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

J Appl Toxicol. 2017 Sep;37(9):1036-1045. doi: 10.1002/jat.3453. Epub 2017 Mar 17.

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 14 C-radiolabelled sulphur mustard (14 C-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, 14 C-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 14 C-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 14 C-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 14 C-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. Copyright © 2017 John Wiley & Sons, Ltd.

Keywords: haemostats; laser Doppler imaging; pig; skin reflectance spectroscopy; topical decontaminants; vesicants.

MeSH terms

  • Animals
  • Chemical Warfare Agents / pharmacokinetics
  • Chemical Warfare Agents / toxicity
  • Decontamination*
  • Disease Models, Animal
  • Female
  • Intestine, Small / drug effects
  • Intestine, Small / metabolism
  • Kidney / drug effects
  • Kidney / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Mustard Gas / pharmacokinetics*
  • Mustard Gas / toxicity*
  • Skin / drug effects*
  • Skin / pathology
  • Skin Absorption / drug effects
  • Swine
  • Toxicokinetics

Substances

  • Chemical Warfare Agents
  • Mustard Gas