Hydrolysis and binding of a toxic stereoisomer of soman in plasma and tissue homogenates from rat, guinea pig and marmoset, and in human plasma.
The fallen concentration of one of the two isomers of soman (1,2,2-trimethylpropyl methylphosphonofluoridate), i.e., C(+)P(-)-soman, was investigated in plasma and in homogenates of brain, lung, liver, kidney, diaphragm, skeletal muscle and mucosa of small intestines from rat, guinea pig and marmoset, and in human plasma (pH 7.5, 37 degrees). The decrease of the isomer concentration was followed by gas chromatographic determination of the residual concentration and proceeded in two phases due to a very rapid saturation of covalent binding sites for the isomer followed by catalysed hydrolysis. Estimates for the concentrations of covalent binding sites were obtained, which were relatively high in liver and kidney. Time periods for the hydrolysis of the isomer from a concentration of 40 ng/mL to 20 ng/mL were evaluated from the second reaction phase. It is concluded that the spontaneous and enzyme-catalyzed hydrolytic activities found for degradation of C(+)P(-)-soman in organs participating in central elimination are sufficiently high to account for the terminal half-life times of the isomer found in our toxicokinetic studies for the blood concentration after intoxication with 2-6 LD50 C(+/-)P(+/-)-soman. The hydrolytic activities are lower in the target organs for toxic action of soman, e.g., diaphragm and brain, especially for guinea pigs and marmosets.
de Jong
L P
LP
Prins Maurits Laboratory TNO, Rijswijk, The Netherlands.
van Dijk
C
C
Berhitoe
D
D
Benschop
H P
HP
D000818:Animals; D001665:Binding Sites; D002144:Callithrix; D006168:Guinea Pigs; D006207:Half-Life; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051381:Rats; D012999:Soman / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D013237:Stereoisomerism
D012999:Soman