Cardiopulmonary function and dysregulated cardiopulmonary reflexes following acute oleoresin capsicum exposure in rats.

Cardiopulmonary functions such as respiratory depression, severe irritation, inflamed respiratory tract, hyperventilation and, tachycardia are the most affected ones when it comes to the riot control agent oleoresin capsicum (OC) exposure. However, no studies have been done to elucidate the mechanism underlying deterioration of the combined cardiopulmonary functions. Parameters such as acute respiratory, cardiac, parameters and ultrasonography (USG) measurements were investigated in an in vivo setup using Wistar rats at 1 h and 24 h post inhalation exposure to 2%, 6% and 10% OC, whereas, cell migration in rat peritoneal mast cells (RPMCs), metabolomics and eosinophil peroxidase (EPO) activity in bronchoalveolar lavage fluid (BALF) were investigated in an in vitro setup. Results obtained from electrophysiological recording indicated that OC exposure produces apnea and decrease in mean arterial pressure (MAP) was obtained from hemodynamic parameters whereas cardiac parameters assessment revealed increase in the level of cardiac output (CO) and decrease in stroke volume (SV) with recovery towards the post-exposure period. A decrease in the percentage area of certain fatty acid pathway metabolites in BALF appropriately linked the lung injury following OC exposure which was further cemented by increasing concentration of EPO. Histopathology and SEM also proved to be favorable techniques for the detection of OC induced physiological cardiac and pulmonary modifications respectively. Furthermore, Boyden chamber experiment established the chemoattractant property of OC. It may be concluded from the above studies that these newly reported facets may be utilized pharmacologically to mitigate cardiopulmonary adverse effects owing to OC exposure.

Innate inflammatory response to acute inhalation exposure of riot control agent oleoresin capsicum in female rats: An interplay between neutrophil mobilization and inflammatory markers.

Aim: The use of oleoresin capsicum (OC) sprays, due to their irreversible health effects has now grown into a matter of heated debate. In the present study, the early phase pulmonary events involving chemotactic and inflammatory mediators after short-exposure duration to OC have been presented.Materials and methods: Female Wistar rats used in the evaluation of respiratory parameters at 1 h, 3 h, and 24 h post-exposure, were sacrificed for the evaluation of blood cell counts, BALF cytokine estimation, lung capillary leakage, study of oxidative stress and histopathology of the lungs.Results: Results confirmed a dose-dependent effect of OC exposure on serum clinical chemistry and hematological parameters. Subsequent upregulation of IL-l and TNF-α indicated lung's responses to acute oxidant-induced injury and inflammation after OC exposure. Significant alterations in the pulmonary levels of reactive oxygen intermediates were seen following the inhalation of OC. Infiltration of polymorphonuclear leukocytes, mostly neutrophils, into the site of infection was evident in the cytocentrifuged samples of BALF. Histological samples of rat lung sections revealed the recruitment of inflammatory cells in the airways and around blood vessels in the subepithelium of conducting airways.Conclusion: Results of the present study demonstrated that, exposure to OC spray may mitigate inflammatory response and development of acute lung injury in rats. However, it can be concluded that although OC spray causes pulmonary hazards in the aforementioned concentrations, it can be used as a non-lethal riot control agent in minimal concentration. Understanding the in-depth mechanism of action in the molecular and receptor level will help in developing effective antagonist against OC.

Fundamental pharmacological expressions on ocular exposure to capsaicin, the principal constituent in pepper sprays.

Eye irritation assessment is compulsory to anticipate health risks in military personnel exposed to riot control agents such as capsaicin, the principal constituent of oleoresin capsicum, or pepper sprays. The present work investigates certain fundamental yet unaddressed pharmacological manifestations on ocular exposure to capsaicin. Ocular pharmacology of capsaicin was studied using acute eye irritation (AEI), bovine corneal opacity and permeability (BCOP) assay, corneal fluorescein staining and indirect ophthalmoscopy studies, transcorneal permeation, Schirmer tear secretion test, nerve conduction velocity study and enzyme-linked immunosorbent assay (ELISA). Additionally, histopathology and scanning electron microscopy (SEM) of bovine corneas and rat optic nerves were done to further estimate capsaicin induced morphological variations. Our findings demonstrated that AEI, BCOP, corneal fluorescein staining and indirect ophthalmoscopy were useful in assessing capsaicin induced ocular irritation; AEI and BCOP also contributed towards indicating the eye irritation potential of capsaicin as per the United Nations Globally Harmonized System of Classification and Labelling of Chemicals categorization. Additional experimental observations include considerable transcorneal permeation of capsaicin, capsaicin induced reduction in tear secretions and nerve conduction velocity and increased expression of proinflammatory cytokines by ELISA. Histopathology and SEM were favourable techniques for the detection of capsaicin induced ocular physiological modifications.

Comparative safety evaluation of riot control agents of synthetic and natural origin.

Riot control agents (RCA) are lachrymatory, irritating compounds which temporarily incapacitate the uncontainable crowd. Ortho-Chlorobenzylidene-malononitrile (CS), 2-chloroacetophenone (CN), dibenz[b,f]1:4-oxazepine (CR), and nonivamide (PAVA) are synthetic RCAs, while oleoresin extract of chili known as oleoresin capsicum (OC) a natural irritant has been in use by various law enforcement agencies. Though efficacy of these agents is beyond doubt, they suffer from certain drawbacks including toxicity, production cost, and ecological compatibility. Presently, we have evaluated the safety of CR, OC, and PAVA on inhalation variables along with oral lethality. Additionally, the liver function test (LFT) in serum and lungs function was evaluated in broncho-alveolar-lavage fluid (BALF), both collected on the 14th day after RCA exposure. Animals then sacrificed and histopathology of liver and lungs was carried out. Results showed OC and PAVA to be more toxic than CR with an oral LD50 of 150 and 200 mg/kg body weight, respectively, while CR was safe at >3 g/kg body weight. All three agents caused severe impairment of respiratory variables bringing down normal respiration by >80% with rise in sensory irritation. Recovery from the irritating effect of CR was more rapid than OC and PAVA. LFT and BALF variables were not significantly different from that of control. There were no remarkable histopathological changes in liver and lungs. Hence, as per results, CR is safest among all synthetic and natural origin RCAs and can be safely used for effective dispersion of disobedient mob.

Association between exposure to o-chlorobenzylidene malononitrile (CS riot control agent) and urinary metabolite 2-chlorohippuric acid in U.S. Army Mask Confidence Training.

This study was conducted among U.S. Army soldiers to evaluate the association between exposure to o-chlorobenzylidene malononitrile (CS riot control agent) and urinary metabolite 2-chlorohippuric acid (CHA) detected in test subjects (n = 87) after completion of Mask Confidence Training. CS exposures ranged 0.086-4.9 mg/m³ ([Formula: see text] = 2.7 mg/m³). CHA levels (corrected for creatinine) at 2-, 8-, 24-, and 30-hr post-exposure resulted in ranges of 94.6-1120 µg/g-cr ([Formula: see text] = 389 µg/g-cr), 15.80-1170 µg/g-cr ([Formula: see text] = 341 µg/g-cr), 4.00-53.1 µg/g-cr ([Formula: see text] = 19.3 µg/g-cr), and 1.99-28.4 µg/g-cr ([Formula: see text] = 10.6 µg/g-cr), respectively. Spearman's correlation revealed CHA levels strongly correlated with time sampled (r = -0.748, p < 0.05) and weakly correlated with CS concentration (r = 0.270, p < 0.05). A linear relationship was observed between CHA, CS concentration, and time of urine sample according to the following regression equation: ln(CHA, µg/g-cr) = 5.423 + 0.316 (CS conc., mg/m³) - 0.002 (time sampled), (R = 0.910, R² = 0.827, p < 0.05). This relationship suggests that CHA has the potential to be an effective retrospective indicator of CS exposure in future biomarker developments.

Usage of Riot Control Agents and other methods resulting in physical and psychological injuries sustained during civil unrest in Turkey in 2013.

Turkey has experienced a wave of demonstrations in the summer of 2013, called Gezi Park Demonstrations. Between 31 May and 30 August, 297 people who had been subjected to trauma by several methods of demonstration control and Riot Control Agents applied to the Human Rights Foundation of Turkey Rehabilitation Centers to receive treatment/rehabilitation and/or documentation. 296 patients except one 5-year-old child were included in the study. Of the 296 patients; 175 were male, 120 were female, and one was a transgender individual. The highest number of applications was received by the Istanbul center with 216 patients. The mean age of applicants was 33.85, and the age range was 15-71 years. While 268 of applicants (91%) stated that they had been exposed to Riot Control Agents, 62 patients suffered only chemical exposure who had no other traumatic injuries whereas 234 patients suffered at least one blunt trauma injury. Blunt trauma injuries are due to being shot by gas canisters in 127 patients (43%), by plastic bullets in 31 patients (10%). 59 patients (20%) were severely beaten, and 30 patients (10%) were injured by pressurized cold water ejected by water cannons. Thirteen patients (4.4%) suffered injuries that caused loss of vision or eye. Psychiatric evaluations were carried out for 117 patients while 43% of them were diagnosed with Acute Stress Disorder. Post Traumatic Stress Disorder and Major Depressive Disorder followed this diagnosis. This study includes the medical evaluation of injuries allegedly sustained during Gezi Park demonstrations in 2013 as a result of several methods of demonstration control and/or by being exposed to Riot Control Agents. The aim is to discuss different types of injuries due to those methods and health consequences of Riot Control Agents.

Clinicopathological effects of pepper (oleoresin capsicum) spray.

OBJECTIVES: Pepper (oleoresin capsicum) spray is one of the most common riot-control measures used today. Although not lethal, exposure of pepper spray can cause injury to different organ systems. This review aimed to summarise the major clinicopathological effects of pepper spray in humans. DATA SOURCES: MEDLINE, EMBASE database, and Cochrane Database of Systematic Reviews were used to search for terms associated with the clinicopathological effects of pepper spray in humans and those describing the pathophysiology of capsaicin. A phone interview with two individuals recently exposed to pepper spray was also conducted to establish clinical symptoms. STUDY SELECTION: Major key words used for the MEDLINE search were "pepper spray", "OC spray", "oleoresin capsicum"; and other key words as "riot control agents", "capsaicin", and "capsaicinoid". We then combined the key words "capsaicin" and "capsaicinoid" with the major key words to narrow down the number of articles. A search with other databases including EMBASE and Cochrane Database of Systematic Reviews was also conducted with the above phrases to identify any additional related articles. DATA EXTRACTION: All article searches were confined to human study. The bibliography of articles was screened for additional relevant studies including non-indexed reports, and information from these was also recorded. Non-English articles were included in the search. DATA SYNTHESIS: Fifteen articles were considered relevant. Oleoresin capsicum causes almost instantaneous irritative symptoms to the skin, eyes, and respiratory system. Dermatological effects include a burning sensation, erythema, and hyperalgesia. Ophthalmic effects involve blepharospasm, conjunctivitis, peri-orbital oedema, and corneal pathology. Following inhalation, a stinging or burning sensation can be felt in the nose with sore throat, chest tightness, or dyspnoea. The major pathophysiology is neurogenic inflammation caused by capsaicinoid in the pepper spray. There is no antidote for oleoresin capsicum. Treatment consists of thorough decontamination, symptom-directed supportive measures, and early detection and treatment of systemic toxicity. Decontamination should be carefully carried out to avoid contamination of the surrounding skin and clothing. CONCLUSION: Pepper (oleoresin capsicum) spray is an effective riot-control agent and does not cause life-threatening clinical effects in the majority of exposed individuals. Early decontamination minimises the irritant effects.

Overall view of chemical and biochemical weapons.

This article describes a brief history of chemical warfare, which culminated in the signing of the Chemical Weapons Convention. It describes the current level of chemical weapons and the risk of using them. Furthermore, some traditional technology for the development of chemical weapons, such as increasing toxicity, methods of overcoming chemical protection, research on natural toxins or the introduction of binary technology, has been described. In accordance with many parameters, chemical weapons based on traditional technologies have achieved the limit of their development. There is, however, a big potential of their further development based on the most recent knowledge of modern scientific and technical disciplines, particularly at the boundary of chemistry and biology. The risk is even higher due to the fact that already, today, there is a general acceptance of the development of non-lethal chemical weapons at a technologically higher level. In the future, the chemical arsenal will be based on the accumulation of important information from the fields of chemical, biological and toxin weapons. Data banks obtained in this way will be hardly accessible and the risk of their materialization will persist.

[Analysis of exposure to pepper spray as a part of preparing hospital to help victims of mass chemical incidents]. / Analiza narazenia na gaz pieprzowy jako element przygotowania szpitala do pomocy ofiarom masowych skazen chemicznych.

We analyzed an incident of exposure to pepper spray 35 persons, including 29 children. Medical procedures were difficult because of the lack of reliable information about the nature of exposure, lack of hospital action plan for chemical accidents and established principles of cooperation with poison control center, as well as the need of extensive medical documentation for each patient.

Towards evidence-based emergency medicine: Best BETs from the Manchester Royal Infirmary. BET 1: the best treatment for eye irritation caused by CS spray.

A short-cut review was performed to evaluate whether irrigation or active blown air was the most effective treatment for CS gas irritation of the eyes. No published studies have answered this question. The clinical bottom line is that either treatment could be used to relieve eye symptoms after CS gas exposure.

Educating on CS or 'tear gas'.

Chlorobenzalmalononitrile or 2-chlorobenzylidene malononitrile (CS) is a commonly used riot control agent. Although generally deemed to be safe for this application, it is known that CS can cause a number of adverse effects in those exposed to it. Understanding its properties and its side effects is important in ensuring optimal medical management of its complications and, indeed, this principle applies to every chemical. As the need for CS and other law enforcement devices increases, it is important for the emergency medicine team and other specialties to be aware of correct management protocols.

Medical management of the traumatic consequences of civil unrest incidents: causation, clinical approaches, needs and advanced planning criteria.

In the context of this review, civil unrest is defined as disharmony, expressive dissatisfaction and/or disagreement between members of a community, which leads to a situation of competitive aggression that may find expression as disruption of organisation, conflicts, damage to property and injuries. Such a breakdown of harmonious relationships, which may result in property damage and human injuries that may be threatening to life, varies in magnitude from participation of a very few individuals up to the involvement of large crowds of people, which may evolve into a full-scale riot. It is the latter situation often involving demonstrators, opposing groups and law enforcement personnel that can result in multiple casualties and present a very significant challenge to the resources of local healthcare institutions. The causation of civil unrest incidents is multifactorial and has generic, specific and potentiating elements. With the current national and international societal, political and discriminatory problems, it is likely that civil unrest incidents on both small and large scales will continue to occur at a high and possibly increasing rate on a worldwide basis, and for these not infrequent incidents, the medical community should be in a state of informed preparation. The circumstances of civil unrest incidents are very variable with respect to causation, overall magnitude, frequency, timing, geographical location, numbers of persons involved, demographics of participants, influence of extremists, confrontation with opposing groups and control measures used by law enforcement agencies. Methods used by police and security forces for the control of civil unrest incidents, if advanced negotiations with organisers and verbal warnings have failed, fall basically into two categories: physical and chemical measures. Physical methods include restraint holds, truncheons, batons, mounted horses, projectiles (such as bean bags, plastic and rubber bullets), water cannons, tasers and (rarely) live ammunition. All of these physical measures are associated with pain and immobilisation, and there is a high potential for soft tissue and bone injuries. Some of the more severe physical methods, including plastic and rubber bullets, may cause lethal injuries. The basis for using chemicals in civil unrest incidents is that they cause distraction, transient harassment and incapacitation, temporary impairment of the conduct of coordinated tasks and cause a desire to vacate the area of unrest. Although screening smokes and malodors have sometimes been employed, the major group of chemicals used are peripheral chemosensory irritants (PCSIs), which reversibly interact with sensory nerve receptors in exposed skin and mucosal surfaces, resulting in the production of local uncomfortable sensations and associated reflexes. Major effects are on the eye, respiratory tract and (to a lesser degree) skin. Thus, the induced transient pain and discomfort in the eye, respiratory tract and skin, together with associated lacrimation, blepharospasm, rhinorrhoea, sialorrhoea, cough and breathing difficulties, produce temporary incapacitation and interference with the conduct of coordinated tasks, and form the basis for harassment of malefactors. Currently used peripheral chemosensory irritants are 1-chloroacetophenone, 2-chlorobenzylidene malononitrile, dibenz(b.f)-1,4-oxazepine, oleoresin capsicum and pelargonic acid vanillylamide. Depending on operational circumstances, irritants may be dispersed as a smoke, powder cloud, aerosol, vapour, or in solution; the mode of generation and dispersion of irritant can influence hazard. Brief acute exposure to chemosensory irritants produces effects that generally resolve within an hour, leaving no long-term sequelae. However, sustained exposure to high concentrations may produce tissue injury, notably to the eye, respiratory tract and skin. With solutions of sensory irritants, other formulation constituents may enhance PCSI toxicity or introduce additional local and/or systemic toxicity. By the very circumstances of civil unrest incidents, injuries are inevitable, particularly when emotions are heightened and police and security forces have to resort to various chemical and/or physical means of control. Trauma may include slight to severe physical and/or chemical injuries, psychological problems and occasional deaths. Hospitals should be prepared for a wide range of casualties, and the fact that those seeking help will constitute a heterogeneous group, including wide age range, male, female, and individuals with pre-existing ill health. A major civil unrest incident necessitates that the local receiving hospital should be prepared and equipped for decontamination and triage processes. It is necessary to reassure patients who have been exposed to sensory irritants that the signs and symptoms are rapidly reversible, and do not result in long-term sequelae. With respect to chemical exposures, detailed evaluation should be given to possible ocular, cutaneous, respiratory and gastrointestinal effects. Also, exposure to chemosensory irritants results in transient increases in blood pressure, bradycardia and increased intraocular pressure. This indicates that those with cardiovascular diseases and glaucoma may be at increased risk for the development of complications. This article details the pharmacological, toxicological and clinical effects of chemicals used in civil disturbance control and discusses the management of contaminated individuals. Additionally, the potential for adverse effects from delivery systems and other physical restraint procedures is summarised. Due to the emergency and specialised circumstances and conditions of a civil unrest incident, there is a clear need for advanced planning by healthcare institutions in the event that such an incident occurs in their catchment area. This should include ensuring a good information base, preparations for medical and support staff readiness, and availability of required equipment and medications. Ideally, planning, administration and coordination should be undertaken at both local (regional) and central (governmental) centres. Regional centres should have responsibilities for education, training, ensuring facilities and staffing are appropriate, and that adequate equipment and medicines are available. There should be cooperative interactions and communications with local police and other emergency services. Centrally directed functions should include ensuring adequacy of the information base, coordinating activities and agreeing approaches between the regional centres, and periodic audits of regional centres with respect to the staffing, facility, equipment and training needs. Also, there is a need for most countries to introduce detailed guidelines and formal (regulatory) schemes for the assessment of the safety-in-use of chemicals and the delivery systems that are to be used against heterogeneous human populations for the control of civil unrest incidents. Such regulatory approval schemes should also cover advisory functions for safe use and any required restrictions.

Postoperative complications after CS spray exposure.

Summary We report on airway complications associated with general anaesthesia in a subject who had been exposed to CS spray several hours before surgery. CS spray is a form of tear gas that is said to have a short half-life when the subject is removed from exposure. Induction of anaesthesia was uneventful. Marked laryngospasm occurred when the tracheal tube was removed at the end of the operation, and the anaesthetists experienced lacrimation and burning sensations typical of CS exposure. The effects on the attending anaesthetist made tracheal re-intubation difficult. There were no long-term adverse sequelae for the patient or anaesthetists. Suggestions are made for changes to anaesthetic practice and the advice given by the police about patients who have been exposed to CS spray.

An investigation into the short term and medium term health impacts of personal incapacitant sprays. A follow up of patients reported to the National Poisons Information Service (London).

OBJECTIVES: The aim of this study is to describe the pattern of ill health after personal incapacitant spray (PIS) exposures reported to the National Poisons Information Service-London (NPIS-L) and the Chemical Incident Response Service and to evaluate the relation between sub-categories of PIS exposure and adverse health effects. METHODS: Case series study of patients reported to the NPIS-L, by attending medical personnel during the period 16 January to 31 September 1998. Data collected by questionnaire sent to these medical personnel. RESULTS: Several "adverse" symptoms, particularly dermatitis and blisters were reported for cases exposed to police PIS. These cases were more frequent than in those people exposed to non-police PIS. Adverse effects occurring more than six hours after exposure were also observed, which is in conflict with the recorded immediate, short lived, and self limiting symptoms that PIS are designed to cause. Most patients with persisting symptoms required further treatment. CONCLUSIONS: These findings suggest that the formulation of CS (o-chlorobenzylidine malononitrile) with MiBK (methyl iso-butyl ketone) used by the police is more harmful that has been previously assumed. If confirmed then the continued use of this formulation should be reviewed because of longer duration of adverse effects. Less concentrated formulations may reduce the severity or persistence of the adverse effects.

Tear gases and irritant incapacitants. 1-chloroacetophenone, 2-chlorobenzylidene malononitrile and dibenz[b,f]-1,4-oxazepine.

Irritant incapacitants, also called riot control agents, lacrimators and tear gases, are aerosol-dispersed chemicals that produce eye, nose, mouth, skin and respiratory tract irritation. Tear gas is the common name for substances that, in low concentrations, cause pain in the eyes, flow of tears and difficulty in keeping the eyes open. Only three agents are likely to be deployed: (i) 1-chloroacetophenone (CN); (ii) 2-chlorobenzylidene malononitrile (CS); or (iii) dibenz[b,f]-1,4-oxazepine (CR). CN is the most toxic lacrimator and at high concentrations has caused corneal epithelial damage and chemosis. It has accounted for at least five deaths, which have resulted from pulmonary injury and/or asphyxia. CS is a 10-times more potent lacrimator than CN but is less systemically toxic. CR is the most potent lacrimator with the least systemic toxicity and is highly stable. CN, CS and CR cause almost instant pain in the eyes, excessive flow of tears and closure of the eyelids, and incapacitation of exposed individuals. Apart from the effects on the eyes, these agents also cause irritation in the nose and mouth, throat and airways and sometimes to the skin, particularly in moist and warm areas. In situations of massive exposure, tear gas, which is swallowed, may cause vomiting. Serious systemic toxicity is rare and occurs most frequently with CN; it is most likely to occur when these agents are used in very high concentrations within confined non-ventilated spaces. Based on the available toxicological and medical evidence, CS and CR have a large safety margin for life-threatening or irreversible toxic effects. There is no evidence that a healthy individual will experience long-term health effects from open-air exposures to CS or CR, although contamination with CR is less easy to remove.

Riot control agents: pharmacology, toxicology, biochemistry and chemistry.

The desired effect of all riot control agents is the temporary disablement of individuals by way of intense irritation of the mucous membranes and skin. Generally, riot control agents can produce acute site-specific toxicity where sensory irritation occurs. Early riot control agents, namely, chloroacetophenone (CN) and chlorodihydrophenarsazine (DM), have been replaced with 'safer' agents such as o-chlorobenzylidene malononitrile (CS) and oleoresin of capsicum (OC). Riot control agents are safe when used as intended: however, the widespread use of riot control agents raises questions and concerns regarding their health effects and safety. A large margin exists between dosages that produce harassment and dosages likely to cause adverse health effects for modern riot control agents such as CS and dibenz[b,f]1 : 4-oxazepine (CR). Yet, despite the low toxicity of modern riot control agents, these compounds are not entirely without risk. The risk of toxicity increases with higher exposure levels and prolonged exposure durations. Ocular, pulmonary and dermal injury may occur on exposure to high levels of these substances, and exposure to riot control agents in enclosed spaces may produce significant toxic effects. Reported deaths are few involving riot control agents, and then only under conditions of prolonged exposure and high concentrations. Recently, concern has focused on the deaths resulting from law enforcement use of OC, a riot control agent generally regarded as safe because it is a natural product. As with other xenobiotics, not enough is known concerning the long-term/chronic effects of riot control agents. Clearly, there is considerable need for additional research to define and delineate the biological and toxicological actions of riot control agents and to illuminate the full health consequences of these compounds as riot control agents.