Medical Aspects of Chemical Warfare (2008) - The Black Vault

Nerve Agentsactivity but only 15% to 20% of RBC-ChE activity.Symptoms correlated with depression of RBC-ChE,but not with depression of BuChE (see below). Inhumans, some pesticides, such as parathion, 39–41systox, 39 and malathion, 22 also preferentially inhibitthe plasma enzyme, while others, such as dimefox 41and mevinphos, 42 initially bind with the RBC enzyme.In animals, there appears to be a species differencebecause parathion preferentially inhibits RBC-ChE inrats and the plasma enzyme in dogs. 22The nerve agent VX preferentially inhibits RBC-ChE; in two studies, 43,44 a small amount caused a 70%or greater decrease in the activity of this enzyme,whereas the activity of BuChE was inhibited by nomore than 20%. Sarin also preferentially inhibits theRBC-ChE; 80% to 100% inhibition of RBC-ChE activitywas observed in two studies, 37,45 while BuChE wasinhibited by 30% to 50%. Therefore, estimation of theRBC-ChE activity provides a better indicator of acutenerve agent exposure than does estimation of theplasma enzyme activity.When the blood enzymes have been irreversiblyinhibited, recovery of ChE activity depends on productionof new plasma enzymes or production of newerythrocytes. Hence, complete recovery of BuChEactivity that has been totally inhibited by sarin willoccur in about 50 days, and recovery of the RBC-ChE, in 120 days (about 1% per day). 46 In humans,after inhibition by VX, the RBC-ChE activity seemsto recover spontaneously at the rate of about 0.5% to1% per hour for a few days, but complete recoverydepends on erythrocyte production. 43,44Time Course of InhibitionAfter very large amounts of nerve agent (multipleLD 50s [ie, multiples of the dose that is lethal to 50%of the exposed population]) are placed on the skin,signs and symptoms occur within minutes, and inhibitionof blood ChE activities occurs equally quickly.However, with smaller amounts of agent, the onsetis not so rapid. In studies in which small amounts ofVX were applied on the skin of humans, the onset ofsymptoms and the maximal inhibition of blood ChEactivity were found to occur many hours after applicationof the agent. In one study 44 in which equipotentamounts of VX were applied to the skin in differentregions, the time to maximal inhibition was 5 hoursfor the head and neck, 7 hours for the extremities, and10 hours for the torso. In a similar study, 47 the averagetime from placing VX on the skin to the onset ofnausea and vomiting and maximal drop of blood ChEactivity was 10.8 hours.In a third study, 48 VX was applied to the cheekor forearm at environmental temperatures rangingfrom 0°F to 124°F, and 3 hours later the subjects weredecontaminated and taken to a recovery area (about80°F). In all temperature groups, the RBC-ChE activitycontinued to decline after decontamination, and maximalinhibition occurred at 5.6 hours after exposureat 124°F, 8.5 hours after exposure at 68°F, 10.4 hoursafter exposure at 36°F, and 12.2 hours after exposureat 0°F. At the two lowest temperatures, the rates ofagent penetration and of decline in RBC-ChE activityincreased after the subjects were taken from the coldenvironment and decontaminated. These results suggestthat agent absorption through the skin is morerapid and complete at higher temperatures, and thateven after thorough decontamination, a considerableamount of agent remains in the skin.Inhalation of nerve agent vapor inhibits blood ChEactivity and produces signs and symptoms of exposuremore rapidly than does dermal contact. Althoughthere is no correlation between ChE activity and clinicaleffects after exposure to small amounts of vapor,both clinical effects and ChE inhibition occur withinminutes. In one study, 43 both the maximal inhibitionof RBC-ChE activity and the appearance of signs andsymptoms occurred about 1 hour after intravenous(IV) administration of small amounts of VX. Afteringestion of VX, the interval was 2 to 3 hours.Relation to Signs and SymptomsThe local signs and symptoms in the eye, nose, andairways caused by small amounts of vapor are dueto the direct effect of the vapor on the organ. Thereappears to be no correlation between the severity ofthese effects and the blood ChE activity. Early experimentaldata 49–51 indicating the lack of correlation weresupported by a retrospective analysis of 62 individualsseen at the Edgewood Arsenal Toxic Exposure Aid Stationbetween 1948 and 1972. Although all individualshad physical signs or definite symptoms (or both) ofnerve agent vapor exposure, there was no correlationbetween local effects from vapor exposure and RBC-ChE activity (Table 5-1). 52 More recently, clinical datafrom the Tokyo incident has shown that symptomsand signs can both be present with normal bloodChE levels. 53Minimal systemic effects, such as vomiting, occurin half the population when the RBC-ChE is inhibitedto 25% of its control activity. 43,44 In a study 44 in whichVX was placed on the skin, no vomiting occurred in30 subjects whose minimal RBC-ChE activities were40% of control or higher. Vomiting occurred in 9 (43%)of 21 subjects whose minimal RBC-ChE activities were30% to 39% of control, in 10 (71%) of 14 subjects whose165