ABSTRACT
Riot control agents (RCA) are highly potent peripheral sensory irritants (PSI) that elicit “irritative” or “noxious” sensation due to action on the sensory nervous system of the eyes, the respiratory tract, and the skin. PS irritants are chemicals of widely differing structure, which interact nonspecifically with sensory nerve receptors associated with these target organs. Large differences appear in the sensory irritation potency among chemicals; for example, toluene diisocyanate (0.1 ppm) produces a 25 percent decrease in respiratory rate versus a comparable decrease produced by 1,000 ppm of isobutyl alcohol (De Ceaurriz et al., 1981). The RCAs are among the most potent PSI substances known comparable to highly potent PSI irritants such as N-(4-hydroxy-3-methoxyphenyl)- 2-chlordecanamide (plethysmography RD50 values: 3.4107 M and 2.1107 M, chloroacetophenone and N-(4-hydroxy-3-methoxyphenyl)-2-chlorodecanamide, respectively) (Ballantyne, 1999). A model to explain the mode-of-action of sensory irritants was initially proposed by Alarie (1973) and further elaborated by Nielsen and Alarie (1982) and Nielsen (1991). The model is based on the chemical and physical interactions of sensory irritants with a receptor protein in a lipid bilayer. It is postulated that the receptor protein contains multiple sites of interaction. One site containing a disulfide bond that can either be chemically broken or interacts non-covalently with PS irritants, and the other site comprising a nucleophilic moiety (e.g. SH, NH, OH) that can interact chemically with irritant molecules. Interaction with sensory nerve receptors produces discomfort and/or pain at the site of contact along with related reflexes. The effects on exposure to PS irritants disappear within a short time following cessation of exposure. The major characteristics of PS irritants are as follows: (1) their actions are localized (e.g. mucosae, skin), (2) they produce local discomfort and/or pain with locally mediated reflexes, and (3) they may elicit associated systemic reflexes (Figure 5.1). Although PSI effects predominantly involve the eyes and the respiratory tract, involvement of the skin may also occur particularly at higher amounts/concentrations of material. It should be noted that peripheral sensory irritation is a pharmacological effect to be distinguished from a toxicological response. However, most substances producing a PSI effect will usually also produce toxic effect(s) (i.e. inflammation) upon exposure to high concentrations and/or extended exposure periods. Pharmacological actions of PSI substances on the eyes include: copious lacrimation, blepharospasm (uncontrollable closure of the eyelids), itching, burning sensation, and discomfort or pain. Respiratory system effects following exposure to PSI
substances comprise the following responses: decreased breathing rate, increased secretions, coughing, sneezing, burning sensation of the upper and lower respiratory tract, constricting sensations in the chest, and discomfort or pain of the throat, nasopharynx, and nose. The clinical presentation varies somewhat depending on the degree of exposure, the chemical nature of the material, and the site of exposure. Skin effects on exposure to peripheral sensory irritants are generally limited to the production of transient erythema, which occur at exposure levels considerably greater than those concentrations resulting in ocular or respiratory effects. High concentrations of RCAs such as CS and CN can also cause edema and blistering. As mentioned, PSI substances produce local discomfort and/or pain with locally mediated reflexes. Local reflexes resulting from exposure to PS irritants are important protective mechanisms limiting further exposure and uptake (e.g. lacrimation which aids in the dilution and removal of material from the eye; decreased breathing rate which limits the systemic uptake of xenobiotic). Additionally, PS irritants are also associated with tachyphylaxis – decreasing responses that follow consecutive applications of test substance (see also Chapter 12).
