Pulmonary effects of short-term exposure to low levels of toluene diisocyanate in asymptomatic subjects

Isocyanates may be involved in the development of chronic obstructive airwa y disease among exposed workers. A short-term exposure to toluene diisocyan ate (TDT) at concentrations near the permissible levels was investigated to examine whether there was an association with changes in pulmonary functio n tests and in potential markers of airway injury and inflammation in bronc hial lavage (BL) and bronchoalveolar lavage (BAL). Seventeen subjects without respiratory symptoms (eight smokers and nine non smokers) were exposed once to ambient air and once to TDI (5 parts per bill ion (ppb) for 6 h followed by 20 ppb for 20 min) in a randomized, single-bl ind sequence. Pulmonary function tests were repeatedly assessed during expo sure and BAL was performed 1 h after each exposure, Biochemical studies on lavage fluids included albumin, immunoglobulins, antiproteases (alpha(2)-ma croglobulin and alpha(1)-proteinase inhibitor), potential indicators of epi thelial cell function (secretory component and Clara cell protein), and cyt okines (tumour necrosis factor-alpha interleukin (IL)-4, IL-5, IL-6, and IL -8). Exposure to TDI caused a modest decrease in specific airway conductance (sG aw) (p = 0.053) and in maximal expiratory flow at 25% of forced vital capac ity (MEF25%) (p = 0.015) when compared with ambient air. Exposure to TDI re sulted in a slight increase in BAL albumin level (TDI: 26.4 +/- 12.5 versus air: 21.8 +/- 8.6 mu g.mL(-1), p = 0.044) and in BL alpha(2)-macroglobulin concentration (TDI: 0.07 +/- 0.061 versus air: 0.05 +/- 0.04 mu g.mL(-1), p = 0.021). This study suggests that exposure to low toluene disocyanate concentrations is associated with minimal but detectable changes in airway calibre and in epithelial barrier permeability. The pulmonary effects of long-term exposu re to low levels of isocyanates require further investigation.