RESPONSE TO ISOCYANATES - EFFECT OF CONCENTRATION, DURATION OF EXPOSURE, AND DOSE

There is no information on the relative role of dose, concentration, a nd duration of exposure in determining the magnitude of the bronchial response in subjects with isocyanate-induced asthma. Four subjects wit h asthma induced by toluene diisocyanate (TDI) were challenged using a recently described closed-circuit exposure chamber in which stable co ncentrations of TDI monomer can be generated. Each subject was challen ged using various concentrations and durations of exposure on separate days. They were all exposed on three to four occasions to the same do se that had been shown to cause a 20% fall in FEV1 at a concentration of 15 ppb (DR15 ppb) by varying the concentration (5, 10, 15, and 20 p pb) and durations (1 to 90 min), making sure that the total dose (conc entration x duration) remained constant. They were also exposed to low er total doses by modifying the concentration and the duration on the remaining visits. Exposing subjects to the same DR15 ppb by modifying the concentration or the duration resulted in falls in FEV1 greater-th an-or-equal-to 20%, except in one instance. Exposing subjects to doses lower than DR15 ppb, even at higher concentrations or for longer peri ods than in the challenges used for obtaining the DR15 ppb always caus ed falls in FEV1 < 20%. We conclude that the main determinant of bronc hial responsiveness to TDI is not concentration nor duration of exposu re per se but the product of both factors, that is, total dose.