Literature DB >> 29023806

The percutaneous toxicokinetics of VX in a damaged skin porcine model and the evaluation of WoundStat™ as a topical decontaminant.

Helen Lydon1,2, Charlotte Hall1,2, Hazem Matar1,3, Christopher Dalton2,4, J Kevin Chipman2, John S Graham5, Robert P Chilcott1,3.   

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 14 C-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 14 C-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.
Copyright © 2017 John Wiley & Sons, Ltd.

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Keywords:  S-[2-(diisopropylamino)ethyl]-O-ethyl methylphosphonothioate; acetylcholinesterase; coagulation; haemorrhage; haemostasis; nerve agent; organophosphate; percutaneous absorption; splenic contraction

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Year:  2017        PMID: 29023806     DOI: 10.1002/jat.3542

Source DB:  PubMed          Journal:  J Appl Toxicol        ISSN: 0260-437X            Impact factor:   3.446


  2 in total

1.  Effects of polyhydroxyfullerenes on organophosphate-induced toxicity in mice.

Authors:  Marion Ehrich; Jonathan Hinckley; Stephen R Werre; Zhiguo Zhou
Journal:  Toxicology       Date:  2020-09-16       Impact factor: 4.221

2.  Magnetic field-mediated Janus particles with sustained driving capability for severe bleeding control in perforating and inflected wounds.

Authors:  Qing Li; Enling Hu; Kun Yu; Mengxing Lu; Ruiqi Xie; Fei Lu; Bitao Lu; Rong Bao; Guangqian Lan
Journal:  Bioact Mater       Date:  2021-05-18
  2 in total

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