Toxicokinetics of the Four Stereoisomers of Soman in the Rat, Guinea Pig, and Marmoset

摘要

Insight into the toxicokinetics of C + or - P + or - soman is crucial for research on treatment of intoxication with this agent. Therefore, stabilization and gas chromatographic resolution procedures of the four soman stereoisomers were developed, and used for toxicokinetic investigations in rats. With thermodesorption/cold trap injection and NP detection, a minimum concentration 0f 8.3 pM of each highly toxic C + or - P(-)-soman isomer in blood can be measured. The toxicokinetics of C + or - P-soman was studied at iv doses of 495 micro g/kg eliminated from rat blood within 5 min, the toxic C + or - P(-)-isomers can be followed for several hours. Blood curves for the C + or - P(-)-isomers are described with a three-exponential function, interpreted with a toxicokinetic model in which the C + or - P(-)-isomers distribute from the central to a shallow and a deep peripheral compartment. The terminal half-life of C(-)P(-)-soman decreases from 40 to 16 min when the dose is reduced from 6 to 3 LD50. Treatment with the soman stimulant pinacolyl dimethylphosphinate (PDP) before administration of 6 LD50 of C(+ or -)P(-)-soman lowers the half-life to 17 min. Similar results were found for C(+)P(-)-soman. Hence, the persistence of C(+ or -)P(+ or -)-soman decreases rapidly at lower dose and is effectively antagonized by pretreatment with PDP. Keywords: Soman; Soman stereoisomers; Gas chromatographic resolution; Stabilization, rat blood; Toxicokinetics; Rats; Phosphatases.