An in vitro method for predicting sensitizing properties of inhaled chemicals.

A method for monitoring chemical reactivity in aqueous solutions, at neutral pH and 37 degrees C, was developed. The chemical was allowed to react with a lysine-containing peptide, and the reaction was monitored with high-performance liquid chromatography. Simple acids, bases, and solvents did not react with the peptide, whereas isocyanates, anhydrides, and chloramine-T, substances well known for their sensitizing and asthma inducing properties, did. Thus a positive test strongly suggested that the chemical had the potential to act as a hapten and cause sensitization when inhaled. Prepolymers of diphenylmethane diisocyanate were considerably more reactive than prepolymers of toluene diisocyanate or hexamethylene diisocyanate. Isocyanates blocked with caprolactam, butanone oxime, malonic acid diethylester, or isononyl phenol showed no reactivity. This result suggested a significantly reduced risk of respiratory reactions when such blocked isocyanates are handled at room temperature. One blocked isocyanate showed, however, considerable reactivity.