California Department of Health Services in 2004 (CDC, 2007). The next case was reported from another flavor manufacturing worker in 2006 (CDC, 2007). Since then, dozens more workers in flavor manufacturing and microwave popcorn manufacturing plants have been diagnosed with bronchiolitis obliterans (CDC, 2007). Bronchiolitis obliterans is a rare and irreversible respiratory disease that can prove life threatening. Also known as constructive bronchiolitis and obliterative bronchiolitis, it is known to cause fibrosis, obstruction of the bronchioles, and hyperinflation of the lungs (SCOEL, 2010). In plants producing diacetyl, workers with the highest exposure to diacetyl are more likely to develop bronchiolitis obliterans (SCOEL, 2010). In addition, inhalation tests performed on rodents identified diacetyl as the compound most likely responsible for the development of this lung disease (Hubbs et al., 2002). Unlike cases of bronchiolitis obliterans that have been linked to other chemicals, cases of bronchiolitis obliterans associated with diacetyl have not been linked to chemical spills (SCOEL, 2010). Rather, it is believed that exposure to diacetyl in the air leads to the disease.


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The main symptoms observed in workers with bronchiolitis obliterans include wheezing, shortness of breath, and chronic cough. When workers with bronchiolitis obliterans describe their symptoms to physicians, they are often misdiagnosed as having asthma, chronic obstructive pulmonary disease (COPD), bronchitis, or pneumonia (Parmet et al., 2002).

Rats exposed to similar butter flavoring vapors at levels of 285 ppm for 6 hours a day developed inflammation and necrosis of bronchi epithelium. At even higher concentrations, diacetyl resulted in the death of rats within a few hours of exposure (Hubbs et al., 2002). Due to the observed adverse health effects of diacetyl, concerns regarding its use in the food industry are rising. It is unclear what levels and lengths of exposure to diacetyl pose a serious risk for the development of bronchiolitis obliterans. Even short-term exposure to butter flavoring has been linked to lung damage (Kreiss, 2007). Cases of bronchiolitis obliterans have been found in butter flavoring mixing work areas where average 8-hour exposures were measured as low as 0.02 ppm. Onset of bronchiolitis in seven flavor-manufacturing plant workers diagnosed with bronchiolitis obliterans has ranged from 1 month to 5 years after starting work (Gelb and Harber, 2007). In these workers, measured FEV1 values ranged from 17% to 44% of expected values (CDC, 2007). High Resolution Computed Tomography (HRCT) scans of microwave popcorn plant workers have shown bronchial wall thickening, cylindrical bronchiectasis, and ground glass opacities of the lungs (Van Rooy et al., 2007). Treatment plans for these employees included oral corticosteroids and bronchodilators, although these did not lead to any significant improvement in the workers’ conditions. Several of the workers were placed on the lung transplant list (Parmet et al., 2002). One study conducted on employees of a chemical production plant in Europe found a definite link between diacetyl production and bronchiolitis obliterans (van Rooy et al., 2007). This study explored the health histories of 175 workers who were exposed to diacetyl between 1960 and 2003. Out of the 175 workers, 3 were found to have bronchiolitis obliterans. In addition, process operators were found to have significantly lower FEV1 values than non-operators. Studies have shown that flavor-manufacturing plant workers exposed to diacetyl experience significantly more respiratory problems such as daily coughing, trouble breathing, and reported asthma attacks compared to the general public (Quanjer, 1993). The table below from a 2009 study shows respiratory health outcome comparisons between diacetyl production employees in a chemical production plant and the general public. The table also compares three worker groups at the plant: process operators, technical service workers, and quality control workers.


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(van Rooy, 2009) Process operators and quality control workers reported significantly more respiratory problems than technical service workers. This table demonstrates a direct correlation between exposure to diacetyl and respiratory problems. Other diseases involving fixed airway obstruction have been linked to diacetyl exposure. These include asthma, COPD, hypersensitivity pneumonitis, and organizing pneumonia (SCOEL, 2010). The link between diacetyl exposure and these diseases is less strong than that of bronchiolitis obliterans, however. Another study compared the prevalence of respiratory problems between smokers and nonsmokers at popcorn plants. The study found that nonsmokers had a higher rate of prevalence of airway obstruction than former and current smokers. In other cases they


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had similar rates of prevalence of symptoms, such as chronic bronchitis, asthma, and wheezing (National Center for Health Statistics 1996). These findings illustrate that respiratory effects caused by diacetyl are in some cases more severe than those caused by smoking tobacco. An evaluation of 135 microwave popcorn plant workers found that workers had rates of chronic cough and shortness of breath 2.6 times higher than those of the general population (Kulman et al., 2005). They also found that rates of asthma and chronic bronchitis were twice those of the general population (Kulman et al., 2005).


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5. References Few toxicological studies have been conducted to determine the negative health effects of diacetyl. Most studies analyzing the human health effects of diacetyl have focused on worker exposure in microwave popcorn factories and chemical production plants, while few studies have examined other occupational exposures to diacetyl. These studies have largely examined the effects of exposure to the butter flavoring itself, which includes a large number of chemicals in addition to diacetyl. It is unknown whether the correlation between exposure to butter flavoring and negative health effects is due to diacetyl itself or due to other volatile organic compounds that butter flavoring commonly contains. Chemical production company workers are also commonly exposed to acetoin and acetaldehyde during the diacetyl production process (van Rooy, 2007). In chemical production plants, employees often work in several different plants for their employer and are exposed to other chemicals known to be respiratory irritants (van Rooy, 2007). It is possible that diacetyl may act as a marker of another causative chemical that leads to bronchiolitis obliterans instead of being the causative agent itself (van Rooy, 2007). Study populations are often small due to the limited employee population sizes at microwave popcorn or chemical production plants, as well as due to the low occurrence of bronchiolitis obliterans (van Rooy, 2007). The majority of studies have been cross sectional or case series studies, making it difficult to determine causality. Research has been limited to studying the inhalation pathway, largely ignoring dermal contact and ingestion. In addition, most focus has been on respiratory effects, not skin, eye, or other health effects. Lastly, exposure estimates widely vary even within studies, and are affected largely by environmental conditions such as relative humidity. Akpinar-Elci, M., Travis, W. D., Lynch, D. A., & Kreiss, K. (January 01, 2004). Bronchiolitis obliterans syndrome in popcorn production plant workers. The European Respiratory Journal : O fficial Journal of the European Society for Clinical Respiratory Physiology, 24, 2, 298-302. Bartowsky, E. J., & Henschke, P. A. (January 01, 2004). The 'buttery' attribute of wine--diacetyl--desirability, spoilage and beyond. International Journal of Food Microbiology, 96, 3, 235-52. Bibek R. (2004). Fundamental Food Microbiology. CRC Press, 228, 608. (1997). BJCP Style Guidelines. Beer Judge Certification Program (BJCP). Retrieved from http://www.bjcp.org/stylecenter.php Bronchiolitis Obliterans: Treatment - National Jewish Health. #1 Respiratory Hospital in the U .S. - National Jewish Health. Retrieved from http://www.nationaljewish.org/ healthinf

http://www.bjcp.org/stylecenter.php


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Centers for Disease Control (CDC) . (2007) NIOSH Publications and Products - Preventing Lung Disease in Workers: Who Use or Make Flavorings. Centers for Disease Control and Prevention. Retrieved March 1, 2012, from http://www.cdc.gov/niosh/docs/ 2004-110/ Castranova,V.,Kullman, G., Fedan, J.S., Dowdy, J., and Jones, W.G.(2002). Necrosis of nasal and airway epithelium in rats inhaling vapors of artificial butter flavoring. Toxicol Appl Pharmacol 185:128–135. ConAgra Foods. (2007). ConAgra Foods- Media Relations - Overview. Retrieved from http://media.conagrafoods.com/phoenix.zhtml?c=202310&p=irol-newsArticle&ID=1087864&highlight= DefendingScience. (2012). Diacetyl Fact Sheet. Retrieved from http://www.defending science.org/Diacetyl-Fact-Sheet.cfm. Discovery Of Natural Odors Could Help Develop Mosquito Repellents. Science Daily: News & Articles in Science, Health, Environment & Technology. Retrieved from http://www.sciencedaily.com/releases/ Elan Chemical Company. (2007). Material Safety Data Sheet. Retrieved from http://www.elan‐chemical.com/dev/msdspdf/DIACETYL.pdf Garcia, A. I., Garcia, L. A., & Diaz, M. (1994). Modeling of Diacetyl Production During Beer Fermentation. Journal of the Institute of Brewing, 100, 3, 179. Hazard Communication Guidance for Diacetyl and Food Flavorings Containing Diacetyl. Occupational Safety and Health Administration - Home. Retrieved from http://www.osha.gov/dsg/guidance/diacetyl-guidance.html Integrated Laboratory Systems, Inc. (2007). Chemical Information Review Document for Artificial Butter Flavoring and Constituents Diacetyl and Acetoin. Accessed online at http://ntp.niehs.nih.gov/ntp/htdocs/chem_background/exsumpdf/artificial_butter_flavoring.pdf Hubbs, A.F., Battelli, L.A., Goldsmith, W.T., Porter, D.W., Frazer, D., Friend, S.,Schwegler-Berry, D., Mercer, R.R., Reynolds, J.S., Grote, A., Kanwal R, Kullman G, Piacitelli C, Boylstein R, Sahakian N, Martin S, Fedan K, Kreiss K. (2006). Evaluation of Flavorings-Related Lung Disease Risk at Six Microwave Popcorn Plants. JOEM 48(2):149-157. Kreiss, K. (2007). Flavoring-related bronchiolitis obliterans. Curr Opin Allergy Clin Immunol 7:162–167. Lone Star Candle Supply. (2003). Material Safety Data Sheet for Marshmallow Madness Fragrance Oil.


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