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

Abstract

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.

Determination of threshold adverse effect doses of percutaneous VX exposure in African green monkeys

“…Furthermore, this dose produced persistent effects, including severe muscular dysfunction, and muscular paral- ysis has been reported previously from VX in guinea pigs (Bide et al, 2005). Subsequent histology revealed CNS pathology not unlike that seen following high dose exposure to the nerve agent soman (see Appendix A).…”

Skin Decontamination with Mineral Cationic Carrier Against Sarin Determined In Vivo

“…Organophosphate (OP) nerve agents (G-agents and VX) are related to the OP pesticides, but have a much higher mammalian acute toxicity, particularly through skin and inhalation route (1)(2)(3)(4).…”

“…Its acute effects are primarily due to unrestricted cholinergic activity at both muscarinic and nicotinic receptors (1,(3)(4)(5). The threat of skin contamination by nerve agents calls for effective primary decontamination preparation for naked skin (6).…”