Toxicokinetics of soman in cerebrospinal fluid and blood of anaesthetized pigs.

The toxicokinetics of the four stereoisomers of the nerve agent C(+/-)P(+/-)-soman was analysed in cerebrospinal fluid (CSF) and blood in anaesthetized, spontaneously breathing pigs during a 90-min period after injection of soman. The pigs were challenged with different intravenous (i.v.) doses of C(+/-)P(+/-)-soman corresponding to 0.75-3.0 LD50 (4.5, 9.0 and 18 microg/kg in a bolus injection and 0.45 microg/kg per min as a slow infusion). Artificial ventilatory assistance was given if, after soman intoxication, the respiratory rate decreased below 19 breaths/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 mass spectrometry. All four isomers of soman were detected in both blood and CSF samples. The relatively non-toxic C(+/-)P(+) isomers disappeared from the blood stream and CSF within the first minute, whereas the levels of the highly toxic C(+/-)P(-) isomers could be followed for longer, depending on the dose. Concurrently with the soman analyses in blood and CSF, cholinesterase (ChE) activity and cardiopulmonary parameters were measured. C(+/-)P(-) isomers showed approx. 100% bioavailability in CSF when C(+/-)P(+/-)-soman was given i.v. as a bolus injection. In contrast, C(+/-)P(-) isomers displayed only 30% bioavailability in CSF after slow i.v. infusion of soman. The ChE activity in blood decreased below 20% of baseline in all groups of pigs irrespective of the soman dose. The effect of soman intoxication on the respiratory rate, 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.

In vivo distribution of 14C radiolabeled soman [3,3-dimethyl-2-butoxy)-methylphosphorylfluoride) in the central nervous system of the rat.

Radiolabeled 14C soman, a potent anticholinesterase, was administered to rats at a dose of 0.75 LD50 (17.3 micrograms/kg, i.m.). Prior to being quick frozen, the animals were held for 2 min, 32 min or 48 h after dosing. Analysis of autoradiographs taken from cryostat sections through the central nervous system (CNS) showed that at 2 and 32 min radiolabel was primarily distributed in the blood, the choroid plexus and the cerebrospinal fluid (CSF), with several brain nuclei showing small increases in labeling density. At 48 h there was marked accumulation of radiolabel in the caudate and accumbens nuclei compared to all other brain areas. The above results showed little similarity between cholinesterase localization and distribution of radiolabel.