Sawyer T W, Parker D, Thomas N, Weiss M T, Bide R W
Biomedical Defence Section, Defence Research Establishment, Ralston, Alberta, Canada.
Toxicology. 1991 May;67(3):267-77. doi: 10.1016/0300-483x(91)90028-y.
Recent Canadian research efforts have been directed towards the development of a reactive skin decontaminant (RSD) lotion active against classical nerve agents and mustard. The formulation presently under study consists of a 1.25 molal solution of potassium 2,3-butanedione monoximate (KBDO) in polyethylene glycol methylether 550. Although this formulation has shown good efficacy, concern has been expressed as to the potential toxicity of the reaction products of KBDO and organophosphate (OP) nerve agents. This report details the high efficacy of this lotion in inactivating OPs as measured by the systemic toxicity of the OP/RSD mixtures in rats. In addition, primary cultures of chick embryo neurons were also used to test the efficacy of the RSD. By relating the anticholinesterase activity in these cultures of the OP/RSD mixture to that of pure OP standards, a sensitive measure of the value of the RSD in inactivating tabun, sarin, soman and VX was obtained. Experiments with all four nerve agents in this in vitro system provided a good correlation with the in vivo data, and also indicated that the inactivation process was time- and agent-dependent and also related to the ratio of OP to RSD.
加拿大近期的研究工作致力于开发一种对传统神经毒剂和芥子气有效的皮肤反应性去污剂(RSD)洗剂。目前正在研究的配方是2,3-丁二酮一肟钾(KBDO)在聚乙二醇甲醚550中的1.25摩尔溶液。尽管该配方已显示出良好的效果,但人们对KBDO与有机磷酸酯(OP)神经毒剂反应产物的潜在毒性表示担忧。本报告详细介绍了该洗剂在使OP失活方面的高效性,这是通过OP/RSD混合物对大鼠的全身毒性来衡量的。此外,鸡胚神经元原代培养物也被用于测试RSD的效果。通过将这些OP/RSD混合物培养物中的抗胆碱酯酶活性与纯OP标准品的活性相关联,获得了RSD对塔崩、沙林、梭曼和VX失活价值的灵敏测量方法。在这个体外系统中对所有四种神经毒剂进行的实验与体内数据具有良好的相关性,并且还表明失活过程与时间、毒剂有关,也与OP和RSD的比例有关。