Immediate post-dosing paralysis following severe soman and VX toxicosis in guinea pigs.

There have been numerous studies of the central nervous system (CNS) involvement in organophosphate (OP) poisoning showing status epilepticus and/or 'electrographic seizures'. Brain damage has been demonstrated as 'neuronal necrosis' primarily in the cortex, thalamus and hippocampus. To the authors' knowledge there have been no reports of partial/total paralysis following close upon OP exposure although delayed paralysis has been reported. This report summarizes the immediate, OP induced paralytic events recorded in guinea pigs during development of the Canadian reactive skin decontaminant lotion (RSDL). As part of the development work, supra-lethal cutaneous doses of OP were applied to large numbers of guinea pigs followed by decontamination with the RSDL or predecessor lotions and solvents. Soman (pinacolyl methylphosphonofluoridate; GD) challenges were applied to 1277 animals and S-(2-diisopropyl-aminoethyl) methylphosphorothiolate (VX) challenges to 108. The classic sequence of clinical signs--ptyalism, tremors, fasciculations, convulsions, apnea and flaccid paralysis before death--was seen in the 658 animals that died and in many of the survivors. Eighty-four of 688 survivors of GD and 4 of 39 survivors of VX showed random paralysis of various distal regions following recovery from an insult which produced convulsions and/or flaccid paralysis. Because the experiments were designed to assess the decontamination procedures, there were no apparent relationships between the amounts of OP applied and the sequellae recorded. The observations of paralysis were also incidental to the prime focus of the experiments. Because of this, only ten animals paralysed following GD exposure were examined for histological effects. The pathologist diagnosed 'encephalomalacia' and 'focal necrotic lesions' in the cerebral cortex and 'focal necrotic lesions' in one spinal cord. Of the 84 guinea pigs paralysed after GD challenge, one was not decontaminated and the decontaminants used on the remainder were sufficiently varied that there appeared to be no relationship between the type of decontaminant and the resulting paralysis.

Inhalation toxicity in mice exposed to sarin (GB) for 20-720 min.

Most of the historical data for the toxicity of sarin (GB) was collected for exposure times of <10 min in attempts to establish the utility of and defence against this agent in offensive military use. However, information concerning the toxicity of GB (and other nerve agents) from longer exposures of 1-12 h is critical for all personnel who must work in or close to low-level concentrations of chemical for extended periods and for all personnel, dressed in Individual Protective Equipment, who need to know when, and if, it is safe to take off these cumbersome garments.The data presented for the toxicity of GB to mice for whole-body exposures of 20 min to 12 h are intended to form part of an ongoing, multi-species effort aimed at establishing toxicity estimates for humans for these longer exposure times: LCT50 values of 430, 540, 900, 1210 and 2210 mg.min m(-3) or LC50 values of 21.5, 9.0, 5.0, 3.4 and 3.1 mg m(-3) were obtained for mice for 20-, 60-, 180-, 360- and 720-min exposures to GB, respectively. The data for longer exposures do not follow Haber's rule (LCT50=CT). The 20- and 60-min data fit the 'toxic load model' involving CnT that was established previously from historical data for 0.17-30 min GB exposures to mice. The LCT(50) and LC50 values for 3, 6 and 12 h are progressively higher (toxicity lower) than predicted by either Haber's rule or the toxic load model.