Nerve agents toxicokinetics

Elaboration of nerve agent toxicokinetics requires sophisticated analytical tools to detect and, if possible, to quantify the free toxicants as well as adducts with proteins and enzymes. Analysis of OP nerve agents has been performed by capillary electrophoresis (CE), biosensors, matrix-assisted laser desorption/ionization (MALDI) MS, desorption electrospray ionization MS (DESI MS), ion mobility time-of-flight MS (IM-TOF MS), nuclear magnetic resonance spectroscopy (NMR), LC-UV, gas chromatography (GC), and many more techniques (Hooijschuur et al, 2002 John et al, 2008). 

Mathematical Simulation for Prediction of Nerve Agent Toxicokinetics... 

Toxicokinetics of Chemical Warfare Agents Nerve Agents and Vesicants... 

This chapter provides readers with a comprehensive overview of the toxicokinetics of OP nerve agents and vesicants. 

Although toxicological characterization in terms of mean acute lethal doses for different species is available for all nerve agents, detailed and extensive toxicokinetic data are rare in the literature for most of them with the exception of soman and sarin (Benschop and de Jong, 2001). For VX and in particular GF only a very limited extent of data is obtainable (Reiter et al, 2007 Van der Schans et al, 2003). 

However, analysis becomes much more complex when stereoisomers are quantified separately (Figure 50.1). Enantiomers cause identical detector responses in NPD, FID, or MS. Therefore, chiral separation systems are required to overcome these detector limitations. Despite enormous progress in separation media and detector systems within the last two decades the number of reports on chiral analysis of nerve agents valuable for toxicokinetic studies is... 

Van der Schans, M.J., Lander, B.J., Van der Wiel, H., Langenberg, J.P., Benschop, H.P. (2003). Toxicokinetics of nerve agent ( )-VX in anesthetized and atropinized hairless guinea pigs and marmosets after intravenous and percutaneous administration. Toxicol. Appl. Pharmacol. 191 48-62. 

Benschop, H.P. (1975). Absolute configuration of chiral organo-phosphorus anticholinesterases.Biocliem. Physiol. 5 348. Benschop, H.P., De Jong, L.P.A. (1988). Nerve agent stereoisomers analysis, isolation and toxicology. Tcc. Chem. Res. 21 368. Benschop, H.P., De Jong, L.P.A. (1991). Toxicokinetics of soman species variation and stereospecificity in elimination pathways. Neurosci. Biobehavi. Rev. 15 73. 

Van der Schans, M.J., Benschop, H.P., Whalley, C.E. (2008b). Toxicokinetics of nerve agents. In Chemical Warfare Agents, Chemistry, Pharmacology, and Therapeutics, 2nd edtition (J.A. Romano, B.J. Lukey, H. Salem, eds). CRC Press, Boca Raton, FL. 

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