Timothy L. Hayes

Efficacy of the topical skin protectant in advanced development.

A topical skin protectant (TSP) (ICD 2289) is being developed to protect service members from exposure to chemical warfare agents (CWA). The TSP is designed for use on the skin at the overgarment closures and other vulnerable areas to enhance protection. The TSP, which is in phase II clinical studies, is a cream containing two chemically inert substances: perfluoroalkylpolyether and polytetrafluoroethylene. Animal data showed that the TSP was effective against percutaneous penetration of a blister agent, sulfur mustard (HD), by reducing the size of skin lesions and against T‐2 mycotoxin by preventing the development of erythema and edema. The insect repellent N,N‐diethyl‐m‐toluamide (DEET) reduced the TSP protection against HD regardless of the order of application on rabbit skin prior to dosing of HD. The protection was sustained when DEET was removed with a dry gauze prior to TSP application. The TSP was also effective against percutaneous exposure of nerve agents—thickened (with 5% methyl methacrylamide) soman (TGD) and VX (O‐ethyl‐S‐[2‐(diisopropylamino)ethyl]methylphosphonothioate)—by reducing the mortality rate and protecting the red blood cell acetylcholinesterase activity. The TSP was effective against VX when DEET was applied prior to TSP application. Because human efficacy studies using CWA cannot be conducted, the efficacy will be demonstrated by the level of protection against poison ivy (urushiol) contact dermatitis in humans.

Evaluation of neutralized Chemical Agent Identification Sets (CAIS) for skin injury with an overview of the vesicant potential of agent degradation products

Vesication and skin irritation studies were conducted in hairless guinea‐pigs to determine the vesicant and skin irritation potential of chemically‐neutralized Chemical Agent Identification Sets (CAIS). The CAIS are training items that contain chemical warfare‐related material—sulfur mustard (HD), nitrogen mustard (HN) or lewisite (L)—and were declared obsolete in 1971. Animals were dosed topically with ‘test article’—neat HD, 10% agent/chloroform solutions or product solutions (waste‐streams) from neutralized CAIS—and evaluated for skin‐damaging effects (gross and microscopic). Product solutions from the chemical neutralization of neat sulfur mustard resulted in microvesicle formation. All agent‐dosed (HD or agent/chloroform solutions) sites manifested microblisters as well as other histopathological lesions of the skin. Waste‐streams from the neutralization of agent (agent/chloroform or agent/charcoal) were devoid of vesicant activity. Cutaneous effects (erythema and edema) were consistent with the skin‐injurious activity associated with the neutralizing reagent 1,3‐dichloro‐5,5‐dimethylhydantoin (DCDMH). Chemical neutralization of CAIS was effective in eliminating/reducing the vesicant property of CAIS containing agent in chloroform or agent on charcoal but was inefficient in reducing the vesicant potential of CAIS containing neat sulfur mustard.Copyright

Measuring Liquid Sulfur Mustard Recovery to Characterize a Weanling Swine Skin Short-Term Exposure Model

ABSTRACT Sulfur mustard [bis(2-chloroethyl)sulfide, SM] is a chemical warfare agent that penetrates the skin and causes extensive blistering. A weanling swine model was previously developed to evaluate wound healing associated with SM-induced cutaneous injuries. This study was performed to characterize short-term liquid SM exposures using this weanling swine skin model by measuring SM recovery from dosing templates and associated components. Female Yorkshire crossbred swine were exposed cutaneously to approximately 467 mg SM for 15, 20, and 25 seconds as well as for 4, 5, 6, and 7 minutes. At the end of each time period, the dosing template and associated components were removed, the skin was immediately wiped, and the amount of SM present in the dosing template, polytetrafuloroethylene (PTFE) disc, rubber stopper, and towel wipe was measured. The mean total SM extracted from the dosing template, PTFE disc, rubber stopper, and towel wipe decreased significantly (p ≤ 0.05) over the observed time period with the majority (>99%) of the SM recovered from the dosing template. Significantly higher (p ≤ 0.05) amounts of SM were extracted from the PTFE disc over time, whereas a significant time-dependent decrease in SM was extracted from the towel wipes. These results showed significant decreases in total SM recovered from the dosing templates and associated components over the observed time period. The data from this study provide further insight into using the weanling swine skin model for short-term liquid SM exposures. Ultimately, this information may help determine the appropriate length of cutaneous SM exposure resulting in consistent, uniform injuries for evaluating the efficacy of newly developed and existing treatment regimens for SM-induced skin injury.

Stability of sulfur mustard in vehicles suitable for cutaneous exposure of swine

Sulfur mustard (SM) is a blistering chemical warfare agent capable of forming deep, bullous lesions in man that heal very slowly and tend to become infected. We have developed a swine model that is used to evaluate candidate treatment regimens for the SM injury. To expand our wound-healing studies, SM mixtures suitable for cutaneous exposure were needed so that a large total body surface area (TBSA) could be covered during the SM application. The vehicles selected for use in the SM exposure experiments would have to be miscible with SM, form a stable mixture, be soluble in an organic solvent that is required for the stability evaluation, be nontoxic, and not interfere with the SM reaction on the skin. Four candidate vehicles were selected for testing. The vehicles were peanut oil, propylene glycol, polyethylene glycol (PEG) 200, and PEG 400. During preliminary screening, PEG 400 was eliminated as a candidate because it was not soluble in hexane, and least soluble in chloroform and methylene chloride. Propylene glycol was eliminated since it did not mix with SM. The SM mixtures of peanut oil and PEG 200 were prepared for stability testing over the 25–75% SM concentration range. The results show that the SM mixtures prepared with peanut oil and PEG 200 at the 25, 50, and 75% levels are stable for more than 8 days when stored at 21°C (room temperature) and more than 35 days when stored at −70°C (freezer).