Dermal Toxicity of Sulfur Mustard

Publisher Summary This chapter deals with the cutaneous actions of sulfur mustard (SM) and discusses the basic mechanism of action and mediators involved. While stable in lipophilic solvents, SM has a half life of only 24 min at room temperature in aqueous physiological solutions, since it rapidly reacts with water to form thiodiglycol and HCl. This rapid activation of SM in an aqueous environment also allows it to react with small molecules of biological interest, as well as proteins, carbohydrates, lipids, RNA, and DNA. The initial reaction involves the formation of a cyclic ethylene sulfonium ion, which readily targets reactive groups on skin components, including sulfhydryls, phosphates, ring nitrogens, and carboxyl groups. As a bifunctional alkylating agent, SM forms monofunctional adducts and intra- and intermolecular crosslinks. Since it is so reactive and indiscriminate in its molecular targets, SM affects many pathways and is cytotoxic on many levels. There are three independent mechanisms of cytotoxicity alkylation of DNA/POLY(ADP-RIBOSE) or polymerase (PARP) activation, reactions with glutathione/lipid peroxidation, and reactions with glutathione/calcium homeostasis. Countermeasure research to date has focused primarily on the development of therapeutics, but little attention has been given to the use of advances in drug delivery, or pharmaceutics. Drug delivery by encapsulation of active moieties in nanoparticles has been increasingly used for chemotherapeutic agents such as doxorubicin. However, with the exception of barrier creams, nanoparticle-mediated cutaneous SM detoxification has largely been limited to decontamination