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

Charlotte Hall, Helen Lydon, Christopher Dalton, J. Kevin Chipman, John Graham, Robert Chilcott

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Abstract

This study used a damaged skin, porcine model to evaluate the in vivo efficacy of WoundStat™ for decontamination of
superficial (non-haemorrhaging), sulphur mustard-contaminated wounds. The dorsal skin of 12 female pigs was subjected to controlled
physical damage and exposed to 10 μL 14C–radiolabelled sulphur mustard (14C–SM). Animals were randomly assigned to
either a control or a treatment group. In the latter, WoundStat™ was applied 30 s post exposure and left in situ for 1 h. Skin lesion
progression and decontaminant efficacy were quantified over 6 h using a range of biophysical measurements. Skin, blood and
organ samples were taken post mortem for histopathological assessment, 14C–SM distribution and toxicokinetic analyses. Application
of SM to damaged skin without decontamination was rapidly followed by advanced signs of toxicity, including ulceration
and decreased blood flow at the exposure site in all animals. WoundStat™ prevented ulceration and improved blood flow at the
exposure site in all decontaminated animals (n = 6). Furthermore, significantly smaller quantities of 14C–SM were detected in the
blood (45% reduction), and recovered from skin (70% reduction) and skin surface swabs (99% reduction) at 6 h post-challenge.
Overall, the distribution of 14C–SM in the internal organs was similar for both groups, with the greatest concentration in the kidneys,
followed by the liver and small intestine. WoundStat™ significantly reduced the amount of 14C–SM recovered from the liver,
a key organ for SM metabolism and detoxification. This study demonstrates that WoundStat™ is a suitable product for reducing
the ingress and toxicity of a chemical warfare agent.
Original languageEnglish
Pages (from-to)1036-1045
Number of pages10
JournalJournal of Applied Toxicology
Volume37
Issue number9
Early online date17 Mar 2017
DOIs
Publication statusPublished - 18 Jul 2017

Keywords

  • vesicants
  • pig
  • topical decontaminants
  • haemostats
  • laser Doppler imaging
  • Skin reflectance spectroscopy

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