Bide R W, Schofield L, Risk D J
Defence R&D Canada-Suffield, Box 4000, Medicine Hat, Alberta, Canada T1A 8K6.
J Appl Toxicol. 2005 Sep-Oct;25(5):410-7. doi: 10.1002/jat.1086.
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.
已有大量关于有机磷(OP)中毒累及中枢神经系统(CNS)的研究,显示出癫痫持续状态和/或“脑电图癫痫发作”。脑损伤主要表现为皮质、丘脑和海马体的“神经元坏死”。据作者所知,虽有关于OP暴露后迟发性麻痹的报道,但尚无OP暴露后立即出现部分/完全麻痹的报告。本报告总结了在加拿大反应性皮肤去污洗剂(RSDL)研发过程中,豚鼠身上记录到的由OP立即诱发的麻痹事件。作为研发工作的一部分,对大量豚鼠施加超致死剂量的皮肤OP,随后用RSDL或先前的洗剂及溶剂进行去污处理。对1277只动物进行了梭曼(频哪基甲基膦酰氟;GD)攻击试验,对108只动物进行了S-(2-二异丙基氨基乙基)甲基硫代膦酸酯(VX)攻击试验。在658只死亡动物以及许多存活动物中,观察到了典型的临床症状序列——流涎、震颤、肌束震颤、惊厥、呼吸暂停以及死前的弛缓性麻痹。在GD攻击试验的688只存活动物中,有84只,在VX攻击试验的39只存活动物中,有4只,在经历了导致惊厥和/或弛缓性麻痹的损伤恢复后,出现了不同远端区域的随机麻痹。由于实验旨在评估去污程序,所施加的OP量与记录的后遗症之间没有明显关联。麻痹的观察结果对于实验的主要关注点而言也是偶然的。因此,仅对10只GD暴露后麻痹的动物进行了组织学效应检查。病理学家诊断出大脑皮质有“脑软化”和“局灶性坏死病变”,脊髓有“局灶性坏死病变”。在GD攻击后麻痹的84只豚鼠中,有1只未进行去污处理,其余豚鼠使用的去污剂种类繁多,以至于去污剂类型与由此导致的麻痹之间似乎没有关联。