Medical defense against blistering chemical warfare agents

Smith, William J.

doi:10.1001/archderm.127.8.1207

Cited by 53 publications

(36 citation statements)

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“…As a weapon, SM exposure may be lethal, but its main function is to cause incapacitating injury to the eyes, respiratory tract or skin [5]. Exposure to the liquid or aerosol (fine droplets) leads to the formation of blisters one to several hours after exposure [6]. While the vesicant activity of SM and related compounds is without dispute, the mechanism responsible for skin blistering is currently unknown, thus a rational approach to prevention/treatment is precluded.…”

Section: Introductionmentioning

confidence: 99%

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Treatment of keratin intermediate filaments with sulfur mustard analogs

Hess

Fitzgerald

2007

Biochemical and Biophysical Research Communications

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Sulfur mustard (SM) is an alkylating agent with a history of use as a chemical weapon. The chemical reactivity of sulfur mustard toward both proteins and nucleic acids coupled with the hours long delay between exposure and appearance of blisters has prevented the determination of the mechanism of blister formation. We have treated assembled keratin intermediate filaments with analogs of sulfur mustard to simulate exposure to SM. We find that treatment of intact filaments with chloroethyl ethyl sulfide (CEES) or mechlorethamine (MEC) produces aggregates of keratin filaments with little native appearing structure. Treatment of a mix of epidermal keratins 1/10 (keratin pair 1 and 10) and keratins 5/14 with a sulfhydryl-specific modification reagent also results in filament abnormalities. Our results are consistent with the hypothesis that modification of keratins by SM would result in keratin filament destruction, leading to lysis of epidermal basal cells and skin blistering.

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Section: Introductionmentioning

confidence: 99%

“…Light microscope characterization of the blisters formed following exposure to SM reveals the location of the blister is between the dermis and epidermis [6]. One hypothesis for vesicant action is the activation of an endogenous protease by SM [7][8][9][10] and an endogenous inhibitor of this protease has been identified [11,12].…”

Section: Introductionmentioning

confidence: 99%

Treatment of keratin intermediate filaments with sulfur mustard analogs

Hess

Fitzgerald

2007

Biochemical and Biophysical Research Communications

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“…These operational data for unprotected military personnel indicate that the most vulnerable (dermal) areas to the vesicant action of sulfur mustard are not only moist and warm, but are also characterized by relatively thin skin (Smith and Dunn 1991;IOM 1993;Papirmeister et al 1991). …”

Section: Vesicant Agentsmentioning

confidence: 96%

“…The biological activity of HD is characterized by a latent period of hours to days, and may be followed by inflammation, blistering, and local necrosis (depending on agent concentration and exposure duration). Toxicological effects are local at the point of agent contact with the skin, and begin to manifest (depending on exposure concentrations) within approximately 2-3 hours post-exposure (Dixon and Needham 1946;McNamara et al 1975;Papirmeister et al 1985Papirmeister et al , 1991Smith and Dunn 1991;Watson and Griffin 1992;Smith 2002). The earliest manifestation is usually an itching rash at the point of contact, which may progress to swelling and erythema, and (sometimes large) blisters.…”

Section: Vesicant Agentsmentioning

confidence: 99%

“…In marked contrast to sulfur mustard, Lewisite exposure is characterized by prompt onset of pain and/or stinging or burning sensations; necrosis is early and complete. Erythema is "immediate" (Smith and Dunn 1991), followed by the production of vesicles that coalesce to form larger blisters in approximately 2-3 hours (Goldman and Dacre 1989;Smith and Dunn 1991). Larger exposures result in agent penetration through subcutaneous tissue to muscle, with associated edema and necrosis (IOM 1993).…”

Section: Vesicant Agentsmentioning

confidence: 99%

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Evaluation of Chemical Warfare Agent Percutaneous Vapor Toxicity: Derivation of Toxicity Guidelines for Assessing Chemical Protective Ensembles.

Watson¹

2003

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Reactions of sulfides with S‐330, a potential decontaminant of sulfur mustard in formulations

Shih¹,

Korte²,

Smith³

et al. 1999

J. Appl. Toxicol.

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Because the vesicant sulfur mustard (HD) remains a major chemical threat from either domestic terrorists or countries in conflict, topical preparations are being evaluated as protectants from HD exposure. The objective of this study was to evaluate the effectiveness of chloroamide S‐330 as a potential reactive component in topical formulations. Therefore, the rate, mechanism and by‐products of the oxidation reactions of sulfides by S‐330 in solvent media or specific formulation vehicles were investigated. Using NMR, LC, LC–MS and GC–MS, the reactions of S‐330 with HD, dibutyl sulfide (DBS) and methyl phenyl sulfide (MPS) were studied in acetonitrile, chloroform and perfluoropolyether (PFPE) oil. The oxidation of the three sulfides with S‐330 was very rapid and completed in <4 min in acetonitrile–water or PFPE oil, but the rates of reaction in chloroform were significantly slower. In a large excess of S‐330, the major products resulted from chlorination of the side chains. At a high HD/S‐330 ratio, the major product was HD sulfoxide. Under both conditions, only a trace of HD sulfone, also a blistering agent, was observed. Reactions with DBS and MPS primarily gave sulfoxides and sulfones, with less side‐chain chlorination. The chloroamide S‐330 appeared to be a rapid and effective decontaminant of HD in either polar media or in a PFPE oil. The two alkyl and aryl sulfides are suitable simulants of HD for the initial screening and evaluation of S‐330 or other similar oxidizing agents.

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Medical defense against blistering chemical warfare agents

Cited by 53 publications

References 0 publications

Treatment of keratin intermediate filaments with sulfur mustard analogs

Treatment of keratin intermediate filaments with sulfur mustard analogs

Evaluation of Chemical Warfare Agent Percutaneous Vapor Toxicity: Derivation of Toxicity Guidelines for Assessing Chemical Protective Ensembles.

Reactions of sulfides with S‐330, a potential decontaminant of sulfur mustard in formulations

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