title: Site-specific percutaneous absorption of methyl salicylate and VX in domestic swine.
abstract: The site specificity of the percutaneous absorption of methyl salicylate (MeS) and the organophosphate nerve agent VX (O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothioate) was examined in anaesthetized domestic swine that were fully instrumented for physiological endpoints. Four different anatomical sites (ear, perineum, inguinal crease and epigastrium) were exposed to the MeS and the serum levels were measured over a 6-h time period. The dose absorbed at the ear region was 11 microg cm(-2) with an initial flux of 0.063 microg cm(-2)min(-1), whereas at the epigastrium region the dose absorbed was 3 microg cm(-2) with an initial flux of 0.025 microg cm(-2)min(-1). For this reason further studies were carried out with VX on the ear and the epigastrium only. In animals treated with agent on the epigastrium, blood cholinesterase (ChE) activity began to drop 90 min after application and continued to decline at a constant rate for the remainder of the experiment to ca. 25% of awake control activity. At this time there were negligible signs of poisoning and the medical prognosis was judged to be good. In contrast, the ChE activity in animals receiving VX on the ear decreased to 25% of awake control values within 45 min and levelled out at 5-6% by 120 min. Clinical signs of VX poisoning paralleled the ChE inhibition, progressing in severity over the duration of the exposure. It was judged that these animals would not survive. The dramatic site dependence of agent absorption leading to vastly different toxicological endpoints demonstrated in this model system has important ramifications for chemical protective suit development, threat assessment, medical countermeasures and contamination control protocols.
authors.affiliation: Chemical Biological Defence Section, Defence Research Establishment, Suffield, PO Box 4000, Station Main, Medicine Hat, Alberta, Canada T1A 8K6.
authors.forename: E J Scott
authors.initials: EJ
authors.lastname: Duncan
authors.forename: April
authors.initials: A
authors.lastname: Brown
authors.forename: Paul
authors.initials: P
authors.lastname: Lundy
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Sawyer
authors.forename: Murray
authors.initials: M
authors.lastname: Hamilton
authors.forename: Ira
authors.initials: I
authors.lastname: Hill
authors.forename: John D
authors.initials: JD
authors.lastname: Conley
mesh_terms: D000005:Abdomen; D000279:Administration, Cutaneous; D000818:Animals; D002619:Chemical Warfare Agents / Q000493:pharmacokinetics*; D002802:Cholinesterases / Q000097:blood; D004423:Ear; D007264:Inguinal Canal; D008297:Male; D023421:Models, Animal; D009946:Organothiophosphorus Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010502:Perineum; D012459:Salicylates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D013552:Swine / Q000502:physiology*
chemical_list: D002619:Chemical Warfare Agents; D002802:Cholinesterases; D009946:Organothiophosphorus Compounds; D012459:Salicylates; C009680:VX-agent; C033069:methyl salicylate