Reactive skin decontamination lotion (RSDL) for the decontamination of chemical warfare agent (CWA) dermal exposure.

Rapid decontamination of the skin is the single most important action to prevent dermal absorption of chemical contaminants in persons exposed to chemical warfare agents (CWA) and toxic industrial chemicals (TICs) as a result of accidental or intentional release. Chemicals on the skin may be removed by mechanical means through the use of dry sorbents or water. Recent interest in decontamination systems which both partition contaminants away from the skin and actively neutralize the chemical has led to the development of several reactive decontamination solutions. This article will review the recently FDA-approved Reactive Skin Decontamination Lotion (RSDL) and will summarize the toxicity and efficacy studies conducted to date. Evidence of RSDL's superior performance against vesicant and organophosphorus chemical warfare agents compared to water, bleach, and dry sorbents, suggests that RSDL may have a role in mass human exposure chemical decontamination in both the military and civilian arenas.

Detection and measurement of sulfur mustard offgassing from the weanling pig following exposure to saturated sulfur mustard vapor.

Animal models are employed to investigate mechanisms of injury and to evaluate protective measures against sulfur mustard (HD) exposure. The ability to detect and quantify HD enables the researcher to follow safe procedures in handling skin samples. We designed an experimental procedure to measure HD offgassing from animal models. A Minicams--a portable gas chromatograph equipped with a flame photometric detector and on-line sorbent collection and desorption--was used to monitor the HD concentration. Confirming measurements were made using a two-step process that trapped HD on a Tenax sorbent off-line and then transferred the sample by means of an ACEM 900 to a gas chromatograph equipped with either a flame photometric detector or a mass spectrometer. Sulfur mustard offgassing data are presented from three experiments in which weanling pigs were exposed to saturated HD vapor via vapor caps containing 10 microl of HD. The HD concentration was measured in time-weighted-average (TWA) units at a specific HD application site. The current 8-h maximum exposure limit for HD is 3-ng l(-1), (1 TWA unit). The largest TWA value measured near a 3 h time point was a Minicams measurement of 0.48 TWA at 2 h and 53 min after removal of a vapor cap containing HD from a single exposure site on an animal that had 24 concurrent dorsal exposure sites. Gas chromatography/flame photometric detection and gas chromatography/mass spectrometry were used to confirm the Minicams data and to provide greater sensitivity and selectivity down to 0.1 TWA. The gas chromatography/mass spectrometry data confirmed that HD concentrations fell below 0.1 TWA in <5 h for a specific site. These measurements of HD concentrations provided information on the expeditious and safe handling of HD-exposed tissue.

Development of a reactive topical skin protectant.

The use of a topical skin protectant (TSP) as a means of protecting troops from percutaneous chemical warfare agent (CWA) exposure has been proposed since these weapons were first used during World War I. The TSP is applied to vulnerable skin surfaces prior to entry into a chemical combat area. In 1990, the US Army Medical Research Institute of Chemical Defense transferred two non-reactive TSPs into advanced development. Following US Food and Drug Administration approval, the final product is expected to be available to soldiers in 1999. A continuing research effort is designed to develop a second-generation TSP that will increase effectiveness and also decontaminate CWAs into non-toxic products. We identified a list of 29 reactive moieties as potential additives to the TSP formulation. All candidate formulations are evaluated in a decision tree network, consisting of a series of 11 efficacy testing models. A prototype formulation (ICD 2701) containing the reactive ingredient S-330 has dramatically improved the protection against saturated sulfur mustard vapor. In addition, we have discovered a compound (ICD 2837) that significantly increases the skin's natural resistance to CWA penetration. Our goal is to transfer a significantly improved TSP formulation into advanced development by 1999.

Model for assessing efficacy of topical skin protectants against sulfur mustard vapor using hairless guinea pigs.

Sulfur mustard (HD; 2,2'-dichlorodiethyl sulfide) can produce incapacitating blisters in humans following dermal exposure. Most non-human animal models, however, do not form the large fluid-filled blisters observed in humans. Many models, nevertheless, do produce similar damage at the dermal/epidermal junction when evaluated by histopathology. In this study, it was observed that the hairless guinea pig (HGP) exhibits similar histopathological responses following exposure to HD vapor. Two sets of HGPs were exposed percutaneously for various lengths of time to HD vapor. In one set, the HGPs were sacrificed 24 h after exposure, and skin specimens were collected and processed for histopathology. In the other set, light reflectance was measured at skin test sites 4, 5, 6 and 24 h after exposure, to assess erythema. The Nikolsky's sign test was also performed 24 h after exposure by rotating a metal disk glued to the skin test site and inspecting the skin for loss of epidermis. Probit analysis of data indicated that the exposure durations that produced a 50% incidence of microblisters and Nikolsky's sign were ca. 7.5 and 4.5 min, respectively. Maximum erythema was observed 6 h following a 6 min exposure. Operating parameters for assessing the efficacies of skin protectants have been characterized.

Characterization of sulfur mustard vapor-induced cutaneous lesions on haired guinea pigs.

BACKGROUND/AIMS: Sulfur mustard (2,2'-dichlorodiethyl sulfide, HD) is a potent vesicating (blistering) agent. In this report, we describe the time-course and the dose-dependent response following cutaneous exposure to sulfur mustard (HD) in the haired guinea pig model. The purpose of this study was to evaluate the usefulness of the haired guinea pig as a vesicant research model. METHODS: Seventy-two animals were divided into nine groups of eight animals each. Hair on the dorsal side of each animal was removed by clipping with an electric clipper followed by application of a chemical depilating agent (MAGIC Shaving Powder). Six dorsal skin sites on each animal of a given group were exposed to saturated HD vapor (1.4 mg/l) for one of nine exposure times between 0-8 min. Lesions were evaluated for erythema (reflectance colorimeter) and edema (ultrasound imaging) at 4, 6, 12, and 24 h postexposure. Damage at the dermal-epidermal junction (DEJ) was evaluated by histopathology at 24 h postexposure. RESULTS: We observed that the hair removal process was time-consuming, produced significant initial erythema, and resulted in increased dorsal skin sensitivity to low HD exposure levels. The time-course of exposure response to HD was observed to be dose-dependent and similar to the hairless guinea pig model. CONCLUSIONS: The haired guinea pig is inferior to the hairless guinea pig as a vesicant model due to the complications resulting from the hair removal process. However, the haired guinea pig is a useful model for evaluating the cutaneous effects of HD vapor and can be developed into a routine screening tool for the evaluation of topical barriers against HD vapor exposure.

Nikolsky's sign: a novel way to evaluate damage at the dermal-epidermal junction.

BACKGROUND/AIMS: Sulfur mustard (2,2'-dichlorodiethyl sulfide, HD) is a potent vesicating (blistering) agent. Cutaneous exposure causes the destruction of basal cells and leads to a separation at the dermal-epidermal junction. To evaluate the efficacy of candidate antivesicant compounds, suitable animal models are needed. A tape stripping method and the Dermal Torque Meter (DTM) have been used in novel applications to evaluate for the Nikolsky's sign in the hairless guinea pig. The Nikolsky's sign is the separation and loss of the epidermis from the dermis when the skin is pressed with a sliding or twisting motion. The purpose of this study was to find an objective, reproducible, and quantitative method that could be used as an end-point to evaluate the degree of damage at the dermal-epidermal junction following cutaneous HD vapor exposure. METHODS: Hairless guinea pigs were exposed to saturated HD vapor (1.4 mg/l) for time intervals between 2 and 9 min using 14-mm vapor cups. At 24 h post-exposure, both tape stripping (fabric carpet tape) and a DTM were used to produce the Nikolsky's sign in animals under anesthesia. Using the tape stripping method, 15-mm disks of tape were applied to each skin site. After 5 s the tape was peeled off. The D T M was used to apply a horizontal twisting motion to the skin. The parameters included a 15-mm center disk, a ring gap of 1 mm, a torque of 30 mNm, and a 5-s cycle time. A cyanoacrylate adhesive was used to secure the center disk and guard ring to the skin. The loss of the epidermis was determined by visual observation and confirmed by histopathological examination. The standard D T M unit was modified to use multiple center disk/guard ring assemblies so that several sites on each animal could be evaluated at the same time. RESULTS: The mean (±S E M) percent incidence of positive Nikolsky's sign observations using the tape stripping method for HD vapor exposures of 3,5,7, and 9 min was 0,50 (±16), 94 (±6.2), and 100, respectively. The mean (±S E M) percent incidence of positive Nikolsky's sign observations using the D T M method for HD vapor exposures of 2, 3, 4, and 5 min was 0, 25 (±7.1), 91 (±2.9), and 96 (±2.3), respectively. CONCLUSIONS: The Nikolsky's sign produced by the tape stripping method and the D T M were useful in evaluating damage at the dermal-epidermal junction following cutaneous HD vapor exposures. These methods have the potential to replace histopathology as an end-point for routine screening procedures designed to evaluate the efficacy of antivesicant compounds.

Hairless guinea pig bioassay model for vesicant vapor exposures.

Sulfur mustard (HD; 1,1'-thiobis[2-chloroethane]) induces fluid-filled blisters in man but not in conventional laboratory animals. An animal model is needed to emulate both cytotoxic (vesicant) and vascular (irritant) responses of human skin to HD exposures. An acceptable model must permit reproducible comparisons of uniformly graded and dose-related HD control responses with reduced responses that may follow antivesicant treatments. Hairless guinea pigs were evaluated by exposing six or eight dorsal skin sites 12 mm in diameter to similar HD vapor concentrations for graded intervals (1-16 min). HD vapor was delivered under occlusive caps holding 10 microliters of HD in filter paper located 5 mm above the skin. Four-minute exposures induced moderate erythema, slight edema, and microblisters in 1 of 39 sites. Eight-minute exposures induced severe erythema, moderate edema, and microblisters in 31 of 40 sites. Gross blistering was not seen after use of vapor cups, but damage to basal cells resembled lesions of vesicant injury in man. The hairless guinea pig model, with graded HD vapor exposures, provides acceptable comparisons of responses. Exposures of both 4- and 8-min durations were used to show the feasibility of using this model to bioassay antivesicant topical protectants. These methods may be useful for measurements of irritant and cytotoxic responses of skin to other toxic vapors.