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

Medical Aspects of Chemical WarfareSarin (GB)OSoman (GD)OCyclosarin (GF)OH 3C P OCH(CH 3 ) 2H 3C P OCHC(CH 3 ) 3H 3CPOFF CH 3FOOOH 3 C P OCH(CH 3 ) 2H 3 C P OCHC(CH 3 ) 3H 3 CPOOHOH CH 3OHIMPAPMPACMPAOH 3 CPOHOHMPAFig. 22-2. Hydrolysis pathway of sarin (GB), soman (GD), and cyclosarin (GF). Hydrolysis pathway of nerve agents proceedsthrough the alkyl methylphosphonic acids IMPA, PMPA, and CMPA to MPA. Analysis of the alkyl methylphosphonic acidsallows identification of the parent agent, while assay of MPA is nonspecific.CMPA: cyclohexyl methylphosphonic acidIMPA: isopropyl methylphosphonic acidMPA: methylphosphonic acidPMPA: pinacolyl methylphosphonic acidAlthough the report on the Tokyo 23 incident did notdirectly indicate urinary concentrations, total sarinexposure was estimated. The exposure estimates in acomatose individual was 0.13 to 0.25 mg/person and0.016 to 0.032 mg/person in a less severely exposedcasualty. 23 These numbers are approximately 10-foldless than those reported by Nakajima et al 24 for a severelyintoxicated patient. Consistent with rapid elimination,the maximum urinary concentration of thesecompounds was reported to have occurred in 12 hoursof exposure. Using LC-MS-MS methods, Noort et al 25and Polhuijs et al 28 detected IMPA in serum samplesfrom both the Tokyo and Matsumoto incidents. Thisassay involves fairly sophisticated instrumentation,but allows for a simplified sample processing procedure.Reported serum concentrations ranged from 2to 127 ng/mL and 2 to 135 ng/mL in the Tokyo andMatsumoto incidents, respectively. 25,28 Samples wereobtained 1.5 hours after the incident. In some cases asecond sample was obtained 2 to 2.5 hours after theincident; in those samples, the authors report significantlylower IMPA concentrations consistent with therapid elimination of these compounds. The sarin dosein both incidences was calculated to be 0.2 to 15 mg/person. 25 These reported values for sarin exposure arein the range of those reported by Nakajima et al 24 andare approximately 10-fold greater than those reportedby Minami et al. 23Alkyl MPAs provide a convenient marker fordetermining exposure to nerve agents. Numerous696