Inhibition of acetylcholinesterase by diisocyanates and its spontaneous reactivation

Abstract

The inhibition of human acetylcholinesterase (AchE) by 4,4'-diphenylmethane diisocyanate (MDI) is determined and compared with the previously described inhibition of this enzyme by two other industrially used diisocyanates: toluene diisocyanate (TDI) and hexamethylene diisocyanate (HDI). The inhibition potency of these three diisocyanates is found to be in the oder HDI greater than TDI greater than MDI. The spontaneous reactivation of inhibited AchE is reanalysed with the help of a computer program designed to fit the reactivation data to the exponential rate equation Vt = Vinf (1 - e-Kobs X (t - to) ). The enzyme inhibited by HDI and MDI undergoes very slow and limited spontaneous reactivation. The rate of delivery of diisocyanates into the respiratory tract of an exposed worker may be faster than the rate of spontaneous reactivation of the inhibited enzyme. These results are discussed in connection with the obstructive lung disease observed in approximately 5% of the workers employed in the isocyanate industry.