ResH&S 2012 FINAL

The Flavor and ExtractManufacturers Associationof the United StatesAPRIL 2012Respiratory Healthand Safety in theFlavor ManufacturingWorkplace2012 Update

THE FLAVOR AND EXTRACT MANUFACTURERS ASSOCIATIONSafety and Health Act (Section 5(a)(1) of theAct) for broad authority over flavor manufacturingin general, and specifically for possibleexposure to diacetyl. OSHA also implementeda National Emphasis Program for microwavepopcorn manufacturing plants.Flavor manufacturers should be familiarwith, and comply with, the OSHA respiratorstandard. This standard remains the most commonsource of OSHA citations among flavormanufacturers.The federal Hazard CommunicationStandard applies to many areas of flavor manufacturing.OSHA issued specific guidance in2007 on hazard communication as it relates todiacetyl. OSHA has informally stated that thisguidance also applies to 2,3-pentanedione, althoughOSHA has not yet amended the 2007guidance to include this flavoring substance.OSHA’s confined space regulations mayapply to some flavor manufacturers employinglarge vessels or tanks in their operations.OSHA and NIOSH maintain web pageson flavorings-related lung disease. The OSHApage can be found at www.osha.gov/SLTC/flavoringlung/index.html.The NIOSH page canbe found at www.cdc.gov/niosh/topics/flavorings/current-niosh.html.NIOSH also maintainsa science blog on diacetyl and food flavorings atwww.cdc.gov/niosh/blog/nsb111008_diacetyl.html.Important information is availablethrough the NIOSH program of Health HazardEvaluations (HHEs). These are evaluationsconducted by NIOSH staff on a wide variety ofworkplaces. Several types of facilities relevantto the flavor industry have been evaluated byNIOSH, including microwave popcorn manufacturingplants and flavor manufacturing facilities.Reports of NIOSH HHEs are availableon the NIOSH website at www.cdc.gov/niosh/hhe/.CaliforniaIn 2006, the California Division of OccupationalSafety and Health (Cal/OSHA) implementedthe innovative program the FlavorIndustry Safety and Health Evaluation Program(FISHEP) with the assistance of FEMA. Thisprogram resulted in workplace safety consultationsby Cal/OSHA with flavor manufacturersoperating in California. FISHEP also resultedin the completion of serial spirometry testing ofseveral hundred California flavor manufacturingworkers. FISHEP assisted California flavormanufacturers in maintaining safe workplacesand also provided important information used inthe development and adoption of the Californiaflavor manufacturing workplace regulations.In 2010, California implemented aworkplace safety regulation specifically for flavormanufacturing in California. The regulationcontains a “1% cut-off” for diacetyl in compoundedflavors and contains provisions relatedto flavoring substances considered as “alternatives”to diacetyl – acetoin, 2,3-pentanedione,diacetyl trimer, 2,3-hexanedione, and 2,3-heptanedione.The state’s final statement of reasonsexplains the rationale for the regulations.WashingtonIn 2008, the Washington State Departmentof Labor and Industries published an informationsheet for restaurant owners and workersabout diacetyl. The sheet states that it “providesinformation to cooks and restaurant workersabout possibly harmful exposures to diacetylduring cooking.”3

RESPIRATORY HEALTH AND SAFETY IN THE FLAVOR MANUFACTURING WORKPLACEOccupational ExposureGuidelinesPermissible Exposure Limits and OccupationalExposure GuidelinesFew flavoring substances have permissibleexposure limits (PELs) promulgated byOSHA. PELs have the force of regulation andare an important way that OSHA regulates workplacesafety. Table 1 lists priority flavoring substanceswith OSHA PELs. Diacetyl and relatedsubstances such as 2,3-pentanedione and acetoinhave not been assigned PELs by OSHA.Three groups have published voluntaryoccupational exposure guidelines for diacetyl,and in one case for 2,3-pentanedione. Whilethey don’t have the regulatory authority of anOSHA PEL, these guidelines can be helpful toflavor manufacturers.The American Conference of GovernmentIndustrial Hygienists (ACGIH) publishesthreshold limit values (TLVs) and short-termexposure limits (STELs) for a wide variety ofcommercial substances including a small numberof flavoring substances. In 2010, ACGIHproposed a TLV and STEL for diacetyl that wereadopted in January, 2012. The ACGIH TLV fordiacetyl is 0.01 ppm/8 hr. time-weighted average(TWA) and the STEL is 0.02 ppm/15 minutes.In 2010, the non-governmental nonprofitorganization Toxicology Excellence forRisk Assessment (TERA) proposed an occupationalexposure limit for diacetyl of 0.2 ppm/8hr. TWA (Maier et al., 2010).In its draft criteria document issued in2011, NIOSH recommended exposure limitsfor diacetyl and 2,3-pentanedione of 5 ppb/8hr. TWA and 9.3 ppb/8 hr. TWA, respectively.NIOSH also recommended short-tem exposurelimits for each substance in the draft criteriadocument – 25 ppb/15 minutes for diacetyl and31 ppb/15 minutes for 2,3-pentanedione.The three groups publishing occupationalexposure guidelines (TERA, ACGIH, andNIOSH) all employed different methods anddata in arriving at their conclusions. Brosseau(2012) commented on the need for the applicationof consistent best practices in the developmentof occupational exposure guidelines.Management andEmployee AwarenessThrough Education,Training and HazardCommunicationA variety of information resources areavailable for management from both OSHA andNIOSH on their websites on flavorings-relatedlung disease. The OSHA page can be found atwww.osha.gov/SLTC/flavoringlung/index.html.The NIOSH page can be found at www.cdc.gov/niosh/topics/flavoring. Among the available resourcesare an OSHA worker alert published in2010 and a NIOSH brochure for healthcare providerspublished in 2011.Thorough education and communicationamong both management and employees offlavor manufacturers are critical to the successof any workplace health and safety program.Formal, mandatory hazard communication and4

THE FLAVOR AND EXTRACT MANUFACTURERS ASSOCIATIONtraining sessions assure that employees have theappropriate awareness of respiratory safety issues.Personnel in task areas that merit focusinclude:■■ Personnel who blend and mix flavorsin bulk quantities, especially those exposed toheated flavors, and the powder flavor and spraydrymanufacturing processes.■■ Personnel who pack flavors (liquid ordry).■■ Quality assurance personnel and flavoristswho may have repeated exposure to flavors, eventhough exposure may be in smaller amounts.Hazard identificationOver 2,700 chemically-defined flavoringsubstances and natural flavoring complexes arecommonly used to formulate flavors. The U.S.Food and Drug Administration (FDA) is primarilyresponsible for the regulation of the additionof flavoring substances to food through severalregulatory pathways (Hallagan and Hall, 2009).The vast majority of these materials have chemicaland physical characteristics that would makeit highly unlikely that they would pose a risk ofrespiratory injury in the workplace. Most of thematerials are not very volatile and do not have asignificant degree of reactivity. However, somelow molecular weight chemically-defined flavoringsubstances may have sufficient volatility,and possibly reactivity, to pose a risk of respiratoryinjury when improperly handled. Table 1contains a list of chemically-defined flavoringsubstances that may pose potential respiratoryhazards when improperly handled.The priority levels in Table 1 were assignedbased on available inhalation exposuredata in animals and humans, chemical structure,volatility, and volume of use. In many instances,data on one flavoring substance was used toevaluate the priority level for other structurallyrelatedsubstances. In many cases, relevant inhalationexposure information is limited and, onoccasion, is available for flavoring substancesthat have other, larger-scale industrial uses. Theassignment of priority levels required the applicationof significant judgment and also tookinto account anecdotal information provided byworkers in the flavor industry who shared theirvaluable experience related to the handling offlavoring substances.Since the original edition of this reportwas published in 2004, new information hasbecome available on substances structurallyrelatedto diacetyl resulting in their addition tothe table as high priority substances. These substancesinclude 2,3-pentanedione, 2,3-hexandione,3,4-hexanedione, 2,3-heptandione, and diacetyltrimer. A few substances were reassignedfrom high priority to low priority based on newinformation. No substances were removed fromTable 1.Table 1 contains updated information oneach flavoring substance from the FEMA PoundageSurvey. Data from the 1995, 2005, and 2010surveys are included and represent the amountof each flavoring substance estimated to “disappear”into the U.S. food supply in a given year.This information allows a rough estimate on thetrends of use for the listed substances.Hazard communication - MSDSsClear communication of potential hazardsis of critical importance. The OSHA HazardCommunications Standard establishes aminimum for hazard communication through itsmaterial safety data sheet (MSDS) requirements.5

RESPIRATORY HEALTH AND SAFETY IN THE FLAVOR MANUFACTURING WORKPLACEThe development and provision of MSDSs is anindividual company obligation. FEMA does not,and has never, compiled or published MSDSs, orreviewed or approved company MSDSs. FEMAhas assisted members in meeting their hazardcommunications obligations only through servingas a “library” for information.FEMA members have access to theFlavor and Fragrance Ingredient Data Sheet(FFIDS) program that provides information onworkplace hazards and that can be used as onesource of information to formulate MSDSs onflavoring substances.Another resource available to FEMAmembers is the IFRA/IOFI GHS Labeling Manualissued jointly by the International FragranceAssociation (IFRA) and the International Organizationof the Flavor Industry (IOFI). FEMAis a member of IOFI. The Labeling Manualprovides information on the harmonization ofhazard statements for hazard communicationspurposes according to the Globally HarmonizedSystem of Classification and Labeling of Chemicals(the “GHS”). OSHA published its final ruleadopting the GHS in March 2012.Hazard communication - labelingIn addition to the various types of labelingrequirements under relevant regulations, thelabeling of bulk flavors may also be appropriatein certain circumstances to alert workers to potentialrespiratory hazards. It is recommendedthat the following bulk flavors bear a label usingthe language described below, or language thatconveys a similar warning.■■ Containers of “high priority” neat substanceslisted in Table 1 such as diacetyl,2,3-pentanedione and acetaldehyde.■■ Containers of compounded flavors (liquidand dry or powdered) or natural flavoringcomplexes that contain “high priority” flavoringsubstances in concentrations >1.0%.■■ Any compounded flavors (liquid and dryor powdered) containing any flavoring substanceslisted in Table 1 in any concentrations ifthe compounded flavor or any of its individualflavoring substances will be heated during processing.WARNING – This flavor may posean inhalation hazard if improperlyhandled. Please contact your workplacesafety officer before openingand handling, and read the MSDS.Handling of this flavor that results ininhalation of fumes, especially if theflavor is heated, may cause severeadverse health effects.It is recommended that the followingbulk flavors bear a label using the language describedbelow, or language that conveys a similarwarning.■■ Containers of neat “low priority” chemically-definedsubstances as listed in Table 1.■■ Containers of natural flavoring complexesknown to contain chemically-defined flavoringsubstances listed in Table 1.■■ Containers of compounded flavors (liquidand dry or powdered) containing “high priority”chemically-defined substances at concentrations

THE FLAVOR AND EXTRACT MANUFACTURERS ASSOCIATIONATTENTION - Safe flavors can beused in an unsafe manner. Pleasecontact your workplace safety officerbefore opening and handling thisflavor, and read the MSDS.Flavor manufacturers and suppliers cannotin all instances know how their customer willuse a flavoring material. In many instances, thecustomer chooses to keep information related tohow they will use a flavoring material confidentialto protect valuable trade secret informationrelated to their products. In other instances, customersmay communicate to a supplier how theyplan to use a flavor but then modify their plans.The warning statements suggested in this sectionprovide a means for flavor manufacturersto assure their customers receive helpful informationrelated to the safe handling and use offlavors.Important resources on the subject ofmanagement and employee awareness include:■■ The OSHA Hazard Communications Standard.■ ■ OSHA GHS Implementation Program.■■ Hazard Communication Guidance for Diacetyland Food Flavorings Containing Diacetyl(OSHA, 2007).■■ Occupational Exposure to Flavoring Substances:Health Effects and Hazard Control(OSHA, 2010).■■ OSHA National Emphasis Program forFacilities that Manufacture Food FlavoringsContaining Diacetyl (OSHA, 2011).Exposure Assessmentand ControlAssessment of potential exposuresEnvironmental monitoring is a necessarycomponent of a sound respiratory healthand safety program. Monitoring at regular intervalscan provide valuable information on potentialexposures. In addition to monitoring forthe presence of certain vapors in air, monitoringof particulates, when appropriate, should also beconducted if reliable methods are available. Acritical issue in any monitoring program is identifyingthe appropriate substances to monitor.NIOSH has focused on diacetyl and 2,3-pentanedioneand provides a thorough discussionof analytical methods and sampling in the draftreport Occupational Exposure to Diacetyl and2,3-Pentanedione (NIOSH, 2011). Also relevantare reports by Cox-Gansler et al. (2011)and Day et al. (2011).Exposure controlFlavor manufacturing facilities varygreatly in size, structure, age, manufacturingtechnologies employed, flavoring substancesstocked and handled, types of flavors manufactured,and many other characteristics. Manufacturingprocesses may range from simpleblending and packaging to more complicatedprocesses that include repeated heating of flavoringsubstances that are mixed and heatedagain, extraction at room temperature and withheat, and other processes that may result in significantopportunities for exposure.Some facilities have extensive automatedprocesses that minimize opportunities for exposurewhile others have little automation and7

RESPIRATORY HEALTH AND SAFETY IN THE FLAVOR MANUFACTURING WORKPLACErely on workers manipulating large quantities offlavors and other materials by hand during theformulation and packing processes. Because ofthis great variability, “one size fits all” solutionsto material handling strategies and engineeringcontrols is inappropriate. However, a number ofbasic principles can greatly reduce opportunitiesfor hazardous exposures.Product substitutionAwareness that specific substances arehazardous often results in the application of asimple industrial hygiene strategy – productsubstitution. Product substitution may be employedwhen it is known that a substance is hazardousand can be replaced with one that isn’t.The unique nature of the flavor imparted by certainsubstances, many of which are naturally occurringconstituents of food, makes it difficult toidentify substitutes that are effective.In 2010 OSHA published a “WorkerAlert” on diacetyl and substitutes noting that“some diacetyl substitutes may also cause harm.”The Alert stated, “Diacetyl substitutes that havenot been proven to be safe include diacetyltrimer, 2,3-hexanedione, 2,3-heptanedione, and2,3-pentanedione.” In January, 2011, NIOSHrequested information on flavoring substancesthat may be used as substitutes for diacetyl (76Fed. Reg. 1434. 10 January 2011). FEMA providedinformation to NIOSH on six flavoringsubstances that it was aware of that may serveas substitutes for diacetyl:■■ Four alpha-diketone substances: 2,3-pentanedione,2,3-hexanedione, 3,4-hexanedione,and 2,3-heptanedione.■■ Two other related substances: acetoin anddiacetyl trimer.NIOSH published results from environmentalmonitoring at a microwave popcorn productionplant focusing on the possible presenceof “diacetyl substitutes” (Boylstein, 2012).Heating of flavorsHeating of flavors is of particular concernwith regard to potential hazardous exposures.Heating will increase volatility andgreatly increase air concentrations of flavoringsubstances. Mixing of heated flavors should beconducted in closed vessels with local ventilation.Workers should not open heated vessels toconduct visual inspections in such a way as tocreate an opportunity for exposure. In instanceswhen workers must work near open vesselsthat are heated and cannot be closed or do nothave local ventilation, their exposures should bepromptly evaluated by environmental sampling.If exposures are elevated then the proper personalprotective equipment should be employed.Facility structure and organizationOpportunities for exposure can be greatlydecreased by segregating functions that involvethe handling of flavors from functions that donot. For example, a flavor compounding, packing,or shipping area should not share space witha sales office. Flavor production areas shouldbe separate from non-production areas and theyshould not share the same air handler.VentilationFlavoring substances and mixtures,whether liquid or dry, must be handled in sucha way as to minimize the creation of airborneaerosols or particulate matter. This means thatmixing, blending, and other physical manipulationactivities should be performed in closed8

THE FLAVOR AND EXTRACT MANUFACTURERS ASSOCIATIONsystems when possible. When systems mustremain open, local (“spot”) ventilation (e.g. “elephanttrunks”) should be used. Fume hoods arecommonly used in research and developmentlaboratories. Dilution through general roomventilation seldom results in exposure reductionunless extremely high volumes of air are circulated.Material handling – flavor compounding andpacking activitiesSimple flavor compounding activitiessuch as mixing or pouring can result in significantexposures. In most instances, mixing of liquidand dry flavors should be conducted in fullyor partially closed vessels with local ventilation.Opportunities for the generation of airborne particlesand aerosols should be minimized.Proper pouring techniques for liquid anddry flavors can greatly reduce opportunities forexposure. For liquid flavoring substances, techniquescan be adopted that pipe material intomixing vessels so that workers do not have topour. In some instances it is appropriate to pipein liquids below the surface of solutions in vesselsto minimize splashing. This is particularlyimportant for volatile substances.For dry and powdered flavors, pouringshould be conducted in such a way that the generationof airborne particulates is minimized.Simple, proper pouring techniques such as pouringslowly close to the mixing vessel can greatlyminimize airborne particulates. Mixing ingredientsin an order in which dry ingredients areadded last to liquid mixtures also can minimizeparticulate generation. Local exhaust is the mosteffective control for these operations. Systemscan be designed that will allow easy pouring andat the same time control exposures.Packaging activities can result in significantopportunities for exposure, especially whendry flavors are filled into bags, boxes, or drumsunder pressure. Closed systems should be usedwhen possible. But unless there is an unusuallyhigh degree of automation, workers will haveopportunities for exposure as filled containersmust be replaced with empty ones. The use ofpersonal protective equipment may then need tobe considered to minimize exposure.Material storageFlavoring substances that are volatileshould be stored in cooled storage areas. Substancessuch as acetaldehyde are often stored incooled rooms, and are often also used in flavormanufacture in a cooled state. Liquid and dryand powdered flavors should ideally be storedin store-rooms with their own air handler thathas minimum recirculation. In some instances,flavor facilities have negative air flow in storageareas to reduce opportunities for exposure.Cleaning of vessels and work areasCleaning of process vessels that containedliquid flavors or viscous mixtures, orwork areas with spilled material, especially withsteam or heated water, may create opportunitiesfor exposure to flavoring substances. Similarly,cleaning vessels or areas used to manufacture ormix powdered flavors with compressed air mayalso result in airborne particulates.It is important that cleaning activities beconducted in a manner that does not result in significantair concentrations of flavors and othermaterials present in the vessel. Cleaning areasshould be isolated and contained to prevent thedissemination of airborne flavors. Automatedcleaning processes will greatly reduce opportu-9

RESPIRATORY HEALTH AND SAFETY IN THE FLAVOR MANUFACTURING WORKPLACEnities for exposure. In some instances, the mosteffective way to protect workers responsible forcleaning activities will be to use respirators.It is also important that adequate care beexercised if workers are to enter or partially enterequipment in order to clean it. In addition toconcerns about possible respiratory exposures,in some instances, cleaning activities involvingvessel entry may be subject to the requirementsof OSHA’s confined space regulations (29 CFR1910.146).Personal respiratory protectionThe implementation of appropriate processand engineering controls is preferable tosimply providing employees with personal respiratoryprotection. However, respirators dohave a role in many respiratory health and safetyprograms. Critical to their success is the selectionof the proper respirator for the conditionspresent in a given facility, the proper fit of thatrespirator to the person using it, and the trainingin its use, maintenance, and storage. OSHA alsorequires that employees wearing most types ofrespirators undergo medical clearance prior totheir use.In terms of specific duty requirementsrelevant to protection against respiratory hazards,OSHA regulations require that personalprotective equipment must be provided to employeeswhenever necessary to address chemicalor other hazards which are “capable of causinginjury or impairment in the function of anypart of the body through absorption, inhalationor physical contact.” Under OSHA’s RespiratoryProtection Standard, the “primary objectiveshall be to prevent atmospheric contamination.”Where, however, that is not feasible through engineeringand process controls, respirators shallbe used. The regulations contain a range of requirements,including the proper selection ofrespirators, standard procedures for use, trainingof employees, respirator maintenance, andother safety measures. The standard and relevantbackground information were publishedin the Federal Register notice announcing thestandard (63 Fed. Reg. 1152. 8 January 1998).Important resources on the subjects ofexposure assessment and control include:■■ Diacetyl exposures in the flavor manufacturingindustry (Martyny et al., 2008).■■ Evaluation of a local exhaust ventilationsystem for controlling exposures during liquidflavor production (Dunn et al., 2008).■■ Occupational Exposure to Flavoring Substances:Health Effects and Hazard Control(OSHA, 2010).■■ OSHA National Emphasis Program forFacilities that Manufacture Food FlavoringsContaining Diacetyl (OSHA, 2011).■■ OSHA National Emphasis Program forMicrowave Popcorn Processing Plants (OSHA,2011).■■ Draft Criteria Document - OccupationalExposure to Diacetyl and 2,3-Pentanedione(NIOSH, 2011).■■ Occupational lung disease risk and exposureto butter-flavoring chemicals after implementationof controls at a microwave popcornplant (Kanwal et al., 2011).Medical surveillanceMedical surveillance is a key componentof an effective respiratory health and safety programin the flavor industry. This is especiallythe case when it is difficult to identify a specificcausative agent for an observed effect and when10

THE FLAVOR AND EXTRACT MANUFACTURERS ASSOCIATIONsymptoms and/or lung function abnormalitiesmay be the first clue to an exposure-relatedproblem. Appropriate medical surveillance canidentify health issues before progression to severeillness occurs and when opportunities forreducing or eliminating exposure exist.Medical surveillance should include anevaluation at the time of hire and at least annuallythereafter. The exam should include both amedical and occupational history and a pulmonaryfunction component. Spirometry is a simpleand inexpensive way to monitor pulmonaryfunction status and should be included in theexam at hire and in follow-up exams thereafter.It is important that spirometry testing follow themost recent American Thoracic Society guidelinesfor accurate testing.A sound medical surveillance programwill facilitate the identification of respiratorysymptoms and lung function abnormalities. Asreported by NIOSH, some workers in microwavepopcorn manufacturing facilities, and ina few flavor manufacturing facilities, exhibitedfindings of fixed airway obstruction manifestedby symptoms of cough (often without the productionof phlegm) and shortness of breath afterexertion as well as spirometric abnormalities(e.g. decreased FEV-1, a parameter of airflow).Frequent or persistent symptoms of eye, nose,throat or skin irritation have also been reportedby NIOSH in some affected workers. A planshould be in place to refer employees for furthermedical follow-up and evaluation if suchsymptoms and lung function abnormalities areidentified in the surveillance examinations orif there are significant unexplained declines inemployee lung function as measured by periodicspirometry.It is particularly important to note thatbronchiolitis obliterans, a very serious lung disease,has been implicated in cases of respiratoryillness seen in microwave popcorn manufacturingplants and in flavor manufacturing facilities.Early detection of symptoms and spirometricabnormalities through a medical surveillanceprogram will allow workers to seek timely follow-upand may prevent progression of disease.Early detection is especially important withbronchiolitis obliterans because the disease isdifficult to treat.Important information resources on thesubject of medical surveillance include:Establishing a quality medical surveillance programin your flavor company. Rose C. and SellsT. National Jewish Health. Presentation at theconference “Respiratory Health and Safety inthe Flavor Manufacturing Workplace – A TrainingSession for Flavor Plant Staff.” FEMA.2005.Occupational Exposure to Flavoring Substances:Health Effects and Hazard Control (OSHA,2010).Occupational Exposure to Diacetyl and 2,3-Pentanedione(NIOSH, 2011).11

RESPIRATORY HEALTH AND SAFETY IN THE FLAVOR MANUFACTURING WORKPLACEDeveloping aRespiratory SafetyProgram for FlavorManufacturingFacilitiesFEMA and a number of its membershave worked with National Jewish Health inDenver, Colorado (NJH) through Cecile Rose,M.D., M.P.H., and Mike VanDyke, Ph.D., C.I.H.Dr. Rose is an expert in pulmonary diseases, andDr. VanDyke is a certified industrial hygienist.Both have worked extensively with the flavorindustry and have significant experience withflavors and flavor manufacturing. Other sourcesof expert assistance include occupational medicinephysicians and industrial hygiene consultantslocated in the communities where flavormanufacturing facilities are located. Amongother sources of information, consultants canbe identified through the consultant directorymaintained by the American Industrial HygieneAssociation (www.aiha.org).National Jewish Health was awarded agrant by OSHA in late 2011 to conduct trainingon respiratory health and safety programsfor flavor manufacturers. NJH has been providedfunding by OSHA to train 500 peopleworking in flavor manufacturing. The focus isexpected to be on workers employed in directflavor manufacturing, i.e. workers responsiblefor handling and formulating flavorings. Pleasecontact John Hallagan of FEMA for information(202.331.2333; Hondobear@aol.com).References and OtherRelevant PublicationsSince 2004, a number of reports havebeen published relevant to the safety of possibleexposure to flavoring substances in the workplaceand other aspects of respiratory health andsafety in flavor manufacturing. References forpublications cited in the body of this report maybe found in this list in addition to publicationsnot cited but of interest.Auttachoat W., White K.L. and Guo T.L. Diacetyl,an artificial flavoring compound inpopcorn causes contact sensitization in femaleBALB/c mice. The Toxicologist, 96, 239. 2007.Boylstein R. Identification of diacetyl substitutesat a microwave popcorn production plant.Journal of Occupational and EnvironmentalHygiene. 9, D33. 2012.Brosseau L.M. Occupational exposure guidelines- why process is as important as science.Journal of Occupational and EnvironmentalHygiene. 8, D109. 2012.Cox-Ganser J., Ganser G., Saito R., Hobbs G.,Boystein R., Hendricks W., Simmons M., EideM., Kullman G. and Piacitelli C. Correcting diacetylconcentrations from air samples collectedwith NIOSH method 2557. Journal of Occupationaland Environmental Hygiene. 8, 59. 2011.Day G., LeBouf R., Grote A., Pendergrass S.,Cummings K., Kreiss K. and Kullman G. Identificationand measurement of diacety substitutes12

THE FLAVOR AND EXTRACT MANUFACTURERS ASSOCIATIONin dry bakery mix production. Journal of Occupationaland Environmental Hygiene. 8, 93.2011.Dunn K.H., Garcia A. and Echt A. Evaluation ofa local exhaust ventilation system for controllingexposures during liquid flavoring production.Journal of Occupational and EnvironmentalHygiene. 5, D103. 2008.Fedan J.S., Dowdy J.A., Fedan K.B. and Hubbs,A.F. Popcorn worker’s lung: In vitro exposureto diacetyl, an ingredient in microwave popcornbutter flavoring, increases reactivity to methacholine.Toxicol. Appl. Pharmacol., 215, 17.2006Flake G.P., Kirby P.J., Price H.C., Gage P.S.,Kelly F.L., Palmer S.M., Foley J.F. and MorganD.L. Bronchiolitis obliterans-like lesions in ratstreated with diacetyl, acetoin, or acetyl propionylby intratracheal instillation. The Toxicologist,114, 316. 2010.Hallagan J.B. and Hall R.L. Under the conditionsof intended use – new developments in theFEMA GRAS program and the safety assessmentof flavor ingredients. Food & ChemicalToxicology. 47, 267. 2009.Harber P., Saechao K. and Boomus C. Diacetylinducedlung disease. Toxicol. Rev. 25, 261.2006.Hubbs A.F., Battelli L.A., Goldsmith W.T., PorterD.W., Frazer D., Friend S., Schwegler-BerryD., Mercer R.R., Reynolds J.S., Grote A., CastranovaV., Kullman G., Fedan J.S., Dowdy J.,and Jones, W.G. Necrosis of nasal and airwayepithelium in rats inhaling vapors of artificialbutter flavoring. Toxicol. Appl. Pharmacol. 185,128. 2002.Hubbs A.F., Battelli L.A., Mercer R.R., KashonM., Friend S., Schwegler-Berry D., and GoldsmithW.T. Inhalation toxicity of the flavoringagent, diacetyl (2,3-butanedione) in the upperrespiratory tract of rats. The Toxicologist 78(S-1), 438. 2004.Hubbs AF, Goldsmith W.T., Kashon M.L., FrazerD., Mercer R.R., Batelli L.A., Kullman G.J.,Schwegler-Berry D., Friend, S. and CastranovaV. Respiratory toxicologic pathology of inhaleddiacetyl in Sprague-Dawley rats. Toxicol.Pathol. 36, 330. 2008.Hubbs A.F., Moseley A.E., Goldsmith W.T.,Jackson M.C., & Kashon M.L. Airway epithelialtoxicity of the flavoring agent, 2,3-pentanedione.The Toxicologist 114(1): 319. 2010.Kanwal R., Kullman G., Piacitelli C., BoylsteinR., Sahakian N., Martin S., Fedan K. and KreissK. Evaluation of flavorings-related lung diseaserisk at six microwave popcorn plants. J. Occup.Environ. Med., 48, 149. 2006.King T.E. and Kinder B.W. Bronchiolitis. InFishman’s Pulmonary Diseases and Disorders,Vol. 1, Chapter 52. Fishman et al. Eds. 4th Ed.2008.Kreiss K., Gomaa A., Kullman G., Fedan K., SimoesE.J. and Enright P.L. (2002) Clinical bronchiolitisobliterans in workers at a microwavepopcornplant. N. Engl. J. Med. 347, 330. 2002.13

RESPIRATORY HEALTH AND SAFETY IN THE FLAVOR MANUFACTURING WORKPLACEKovacic P. and Cooksy A.L. Electron transfer asa potential cause of diacetyl toxicity in popcornlung disease. Rev. Environ. Contam. Toxicol.,204,133. 2010.Maier A., Kohrman-Vincent M., Parker A., andHaber L. Evaluation of concentration-responseoptions for diacetyl in support of occupationalrisk assessment. Regulatory Toxicology & Pharmacology.58, 285. 2010.Mathews J. M., Burgess J. P., Snyder R. W.,Etheridge A. S., Burka L. T. Reaction of the butterflavorant butanedione with N-R-acetylarginine.Drug Metab. Rev., 37, 273. 2005.Mathews J.M., Watson S.C., Snyder R.W., BurgessJ.P. and Morgan D.L. Reaction of the butterflavorant diacetyl (2,3-butanedione) withN-r-acetylarginine: A model for epitope formationwith pulmonary proteins in the etiology ofobliterative bronchiolitis. J. Agric. Food Chem.,58,12761. 2010.Morgan D.L., Flake G.P., Kirby P.J. and PalmerS.M. Respiratory toxicity of diacetyl in C57B1/6mice. Toxicol. Sci., 103(1): 169-180. 2008.Gloede E., Cichoki J.A., Baldino J.B. and MorrisJ.B. A validated hybrid computational fluiddynamics-physiologically based pharmacokineticmodel for respiratory tract vapor absorptionin the human and rat and its application toinhalation dosimetry of diacetyl. ToxicologicalSciences. Advanced access. 24 June 2011.VanRooy F.G.B.G.J., Rooyackers J.M., ProkopM., Houba R., Smit A.M. and Heederik D.J.J.Bronchiolitis obliterans syndrome in chemicalworkers producing diacetyl for food flavorings.Am. J. Respir. Crit. Care Med., 176(5): 498-504.2007.VanRooy F.G.B.G.J., Smit L.A.M., Houba R.,Zaat V.A.C., Rooyackers J.M. and HeederikD.J.J. A cross sectional study on lung functionand respiratory symptoms among chemicalworkers producing diacetyl for food flavourings.Occup Environ Med, 66,105. 2009.Zviely M. Molecule of the month: 2,3-pentanedione.Perfumer & Flavorist. 34(7), 20.2009.Morgan D.L., Kirby P.J., Price H.C., BousquetR.W., Taylor G.J., Gage N. and Flake G.P. Inhalationtoxicity of acetyl propionyl in rats andmice. The Toxicologist, 114, 316. 2010.Morris J.B. and Hubbs A.F. Inhalation dosimetryof diacetyl and butyric acid, two componentsof butter flavoring vapors. Toxicol. Sci. 108(1):173. 2009.14

THE FLAVOR AND EXTRACT MANUFACTURERS ASSOCIATIONCONTINUEDTABLE 1FEMA CAS Principal NameHigh PriorityMolecularWeightCalculated VaporReportedPressureValue PEL Data a,b Poundage c (lbs)2003 75-07-0 AcetaldehydeO44.05 759 mm Hg 20 ºC910 mm Hg 25 ºCH2006 64-19-7 Acetic acid 60.05 12.9 mm Hg 20 ºC17.2 mm Hg 25 ºCOOHOSHA PEL - TWA 200ppm, 360 mg/m3OSHA PEL - TWA 10ppm, 25 mg/m31995: 321,0002005: 70,2002010: 59,0001995: 310,0002005: 271,0002010: 373,0002008 513-86-0 Acetoin 88.11 1.36 mm Hg 20 ºC2 mm Hg 25 ºCONA 1995: 116,0002005: 133,0002010: 150,000OH2841 600-14-6 2,3-PentanedioneO100.12 23.8 mm Hg 20 ºC31.1 mm Hg 25 ºCONIOSH REL- TWA 9.3ppb NIOSH STEL 31 ppb1995: 2,6002005: 4,5902010: 38,0002127 100-52-7 BenzaldehydeO106.13 0.705 mm Hg 20 ºC1.01 mm Hg 25 ºCHNA 1995: 603,0002005: 1,410,0002010: 578,0002221 107-92-6 Butyric Acid 88.11 1.5 mm Hg 20 ºC2.11 mm Hg 25 ºCONA 1995: 180,0002005: 130,0002010: 229,000OH2370 431-03-8 Diacetyl 86.09 55 mm Hg 20 ºC70.2 mm Hg 25 ºCOONIOSH REL- TWA 5 ppbNIOSH STEL 25 ppbTERA OEL- TWA 0.2ppm1995: 211,0002005: 228,0002010: 85,00015

RESPIRATORY HEALTH AND SAFETY IN THE FLAVOR MANUFACTURING WORKPLACECONTINUEDFEMA CAS Principal NameMolecularWeightCalculated VaporReportedPressureValue PEL Data a,b Poundage c (lbs)4303 18114-49-3 Diacetyl trimer 258.27 NA See Diacetyl 1995: NA2005: NAOH O2010: 0OOOO2418 140-88-5 Ethyl acrylate 100.12 29.4 mm Hg 20 ºC38.4 mm Hg 25 ºCOO2487 64-18-6 Formic Acid 46.03 27.4 mm Hg 20º CO35.9 mm Hg 25 ºCH OH2489 98-01-1 Furfural 96.09 1.65 mm Hg 20 ºCOO2.32 mm Hf 25 ºCHPEL - Skin TWA 25 ppm,100 mg/m3OSHA PEL - TWA 5 ppm,9 mg/m3OSHA PEL - Skin TWA 5ppm, 20 mg/m31995: 112005: 32010: 591995: 20,6002005: 7,1502010: 9,5001995: 7,7102005: 8,2402010: 9,3002543 96-04-8 2,3-HeptanedioneO128.17 0.785 mm Hg 20 ºC1.11 mm Hg 25 ºCO2558 3848-24-6 2,3-Hexanedione 114.14 2.11 mm Hg 20 ºCO2.93 mm Hg 25 ºCNA 1995: 1002005: 782010: 120NA 1995: 6202005: 4002010: 2,500O3168 4437-51-8 3,4-Hexanedione 114.14 9.2 mm Hg 20 ºCO12.3 mm Hg 25 ºCNA 1995: 392005: 132010: 200O16

THE FLAVOR AND EXTRACT MANUFACTURERS ASSOCIATIONCONTINUEDFEMA CAS Principal NameMolecularWeight3779 7783 - 06 4 Hydrogen sulfide 34.08 3.81 x 10-9 mm Hg25 ºC2220 78-84-2 Isobutyraldehyde 72.11 131 mm Hg 20 ºC164 mm Hg 25 ºCOHH S HCalculated VaporReportedPressureValue PEL Data a,b Poundage c (lbs)OSHA PEL - Exposuresshall not exceed 20 ppm(ceiling) with the followingexception: if no othermeasurable exposureoccurs during the 8-hourwork shift, exposures mayexceed 20 ppm, but notmore than 50 ppm (peak),for a single time periodup to 10 minutes NIOSHREL - 10 ppm, ceiling limit15 mg/m3 (10 minutes)1995: 32005: 2102010: 22NA 1995: 1,1002005: 1,0102010: 1,4002222 79-31-2 Isobutyric acid 88.11 2.35 mm Hg 20 ºC3.27 mm Hg 25 ºCONA 1995: 8,7502005: 6,8402010: 8,700HO2716 74-93-1 Methyl mercaptan 48.11 1.28 X 103mmHg 20 ºC1510 mm Hg 25 ºCSHOSHA PEL - ceiling limitTWA 10 ppm, 20 mg/m31995: 522005: 2402010: 4002746 75-18-3 Methyl sulfide 62.13 391 mm Hg 20 ºC479 mm Hg 25 ºCSNA 1995: 8,2002005: 22,9002010: 17,0003217 764-40-9 2,4-Pentadienal 82.1 20 mm Hg 25 ºC NA 1995: 0O2005: 02010: 0H3218 764-39-6 2-Pentenal 84.12 13.9 mm Hg 20 ºCO18.5 mm Hg 25 ºCHNA 1995: 32005: 242010: 5417

RESPIRATORY HEALTH AND SAFETY IN THE FLAVOR MANUFACTURING WORKPLACECONTINUEDFEMA CAS Principal NameMolecularWeight2900 7664-38-2 Phosphoric acid 67.02 6.09 x 10-11 mm Hg25 ºCOHOPHOOHCalculated VaporReportedPressureValue PEL Data a,b Poundage c (lbs)OSHA PEL - TWA 1 mg/m31995: 4,840,0002005: 5,780,0002010: 423,0002923 123-38-6 Propionaldehyde 58.08 256 mm Hg 20 ºCO317 mm Hg 25 ºCHNA 1995: 3,8702005: 5902010: 7002924 79-09-4 Propionic acid 74.08 4.41 mm Hg 20 ºCO6.04 mm Hg 25 ºCHONIOSH REL- TWA 10ppm, 30 mg/m31995: 44,4002005: 24,5002010: 33,0003039 9/5/7446 Sulfur dioxide 64.06 2600 mm Hg 25 ºC OSHA PEL - TWA 5 ppm,13 mg/m3O S O1995: 4,1002005: 4702010: 3303241 75-50-3 Trimethylamine 59.11 1680 mm Hg 25 ºC NIOSH REL - TWA 10ppm; STEL 15 ppmN1995: 8702005: 6402010: 32003098 110-62-3 Valeraldehyde 86.13 25.1 mm Hg 20 ºC32.9 mm Hg 25 ºCOHLow PriorityNOSH REL -TWA 50ppm, 176 mg/m31995: 1402005: 1502010: 16003326 67-64-1 Acetone 58.08 249 mm Hg 25 ºC OSHA PEL - TWA 1000ppm, 2400 mg/m3O1995: 4002005: 3602010: 3702035 870-23-5 Allyl mercaptan 74.14 161 mm Hg 25 ºC NA 1995: 12005: 1SH2010: 118

THE FLAVOR AND EXTRACT MANUFACTURERS ASSOCIATIONCONTINUEDFEMA CAS Principal Name2053 12124-99-1 Ammonium sulfide(NH 4) 2SMolecularWeightCalculated VaporReportedPressureValue PEL Data a,b Poundage c (lbs)68.15 9.2 x 10-15 mm Hg25 ºCNA 1995: 6602005: 6002010: 13003965 78-96-6 1-Amino-2-propanol 75.13 0.768 mm Hg 25 ºC NA 1995: NA2005: 02010: 0NHHO23616 108-98-5 Benzenethiol 110.18 1.63 mm Hg 25 ºC "NIOSH REL-ceiling limitSHTWA 0.1 ppm, 0.5 mg/m3(15 minutes)"1995: 42005: 12010: 38002147 100-53-8 Benzyl mercaptan 124.21 0.3 mm Hg 20 ºC0.474 mm Hg 25 ºCSHNA 1995: 02005: 0.12010: 0.13129 92-52-4 Biphenyl 154.21 0.00419 mmHg 20 ºC0.00749 mm Hg25 ºCOSHA PEL - TWA 0.2ppm, 1mg/m31995: 02005: 02010: 02170 78-93-3 2-Butanone 72.11 77.9 mm Hg 20 ºC98.5 mm Hg 25 ºCOOSHA PEL - TWA 200ppm, 590 mg/m31995: 5302005: 9602010: 12002174 123-86-4 Butyl acetate 116.16 8.85 mm Hg 20 ºCO11.9 mm Hg 25 ºC2178 71-36-3 Butyl Alcohol 74.12 5.49 mm Hg 20 ºC7.78 mm Hg 25 ºCHOOOSHA PEL- TWA 150ppm, 710 mg/m3OSHA PEL - TWA 100ppm, 300 mg/m31995: 26,3002005: 36,7002010: 37,0001995: 13,3002005: 6,5802010: 7,2003130 109-73-9 Butylamine 73.14 71 mm Hg 20 ºC94.7 mm Hg 25 ºCH 2 NOSHA PEL - TWA 5 ppm,15 mg/m3 ceiling; skin1995: 02005: 02010: 019

RESPIRATORY HEALTH AND SAFETY IN THE FLAVOR MANUFACTURING WORKPLACECONTINUEDFEMA CAS Principal NameMolecularWeight2219 123-72-8 Butyraldehyde 72.11 84.9 mm Hg 20 ºCHOCalculated VaporPressureValue PEL Data a,b ReportedPoundage c (lbs)NA 1995: 340108 mm Hg 25 ºC2005: 2402010: 1002286 104-55-2 Cinnamaldehyde 132.16 0.0214 mmHg 20 ºCO0.0337 mm Hg 25ºCHNA 1995: 993,0002005: 683,0002010: 421,0003530 108-39-4 m-Cresol 108.14 0.109 mm Hg 20 ºC0.167 mm Hg 25 ºCOH3480 95-48-7 o-Cresol 108.14 0.15 mm Hg 20 ºC0.25 mm Hg 25 ºCOHOSHA PEL - Skin TWA 5ppm, 22 mg/m3. OSHAstandard is for all cresolscombined under CASNumber 1319-77-3 (FederalRegister 7/5/89).OSHA PEL - Skin TWA 5ppm, 22 mg/m3. OSHAstandard is for all cresolscombined under CASNumber 1319-77-3 (FederalRegister 7/5/89).1995: 02005: 0.12010: 01995: 12005: 0.12010: 22337 106-44-5 p-Cresol 108.14 0.073 mm Hg 20 ºC0.124 mm Hg 25 ºCHOOSHA PEL - Skin TWA 5ppm, 22 mg/m3. OSHAstandard is for all cresolscombined under CASNumber 1319-77-3 (FederalRegister 7/5/89).1995: 172005: 1702010: 8103909 108-94-1 Cyclohexanone 98.15 2.94 mm Hg 20 ºC4.04 mm Hg 25 ºCOOSHA PEL - TWA 50ppm, 200 mg/m31995: NA2005: 02010: 03536 624-92-0 Dimethyl disulfide 94.2 18.5 mm Hg 20 ºC24.5 mm Hg 25 ºCS SNA 1995: 4,1702005: 322010: 3,60020

THE FLAVOR AND EXTRACT MANUFACTURERS ASSOCIATIONCONTINUEDFEMA CAS Principal NameMolecularWeight3667 101-84-8 Diphenyl ether 170.21 0.00973 mmHg 20 ºCO0.017 mm Hg 25 ºCCalculated VaporReportedPressureValue PEL Data a,b Poundage c (lbs)OSHA PEL - Vapor TWA1ppm, 7 mg/m31995: 862005: 2802010: 4,0002414 141-78-6 Ethyl acetate 88.11 77 mm Hg 20 ºC98.3 mm Hg 25 ºCO2419 64-17-5 Ethyl alcohol 46.07 45.3 mm Hg 20 ºC60.9 mm Hg 25 ºC2434 109-94-4 Ethyl formate 74.08 198 mm Hg 20 ºCO246 mm Hg 25 ºCHOOOH2491 98-00-0 Furfuryl alcohol 98.1 0.267 mm Hg 20 ºC0.409 mm Hg 25 ºCO OHOSHA PEL - TWA 400ppm, 1400 mg/m3OSHA PEL - TWA 1000ppm, 1900 mg/m3OSHA PEL - TWA 100ppm, 300 mg/m3OSHA PEL - TWA 50ppm, 200 mg/m31995: 462,0002005: 514,0002010: 460,0001995: 23,500,0002005: 30,600,0002010: 20,200,0001995: 18,6002005: 21,4002010: 19,0001995: 4102005: 5602010: 1,0003173 5077-67-8 1-Hydroxy-2-butanone 88.11 0.768 mm Hg 25 ºC NA 1995: 02005: 0OH2010: 0O2055 123-92-2 Isoamyl acetateO130.19 4.13 mm Hg 20 ºC5.67 mm Hg 25 ºCO2175 110-19-0 Isobutyl acetate 116.16 13.7 mm Hg 20 ºCO18.3 mm Hg 25 ºCOOSHA PEL - TWA 100ppm, 525 mg/m3OSHA PEL - TWA 150ppm, 700 mg/m31995: 441,0002005: 372,0002010: 270,0001995: 35,6002005: 39,3002010: 60,0002179 78-83-1 Isobutyl alcohol 74.12 9.55 mm Hg 20 ºC13.4 mm Hg 25 ºCOHOSHA PEL - TWA 100ppm, 300 mg/m31995: 27,7002005: 20,0002010: 8,80021

RESPIRATORY HEALTH AND SAFETY IN THE FLAVOR MANUFACTURING WORKPLACECONTINUEDFEMA CAS Principal NameMolecularWeight3219 107-85-7 Isopentylamine 87.17 40 mm Hg 20 ºC44.5 mm Hg 25 ºCNH 2Calculated VaporReportedPressureValue PEL Data a,b Poundage c (lbs)NA 1995: 12005: 02010: 0.43553 78-59-1 Isophorone 138.2 0.169 mm Hg 20 ºCO0.249 mm Hg 25 ºCOSHA PEL - TWA 25ppm, 140 mg/m31995: 22005: 2202010: 32926 108-21-4 Isopropyl acetate 102.13 47.1 mm Hg 20 ºCO60.8 mm Hg 25 ºCO2929 67-63-0 Isopropyl alcohol 60.1 36.7 mm Hg 20 ºC49.6 mm Hg 25 ºCOHOSHA PEL - TWA 250ppm, 950 mg/m3OSHA PEL - TWA 400ppm, 980 mg/m31995: 1,1802005: 702010: 1901995: 176,0002005: 14,3002010: 96,0002944 625-55-8 Isopropyl formate 88.11 110 mm Hg 20 ºCO142 mm Hg 25 ºCOH2676 79-20-9 Methyl acetate 74.08 40.6 mm Hg 20 ºC52.7 mm Hg 25 ºCONA 1995: 02005: 02010: 0OSHA PEL - TWA 200ppm, 610 mg/m31995: 1,0602005: 1,3702010: 1,500O3860 624-89-5 Methyl ethyl sulfide 76.16 150 mm Hg 25 ºC NA 1995: NA2005: 02010: 0S4002 80-62-6 Methyl methacrylate 100.12 36.7 mm Hg 25 ºC OSHA PEL - TWA 100ppm, 410 mg/m3O1995: NA2005: 02010: 0O22

THE FLAVOR AND EXTRACT MANUFACTURERS ASSOCIATIONCONTINUEDFEMA CAS Principal NameMolecularWeight2742 554-12-1 Methyl propionate 88.11 68.8 mm Hg 20 ºCOOCalculated VaporPressureValue PEL Data a,b ReportedPoundage c (lbs)NA 1995: 27087.9 mm Hg 25 ºC2005: 4002010: 1,0003647 556-82-1 3-Methyl-2-buten-1-ol 86.13 1.61 mm Hg 20 ºC2.36 mm Hg 25 ºCNA 1995: 652005: 12010: 6OH3407 497-03-0 2-Methyl-2-butenalO84.12 13.4 mm Hg 20 ºC17.9 mm Hg 25 ºCH3646 107-86-8 3-Methyl-2-butenal 84.12 6.14 mm Hg 20 ºCH8.35 mm Hg 25 ºCONA 1995: 32005: 0.72010: 0.1NA 1995: 02005: 42010: 32731 108-10-1 4-Methyl-2-pentanone 100.16 16.6 mm Hg 20 ºC21.8 mm Hg 25 ºCOOSHA PEL -TWA 100ppm, 410 mg/m31995: 192005: 52010: 13368 141-79-7 4-Methyl-3-penten-2-one 98.15 7.9 mm Hg 20 ºCO12.3 mm Hg 25 ºCOSHA PEL - TWA 25ppm, 100 mg/m31995: 02005: 02010: 152691 96-17-3 2-Methylbutyraldehyde 86.13 6.9 mm Hg 20 ºC10.4 mm Hg 25 ºCONA 1995: 332005: 872010: 38H2692 590-86-3 3-Methylbutyraldehyde 86.13 39.8 mm Hg 20 ºC51.6 mm Hg 25 ºCONA 1995: 3,2902005: 6,4802010: 6,700H23

RESPIRATORY HEALTH AND SAFETY IN THE FLAVOR MANUFACTURING WORKPLACECONTINUEDFEMA CAS Principal NameMolecularWeight3946 583-60-8 2-Methylcyclohexanone 112.17 2.17 mm Hg 20 ºCO3.01 mm Hg 25 ºCCalculated VaporReportedPressureValue PEL Data a,b Poundage c (lbs)OSHA PEL - Skin TWA100 ppm, 460 mg/m31995: NA2005: 02010: 03875 67-68-5 Methylsulfinylmethane 78.14 0.427 mm Hg 20 ºC0.622 mm Hg 25 ºCOSNA1995: NA2005: 0.92010: 0.82785 821-55-6 2-Nonanone 142.24 0.449 mm Hg 20 ºC0.647 mm Hg 25 ºCONA 1995: 3,5202005: 1,0002010: 3,5002842 107-87-9 2-Pentanone 86.13 30.5 mm Hg 20 ºC39.4 mm Hg 25 ºCOOSHA PEL - TWA 200ppm, 700 mg/m31995: 6402005: 1,1402010: 1,9003417 625-33-2 3-Penten-2-one 84.12 17.3 mm Hg 25 ºC NA 1995: 02005: 0O2010: 0.13584 616-25-1 1-Penten-3-ol 86.13 6.47 mm Hg 20 ºC9.13 mm Hg 25 ºCOHNA 1995: 202005: 1602010: 1503382 1629-58-9 1-Penten-3-one 84.12 29.5 mm Hg 20 ºC38.2 mm Hg 25 ºCNA 1995: 22005: 3402010: 600O4012 626-38-0 2-Pentyl acetate 130.19 7.22 mm Hg 20 ºC9.78 mm Hg 25 ºCOOOSHA PEL - TWA 125ppm, 650 mg/m31995: NA2005: 02010: 024

THE FLAVOR AND EXTRACT MANUFACTURERS ASSOCIATIONCONTINUEDFEMA CAS Principal NameMolecularWeight3223 108-95-2 Phenol 94.11 0.193 mm Hg 20 ºCOH0.323 mm Hg 25 ºCCalculated VaporReportedPressureValue PEL Data a,b Poundage c (lbs)OSHA PEL - Skin TWA 5ppm, 19 mg/m31995: 92005: 122010: 24002908 110-89-4 Piperidine 85.15 22 mm Hg 20º C28.9 mm Hg 25 ºCNH3521 107-03-9 Propanethiol 76.16 114 mm Hg 20 ºC144 mm Hg 25 ºCSHNA 1995: 1,6102005: 2002010: 52NA 1995: 1202005: 122010: 53897 75-33-2 2-Propanethiol 76.16 265 mm Hg 25 ºC NA 1995: NA2005: 02010: 0.1SH2925 109-60-4 Propyl acetate 102.13 26.8 mm Hg 20 ºCO35.1 mm Hg 25 ºCO2928 71-23-8 Propyl alcohol 60.1 16.9 mm Hg 20 ºC23.2 mm Hg 25 ºCOHOSHA PEL - TWA 200ppm, 840 mg/m3OSHA PEL - TWA 200ppm, 500 mg/m31995: 3,1102005: 2,6102010: 7,2001995: 8,4702005: 9,0102010: 8,0002943 110-74-7 Propyl formate 88.11 64 mm Hg 20 ºCO H84 mm Hg 25 ºCO2966 110-86-1 Pyridine 79.10 14.5 mm Hg 20 ºC19.3 mm Hg 25 ºCNNA 1995: 1102005: 8902010: 1,400OSHA PEL - TWA 5 ppm,15 mg/m31995: 712005: 1202010: 1,1003523 123-75-1 Pyrrolidine 71.12 49 mm Hg 20 ºCH66.5 mm Hg 25 ºCNNA 1995: 282005: 122010: 925

RESPIRATORY HEALTH AND SAFETY IN THE FLAVOR MANUFACTURING WORKPLACECONTINUEDFEMA CAS Principal NameMolecularWeightCalculated VaporReportedPressureValue PEL Data a,b Poundage c (lbs)3898 5724-81-2 1-Pyrroline 69.1 80.7 mm Hg 25 ºC NA 1995: NA2005: 0N2010: 03589 108-46-3 ResorcinolOH110.1 5.90 x 10-5mm Hg 20 ºC1.2 x 10-4 mm Hg25 ºCPEL-TWA 10 ppm; STEL20 ppm (see Footnote d)1995: 52005: 02010: 0OHOther Flavoring Substances with OSHA PEL’s3478 109-79-5 1-Butanethiol 90.19 39.9 mm Hg 25 ºC OSHA PEL - TWA 10ppm, 35 mg/m3SH1995: 0.12005: 12010: 22205 138-22-7 Butyl lactate 146.19 0.109 mm Hg 20 ºCO0.17 mm Hg 25 ºCOOHNIOSH REL-TWA 5 ppm 1995: 4102005: 1,0602010: 2,0002230 464-49-3 d-Camphor 152.24 0.00604 mmHg 20 ºC0.0107 mm Hg 25OºCOSHA PEL - TWA 2 mg/m31995: 6,6302005: 1402010: 1603537 108-83-8 2,6-Dimethyl-4-heptanoneO142.24 1.54 mm Hg 20 ºC2.15 mm Hg 25 ºCOSHA PEL - TWA 50ppm, 290 mg/m31995: 02005: 02010: 04236 75-04-7 Ethylamine 45.09 153 mm Hg 25 ºC OSHA PEL - TWA 10ppm, 18 mg/m3NH 21995: NA2005: 02010: 026

THE FLAVOR AND EXTRACT MANUFACTURERS ASSOCIATIONCONTINUEDFEMA CAS Principal NameMolecularWeightCalculated VaporReportedPressureValue PEL Data a,b Poundage c (lbs)2433 75-21-8 Ethylene oxide 44.05 1250 mm Hg 25 ºC OSHA PEL- TWA 1ppm,OSHA STEL 5 ppm/15Omin1995: 02005: 02010: 02525 56-81-5 Glycerol 92.10 7.98 x 10-5 mm Hg25 ºCHOOHOHOSHA PEL - Glycerol mist- TWA 15 mg/m3 (totaldust); 5 mg/m3 (respirablefraction)1995: 3,620,0002005: 2,030,0002010: 1,640,0002544 110-43-0 2-Heptanone 114.19 3.59 mm Hg 20 ºC4.91 mm Hg 25 ºCOOSHA PEL - TWA100ppm, 465 mg/m31995: 2,2802005: 3,1002010: 3,6002545 106-35-4 3-Heptanone 114.19 4.31 mm Hg 20 ºC5.86 mm Hg 25 ºCOOSHA PEL - TWA 50ppm,230 mg/m31995: 1202005: 1002010: 1702546 123-19-3 4-Heptanone 114.19 4.93 mm Hg 20 ºC6.69 mm Hg 25 ºCOREL-TWA 50 ppm 1995: 1302005: 572010: 372057 123-51-3 Isoamyl alcohol 88.15 2.66 mm Hg 20 ºC3.84 mm Hg 25 ºCOHOSHA PEL - TWA 100ppm, 360 mg/m3 (forprimary and secondary)1995: 36,6002005: 29,9002010: 42,0002803 106-68-3 3-Octanone 128.22 1.68 mm Hg 20 ºC2.34 mm Hg 25 ºCOOSHA PEL - TWA 25ppm, 130 mg/m3. OSHAlists standard for this materialunder CAS Number541-85-5 (Federal Register7/5/89).1995: 122005: 752010: 1127

RESPIRATORY HEALTH AND SAFETY IN THE FLAVOR MANUFACTURING WORKPLACECONTINUEDFEMA CAS Principal NameMolecularWeight3233 100-42-5 Styrene 104.15 3.67 mm Hg 20 ºC5.05 mm Hg 25 ºCCalculated VaporReportedPressureValue PEL Data a,b Poundage c (lbs)OSHA PEL - TWA 100ppm; Acceptable ceilingconcentration - 200 ppm;Acceptable maximumpeak above the acceptableceiling concentrationfor an 8-hr shift is 600ppm for 5 minutes in any2 hours1995: 92005: 22010: 0.64246 121-44-8 Triethylamine 101.19 59.1 mm Hg 25 ºC OSHA PEL - TWA 25ppm,100mg/m3N1995: NA2005: 92010: 0a Additional occupational exposure guidance may be available from the American Conference of GovernmentalIndustrial Hygienists (ACGIH®).b PEL=OSHA Permissible Exposure Limit; REL=NIOSH Recommended Exposure Limit; STEL=Short TermExposure Limit;TWA=8 hour Time Weighted Average Exposurec NA=Not availabled PEL for resorcinol subsequently rescinded and is currently not in force.28

THE FLAVOR AND EXTRACT MANUFACTURERS ASSOCIATIONList of AcronymsACGIHAIHACal/OSHACASFDAFEMAFFIDSFISHEPGHSHCSHHEIFRAIOFIMSDSNEPNJHNIOSHOELOSHAPELRELSTELTERATLVTWAAmerican Conference of Government Industrial HygienistsAmerican Industrial Hygiene AssociationCalifornia Division of Occupational Safety and HealthChemical Abstract ServiceFood and Drug AdministrationFlavor and Extract Manufacturers AssociationFlavor and Fragrance Ingredient Data SheetFlavor Industry Safety and Health Evaluation ProgramGlobally Harmonized System of Classification and Labeling of ChemicalsOSHA Hazard Communication StandardNIOSH Health Hazard EvaluationInternational Fragrance AssociationInternational Organization of the Flavor IndustryMaterial Safety Data SheetOSHA National Emphasis ProgramNational Jewish HealthNational Institute of Occupational Safety and HealthOccupational Exposure LimitOccupational Safety and Health AdministrationPermissible Exposure LimitRecommended Exposure LimitShort-Term Exposure LimitToxicology Excellence for Risk AssessmentThreshold Limit ValueTime-Weighted Average29

Maintaining safe and healthy workplaces is a matter of utmost importance to FEMA and its members. FEMAconsulted with experts on the development of this document and made extensive use of a wide varietyof information resources. As described in detail in their report, the application of this information to yourworkplace is a function of specific aspects of your workplace and the products manufactured and handled.Because of the unique nature of each workplace, the information in this report should be considered onlya general guide. FEMA is not responsible for either the use or nonuse of the information, or any actions, orfailure to act, in any specific workplace based on reliance on the report. It is your individual responsibility toverify this information as it applies to your workplace before acting, and to comply with all relevant federal,state, and local laws and ordinances. We strongly urge you to consult with appropriate experts regardingthe circumstances relevant to respiratory health and safety in your facilities.© Copyright 2012. The Flavor and Extract Manufacturers Association of the United States. 1620 I Street,N.W., Suite 925, Washington, D.C. 20006

The Flavor and ExtractManufacturers Association ofthe United States1620 I Street, N.W., Suite 925Washington, D.C., 20006www.femaflavor.org