Determination of parameters for development of a physiologically based model for the toxicokinetics of C(+)P(+)-soman. Final report
report
Toxicant-specific parameters needed for development of a physiologically based model for the toxicokinetics of C-P--soman in guinea pig were determined in blood, and in homogenates of brain, liver, kidney, lung, and a skeletal muscle gastrocnemius et soleus. Tissueblood partition coefficients for the diastereoisomers of C-P--soman were obtained from the partition coefficients determined for bloodair and tissue homogenateair by gas chromatographic analysis in the air phase. Elimination of C-P--soman by covalent binding was blocked by pretreatment with the very labile crotyl sarin 2-butenyl methylphosphonofluoridate. Enzymatic hydrolysis was stopped by lowering the pH. Relatively high concentrations of sites for covalent binding of C-P--14C-soman were found in liver and kidney homogenates, whereas these concentrations were low in the target organs, i.e., brain and muscle. Only a fraction of the available binding sites reacts rapidly with C-P- soman. Indications were obtained for contribution of C-P-soman to binding in liver and kidney homogenates. The half-life times of hydrolysis for C-P-- soman in plasma and in tissue homogenates were similar to the values obtained previously for CP--soman hydrolysis. Physiologically based modelling, Toxicokinetics, C-P--soman, C-P-soman, C-P--14C-soman, Toxicant-specific parameters, blood, tissue Homogenates, Partition coefficients, Covalent binding, Hydrolysis, Cardiac output, Tissue blood flows, Stereoselective, Gas chromatography, Microspheres.
Topics
ModelsDeterminationSoman / GD agentToxicokineticsGuinea pigsBloodTissues (biology)GC - Gas chromatographyIn vitro analysisReaction kineticsToxicityAirParametersSynthesis (chemistry)Targets coefficientsStrain (biology)LungMusclesLiverHydrolysisEliminationBloodChromatographic analysisKidneysSwineGuinea pigsBlood analysisHalf lifeIntoxicationMicrospheres
TNO Identifier
122498
Publisher
TNO
Place of publication
Rijswijk