Irritants – CS, CN, CNC, CA, CR, CNB, PS
Riot control agents are chemical compounds that temporarily disable victims due to their noxious contamination of skin, eyes, mucous membranes, and respiratory tract. They are not meant to kill, but to render a victim momentarity helpless. However, in certain circumstances, they can cause long-term medical sequelae, including death. [1, 2]
The sole purpose of irritants (also known as tear gas, riot control agents, and lachrymators) is to produce immediate dermatological, respiratory, and ocular discomfort in order to render the victim incapable of fighting or resisting. Police forces use them for crowd control, and military forces currently use them mainly for training. These agents were used before World War I, and in that war, they were the first chemical agents used—well before the better-known chlorine, phosgene, and mustard gas. The United States used them during the Vietnam War to deny tunnel access to its enemies. 
The United States excludes these agents from the 1925 Geneva Convention banning other chemical and biological weapons. Dispersal is allowed in specific US military operations but only by presidential order.
Tear gas (CS) and chloroacetophenone (CN) are by far the most important pulmonary irritants. The two-letter codes designating these types of compounds were assigned by the North Atlantic Treaty Organization (NATO); the abbreviation for tear gas reflects the fact that it was first synthesized by Corson and Stoughton. 
CN was the primary pulmonary irritant after World War I until the development of CS in 1928. CS was found to be more potent (10 times more potent as a lachrymator than CN) but less toxic. In approximately 1959, CS replaced CN as the principal military and law enforcement riot control agent.
CS is the familiar tear gas most often used by police for crowd control (eg, the police in the United Kingdom have used CS as an incapacitant for the past decade). CN has been available as Mace, a product that had been used for personal protection. Capsaicin, or pepper spray, has to some extent replaced CN as a personal protective agent, with less dangerous effects. 
Although CS and CN are the most important agents in this class, several others require mention. Chloropicrin (PS) and bromobenzenecyanide (CA) were developed before World War I. Both largely have been replaced, as they were too lethal for their intended effects but not lethal enough to compete with the more effective blistering and nerve agents. PS is still seen occasionally as a soil sterilant, fumigant or grain disinfectant. [3, 6]
Attempts to make CN more effective resulted in the creation of CNB (CN, carbon tetrachloride, and benzene), chloroacetophenone in chloroform (CNC), and CNS (CN, chloroform, and PS). However, CS proved more effective and less toxic than any of the CN series and largely has replaced them. While the clinical effects of a CS spray may last for days, subjects sprayed with CS have shown no convincing physical evidence of pathology for up to 10 months afterward. 
Dibenz-(b,f)-1,4-oxazepine (CR) is a more recent tear gas, first synthesized in 1962. It reportedly is more potent and less toxic than CS. Part of its high safety profile is due to its low volatility, which minimizes its effects deep in the pulmonary system. However, it is still is not used widely. Pepper spray, or oleoresin capsicum (OC), is also considered a riot control agent. A 1% solution is sold commercially to the public, but 10% solutions exist. OC causes the release of a neuropeptide (substance P) that causes pain and inflammation. A recent review states that the neurogenic inflammation caused by capsaicinoid in the pepper spray is the cause of the compound’s irritative effects.  However, at high concentrations and with prolonged exposure, fatalities with capsaicinoids have been reported. 
The possibility of secondary contamination is very real. In one incident, CS was used to flush out possible stowaways on a cargo vehicle. When the cargo was finally delivered to 16 stores within Scotland, 21 workers experienced itching and running eyes, rhinorrhea, a burning sensation on the face and hands, and a burning throat.  In case studies, secondary exposures have also affected emergency department personnel and anesthetists. 
Onset of symptoms occurs in seconds to several minutes after exposure to pulmonary irritants. Most cases are brief and self-limited, and most persons do not seek medical care. Without continuing exposure, symptoms typically resolve spontaneously in 15-30 minutes, and most persons do not seek medical care. However, serious effects, including death, have been reported. [3, 4, 5, 6] See Presentation.
Riot control agents are solids with low vapor pressures that are dispersed as fine particles or in solution. CS and CN are SN2 alkylating agents and react at nucleophilic sites. Although the mechanism is presently unclear, injuries caused by this class of agents may be caused by inactivation of sulfhydryl-containing enzymes such as lactic dehydrogenase and a specific coenzyme in the pyruvate decarboxylase system (disulfhydryl form of lipoic acid). 
Research has indicated that these agents are extremely potent activators of the body’s TRPA1 (a family of transient receptor potential ion channel) receptors (ie, mechanical stress sensors). [13, 1] Since anti‐inflammatory and analgesic effects have been observed for TRPA1 inhibitors in multiple models of chemical injury and inflammation, it is possible that TRPA1 inhibitors could alleviate at least some of the tear gas–induced effects. The conclusion of clinical trials using TRPA1 inhibitors in diabetic neuropathic patients is eagerly awaited with the hope that more advanced inhibitors will be made available for testing in other conditions, including irritant and tear gas agent exposures. 
Short-term effects of pulmonary irritants predominate. Fatalities, albeit few, have occurred at high concentrations and with prolonged exposure.  In fact, the risk of death is directly related to the agent, the concentration of the agent, the duration of exposure, the proximity to the source, and location (ie, indoors vs. outdoors) 
A systematic review of CS that included 90 cases of CS exposure reported the following distribution of effects  :
No race- or sex-related susceptibility to pulmonary irritants exists. Chemical irritants, especially those deployed in aerosolized forms, are inherently indiscriminate and can affect not only the intended targets but also peaceful demonstrators, bystanders, nearby communities and residences, and law enforcement officers themselves. The majority of people injured are young adults, consistent with typical protest demographics. Children are more vulnerable to severe injuries from chemical toxicity. The elderly and those with chronic diseases are also prone to worse outcomes. 
The prognosis for patients with irritant exposure is excellent. The few reported dangerous effects occur rapidly. Complications include the following:
A 2015 review of 10 RCA-related deaths found that RCAs were the sole cause of death in three cases, a secondary cause in three (asthma, asphyxia), and contributory in four. Pepper spray (oleoresin capsicum; OC) was the RCA involved in eight of the cases, while chloroacetophenone (CN) and tear gas (CS) caused one apiece. 
Different types of symptoms tend to vary in their duration. A systematic review of CS exposure found the following typical durations  :
In rare cases, particular reactions may persist for much longer than usual (eg, dermatitis lasting for several months).
Upon exposure to a riot control agent, the key steps are to remove oneself from the site of dissemination as quickly as possible—the mantra is to go “uphill, upwind, upstream—and then begin the process of decontamination, should sufficent material remain in contact with eyes, skin, and clothes.
Symptoms caused by a riot control agent should subside within half an hour. Persistence of effects beyond that time suggests that the agent may, in fact, not be a relatively harmless RCA, but a more toxic substance such as lewisite or phosgene, in which case, thorough decontamination is necessary.
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Paul P Rega, MD, FACEP Assistant Professor, Department of Public Health and Preventive Medicine, Assistant Professor, Emergency Medicine Residency Program, Department of Emergency Medicine, The University of Toledo College of Medicine; Director of Emergency Medicine Education and Disaster Management, OMNI Health Services
Paul P Rega, MD, FACEP is a member of the following medical societies: American College of Emergency Physicians
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Zygmunt F Dembek, PhD, MPH, MS, LHD Associate Professor, Department of Military and Emergency Medicine, Adjunct Assistant Professor, Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine
Disclosure: Nothing to disclose.
Mark Keim, MD Founder, DisasterDoc, LLC; Adjunct Professor, Emory University Rollins School of Public Health; Adjunct Professor, Harvard Affiliated Disaster Medicine Fellowship
Mark Keim, MD is a member of the following medical societies: American College of Emergency Physicians
Disclosure: Nothing to disclose.
The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors, Eric Mowatt-Larssen, MD, and David P Sole, DO, to the development and writing of this article.
Irritants – CS, CN, CNC, CA, CR, CNB, PS