Urethane Chemistry and Applications - American Chemical Society

7 Health Considerations for Isocyanates RICHARD HENDERSON

Downloaded by FUDAN UNIV on December 7, 2016 | http://pubs.acs.org Publication Date: November 30, 1981 | doi: 10.1021/bk-1981-0172.ch007

Health Sciences and Toxicologic Research, Olin Corporation, New Haven, CT 06511

Isocyanates were discovered by Wurtz in 1849 and their uses in polyurethane began in 1937. The isocyanates and abbrevia tions that will be used in this presention are shown in Table I. Abbreviations

of

Isocyanates

Table I Toluene d i i s o c y a n a t e Diphenyl methane d i i s o c y a n a t e Hexamethylene d i i s o c y a n a t e Napthalene d i i s o c y a n a t e Isophorene d i i s o c y a n a t e Dicyclohexylethane 4 , 4 - d i i s o c y a n a t e

TDI MDI HDI, HMDI NDI IPDI — -

There were 650,000 metric tons of TDI and 450,000 metric tons of MDI produced in 1978, not including production in coun tries having central economic planning (Table II). These two isocyanates constitute the largest volume; the other isocyanates were produced in much smaller quantities. Production o f Isocyanates

- 1978

( 1000 metric tons) Table II TDI MDI

650 450

Polyurethanes are the major products in which isocyanates are used. The percent of total polyuretahnes in different uses is given in Table III.

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© 1981 American Chemical Society

Edwards et al.; Urethane Chemistry and Applications ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

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Uses o f Polyurethanes Table

III


Use F u r n i t u r e and mattresses Automotive Building construction Refrigeration Shoes Textiles Coatings Other

Percent 40 20 11 6 4 6 5 8

It is estimated that there are more than 200,000 workers en gaged in the production and uses of isocyanates. The isocyanates are used for their reactivity as crosslinking agents. Considering their reactivity, it is a tribute to the industry that research has enabled the establishment of safe work practices and safe levels of exposure. Even though uses of isocyanates in polyurethanes started in 1937, it was not until 1951 that the first occupational health problems associated with isocyanates appeared in the medical liter ature. There have been many more cases of effects of excessive ex posure to isocyanates reported in the 1950's than in the 1970's. Greater care is now taken to explain potential adverse effects from excessive exposure and to adequately control exposures. Fuchs et. al. (1) published observations on an asthmatic syndrome in seven out of nine persons exposed to TDI. In 1953, Reinl (2) reported cases of respiratory problems in 17 workers exposed to TDI and/or other isocyanates; 13 of these cases were severe and death of one was attributed to occupational exposures. There were many other reports (3-10) published in the 1950's of similar cases of occupational health problems, primarily res piratory, in workers exposed to isocyanates in manufacture of polyurethane foams and polyisocyanate-based lacquers and glues. One additional fatality was reported (6). Elkins (11) in 1962 reviewed the published occupational health problems attributed to TDI and identified 222 cases in the literature through 1960. The concentrations of isocyanates involved in most of the cases and the possible exposures to other respiratory irritants were not usually reliably determined. It is possible that the concentrations of isocyanates to which workers may have been exposed occasionally in the 1950's and early 1960's may have been above presently accepted allowable limits. Examples of concentrations to which workers were reportedly exposed are shown in Table IV.


7.

HENDERSON

Health Considerations for Isocyanates

Reported Concentrations of Table Type o f Operation


Spray TDI d i s t i l l a t i o n TDI production *Depending on job

89

Isocyanates

IV

TDI Concentration (ug/m3)

Reference Gandevia (12) Williamson (13) Weill e t a]_. (15)

6400 140 14-40* category

In e v a l u a t i n g any data on concentrations to which persons may have been exposed, i t must be remembered that a n a l y t i c a l methods r e q u i r e time f o r sampling; and the longer the sampling time, the greater the p o s s i b i l i t y of short term peak concentrations being averaged out and missed. Such short term peak concentrations may be o f great s i g n i f i c a n c e i n terms of r e s p i r a t o r y i r r i t a n t e f f e c t s . Bunge et^ al_. (T4J found a mean concentration o f 0.0197 ppm o f d i f f e r e n t isocyanates (TDI, MDI, and NDI) i n the work environment of a polyurethane p l a s t i c s l a b o r a t o r y . The concentrations of the d i f f e r e n t isocyanates are not s p e c i f i e d i n t h e i r paper. The allowable exposure l i m i t s (TLV) f o r TDI i n major i n d u s t r i a l c o u n t r i e s was 0.14 mg/m3 a t the time of the s t u d i e s r e f e r r e d to above. The f a c t that these concentrations have been measured does not mean that occupational exposures o c c u r ; persons may use r e s p i r a t o r y p r o t e c t i o n equipped to prevent exposure. A l l persons who have excessive occupational exposure to isocyanates may experience primary i r r i t a n t e f f e c t s i n the r e s p i r a t o r y t r a c t depending on the extent of excessive exposure. B r i e f a c c i d e n t a l exposures to concentrations o f isocyanates t e n f o l d or more above the TLV may cause short term r e s p i r a t o r y i r r i t a t i o n with recovery 24-48 hours f o l l o w i n g c e s s a t i o n o f exposure. Continuing repeated workday exposures s e v e r a l - f o l d higher than the TLV can cause c h r o n i c r e s p i r a t o r y i r r i t a t i o n . A l l i n d i v i d u a l s w i l l not s u f f e r the same degree of r e s p i r a t o r y i r r i t a t i o n from excessive exposures due to i n d i v i d u a l biochemical and p h y s i o l o g i c a l d i f f e r e n c e s . Studies have shown that on the order o f f i v e percent o f persons who have had an occupational exposure to TDI develop a bronchial asthmatic type o f response to subsequent exposures that are below c o n c e n t r a t i o n s causing any detectable primary i r r i t a t i o n . Persons who have developed a b r o n c h i a l asthmatic r e a c t i v i t y to one isocyanate may show bronchial asthmatic r e a c t i v i t y to other isocyanates according to studies reported by O ' B r i e n et_ a]_. (16). The mechanism f o r the development o f the bronchial asthmatic r e a c t i v i t y from exposure to isocyanates has not been c l e a r l y d e f i n e d , although there has been and continues to be c o n s i d e r a b l e research on t h i s e f f e c t . Bruchner {Y7) Scheel 0 8 ) , Nava et 9



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a]_. (19), Butcher e t a K (20), T a y l o r ( 2 Ί ) , Porter et a l . (22), Karol et^ a l . (23), are among the research workers who have i n v e s t i gated the mechanism of bronchial asthmatic response. Only i n cases that have developed an extreme s e n s i t i v i t y as demonstrated by bronchial asthmatic response to a few minutes exposure to c o n c e n t r a t i o n s of isocyanate on the order of 25 ug/m3 has there been a demonstration of a c i r c u l a t i n g antibody that w i l l r e a c t with a human serum albumin-toluene monoisocyanate a n t i g e n . Research i s continuing to define the mechanism o r mechanisms o f the bronchial asthmatic response that some persons develop from exposures to isocyanates. Of p a r t i c u l a r i n t e r e s t i s one case reported by Butcher (24) that appears to suggest that the bronchial asthmatic r e a c t i v i t y to TDI may be r e v e r s i b l e . O r i g i n a l challenge exposure of 25 ug/m3 of TDI f o r 15 minutes to confirm c l i n i c a l l y observed r e a c t i v i t y r e s u l t e d i n s i g n i f i c a n t d e c l i n e i n lung f u n c t i o n . A f t e r the per son had been removed from occupational exposure for s i x months, there was no d e c l i n e i n lung f u n c t i o n following a c o n t r o l l e d c h a l lenge exposure. The primary r e s p i r a t o r y i r r i t a n c y and bronchial asthmatic r e a c t i v i t y discussed above are g e n e r a l l y accepted as occupational health problems that can occur from excessive exposure to i s o c y a n ates e i t h e r as vapor or as i n h a l a b l e p a r t i c l e s in workplace a i r . If s p i l l e d or splashed on the s k i n or i n the eyes, the isocyanates can cause i r r i t a t i o n . Nava e t a]_. (19j have reported a case of eczematous d e r m a t i t i s from TDI. Karol e t a]_. (23) reported f i n d i n g t o l y l - s p e c i f i c a n t i bodies i n serum o f two persons who d i s p l a y e d skin r e a c t i o n s when exposed to TDI. Rothe (25) described 12 cases of contact eczema in workers exposed to MDI or p a r t i a l l y polymerized MDI and four s i m i l a r cases i n workers exposed to IPDI. As with many other chemicals, there have been some reports (26-29) of p s y c h o l o g i c a l problems i n workers having p o t e n t i a l ex posure to isocyanates and other chemicals i n polyurethane produc tion operations. It i s not p o s s i b l e to determine a c a u s e - e f f e c t r e l a t i o n s h i p to a p a r t i c u l a r chemical exposure nor a l e v e l of ex posure from the published r e p o r t s . These reports on p s y c h o l o g i c a l problems are mentioned here f o r completeness i n reviewing the l i t e r a t u r e on occupational health aspects i n the uses of isocyanates and not because great importance i s placed on t h i s aspect. The present Occupational Safety and Health A d m i n i s t r a t i o n l e g a l l i m i t f o r exposure to TDI and MDI i s 0.02 ppm (0.14 mg/m3 f o r TDI and 0.2 mg/m3 f o r MDI). These are c e i l i n g v a l u e s . In order to operate w i t h i n t h i s c e i l i n g l i m i t , the time-weighted average concentration w i l l be below 0.02 ppm. Thus, operations that are meeting the present l e g a l l i m i t probably would have l i t t l e or no d i f f i c u l t y meeting the 0.005 ppm 10 hour time-weighted average l i m i t proposed by the National I n s t i t u t e f o r Occupational Safety and H e a l t h .



7.

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91

The f i v e year prospective study o f employees i n a TDI p l a n t conducted by W e i l l et a K (15) i n c l u d e d preplacement and p e r i o d i c r e s p i r a t o r y f u n c t i o n and immunologic evaluations as well as measurements o f exposures using continuous personnel monitors. The c o s t o f t h i s study was over $750,000. A two-year i n h a l a t i o n c a r c i n o g e n i c i t y study o f TDI using r a t s and mice i s c o s t i n g over $400,000. Individual producers o f TDI have done experimental animal t o x i c o l o g y and employee health e v a l u a t i o n s . In summary, the major p o t e n t i a l occupational health problem from excessive exposure to isocyanates i s primary r e s p i r a t o r y irritation. A f r a c t i o n o f workers exposed may develop a bronchial asthmatic r e a c t i o n to isocyanates and there appears to be some cross r e a c t i v i t y . The most extensive study, i n c l u d i n g preexposure b a s e l i n e r e s p i r a t o r y f u n c t i o n measurements, has provided data i n d i c a t i n g that keeping exposures to TDI below 0.02 ppm (0.14 ug/ m3) appears to prevent decrement i n r e s p i r a t o r y f u n c t i o n . There are l e s s data on exposures and r e s p i r a t o r y f u n c t i o n o f workers using other i s o c y a n a t e s . Isocyanates such as MDI are l e s s v o l a t i l e than TDI. There i s l e s s p o t e n t i a l f o r exposure to vapors of the lower v o l a t i l i t y i s o c y a n a t e s , but exposures to vapor and to p a r t i c u l a t e s can occur and exposures to a l l isocyanates do need to be c o n t r o l l e d i n order to p r o t e c t workers.

Literature Cited 1. Fuchs, S.; Valade, P. Clinical and experimental study of several cases of intoxication by Desmodur Τ (toluene diisocyanate 1-2-4 and 1-2-6). Arch Mal Prof, 1951, 12, 191-96. 2. Reinl, W. Diseases in the manufacture of polyurethane based plastics. Zentralbl Arbeitsmed Arbeitsschutz, 1953, 3, 102-07. 3. Schur, E. Injury from Desmodur lacquers--irritating gas or allergy? Med Klin, 1959, 54, 168-70. 4. Reinl, W. Occupational asthma and similar illnesses and their insurance coverage. Zentralbl Arbeitsmed Arbeitsschutz, 1955, 5, 33-37. 5. Ganz, H.; Mager, E. Injuries to health by Molotpren foam material. Zentralbl Arbeitsmed Arbeitsschutz, 1954, 4, 42-44. 6. Schuermann, D. Injuries to health caused by modern varnishes and foam materials. Dtsch Med Wochenschr, 1955, 80, 1661-63. 7. Woodbury, J. W. Asthmatic syndrome following exposure to tolylene diisocyanate. Ind Med Surg, 1956, 25, 540-43. 8. Johnstone, R. T. Toluene 2,4-diisocyanate--Clinical features. Ind Med Surg, 1957, 26, 33-34. 9. Sands, F. W.; Boffardi, G.; James, Κ. E.; Lundy, W.; Walsh, W. S. Toluene diisocyanate--engineering and medical control of exposures in polyurethane foam manufacturing. Am Ind Hyg Assoc Q, 1957, 18, 331-34. 10. Walworth, H. T.; Virchow, W. E. Industrial hygiene experiences with toluene diisocyanate. Am Ind Hyg Assoc J , 1959, 20, 205-10. 11. Elkins, H. B.; McCarl, G. W.; Brugsch, H. G.; Fahy, J. P. Edwards et al.; Urethane Chemistry and Applications ACS Symposium Series; American Chemical Society: Washington, DC, 1981.


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Massachusetts experience with toluene diisocyanate. Am Ind Hyg Assoc J . 23:265-72, 1962. 12. Gandevia, G. Studies ov ventilatory capacity and histamine response during exposure to isocyanate vapour in polyurethane foam manufacture. Br J Ind Med 20:204-09, 1963. 13. Williamson, K. S. Studies of diisocyanate workers (1). Trans Assoc Ind Med Off 14:81-88, 1964. 14. Bunge, W., Ehrlicher, H., Kimmerle, G. Medical aspects of work with surface coating systems using the spraying technique. Ζ Arbeitsmed Arbeitsschutz Prophylaxe 4 (Special Ed.): 1-46, 1977. 15. Weill, Η., Salvaggio, J., Ziskind, Μ., Jones, R. Ν., Diem, J., Butcher, Β., Carr, J., Glindmeyer, H., Dharmarajan, V. Annual Report--Respiratory and Immunologic Evaluation of Isocyanate Exposure in a New Manufacturing Plant. Unpublished report submitted to NIOSH by Tulane University School of Medi cine, New Orleans, LA, April 1978, 27 pp. 16. Weill, Η., Diem, J. Ε., Dharmarajan, V., Glindmeyer, Η., Jones, R., Carr, J., O'Neil, C., Salvaggio, J. Final Report-Respiratory and Immunologic Evaluation of Isocyanate Exposure in a New Manufacturing Plant. Unpublished report submitted to NIOSH by Tulane University School of Medicine, New Orleans, LA. September, 1979., 52 pp. 17. O'Brien, I. Μ., Harries, M. G., Burge, P. S., Pepys, J., Diisocyanate induced asthma--reactions to TDI, MDI, HDI, and histamine. Clin All 1979, Vol. 9, pp. 1-6. 18. Bruckner, H. D., Avery, S. Β., Stetson, D. Μ., Dodson, V. Ν., Ronayne, J. J. CIinical and immunologic appraisal of workers exposed to isocyanates. Arch Environ Health 16:619-25, 1968. 19. Scheel, L. D., Killens, R., Josephson, A. Immunochemical aspects of toluene diisocyanate (TDI) toxicity. Am Ind Hyg Assoc J. 25:179-84, 1964. 20. Nava, C., Arbosti, G., Briatico-Vangosa, G., Cirla, Α. Μ., Marchisio, M., Zedda, S. Pathology produced by isocyanates-methods of immunological investigation. Ric Clin Lab 5:135-45, 1975. 21. Butcher, B. T., Savaggio, J. Ε., Weill, Η., Ziskind, M. M. Toluene diisocyanate (TDI) pulmonary disease--immunologic and inhalation challenge studies. J Allergy Clin Immunol 58:89-100, 1976. 22. Taylor, G. Immune responses to tolylene diisocyanate (TDI) exposure in man. Proc R Soc Med 63:379-80, 1970. 23. Porter, C. V., Higgins, R. L., Scheel, L. D. A retrospec tive study of physiologic and immunologic changes in workers exposed to toluene diisocyanate. Am Ind Hyg Assoc J 36:159-68, 1975. 24. Karol, M. H., Ioset, H. H., Alarie, Y. C. Tolyl-specific IgE antibodies in workers with hypersensitivity to toluene diiso cyanate. Am Ind Hyg Assoc J 39:454-58, 1978. Edwards et al.; Urethane Chemistry and Applications ACS Symposium Series; American Chemical Society: Washington, DC, 1981.


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25. Butcher, B. Six-Month Progress Report to International Isocyanate Institute: Study of TDI Asthma. June 30, 1979. 26. Rothe, A. Occupational skin diseases caused by polyure thane chemicals. Derufs-Dermatosen 24:7-24, 1976. 27. Mastromatteo, E. Recent occupational health experiences in Ontario. J Occup Med 7:502-11, 1965. 28. Le Quesne, P. M., Axford, A. T., McKerrow, C. B., Jones, A. P. Neurological complications after a single severe exposure to toluene diisocyanate. Br J Ind Med 33:73-78, 1976. 29. Axford, A. T., McKerrow, C. B. Jones, A. P., Le Quesne, P. M. Accidental exposure to isocyanate fumes in a group of firement. Br J Ind Med 3:65-71, 1976. 30. Filatova, V. S., Babochkina, M. S., Jurando, T. B. Prob lems of industrial hygiene and the state of health of workers in diisocyanate production plants. Gig Tr Prof Zabol 6:25-31, 1962. RECEIVED June

1, 1981.


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