Asthma isocyanates

In addition to the proteins discussed above, a large number of reactive chemicals used in industry can cause asthma and rhinitis. Hypersensitivity pneumonias have also been described. Isocyanates and acid anhydrides are industrial chemicals that cause occupational asthma. Acid anhydrides, such as phthalic anhydride, seem to cause mainly type I reactions, whereas the IgE-mediated mechanism explains only a part of the sensitizations to isocyanates. Several mechanisms have been suggested, but despite intensive research no models have been generally accepted. The situation is even more obscure for other sensitizing chemicals therefore, the term specific chemical hypersensitivity is often used for chemical allergies. This term should not be confused with multiple chemical sensitivity (MCS) syndrome, which is a controversial term referring to hypersusceptibility to very low levels of environmental chemicals. ... 

Respiratory sensitizers, e.g. isocyanates or formaldehyde, result, in mild cases, in a sense of tightness of the chest and occasionally a troublesome cough. Severe cases involve bronchial asthma. Refer to Table 4.6. With such sensitizers, complete cessation of contact is often followed by rapid recovery but no further exposure is generally permitted. 

Mapp, C. E. et al., Glutathione S-transferase GSTP1 is a susceptibility gene for occupational asthma induced by isocyanates, J. Allergy Clin. Immunol., 109, 867, 2002. 

Cartier, A., et al., Specific serum antibodies against isocyanates association with occupational asthma, J. Allergy. Clin. Immunol., 84, 507, 1989. 

It has been estimated that 200 to 300 agents have been identified as inducers of occupational asthma [4], The LMW agents can be broadly classified by chemical class such as isocyanates, anhydrides, metals, dyes, amines, drugs, acrylates and other compounds. The HM W agents can be broadly classified as animal protein, plant protein and microbial byproducts. Table 33.1 shows apartial listing of LMW and HMW sensitizers along with the workplace environments where these agents can be encountered. 

Bentley, A.M. et al., Activated T-lymphocytes and eosinophils in the bronchial mucosa in isocyanate-induced asthma, J. Allergy Clin Immunol., 89, 821, 1992. 

Meredith, S.K., Bugler, J., and Clark, R.L., Isocyanate exposure and occupational asthma a case-referent study, Occup. Environ. Med., 57, 830, 2000. 

Mapp, C.E. et al., Human leukocyte antigen associations in occupational asthma induced by isocyanates, Am. J. Respir. Crit Care Med., 156, S139, 1997. 

Test Guideline methods have so far only been developed for skin sensitization, while standard methods for sensitization via the respiratory and oral route have not yet been established. Therefore, the emphasis in this section is on skin sensitization. This does not mean that sensitization via the other routes is not important. Certain substances are known sensitizers via inhalation, e.g., the isocyanates are inducers of asthma in humans. 

Cockcroft DW, Mink JT Isocyanate-induced asthma in an automobile spray painter. J Can Med Assoc 121 602-604, 1979... 

Tanser AR, Bourke MP, Blandford AG Isocyanate asthma respiratory symptoms caused by diphenyl-methane-diisocyanate. Thorax 2 -. 

Burge P, O Brien I, Harries M Peak flow rate record in the diagnosis of occupational asthma due to isocyanates. Thorax 34 317, 1979... 

International Isocyanates Institute. 1987a. Isocyanate inhalation tests - diisocyanate induced asthma. EPA/OTS doc 86-870000661. 

Important commercial isocyanates include the diisocyanate monomers toluene diisocyanate (TDI), methylene diphenyl diisocyanate (MDI), hexamethylene diisocyanate (HDI), and MDI-, TDI-, and HDI-based isocyanates (e.g., prepolymers and polyisocyanates). World-wide production volume is estimated at over 12 billion lb. Isocyanates (diisocyanates, polyisocyanates, and prepolymers) all cause similar health effects, most commonly asthma [32]. Isocyanates are reported to be the leading attributable cause of work-related asthma [16]. Isocyanates are potent sensitizers that can trigger a severe and potentially fatal asthma attack in sensitized persons at very low isocyanate exposure levels [16]. Toluene diisocyanate is reasonably anticipated to be a human carcinogen by National Toxicology Program. 

Isocyanate-induced asthma and hypersensitivity pneumonitis in humans have been reviewed (Baur, 1995 Bernstein, 1996). A case of fatal asthma of a 4,4 -mcthylcncdiphcnyl diisocyanate-scnsitized subject has been described (Carino et al., 1997). Exposure to 4,4 -methylenediphcnyl diisocyanate is a frequent cause of occupational asthma (Liss et al., 1988 Vogelmcicr et al., 1991 Bernstein et al., 1993) but may also induce hypersensitivity pneumonitis (Malo Zeiss, 1982 Vandenplas et al., 1993) and inflammatory upper respiratory tract diseases (Liss et al., 1988 Littorin et al., 1994). Most patients with 4,4 -methylenediphcnyl diisocyanate-induced asthma have elevated levels of IgG-class antibodies towards 4,4 -methylenediphenyl diisocyanate-albumin conjugates in the plasma, while IgE-class antibodies are rare (Liss et al., 1988). 

Vogelmeier, C., Baur, X. Fruhmann, G. (1991) Isocyanate-induced asthma results of inhalation tests with TDI, MDI and methacholine. Int. Arch, occup. environ. Health. 63. 9-13... 

H. Norppa, A. Hirvonen, Role of NAT1 and NAT2 Polymorphisms in Individual Susceptibility to Isocyanate-Induced Asthma, First International Workshop on... 

All isocyanates are known to cause pulmonary toxicity. Isocyanates are the most common causes of occupational asthma and have led to the development of immediate or late asthma among workers. Isocyanates have caused bronchitis, rhinitis, conjunctivitis, chronic obstructive lung disease, contact sensitivity, dermatitis, allergic alveolitis, and immunologic hemorrhagic pneumonitis.29... 

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