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

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 C-radiolabelled sulphur mustard ( 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, 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 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 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 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.

The percutaneous absorption of soman in a damaged skin porcine model and the evaluation of WoundStat™ as a topical decontaminant

“…WoundStat™ decontamination 30 seconds post GD challenge sequestered 68% ± 26% of the 14 C-GD applied. Contemporary studies evaluating WoundStat™ as a decontaminant against the vesicating agent sulphur mustard gave increased recoveries of 99% ± 8% (19). Given that similar experimental procedures were used, it is likely that the differences in recovery are ascribable to differences in physicochemical properties, such as volatility, between the two CWAs.…”

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

“…Furthermore, porcine models have been explored extensively for research and development of strategies and technologies to treat severely haemorrhaging wounds (Pusateri et al, ; Pusateri et al, ), which would be the intended target of a haemostatic decontaminant. The 30 second interval between exposure and decontamination was selected to be representative of a self‐ or ‘buddy’‐administered haemostat response time, as well as representing a time interval beyond which an arterial haemorrhage would most likely be lethal, and was in line with previous dose‐decontamination regimens used in vitro (Dalton et al, ; Hall et al, ; Lydon et al, ) and in vivo (Hall et al, ).…”

Further studies of the efficacy of military, commercial and novel skin decontaminants against the chemical warfare agents sulphur Mustard, Soman and VX

“…removing it from skin, thus preventing or at least ameliorating the subsequent lesion severity (Chilcott, 2007;Hall, 2017).…”