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workers, building, architect

NORA Manufacturing Sector Strategic Goals

927ZCSV - Diacetyl Exposure Assessment Research Study

Start Date: 12/1/2007
End Date: 9/30/2010

Principal Investigator (PI)
Name: Robert Streicher
Phone: 513-841-4296
Organization: NIOSH
Sub-Unit: DART
Funded By: NIOSH

Primary Goal Addressed

Secondary Goal Addressed


Attributed to Manufacturing


Project Description

Short Summary

The purpose of this project is to develop and evaluate sampling and analytical methods for diacetyl and other flavoring compounds to enable accurate exposure assessment and evaluation of the effectiveness of control technology. Several alternative methods will be investigated for diacetyl vapor. A procedure will be developed to measure diacetyl in powders and to measure diacetyl substitutes as necessary. Finally, broader GC-MS method(s) will be developed for a range of compounds present in flavorings. This project addresses goals of the Manufacturing sector program and the Respiratory Diseases and Exposure Assessment cross-sector programs. Anticipated intermediate outcomes include dissemination and use of the developed methods both within NIOSH and among external stakeholders. The anticipated ultimate outcome is reduction in the occurrence of serious respiratory disorders that result from inhalation of flavoring compounds.


This project will develop improved methods for the measurement of flavorings compounds to enable accurate exposure assessment as well as evaluation of the effectiveness of controls. Of foremost concern is the development of a robust method for sampling and analysis of diacetyl in air, in light of the health concerns about exposure to this compound and the associated OSHA rulemaking currently underway.

Current methods for diacetyl used by NIOSH and OSHA have the following limitations: limited storage stability (NIOSH method), sensitivity to air humidity during sampling that reduces recovery and/or limits sample volume, limits of quantitation (LOQs) that may not be adequate for a new Permissible Exposure Limit (PEL), and lack of selectivity that is needed for measuring components of complex environments, such as flavorings. Some of these limitations are related to the sampling method and some to the analytical method. Both will be investigated to develop an overall method with adequate performance.

Recent work by NIOSH and OSHA has pointed toward large-bed silica gel samplers performing best in terms of sample stability and capacity. Additional investigations will be conducted to firmly establish the relationship between recovery of diacetyl and diacetyl levels, humidity, air volume, extraction solvent, and other relevant variables. Several analytical approaches will be investigated with the intent of determining which provides the best performance. The first approach involves direct analysis of the sampler extract by gas chromatography-mass spectrometry (GC-MS). This is the simplest approach and easiest to implement quickly. The MS provides greatly improved selectivity over the current method's FID detection and single-ion monitoring (SIM)-MS may provide adequate sensitivity. The second approach involves derivatization with o-phenylenediamine (OPD). OPD reacts with diacetyl to give a unique derivative that can be measured selectively by either GC-nitrogen-phosphorus detection (NPD) or GC-MS. The third approach involves derivatization with pentafluorobenzylhydroxylamine (PFBHA) followed by GC-MS or GC-electron capture detection (ECD). This reagent has a history of use for measurement of carbonyl compounds. Although derivatization procedures generally improve both chromatography and detection, they add steps to the procedure and may be additional sources of error. It is possible that the derivatizing reagent can be used on the sorbent during sampling, which could have the effect of improving the capacity and stability of the samples.

There is also great interest in measuring diacetyl contained in powders, as these particles could release the diacetyl after their deposition in the respiratory tract. Current samplers are designed for collecting diacetyl vapor. Sampling procedures as well as procedures for extracting the diacetyl from the powder will be developed. Also, methods for measurement of diacetyl substitutes, such as diacetyl trimer and 2,3-pentanedione, must be developed if these chemicals are used in flavorings and they may represent a health hazard. Finally, diacetyl is just one compound in the very complex mixtures found in workplace environments of flavoring manufacturers and users. Sampling and analytical methods based on GC-MS need to be developed that can provide definitive identification and adequate accuracy and sensitivity for the wide variety of compounds that may be encountered.

This is projected to be a 3-year project with the diacetyl in air method development occurring in year 1, development of methods for diacetyl in powders, diacetyl substitutes, and other flavoring compounds taking place in years 2-3.


Development of methodology for use by internal partners in support of the larger flavorings program is the primary goal of the method development. If the sampling and analytical methodology developed in this project is successful and adopted by internal partners, this will be self-evident. The use of this methodology by external stakeholders will require canvassing stakeholders and/or analytical laboratories where sample analyses are conducted. As methods or manuscripts are published, tracking internet hits for the methods and tracking the number of times these publications are cited will gauge their impact.

Mission Relevance

It is well established that exposure to butter flavorings, particularly in the microwave popcorn manufacturing industry, can result in the serious respiratory disorder bronchiolitis obliterans. More recently, two workers involved in the production of flavorings in California were diagnosed with bronchilitis obliterans and five additional flavor manufacturing workers were identified with severe fixed obstructive lung disease. According to U.S. Census data from 2002, there were approximately 21,000 employees working in flavoring production and nearly 1.5 million workers in the food manufacturing industry, which uses flavoring products. Studies have found that a key chemical component of the flavorings associated with the development of bronchiolitis obliterans is diacetyl. Cal/OSHA is currently drafting a proposed rule on diacetyl and other flavorings and federal OSHA has announced that they are initiating rulemaking under section 6(b) of the Occupational Safety and Health Act, which may include establishment of a PEL for diacetyl.

Soon after diacetyl was recognized as a major component of the butter flavorings associated with adverse health effects, NIOSH Method 2557 was developed and used extensively in the field for exposure assessment. Recent evaluations of NIOSH Method 2557 and OSHA Method PV2118 suggested that both methods can be adversely affected by humidity in the sampled air. Thus, measurements of diacetyl levels using NIOSH Method 2557 may be underestimates.

A new sampling and analytical method(s) is needed for diacetyl, particularly in light of current OSHA rulemaking. The new method(s) will be used for future exposure assessments and as the gold standard for side-by-side comparisons with existing methods to evaluate their performance and estimate the degree to which humidity may have impacted past measurements. In addition to being more robust, the new method(s) must provide better sensitivity to accommodate a low PEL and better selectivity to ensure accurate identification and quantification in complex environments, such as flavor manufacturing.

This project addresses the Manufacturing Sector Strategic Goal 5: Reduce the number of respiratory conditions and diseases due to exposures in the manufacturing sector. It directly addresses the Respiratory Diseases Cross-Sector Intermediate Goal 1.3: prevent and reduce flavorings-induced obstructive lung disease, including bronchiolitis obliterans, and more specifically, activity/output goal 1.3.2: develop and improve sampling and analytical methods for assessing exposure to diacetyl and other artificial flavorings. Finally, it addresses the Exposure Assessment Cross-Sector Intermediate Goal 2.3: Develop and evaluate new or improved methods for assessing exposure to workplace chemicals and occupational health stressors either singly or as mixtures, including both prospective and retrospective methods. More specifically, it directly addresses activity/output goal 2.3.1: Development of new or improved methods to measure chemicals or other occupational hazards in the work environment and activity/output goal 2.3.2: Validation of these methods to provide and characterize their performance (specificity, sensitivity, accuracy, etc.) including publication in the NIOSH Manual of Analytical Methods.