Effects of inhaled hexamethylene diisocyanate (HDI) on guinea pig cholinesterases

Hexamethylene diisocyanate, HDI, a starting material in the production of many polyurethane products, was found to inhibit stoichiometrically mammalian and electric eel cholinesterases in an in vivo system (W. E. Brown, A. H. Green, M. H. Karol, and Y. Alarie , 1982, Toxicol . Appl. Pharmacol. 62, 45-52). The current study examined in vivo effects on guinea pig cholinesterases resulting from inhalation of HDI. Guinea pigs were exposed to atmospheres of 0.5, 1.8, or 4.0 ppm HDI (ceiling value = 0.02 ppm) for up to 6 hr. Blood samples were drawn prior to exposure and at specified times during exposure. No inhibition of serum cholinesterase was detected following exposure to 0.5 ppm HDI for 6 hr, to 1.8 ppm HDI for 2 hr, or to 4.0 ppm HDI for 3 hr. Similarly, no inhibition was detected when erythrocytes from each blood sample were assayed for acetylcholinesterase activity. Last, animals were sacrificed and cholinesterase activity determined in bronchial lavage fluid. Enzyme levels of HDI-exposed animals were not significantly different (P greater than 0.05) from those of control animals exposed to water vapor. In conclusion, although in vitro experiments had demonstrated potent anticholinesterase activity by HDI, in vivo inhalation exposure of guinea pigs to HDI at concentrations 25-200 times above the recommended (ACGIH) ceiling value did not produce measurable inhibition of cholinesterase activity.