TOXICOKINETICS OF SOMAN IN CEREBROSPINAL-FLUID AND BLOOD OF ANESTHETIZED PIGS

The toxicokinetics of the four stereoisomers of the nerve agent C(+/-) P(+/-)-soman was analysed in cerebrospinal fluid (CSF) and blood in an aesthetized, spontaneously breathing pigs during a 90-min period after injection of soman. The pigs were challenged with different intraveno us (i.v.) doses of C(+/-)P(+/-)-soman corresponding to 0.75-3.0 LD50 ( 4.5, 9.0 and 18 mu g/kg in a bolus injection and 0.45 mu g/kg per min as a slow infusion). Artificial ventilatory assistance was given if, a fter soman intoxication, the respiratory rate decreased below 19 breat hs/min. Blood samples were taken from a femoral artery and CSF samples from an intrathecal catheter. The concentrations of the soman isomers were determined by gas chromatography coupled with high resolution ma ss spectrometry. All four isomers of soman were detected in both blood and CSF samples. The relatively non-toxic C(+/-)P(+) isomers disappea red from the blood stream and CSF within the first minute, whereas the levels of the highly toxic C(+/-)P(-) isomers could be followed for l onger, depending on the dose. Concurrently with the soman analyses in blood and CSF, cholinesterase (ChE) activity and cardiopulmonary param eters were measured. C(+/-)P(-) isomers showed approx. 100% bioavailab ility in CSF when C(+/-)P(+/-)-soman was given i.v. as a bolus injecti on. In contrast, C(+/-)P(-) isomers displayed only 30% bioavailability in CSF after slow i.v. infusion of soman. The ChE activity in blood d ecreased below 20% of baseline in all groups of pigs irrespective of t he soman dose. The effect of soman intoxication on the respiratory rat e, however, seems to be dose-dependent and the reason for ventilatory failure and death. Artificial ventilation resulted in survival of the pigs for the time-period studied.