title: Absorption of the nerve agent VX (O-ethyl-S-[2(di-isopropylamino)ethyl] methyl phosphonothioate) through pig, human and guinea pig skin in vitro.
abstract: The physico-chemical properties of VX make the skin the most likely route of absorption into the human body. The development of effective medical countermeasures against such percutaneous threat agents relies on the use of appropriate animal models, as the inherent toxicity of nerve agents precludes the use of human volunteers. Previous studies have characterised the mechanism of nerve agent toxicity in rodent models, however, it is generally accepted that one of the most appropriate animal models for human skin absorption is the domestic pig. The purpose of the present study was to measure and compare the skin absorption kinetics of VX in vitro using pig, human and guinea pig skin to highlight any potential species differences in skin permeability. When undiluted VX was applied directly to the skin, the permeability of guinea pig skin was approximately 7-fold greater than human skin. There was no significant difference in the permeability of pig and human skin. When VX diluted with isopropyl alcohol was applied to the skin, the permeability of guinea pig skin was approximately 4-fold greater than human skin. There was no significant difference in the permeability of pig and human skin. From this data it may be inferred that dermatomed, abdominal pig skin is an appropriate model for the human skin absorption of VX.
authors.affiliation: Dstl Biomedical Sciences, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK. chdalton@dstl.gov.uk
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Dalton
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Hattersley
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Rutter
authors.forename: Robert P
authors.initials: RP
authors.lastname: Chilcott
mesh_terms: D000328:Adult; D000818:Animals; D002619:Chemical Warfare Agents / Q000493:pharmacokinetics*; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D015194:Diffusion Chambers, Culture; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D009946:Organothiophosphorus Compounds / Q000493:pharmacokinetics*; D012044:Regression Analysis; D012869:Skin Absorption; D013552:Swine
chemical_list: D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D009946:Organothiophosphorus Compounds; C009680:VX-agent