1996

DHHS (NIOSH) Publication Number 96-111



## Preventing Asthma and Death from Diisocyanate Exposure DHHS
Workers exposed to diisocyanates may develop serious or fatal respiratory disease.
The National Insti tute for Occupational Safety and Heal th (NIOSH) requests assistance in preventing asthma, other respirat ory disease, and death from diis ocyanate exposure. This Alert summarizes seven case reports of disease and deaths following occupa tional exposure to diisocyanates. Information about preventing adverse health effects from exposure to diisocyanates is urgently needed by workers and employers, small businesses, physicians, and other health care providers. NIOSH therefore requests that editors of trade jo urnals, safety and health officials, labor union leaders, employers, educators, and diisocyanate suppl iers and manufacturers bring this Alert to the attention of all workers at risk. Your assistance will help prevent asthma and other respiratory disease in the 28 0,000 U.S. workers potentially exposed to diisocyanates. 

### Background Diisocyanates are a group of low-molecular-weight aromatic and aliphatic compounds. The most common of these are toluene diisocyanate (TDI), methylene bisphenyl isocyanate (MDI), and hexamethylene diisocyanate (HDI). Appendix A lists commonly used synonyms for these three diisocyanates. They ar e widely used in the manufacture of flexible and ri g id foams, fibers, coatings such as paints and va rnishes, and elastomers. Diisocyan ates are increasingly used in the automobile industry, autobody repair, and building insulation materials. In this report, diisocyanates as a group will be referred to as isocyanates. The world production of isocyanates is estima ted to be 3 billion po unds annually [Woods 1987], and 280,000 U.S. workers are potentially exposed [NIOSH 1983; Dunn and Bradstreet Page 1 of 13 CDC - NIOSH Publications and Products - NIO SH Alert: Preventing Asthma and Death f

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1/3/2012 htt p ://www.cdc. g ov/niosh/docs/96-111 /1983]. The major route of occupational ex posure to isocyanates is inhala tion of the vapo r or aerosol; exposure may also occur through skin contact during the handling of liquid isocyanates. Occupational exposure normally occurs duri ng the production an d use of isocyanates-- particularly during the mixing and foaming processes in the polyurethane foam industry. Exposures to airborne isocyanates may also occur from the melting or bu rning of polyurethane foams during fire fighting. 

### Current Exposure Limits Occupational exposure standards for isocyana tes are based on respiratory irritation and sensitization and carcinogenesis. Only the expo sure standards for TDI and MDI are outlined here. 

### OSHA The current Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) for TDI is 0.02 part per million part s of air (0.02 ppm), or 0.14 milligram per cubic meter of air (0.14 mg/m3) as a ceiling limi t [29 CFR* 1910.1000]. Wh en updating its air contaminants standard in 1989, OSHA decr eased this limit to 0.005 ppm (0.036 m g

/m3) as an 8-hour time-weighted average (TWA) and 0.02 ppm (0.14 mg/m3) as a short-term exposure limit. However, th is standard was rescinded by court order in 1992. The OSHA PEL for MDI is 0.02 ppm (0.2 mg/m3) as a ceiling limit.

*Code of Federal Regulation s. See CFR in references. 

### NIOSH In two separate criteria docume nts, NIOSH has recommended that TDI exposure be limited to 0.005 ppm (0.036 mg/m3) as a TWA for up to a 10-hour workday during a 40-hour workweek, with a ceiling concentration of 0.02 ppm (0 .14 mg/m3) for any 10-minute period [NIOSH 1973, 1978]. This NIOSH recomme nded exposure limit (REL) wa s intended to prevent acute and chronic irritation and sensitization of wo rkers but not to preven t responses in workers who are already sensitized. Available data do not indicate a concentr ation at which TDI vapor fails to produce adverse reacti ons in sensitized persons. NIOSH further recognized the carcinogenic potential of TDI and its isomers and recommended that exposures be re duced to the lowest feasible concentrations [NIOSH 1989].
The NIOSH REL for MDI is 0.005 ppm (0.05 mg/m3) as a TWA and 0.02 pp m (0.2 m g

/m3) as a ceiling limit. 

### A CGIH The American Conference of Go vernmental Industrial Hygienists (ACGIH) threshold limit

v

alue (TLV) for TDI is 0.005 ppm (0.036 mg/m3) as an 8- hour TWA and 0.02 ppm (0.14 mg/m3) as a short-term exposu re limit. The ACGIH TLV for MD I is 0.005 ppm (0.05 mg/m3) as a TWA [ACGIH 1995]. 

### Health Effects of Isoyanates Irritation TDI and other isocyanates are po werful irritants to the mucous membranes of the eyes and Page 2 of 13 CDC - NIOSH Publications and Products - NIO SH Alert: Preventing Asthma and Death f

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tracts [Swensson et al. 1955; U pj ohn Com p an y

1970]. Direct skin contact with TDI can also cause marked inflammation [Fisher 1967]. Respiratory irritation may progress to a chemical bronchitis with severe bronchospasm [Williamson 1965]. 

### Sensitization and Asthma Isocyanates can also sensitize workers, making th em subject to severe as thma attacks if they are exposed again--even at concentrations be low the NIOSH REL [NIOSH 1973, 1978]. Death from severe asthma in sens itized subjects has been re ported [Fabbri et al. 1988]. 

### Hypersensitivity Pneumonitis Sporadic cases of hypersensiti vity pneumonitis (HP) have also been reported in workers exposed to isocyanates [Charles et al. 1976; Fi nk and Schlueter 1978; Selden et al. 1989]. Individuals with acute HP ty pically develop symptoms 4 to 6 hours after exposure. Symptoms are often flu-like, with fever, musc le aches, and headaches. Symptoms may also include a dry cough, chest tightn ess, and difficult br eathing. Individuals with chronic HP often experience progressively more difficult breathing, fatigue, and weight loss [Parker et al. 1992]. 

### Cancer Data from recent studies of animals show that cancer is associated with exposure to commercial-grade TDI (an 80:20 mixture of 2,4- and 2,6-TDI) . The responses of both rats and mice treated with TDI meet the OSHA criteria for classifying a subs tance as a potential occupational carcinogen [29 CFR 1990.112]. NIOSH therefore recommends that occupational exposure to TDI and its isomer s be minimized [NIOSH 1989]. The carcinogenic effects of TDI [Loeser 1983 ; NTP 1986] were also investigated by the International Agency for Resear ch on Cancer (IARC) and th e World Health Organization (WHO) [IARC 1986; WHO 1987]. IARC concluded th at data were sufficien t to show that TDI causes cancer in animals. WH O concluded that TDI should be treated as a potential human carcinogen. 

### Case Reports The following case repo rts highlight examples of isocyanat e-induced asthma, other respiratory disease, and death. Case No. 1--Spray Pa inting (One Death)
A

37-year-old male, self -employed car painter was admitted to the ho spital with asthma symptoms [Fabbri et al. 1988]. These symptoms had first deve loped 5 years earlier and were thought to be related to his occupation. He had been work ing in the same environment for more than 20 years. The car painter was diagnosed wi th occupational asthma induce d by isocyanates and advised to change his job or avoid the use of p ol y urethane p aints. He nevertheless continued to work as a car painter and used medica tions such as bronchodilator s, cromolyn, and steroids to treat his asthma. Six years later, he was wearing a mask and sp raying a car with 2-co mponent polyurethane paint when he develo ped severe, prolonged asthma. De spite medication , he remained symptomatic--especially at night. He returned to work, sprayed the poly urethane paint again, and developed severe asthma requiring emergency treatment. He died in the ambulance Page 3 of 13 CDC - NIOSH Publications and Products - NIO SH Alert: Preventing Asthma and Death f

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1/3/2012 htt p ://www.cdc. g ov/niosh/docs/96-111 /enroute to the hos p ital. The manufacturer re p orted that the p aint contained small amounts o f TDI, and a chemical analysis confirmed th e presence of TDI mixed with solvents. Case No. 2--Highway Spill Two police officers developed asthma-like illness after a sing le exposure to TDI in the immediate vicinity of a tank ca r that had overturned on the high way [Luo et al. 1990]. After b riefl y directin g traffic at the accident sc ene, both officers received medical care for severe symptoms, including burning eyes , throat irritation, cough, ch est tightness, and difficult b reathin g . Treatment included steroids and a bronchodilator. Both police officers de veloped a chronic bronchospastic diso rder after their relatively brief exposure to high concentratio ns of TDI. Though considerabl e improvement has occurred in b oth cases, symptoms have pers isted for more than 7 years. Case No. 3--Spray Painting Occupational asthma was report ed in three workers in the pa int shops of a large assembly plant [Seguin et al. 1987]. When coworkers were also examined, six additional workers showed symptoms of occu pational asthma. Of the nine affected workers (mal es aged 23 to 59), six had si gnificantly reduce d lung function after an inhalation test using the paint containing isocyanates. The duration of exposure to isocyanates in the paint shops ranged from 3 to 5 years. The authors of this study re ported a 12% prevalence rate for occupational asthma. Case No. 4--Isocyanate Foam Operation (One Death)
A

maintenance worker became ill after repair ing an MDI foaming syst em at a plant that manufactured artificial plants with polyurethane foam bases [N IOSH 1994a]. The worker later suffered recurrent bouts of respiratory illn ess (diagnosed as is ocyanate- induced HP).
A fter showin g further res p irator y

s

y

m p

toms associated with isocya nate exposure, the worker quit his job but continued to experience coughing and progressive loss of lung function. His illness was eventually complicate d by productive cough, weakne ss, sweats, muscle aches, and shortness of breath. Ultimately, he died.
Worksite evaluations fo und detectable air concentrations of MDI and inadequate ventilation systems in the foaming areas. Va pors and aerosols we re observed rising into the faces of employees working with th e foam. Skin contact with the curing foam was also noted during the survey. Case No. 5--Wood Prod ucts Manufacturing Ten workers at an engineered wood products plant developed occupational asthma from exposure to MDI [NIOSH 1993]. The workers were employed 1 to 8 months at the plant before their diagnosis of occupational asthma. None of the 10 workers reported preexisting asthma. Respiratory symptoms included ch est tightness, wheezi ng, and coughing at night. Six workers reported a relationship between s y

m p

toms and work: the y

either re p orted im p roved s y

m p

toms while away from work or increased symptoms on their first day back at work. Eight workers showed declines in lung functio n over the workweek or over th eir period of employment, or they showed increased lung function after tr eatment with a bronchodilator. Eight workers Page 4 of 13 CDC - NIOSH Publications and Products - NIO SH Alert: Preventing Asthma and Death f

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when tested (methacholine challen g e).
A ll 10 workers re p orted res p irator y

s

y

m p

toms when they were in areas where MDI was used. The physician who examined the 10 workers re commended that they be removed from areas with any potential exposure to MDI. Case No. 6--Coal Mining Coal miners at a longwall mine complained of illness after exposure to MDI-based polyurethane rock glues [NIOSH 1994b]. These miners had sprayed glues onto rock strata. They were supplied with air-pu rifying respirators (organic vapor cartridges) and chemicalresistant gloves that were no t routinely worn. The exposed miners reported respiratory difficulties, asthma, shortness of breath, dizziness, headache, sore throat, fatigue, and contact dermatitis. Company medical records contained ni ne reports of health problems attributed to rock glue exposure. The inappropriate glue-spraying procedure used at this mine was eliminated by the Mine Safety and Health Admi nistration (MSHA). The manufacturer 's instructions specify that the glues are only to be injected for roof support and that workers are to wear supplied-air respirators--not air-purifying respirators. Air-purifying respirator s are not recommended b ecause rock glues are eye irritants and have po or warning properties, and because cartridges for these respirators have no end- of-service indica tors for MDI. Case No. 7--Isocy anate Roofing Foam Isocyanate exposure has also occurred at nonindus trial worksites such as public schools. The management of a large metropol itan school district contacted NIOSH for assistance after a university study documented as thma in 13 of approximately 85 staff members from a middle school [NIOSH 1994c]. The report further suggested that as ma ny as 34 staff members might b e asthmatic. NIOSH investigators determined that large quan tities of polyurethane foams and isocyanate coating materials had recently been applie d to the school roof on several occasions. School staff members reported odors during roofing application, suggesting possible exposures to roofing materials that included isocyana tes. Later air sampling during a test pour of the roofing materials at another location indicated the release of isoc y

anates durin g roofin g

and a p otential for exposure. 

### Conclusion The cases described here reveal the potentially serious nature of respiratory disease after exposures to isocyanates. The following recommend ations are intended to reduce the potential for exposed workers to develo p adverse health effects. Be cause NIOSH regards TDI as a potential occupational carcinog en, appropriate engineering controls† and work practices‡ should be used to reduce worker exposures to the lowe st feasible concentration.

†Engineering controls are hazard controls designed into equipment and workplaces. ‡Work practices are procedures followed by employers and workers to cont rol hazards. 

### Recommendations Product Substitution Page 5 of 13 CDC - NIOSH Publications and Products - NIO SH Alert: Preventing Asthma and Death f

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ers should substitute a less hazardous material for isoc y

anates. 

### Closed Systems and Ventilation Engineering controls such as cl osed systems and ventilation should be the p rinci p al method for minimizing isocyanate exposure in the workpl ace. Exhaust ventilatio n systems should be designed to capture and contain vapors and particulates. Vent ilation equipment should be checked for adequate performa nce at least every 3 months. 

### Worker Isolation A reas containing isocyanat es should be restrict ed to essential workers. If feasible, these workers should avoid direct contact with th ese chemicals by usin g automated equipment operated from a control booth or room with separate ventilation. 

### Protective Clothing and Equipment When there is potential for isoc yanate exposure, workers should be provided with and required to use appropriate personal protective clothing and equipment such as coveralls, footwear, chemical-resistant gloves and goggles, full faceshields, and su itable respiratory equipment. 

### Respiratory Protection The use of respirators is the least preferred method of controlling worker exposures. Respirators should not be used as the prim ary control for routine operations, but NIOSH recognizes that they may be us ed during situations such as implementation of engineering controls, some short-duration maintenance pr ocedures, and emergencies. Only the most protective respirators should be used for situa tions involving exposure s to isocyanates that have poor warning properties, ar e potent sensitizers, or may be carcinogenic. These respirators include any self-contained brea thing apparatus with a full facepiece operated in a pressuredemand or other positive-pressur e mode, and any supplied-air re spirator with a full facepiece operated in a pressure-demand or other posi tive-pressure mode in combination with an auxiliary self-contained breathin g apparatus operated in a pressure-demand or other positivepressure mode.
A n y

res p irator y p rotection p ro g

ram must, at a minimum, meet the requirements of the OSHA respiratory protection standard [29 CFR 1910.1 34]. Respirators must be certified by NIOSH and MSHA according to 30 CFR or by NIOSH (effective July 19, 1995) according to 42 CFR 84. A

com p lete res p irator y

protection program should includ e (1) regular training and medical evaluation of personnel, (2) fit testing, (3) periodic environmental mo nitoring, (4) periodic maintenance, inspection, and cleaning of equipm ent, (5) proper storage of equipment, and (6) written standard operating procedures governin g the selection and use of respirators. The program should be evaluated regularly. The following publ ications contain additional information about selection, fit testing, use, st orage, and cleaning of respiratory equipment: NIOSH Guide to Industrial Respir atory Protection [NIOSH 1987a] NIOSH Respiratory Decision Logic [NIOSH 1987b] 

### Worker and Employer Education Worker education is vital to a good occupational safety and he alth program. OSHA requires that workers be informed ab out materials that may contain or be contaminated with isocyanates, and the nature of the potential hazard [29 CF R 1910.1200]. Employers must transmit this information throug h container labeling, material sa fety data sheets (MSDS), and Page 6 of 13 CDC - NIOSH Publications and Products - NIO SH Alert: Preventing Asthma and Death f

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. 

### Exposure Monitoring Each employer who manufactures, transports, packages, stores, or uses isocyanates or products containing isocyanates should determine whether the potential exists for worker exposure. 

### Decontamination and Waste Disposal Procedures for decontamination, waste disposal , and transport should be established for isocyanate-contaminated materials or equipment. 

### Medical Monitoring A

medical monitorin g p ro g

ram should be established for the early detection and prevention of the acute and chronic effects of exposure to isocyanates. The worker's physician should be given information about the advers e health effects of exposure to isocyanates and the worker's potential for exposure. 

### Surveillance and Disease Reporting NIOSH encourages surveillance of occupational asthma by State heal th departments. To enhance the uniformity of reporting, NIOSH re commends reporting guidelines and an asthma surveillance case definition (see Appendix B). These guidelines and the case definition are recommended for public health surveillance of work-related asthma re ported by physicians and other healthcare providers. As of 1996, four State health departments--California, Massachusetts, Michigan, and Ne w Jersey--are actively engage d in occupational asthma surveillance activities. 

### A cknowledgments The principal contributors to th is Alert are Karl Musgrave; Ch ris Piacitelli; Gregory Kullman; Steve Berardinelli, Jr.; Al Dieffenbach; and John Parker. Please direct comments, questions, or requests for additional information to the following:
Director Division of Respiratory Disease Studies National Institute for Occupa tional Safety and Health 1095 Willowdale Road Morgantown, WV 26505-2888 Telephone number: 1-304- 285-5750 or 1-800-35-NIOSH (1-800-356-4674). We greatly appreciate your assistance in protecting the lives of U.S. workers. Linda Rosenstock, M.D., M.P.H. Director, National Institute for Occupational Safety and Health Centers for Disease Control and Prevention 

### References A CGIH [1995]. Threshold limit values for chem ical substances and physical agents and b iolo g

ical ex p osure indices 1995-1996. Cincinnati, OH : American Conference of Governmental Industrial Hygienists.
A

TS (American Thoracic Societ y

) [1987]. Standards for the diagno sis and care of patients with Page 7 of 13 CDC - NIOSH Publications and Products - NIO SH Alert: Preventing Asthma and Death f

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1/3/2012 htt p ://www.cdc. g ov/niosh/docs/96-111 /chronic obstructive p ulmonar y

disease (COPD) and asthma. Am Rev Res p ir Dis 136:225-244. CDC (Centers for Disease Control) [1990]. Occ upational disease survei llance: occupational asthma. MMWR 39(7):119-123. CFR. Code of Federal Regula tions. Washington, DC: U.S. Government Printin g Office, Office of the Federal Register. Chan-Yeung M, Lam S [1986]. Occupational asthma. Am Rev Respir Dis 133:686-703. Charles J, Bernstein A, Jone s B, Jones DJ, Edwards JH, Seal RME, et al. [1976]. Hypersensitivity pneumonitis after exposu re to isocyanates. Thorax 31:127-136. Dunn and Bradstreet [1983]. Dunn's Market In dex File. New York, NY : Dunn and Bradstreet Corporation. Fabbri LM, Danieli D, Crescioli S, Bevilacqua S, Me li S, Saetta M, et al. [1988]. Fatal asthma in a subject sensitized to toluene diisocyan ate. Am Rev Respir Di s 137: 1494-1498. Fink JN, Schlueter DP [1978]. Bathtub refinisher's lung: an unusual response to toluene diisocyanate. Am Rev Respir Dis 118: 955-999. Fisher AA [1967]. Contact dermatitis. Philad elphia, PA: Lea and Fe biger, pp. 134-135. IARC [1986]. IARC monogr aphs on the eval uation of the carcinogenic risk of chemicals to humans: some chemicals used in plastics and el astomers. Vol. 39. Lyon , France: World Health Organization, International Agency fo r Research on Cancer, pp. 287-323. Loeser E [1983]. Long-term toxicity and ca rcinogenicity studies with 2,4/2,6-toluene diisocyanate (80/20) in rats an d mice. Toxicol Lett 15:71-81. Luo J-C J, Nelsen KG, Fischbein A [1990]. Pe rsistent airway dysfun ction syndrome after exposure to toluene diisocyanat e. Br J Ind Med 47:239-241. NIOSH [1973]. Criteria for a recommended st andard: occupational exposure to toluene diisocyanate. Cincinnati, OH: U. S. Department of Health, Educ ation, and Welfare, Public Health Service, Center for Disease Control, National Institute for Occupational Safety and Health, DHEW (NIOSH) Publ ication No. HSM 73-11022. NIOSH [1978]. Criteria for a recommended standa rd: occupational exposure to diisocyanates. Cincinnati, OH: U.S. Department of Health, Educ ation, and Welfare, Public Health Service, Center for Disease Control, National Institute for Occupational Safe ty and Health, DHEW (NIOSH) Publication No. 78-215. NIOSH [1983]. National Occupational Exposure Survey (NOES), 1981-1983: estimated total and female employees, actual observation and trade-named exposure to toluene diisocyanate and methyl benzene diamine. Cincinnati, OH: U.S. De p artment of Health and Human Services, Public Health Service, Centers for Disease Contro l, National Institute fo r Occupational Safety and Health, Division of Survei llance, Hazard Evaluations and Field Studies, Surveillance Branch. Unpublished database. NIOSH [1987a]. NIOSH guide to industrial re spiratory protection. Cincinnati, OH: U.S. Department of Health and Human Services, Public Health Servic e, Centers for Disease Control, National Institute for Occupation al Safety and Health, DHHS (N IOSH) Publication No. 87-116. Page 8 of 13 CDC - NIOSH Publications and Products - NIO SH Alert: Preventing Asthma and Death f

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1/3/2012 htt p ://www.cdc. g ov/niosh/docs/96-111 /NIOSH [1987b]. NIOSH res p irator decision lo g

ic. Cincinnati, OH: U.S. De p artment of Health and Human Services, Public Health Service, Centers for Disease Co ntrol, National Institute for Occupational Safety and Health, D HHS (NIOSH) Publication No. 87-108. NIOSH [1989]. Current Intelligence Bulle tin 53: toluene diis ocyanate (TDI) and toluenediamine (TDA); evidence of carcino g

enicit y

. Cincinnati, OH: U.S. De p artment of Health and Human Services, Public Health Service, Cent ers for Disease Control, National Institute for Occupational Safety and Health, D HHS (NIOSH) Publication No. 90-101. NIOSH [1993]. Hazard evaluation and technical assistance re port: Trus Joist MacMillian, Deerwood, MN. Morgantown, WV: U.S. Department of Health and Human Serv ices, Public Health Service, Centers for Disease Contro l and Prevention, Nati onal Institute for Occupational Safety and Health, NIOSH Re port No. HETA 93-0436, Interim Report. NIOSH [1994a]. Hazard evalua tion and technical assistance report: Distinctive Designs International, Onc., Russellville , AL. Cincinnati, OH: U.S. Depa rtment of Health and Human Services, Public Health Service, Centers for Di sease Control and Prevention, National Institute for Occupational Safety and Health, NIOSH Report No. HETA 91-0386-2427. NIOSH [1994b]. Hazard evaluation and technical assistance re port: Jim Walter Resources, Inc., Brookwood, AL. Morgantown, WV: U.S. De partment of Health and Human Services, Public Health Service, Centers for Disease Co ntrol and Prevention, Na tional Institute for Occupational Safety and Health, NIOSH Report No. HETA 94-0027. NIOSH [1994c]. Hazard evaluati on and technical assistance re port: J.L. Long Middle School, Dallas, TX. Morgantown, WV: U.S. Department of Health and Hu man Services, Public Health Service, Centers for Disease Control and Preventi on, National Institute fo r Occupational Safety and Health, NIOSH Report No. HETA 94-0265. NTP [1986]. NTP technical report on the toxicolo gy and carcinogenesis studies of commercial grade 2,4(80%)- and 2,6(20%)-toluene diisocyan ate (CAS No. 26471-62-5 ) in F344/N rats and B6C3F1 mice (gavage studies). Research Triang le Park, NC: U.S. Department of Health and Human Services, Public Health Service, Nation al Institutes of Health , National Toxicology Program, NTP TR 251, NIH Publication No. 86-2507. Parker JE, Petsonk EL, Weber SL [1992]. Hypers ensitivity pneumonitis and organic dust toxic syndrome. Immunol and Allergy Clin of North America 12(2):279-290. Salvaggio JE, Taylor G, Weil l H [1986]. Occupational asthma and rhinitis. In: Merchant JA, ed. Occupational respiratory diseases. Cincinnati , OH: U.S. Department of Health and Human Services, Public Health Service, Centers fo r Disease Control, National Institute for Occupational Safety and Health, D HHS (NIOSH) Public ation No. 86-102. Seguin P, Allard A, Cartier A, Malo J-L [1987]. Prevalence of occupational as thma in spray painters exposed to seve ral types of isocyanates, including polymethylene polyphenylisocyanate. J Occ Med 29 (4):340-344. Selden AI, Belin L, Wass U [1 989]. Isocyanate exposure and hy persensitivity pneumonitis-- report of a probable case and prevalence of specific immunoglobulin G antibodies among exposed individuals. Scand J Wo rk Environ Health 15:234-237. Swensson A, Holmquist CE, Lundgren KD [1955]. Injury to the respiratory tract by isocyanates used in making lacquers. Br J Ind Med 12:50-53. Page 9 of 13 CDC - NIOSH Publications and Products - NIO SH Alert: Preventing Asthma and Death f

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1/3/2012 htt p ://www.cdc. g ov/niosh/docs/96-111 /U pj ohn Com p an y

[1970]. Urethanes: en g

ineerin g , medical control and toxicolo g

ic considerations. Kalamazoo, MI: Upjohn Company, Technical Bulletin No. 105. WHO [1987]. Environmental health criteria no. 75: toluene diis ocyanate. Geneva, Switzerland: World Health Organization, International Programme on Chemical Safety (IPCS). Williamson KS [1965]. Studies of diisocyanate workers (2). Trans Assoc Ind Med Off 15:29-35. Woods G [1987]. The ICI polyurethanes b ook. Netherlands: ICI Polyurethanes. 

### A ppendix A Diisocyanate synonyms TDI

MDI

HDI z 2,4-Diisocyanato-1- methylbenzene

z 2,4-Diisocyanatotoluene

z 2,4-TDI

z 2,4-Tolylene diisocyanate

z 4-Methyl-phenylene diisocyanate

z Di-iso-cyanatoluene

z Isocyanic acid, 4-methyl -m-phenylene ester

z Isocyanic acid, methylphenylene ester

z m-tolylene di isocyanate

z Toluene-2,4-diisocyanate

z Toluene diisoc y

anate

z 1,1-Methylenebis(4-isocyanatobenzene)

z 4,4'-Diisocyanatodiphenylmethane

z 4,4'-Diphenylmetha ne diisocyanate

z 4,4'-Methylenebis(phenyl isocyanate)

z 4,4'-Methylenediphen yl diisocyanate

z Bis(1,4-isocyanatophenyl)methane

z Bis(4-isocyanatophenyl)methane

z Diphenylmethane 4,4'-diisocyanate

z Diphenylmethane diisocyanate

z Methylenebis(4-isocyanatobenzene)

z Methylenebis(4-pheny lene isocyanate)

z Methylene bisphenyl isocyanate

z Methylene-di-p-pheny lene isocyanate

z Meth y

lene di (p hen y

lene isoc y

anate )

z 1,6-Diisocyanatohexane

z 1,6-Hexamethylen e diisocyanate

z 1,6-Hexanediol diisocyanate

z Hexamethylene-1,6-diisocyanate

z Hexameth y

lene diisoc y

anate Page 10 of 13 CDC - NIOSH Publications and Products - N IOSH Alert: Preventing Asthma and Deat

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### References Lewis RJ Sr. [1993] Hazardous chemicals desk reference, 3rd ed. New York, NY: Van Nostrand Reinhold Publishers. NIOSH [1995] Registry of toxic effects of chemical substances. Cincinnati, OH: U.S. Department of Health and Huma n Services, Public Health Serv ice, Centers for Disease and Control and Prevention, National Institute for Occupational Safety and Health. Sax NI, Lewis RJ Sr. [1987] Ha wley's Condensed Chemical Dict ionary, 11th ed. New York, NY: V

an Nostrand Reinhold Publishers. 

### A ppendix B Surveillance Guidelines for State Heal th Departments: Oc cupational Asthma 

### Reporting Guidelines State health departments should encourage providers to report all suspected or diagnosed cases of occupational asthma. Thes e should include persons with:

State health departments should collect appropriate clinical, epidemiologic, and workplace information on reported cases to set pr iorities for workplace investigations. 

### Surveillance Case Definition

*Asthma is a clinical syndrome characte rized by increased re sponsiveness of the tracheobronchial tree to a variety of stimuli [ATS 1987]. Symptoms of as thma include episodic wheezing, chest tightness, and dyspnea, or recurrent attacks of "bronchitis" with cough, sputum production, and rhinit is [Chan-Yeung and Lam 1986 ]. The primary physiologic manifestation of airways hyper-re sponsiveness is variable or re versible airflow obstruction, z HMDI (4,4' dicyclohexyl methane diisocyanate)

z Isoc y

anic acid

, hexameth y

lene ester

z A physician diagnosis of asthma AND

z A n association between s y

m p

toms o f asthma and work.

z A physician diagnosis of asthma*

z An association between symptoms of asthma and work† and any one of the following: 1. Workplace exposure to an agent or process previously associated with occupational asthma§ OR 2. Significant work-related ch anges in FEV1 or PEFR 3. Significant work-related changes in airways responsive ness as measured by nonspecific inhalation challenge¶ 4. Positive response to in halation provocation testin g with an agent to which patient is exposed at wo rk. Inhalation provocation testing with workplace substances is potentially danger ous and should be performed by experienced personnel in a hospital se tting where resuscit ation facilities are available and where frequent observ ations can be made over sufficient time to monitor for dela y

ed reactions. Page 11 of 13 CDC - NIOSH Publications and Products - N IOSH Alert: Preventing Asthma and Deat

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1/3/2012 htt p ://www.cdc. g ov/niosh/docs/96-111 /Centers for Disease Control and Prevention 1600 Clifton Rd. Atlanta, GA 30333, USA 800-CDC-INFO (800-232-4636) TTY: (888) 232-6348, New Hours of Operation 8am-8pm ET/Monday-Friday w

hich ma y

be demonstrated b y

si g nificant chan g es in the forced ex p irator y

volume in 1 second (FEV1) or peak expirato ry flow rate (PEFR). Airflow chan ges can occur spontaneously, with treatment, with a precipitating exposure, or wi th diagnostic maneuver s such as nonspecific inhalation challenge. †Patterns of association can vary. The following examples are patterns that may suggest an occupational etiology: sy mptoms of as thma develo p

after a worker starts a new j ob or after new materials are introduced on a job (a substantia l period of time may elapse between initial exposure and development of symptoms); symp toms develop within minutes of specific activities or exposures at wo rk; delayed symptoms occur severa l hours after exposure, during the evenings of workdays; sy mptoms occur less frequently or not at all on da y

s awa y

from work and on vacations; symptoms o ccur more frequently on retur ning to work. Work-related changes in medication requirements may ha ve similar patterns, also suggesting an occupational etiology. §Many agents and processes have been associat ed with occupational asthma [Chan-Yeung and Lam 1986, Salvaggio et al. 1986], and others continue to be recognized. ¶Changes in nonspecific br onchial hyperactivity can be measured b y

serial inhalation challen g e testing with methacholine or hi stamine. Increased bronchial reac tivity (manifeste d by reaction to lower concentrati ons or methacholine or histamine) following exposure and decreased b ronchial reactivity after a period away fr om work are evidence of work-relatedness. Reprinted from CDC [1990], p. 121. Employers should take the foll owing steps to protect workers from diisocyanate exposure:

Workers should take the following steps to pr otect themselves from diisocyanate exposure: z Make workers aware of the serious health effects that may result from diisocyanate exposures.

z Make workers aware of any materials that may contain or be contaminated with diisocyanates.

z When feasible, substitute a less hazardous materi al for diisocyanates.

z If substitution is not poss ible, use engineering controls such as closed systems and ventilation to minimize exposures.

z Provide a pp ro p riate res p irator y p rotection to workers ex p osed to diisoc y

anates.

z Be aware that the highest diisocyanate con centrations may occur inside containment structures.

z Use appropriate respiratory protection when working with diisocyanates.

z Wash hands and face before eating, drinking, or smokin g outside the work area.

z Shower and change into clean clot hes before leavin g the worksite.

z Participate in medical monitoring and examination programs , air monitoring p ro g

rams , or trainin g p ro g

rams , offered b y y our em p lo y

er.
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