Nerve agents, blood cholinesterase effects

Although there is the potential for nerve agents to have direct toxic effects on the nervous system, there is no evidence that such effects occur in humans at doses lower than those causing cholinesterase inhibition. For the purpose of evaluating potential health effects, inhibition of blood cholinesterase is generally considered the most useful biological endpoint. 

In addition to being found in the nervous system, acetylcholinesterase also occurs in the blood where it is bound to the surface of red blood cells (termed RBC-ChE or RBC-AChE). RBC-AChE activity, as well as the activity of a second type of cholinesterase found in blood plasma (butyrylchoUnesterase, or plasma cholinesterase) have been used to monitor exposure to organophosphate compounds (pesticides and nerve agents). Both RBC-AChE and plasma-ChE activity have been used as bioindicators of potential toxic effects. There is some evidence that RBC-AChE is as sensitive as brain ChE to the effects of nerve agents. Grob and Harvey (1958) reported that the in vitro concentrations producing 50% depression of brain-ChE and RBC-AChE activity were the same in the case of GA (1.5 x 10 mol/L),... 

Fusek, J., Bajgar, J., Herink, J., Skopec, F. (1996b). New group of nerve agents cardiovascular and respiratory effects and blood cholinesterase activity during acute intoxication with 2-dimethylaminoethyl-(dimethylamido)-fluorophosphate in rats. Int. Rev. Arm. Forces Med. Serv. 69 291-4. 

GA, a unitary chemical munition, inhibits AChE, the enzyme responsible for the breakdown of the neurotransmitter ACh. When inhaled, its toxicity is half that of sarin. It depresses plasma and RBC-AChE activities significantly in the blood. At 20-25% of red blood cell AChE baseline, the effect of the nerve agent becomes noticeable. There is no evidence of systemic toxicity other than the cholinesterase activity (Parker et al, 1990 Munro et al, 1994). GA has not been shown to produce OPIDN except at extremely high doses. The cardiac effect of GA conforms to OP-caused arrhythmias and AV block. 

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