Toluene diisocyanate-induced airway hyperresponsiveness to intravenous acetylcholine: a study on single and repeated exposure in guinea-pigs.

We examined the changes in airway responsiveness to increasing doses of intravenous acetylcholine (ACh), in groups of 10 anaesthetized and tracheotomized spontaneously breathing guinea-pigs, 20 h after inhalation exposure to toluene diisocyanate (TDI). TDI exposure consisted of a single 4-h exposure to 1.2 ppm, intermittent exposures to 1.078 and 0.126 ppm for 4 h daily for 2 consecutive days, and continuous exposures to 0.118 ppm for 48 h or to 0.045 and 0.023 ppm for 1 week. Airway resistance (Raw) of the corresponding control groups, which inhaled clean filtered air, was used as baseline, and was similar for air and TDI groups. All the patterns of exposure, except exposure to 0.126 ppm TDI for 4 h daily for 2 consecutive days, significantly reduced by 28-60% the dose of ACh calculated to cause a 200% increase in Raw (ED200). The results indicate that TDI-induced airway hyperresponsiveness to ACh in guinea-pigs can occur at a level of exposure as low as 0.023 ppm for 1 week, and is consistent with the hypothesis of a cumulative effect.