title: Efficacy of an oximate-based skin decontaminant against organophosphate nerve agents determined in vivo and in vitro.
abstract: 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.
authors.affiliation: Biomedical Defence Section, Defence Research Establishment, Ralston, Alberta, Canada.
authors.forename: T W
authors.initials: TW
authors.lastname: Sawyer
authors.forename: D
authors.initials: D
authors.lastname: Parker
authors.forename: N
authors.initials: N
authors.lastname: Thomas
authors.forename: M T
authors.initials: MT
authors.lastname: Weiss
authors.forename: R W
authors.initials: RW
authors.lastname: Bide
mesh_terms: D000110:Acetylcholinesterase / Q000032:analysis / Q000097:blood; D000818:Animals; D001921:Brain / Q000201:enzymology; D002642:Chick Embryo; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D003666:Decontamination / Q000379:methods*; D003931:Diacetyl / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D005260:Female; D008297:Male; D009474:Neurons / Q000187:drug effects*; D010755:Organophosphates / Q000037:antagonists & inhibitors / Q000633:toxicity; D009943:Organophosphorus Compounds / Q000037:antagonists & inhibitors / Q000633:toxicity*; D009946:Organothiophosphorus Compounds / Q000037:antagonists & inhibitors / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D012524:Sarin / Q000037:antagonists & inhibitors / Q000633:toxicity; D012999:Soman / Q000037:antagonists & inhibitors / Q000633:toxicity
chemical_list: D000110:Acetylcholinesterase; D002800:Cholinesterase Inhibitors; D003931:Diacetyl; D010755:Organophosphates; D009943:Organophosphorus Compounds; D009946:Organothiophosphorus Compounds; D012524:Sarin; D012999:Soman; C004717:diacetylmonoxime; C009680:VX-agent; C009374:tabun