RESPIRATORY AND OTHER HAZARDS OF ISOCYANATES

Isocyanates are increasingly being used for manufacturing polyurethane foam, elastomers, adhesives, paints, coatings, insecticides, and many other products. At present, they are regarded as one of the main caus es of occupational asthma. The large number of workers who are exposed to these chemicals have a concentration-dependent risk of developing chronic airway disorders, especially bronchial asthma. Different patho physiologic mechanisms are involved. Immunoglobulin E (IgE)-mediated s ensitization and irritative effects have been clearly demonstrated in both exposed subjects and animals. Presumably, neural inflammation due to neuropeptide release of capsaicin-sensitive afferent nerves is cru cial. We collected data on 1780 isocyanate workers who had been examin ed by our groups. Of them 1095 (including subjects from outpatient dep artments) had work-related symptoms, predominantly of the respiratory tract. Specific IgE antibodies were found in 14% of the 1095 subjects. The methacholine challenge test was shown to be an inadequate predict or of the results of inhalative isocyanate provocation tests in worker s and in asthmatic controls. Isocyanate (toluene diisocyanate TDI) air concentrations of 10 ppb (0.07 mg/m(3)) and 20 ppb (0.14 mg/m(3)), re spectively, did not cause significant bronchial obstruction in the maj ority of previously unexposed asthmatics with bronchial hyperreactivit y. IgG-mediated allergic alveolitis, a rare disease among isocyanate w orkers, was found in approximately 1% of the symptomatic subjects. Exp erimental studies exhibit dose-dependent toxic effects and give eviden ce for tachykinin-mediated bronchial hyperreactivity after exposure to isocyanates. The clinical role of genotoxic effects of isocyanates an d their by-products demonstrated here in vitro and in vivo has yet to be clarified.