Brief exposure of air-filled guinea-pig isolated trachea to low levels of toluene diisocyanate (TDI) vapor in vitro increases reactivity to methacholine.
Huang J; Frazier DG; Millecchia LL; Fedan JS
Toxicology 1997 Dec; 124(2):83-93
The direct effects of toluene-diisocyanate (26471625) (TDI) on airway reactivity were examined in an isolated guinea-pig trachea model to test the hypothesis that TDI exerts nonimmune direct effects on the airways that do not involve inflammatory cells, but which can increase reactivity to methacholine. Four centimeter long tracheal segments removed from male English-short-hair-guinea-pigs were mounted in tissue baths and perfused with aerated mucosal modified Krebs-Henseleit (MKH) solution. The ends of the tracheas were connected through catheters to a differential pressure transducer. The tracheas were perfused with MKH solution containing 10(-8) to 10(-2) molar (M) methacholine to establish concentration response curves for methacholine induced contractility. The lumen of the tracheas was then emptied and perfused with air (control condition) or air containing 5, 20, or 70 parts per billion (ppb) TDI vapor for 30 minutes (min). The tracheas were then retested for reactivity to methacholine. Exposure to air alone did not significantly affect reactivity of the tracheal preparations to methacholine. Exposure to 5ppb TDI also did not affect trachea reactivity to methacholine. Exposure to 20 and 70ppb TDI significantly increased tracheal reactivity to methacholine, the effective concentrations inducing a 50% increase in contractility (EC50s) decreasing from 1.32x10(-5) and 1.41x10(-4)M before exposure to 0.56x10(-5) and 0.48(x10(-4)M after exposure, respectively. In tracheas denuded of their epithelium, 70ppb TDI did not increase reactivity to methacholine but caused a slight, nonsignificant inhibition of the response, the EC50 increasing from 0.15x10(-5) to 0.22x10(-5)M. Capsaicin pretreatment caused a four fold shift in the dose response curve to the left following exposure to 70ppb, the EC50 decreasing from 4.36x10(-4) to 1.09x10(-4)M. The authors conclude that brief exposure to low TDI vapor concentrations increases the reactivity of isolated guinea-pig tracheas to methacholine challenge. This effect may be involved in the development of airway hyperreactivity to TDI vapor.
NIOSH-Author; Isocyanates; Muscle-contraction; Pulmonary-system; In-vitro-studies; Physiological-response; Laboratory-animals; Dose-response; Respiratory-hypersensitivity
Pathology and Physiology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road Morgantown, WV 26505-2845 USA