ACETYLCHOLINESTERASE INHIBITION MEASUREMENTS FOR THE EVALUATION OF DECONTAMINANT EFFICACY FOLLOWING PERCUTANEOUS ORGANOPHOSPHORUS COMPOUND EXPOSURE

A rapid and sensitive in vivo method for the evaluation of skin decont aminant efficacy following percutaneous exposure to organophosphonates (OPs) was developed using erythrocyte acetylcholinesterase (AChE; EC 3.1.1.7) inhibition in the rabbit as an end point. The level of AChE i nhibition was evaluated for use as a more humane means of assessing sk in decontaminant efficacy than lethality-based methods. Groups of anes thetized animals were exposed percutaneously to either of two highly t oxic OPs [thickened soman (TGD) or VX], and 2 min later were treated w ith a known effective skin decontaminant or were untreated (negative c ontrol). Blood samples were drawn and assayed for AChE activity 5 min before TGD or VX exposure and at 30, 60, and 120 min after exposure. P ercent AChE inhibition relative to preexposure levels was calculated a t each postexposure time for each animal in control and treatment grou ps. Efficacy data based on percent AChE inhibition were compared with results from previous efficacy studies performed with the same deconta minants using 24-h lethality rate as the end point for evaluation. A h igh correlation between the findings for the two end points demonstrat ed that AChE inhibition can replace lethality as an end point in the r outine evaluation of candidate skin decontaminants against OP compound s. Efficacy data based on the AChE end point were compared with result s from previous efficacy studies performed with the same decontaminant s using 24-h lethality rate as the end point for evaluation.