Acetylcholinesterase Inhibition Measurements for the Evaluation of Decontaminant Efficacy Following Percutaneous Organophosphorus Compound Exposure

Abstract

A rapid and sensitive in vivo method for the evaluation of skin decontaminant 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 inhibition was evaluated for use as a more humane means of assessing skin decontaminant efficacy than lethality-based methods. Groups of anesthetized animals were exposed percutaneously to either of two highly toxic OPs [thickened soman (TGD) or VX], and 2 min later were treated with a known effective skin decontaminant or were untreated (negative control). 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. Percent AChE inhibition relative to preexposure levels was calculated at each postexposure time for each animal in control and treatment groups. Efficacy data based on percent AChE inhibition were compared with results from previous efficacy studies performed with the same decontaminants using 24-h lethality rate as the end point for evaluation. A high correlation between the findings for the two end points demonstrated that AChE inhibition can replace lethality as an end point in the routine evaluation of candidate skin decontaminants against OP compounds. Efficacy data based on the AChE end point were compared with results from previous efficacy studies performed with the same decontaminants using 24-h lethality rate as the end point for evaluation.

Key Words: :

• Organophosphonate
• Acetylcholinesterase
• Inhibition