Riot-Control Agents

I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322 II. Historical Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323

III. Chemistry of Selected Riot-Control Agents . . . . . . . . . . . . . . . . . . . . . . . . 326 A. Chlorobenzylidene Malononitrile (CS) . . . . . . . . . . . . . . . . . . . . . . . . . 326 B. Dibenz(b,f)1:4-Oxazepine (CR) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327 C. Chloroacetophenone (CN) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327 D. Oleoresin Capsicum (OC) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 328 E. Adamsite (DM) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 328

IV. Clinical Aspects of Riot-Control Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . 328 V. Toxicology of Riot-Control Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329

VI. Ocular and Cutaneous Effects of Riot-Control Agents . . . . . . . . . . . . . . . . 329 VII. Specific Riot-Control Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 332

A. o-Chlorobenzylidene Malononitrile (CS) . . . . . . . . . . . . . . . . . . . . . . . 332 1. Mammalian Toxicology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333 2. Ocular and Cutaneous Effects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335 3. Reproductive and Developmental Effects. . . . . . . . . . . . . . . . . . . . . 335 4. Genotoxicity and Carcinogenicity . . . . . . . . . . . . . . . . . . . . . . . . . . 336 5. Metabolism, Metabolic Fate, and Mechanisms . . . . . . . . . . . . . . . . 336 6. Human Toxicology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 338

B. Dibenz(b,f)1:4-Oxazepine (CR) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341 1. Mammalian Toxicology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 342 2. Ocular and Cutaneous Effects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 343 3. Reproductive Toxicity and Developmental Effects. . . . . . . . . . . . . . 344 4. Genotoxicity and Carcinogenicity . . . . . . . . . . . . . . . . . . . . . . . . . . 344 5. Clinical Chemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 345 6. Metabolism, Metabolic Fate, and Mechanisms . . . . . . . . . . . . . . . . 345 7. Human Toxicology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 346 8. Ocular and Cutaneous Effects (Human) . . . . . . . . . . . . . . . . . . . . . . 347

C. Chloroacetophenone (CN) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 349 1. Mammalian Toxicology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 349 2. Ocular and Cutaneous Effects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351 3. Genotoxicity and Carcinogenicity . . . . . . . . . . . . . . . . . . . . . . . . . . 351 4. Metabolism, Metabolic Fate, and Mechanisms . . . . . . . . . . . . . . . . 351 5. Human Toxicology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 352

D. Oleoresin Capsicum (OC) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 352 1. Mammalian Toxicology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 353 2. Ocular and Cutaneous Effects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355 3. Mutagenicity and Carcinogenicity . . . . . . . . . . . . . . . . . . . . . . . . . . 356 4. Metabolism, Metabolic Fate, and Mechanisms . . . . . . . . . . . . . . . . 357 5. Human Toxicology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 357

E. Diphenylaminochloroarsine (Adamsite) . . . . . . . . . . . . . . . . . . . . . . . . 359 1. Toxicology and Physiological Effects. . . . . . . . . . . . . . . . . . . . . . . . 359 2. Human Toxicology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 360

VIII. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 361 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 362

Riot-control agents, chemicals that produce disabling physiological effects when they come in contact with the eyes or skin or when inhaled, are a subset of a larger group of chemicals known as “harassing agents.” These compounds have the capability of causing intense sensory irritation and marked irritation of the skin and mucous membranes of the eye and respiratory tract. Riot-control agents are peripheral sensory irritants and are collectively referred to as lacrimators. In common parlance they are known as “tear gases.” Peripheral sensory irritants are substances that pharmacologically interact with sensory nerve receptors in skin and mucosal surfaces at the site of contamination, resulting in local sensation (discomfort or pain) with associated reflexes. This is a normal biological response giving warning and protective functions. For example, in the eye, sensory irritation results in pain in the eye (warning) and excess reflex lacrimation and blepharospasm (protection). The response is usually concentration-related and disappears on removal of the sensory irritant stimulus. The intense lacrimation best typifies the biological response to such compounds; however, it must be kept in mind that riot-control compounds have multiple physiological effects. A lacrimatory compound may also elicit pulmonary irritation and/or nausea and vomiting. Generally, classification of military chemicals and chemical agents is based on a salient physiologic action although classification may also be based on use, physical state, or persistency.1 –4 Sartori was of the opinion that the physiological classification of chemical agents and military chemicals, although widely used, was less exact than other classification schemes.4 He long ago suggested that classification should be based according to the mechanism of action on the organism.