ABSTRACT
Riot control agents (RCAs) represent highly potent sensory irritants with time-dependent acute site-specific toxicity. The clear genetic mechanism of their action is unclear but it is claimed that these chemicals interact pharmacologically with sensory nerve receptors associated with mucosal surfaces and the skin at the site of contamination, resulting in localized discomfort or pain with associated reflexes. The biological response, for example, ocular irritation, results in pain in the eye, which provides warning followed by excess reflex lacrimation and blepharospasm, which in turn provides protection. The kind of responses produced by these agents is concentration-and dose-dependent and therefore cease on removal of the sensory irritant stimulus. These kinds of compounds may also produce respiratory tract irritation and/or gastrointestinal irritation (i.e. nausea and vomiting). RCAs have both civil and military applications and have received classification as either military chemicals or chemical warfare agents. Common classifications are based on a predominant physiological action, although classification may also be based on use, physical state or persistency (Prentiss, 1937; Jacobs, 1942; Waitt, 1942; Sartori, 1943 – refer to Chapter 1 for a more in-depth discussion). Classifications, based on physical state or persistency are confusing, and therefore a revised classification system would better serve to classify these compounds. Use of genomics, proteomics, and computational toxicology would provide the basis for an improved classification scheme where the classification would be based on expression of families of genes affected by the exposure of these compounds (Figure 17.1). With the help of DNA microarray containing thousands of genes on a single platform, one will ultimately be able to build a library of the different biological pathways that are affected by these RCAs. Computational tools would be used to derive the structure-activity relationships using calculations to help determine the relationship between a chemical’s structure and its biological activity.
