title: 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 μL14C-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 of14C-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 of14C-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 of14C-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.
authors.affiliation: CBRN & Chemical Toxicological Research Group, Centre for Radiation, Chemical and Environmental Hazards, Health Protection Agency, Chilton, UK.|School of BioSciences, University of Birmingham, Birmingham, UK.
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Hall
authors.affiliation: CBRN & Chemical Toxicological Research Group, Centre for Radiation, Chemical and Environmental Hazards, Health Protection Agency, Chilton, UK.|School of BioSciences, University of Birmingham, Birmingham, UK.
authors.forename: Helen L
authors.initials: HL
authors.lastname: Lydon
authors.affiliation: Biomedical Sciences, Dstl Porton Down, Salisbury.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Dalton
authors.affiliation: School of BioSciences, University of Birmingham, Birmingham, UK.
authors.forename: J Kevin
authors.initials: JK
authors.lastname: Chipman
authors.affiliation: Medical Toxicology Branch Analytical Toxicology Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, 21010, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Graham
authors.affiliation: CBRN & Chemical Toxicological Research Group, Centre for Radiation, Chemical and Environmental Hazards, Health Protection Agency, Chilton, UK.|Research Centre for Topical Drug Delivery and Toxicology, University of Hertfordshire, Hatfield, UK.
authors.forename: Robert P
authors.identifier: 0000-0002-8845-9400
authors.initials: RP
authors.lastname: Chilcott
mesh_terms: D000818:Animals; D002619:Chemical Warfare Agents / Q000493:pharmacokinetics / Q000633:toxicity; D003666:Decontamination; D004195:Disease Models, Animal; D005260:Female; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009151:Mustard Gas / Q000493:pharmacokinetics* / Q000633:toxicity*; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D012869:Skin Absorption / Q000187:drug effects; D013552:Swine; D066007:Toxicokinetics
chemical_list: D002619:Chemical Warfare Agents; D009151:Mustard Gas
keywords: haemostats; laser Doppler imaging; pig; skin reflectance spectroscopy; topical decontaminants; vesicants