The percutaneous toxicokinetics of VX in a damaged skin porcine model and the evaluation of WoundStat™ as a topical decontaminant |
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| Authors: | Hazem Matar Christopher Dalton J. Kevin Chipman John S. Graham Robert P. Chilcott |
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| Affiliation: | 1. CBRN & Chemical Toxicological Research Group, Centre for Radiation, Chemical and Environmental Hazards, Health Protection Agency (now Public Health England), Chilton, UK;2. Research Centre for Topical Drug Delivery and Toxicology, University of Hertfordshire, Hatfield, UK;3. School of Biosciences, University of Birmingham, Edgbaston, UK;4. Defence Science & Technology Laboratory, Porton, UK;5. Medical Toxicology Branch Analytical Toxicology Division, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, USA |
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| Abstract: | This study used a damaged skin, porcine model to evaluate the in vivo efficacy of WoundStat? for the decontamination of superficial, nerve agent‐contaminated wounds. Anaesthetized animals were randomly assigned to either control (n = 7), no decontamination (n = 12) or WoundStat? (n = 12) treatment groups. Pigs were exposed to a 5× LD50 dose of neat, radiolabelled S‐[2‐(diisopropylamino)ethyl]‐O‐ethyl methyl‐phosphonothioate (VX; or equivalent volume of sterile saline for the control group) via an area of superficially damaged skin on the ear. WoundStat? was applied at 30 seconds post‐exposure to assigned animals. The VX contaminant (or saline) and decontaminant remained in place for the duration of the study (up to 6 hours). Physiological parameters and signs of intoxication were recorded during the exposure period. Skin and organ samples were taken post mortem for 14C–VX distribution analyses. Blood samples were taken periodically for toxicokinetic and whole‐blood acetylcholinesterase (AChE) activity analyses. VX exposure was accompanied by a rapid decrease in AChE activity in all animals, regardless of decontamination. However, decontamination significantly improved survival rate and time and reduced the severity of signs of intoxication. In addition, the distribution of 14C–VX in key internal organs and post mortem blood samples was significantly lower in the WoundStat? treatment group. This study demonstrates that WoundStat? may be a suitable medical countermeasure for increasing both survival rate and time following VX exposure. The results also suggest that AChE activity is not a useful prognostic indicator. |
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| Keywords: | acetylcholinesterase coagulation haemorrhage haemostasis nerve agent organophosphate percutaneous absorption S‐[2‐(diisopropylamino)ethyl]‐O‐ethyl methylphosphonothioate splenic contraction |
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