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 causes 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 pathophysiologic mechanisms are involved. Immunoglobulin E (IgE)-mediated sensitization 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 crucial. We collected data on 1780 isocyanate workers who had been examined by our groups. Of them 1095 (including subjects from outpatient departments) 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 predictor of the results of inhalative isocyanate provocation tests in workers and in asthmatic controls. Isocyanate (toluene diisocyanate TDI) air concentrations of 10 ppb (0.07 mg/m³) and 20 ppb (0.14 mg/m³), respectively, did not cause significant bronchial obstruction in the majority of previously unexposed asthmatics with bronchial hyperreactivity. IgG-mediated allergic alveolitis, a rare disease among isocyanate workers, was found in approximately 1 % of the symptomatic subjects. Experimental studies exhibit dose-dependent toxic effects and give evidence for tachykinin-mediated bronchial hyperreactivity after exposure to isocyanates. The clinical role of genotoxic effects of isocyanates and their by-products demonstrated here in vitro and in vivo has yet to be clarified.Abbreviations ACH acetylcholine - BALF bronchoalveolar lavage fluid - CGRP calcitonin gene-related peptide - cpm counts per minute - DMSO dimethylsulfoxide - EAST enzyme allergo sorbent test - FEV ₁ forced expiratory volume in one second - HDI hexamethylene diisocyanate - HSA human serum albumin - IGV intrahoracic gas volume, measured by bodyplethysmography - IVC inspiratory vital capacity - LC ₅₀ lethal concentration for 50% of tested animals - MDI diphenylmethane diisocyanate - PD _50(100)/PC _50(100) dose/concentration causing a change of 50% (100%) of the parameter indicated - ppb (ppm) parts per billion (million) - RAST radio allergo sorbent test - Raw airway resistance, measured by bodyplethysmography - sRaw specific airway resistance, measured by bodyplethysmography - TDI toluene diisocyanate - TLV threshold limit value These studies were partly supported by the Ministry of Research and Technology, Federal Republic of Germany, grant 07 ALL 16