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.

Chlorobenzylidene malononitrile tear gas exposure: Rinsing with amphoteric, hypertonic, and chelating solution.

OBJECTIVE: Chlorobenzylidene malononitrile (CS) is the tear gas used by the police. The aim was to evaluate an amphoteric, hypertonic, and chelating rinsing solution in CS exposure. METHODS: The first (CS) group of six police officers was exposed to CS only. The second (preexposure) group of eight sprayed their faces with an aqueous, hypertonic, amphoteric, and chelating solution before CS exposure. The third (postexposure) group of eight sprayed their faces with an aqueous, hypertonic, amphoteric, and chelating solution after CS exposure. The time between exiting the CS cloud and arriving at the "ready for action" checkpoint was measured. Their facial pain both inside the CS cloud and at the checkpoint was assessed (0-10 points). RESULTS: The pain level inside the CS cloud was significantly lower in the preexposed group (5.6 ± 1.1; p = 0.01) than in the CS group (9.7 ± 0.5) and in the postexposure group (9.1 ± 0.4) where it was similar. The time interval between CS exposure and arrival at the checkpoint in the preexposure group (1:26 ± 0:44 min) was significantly shorter than both in the CS group (2:28 ± 0:25 min; p = 0.04) and postexposure group (2:30 ± 0:48 min; p = 0.02) where it was not different. The residual pain at the checkpoint in the preexposure (1.1 ± 0.4) and postexposure (1.4 ± 0.7) groups was similar with a significant lower pain level than in the CS group (2.3 ± 0.5; p = 0.02). CONCLUSION: CS decontamination with an aqueous, hypertonic, amphoteric, and chelating solution reduces facial pain, whereas prevention with it reduces pain and recovery time.

Can CS gas induce myocardial infarction?

"2-chlorobenzylidene malononitrile" also named CS gas is the most used riot-control agent in the world. Its reputation as the least toxic tear gas explains its large use by different authorities. Early exposure to CS spray commonly induces visual irritation, skin reactions, with increased mucous secretion in order to temporarily incapacitate targeted people. However, there is a large agreement that safety data of this product is limited and further studies need to be performed since serious problems could occur after heavy exposure such as loss of consciousness, laryngospasm, pulmonary edema and hemorrhage... Herein, we report a case of a young man who had acute myocardial infarction with serious cardiac sequelae after exposure to tear gas. To our knowledge, this is the second case since forty years in the literature that directly links documented acute heart infarction to CS gas exposure.

Can CS gas induce myocardial infarction?

"2-chlorobenzylidene malononitrile" also named CS gas is the most used riot-control agent in the world. Its reputation as the least toxic tear gas explains its large use by different authorities. Early exposure to CS spray commonly induces visual irritation, skin reactions, with increased mucous secretion in order to temporarily incapacitate targeted people. However, there is a large agreement that safety data of this product is limited and further studies need to be performed since serious problems could occur after heavy exposure such as loss of consciousness, laryngospasm, pulmonary edema and hemorrhage... Herein, we report a case of a young man who had acute myocardial infarction with serious cardiac sequelae after exposure to tear gas. To our knowledge, this is the second case since forty years in the literature that directly links documented acute heart infarction to CS gas exposure.

Towards Development of a Dermal Pain Model: In Vitro Activation of Rat and Human Transient Receptor Potential Ankyrin Repeat 1 and Safe Dermal Injection of o-Chlorobenzylidene Malononitrile to Rat.

During clinical development of analgesics, it is important to have access to pharmacologically specific human pain models. o-Chlorobenzylidene malononitrile (CS) is a selective and potent agonist of the transient receptor potential ankyrin repeat 1 (TRPA1), which is a transducer molecule in nociceptors sensing reactive chemical species. While CS has been subject to extensive toxicological investigations in animals and human beings, its effects on intradermal or subcutaneous injection have not previously been reported. We have investigated the potential of CS to be used as an agonist on TRPA1 in human experimental pain studies. A calcium influx assay was used to confirm the capacity of CS to activate TRPA1 with >100,000 times the selectivity over the transient receptor potential vanilloid receptor 1. CS dose-dependently (EC50 0.9 µM) released calcitonin gene-related peptide in rat dorsal root ganglion cultures, supporting involvement in pain signalling. In a local tolerance study, injection of a single intradermal dose of 20 mM CS to rats resulted in superficial, circular crusts at the injection sites after approximately 4 days. The histopathology evaluation revealed a mild, acute inflammatory reaction in the epidermis and dermis at the intradermal CS injection site 1 day after administration. After 14 days, the epidermal epithelium was fully restored. The symptoms were not considered to be adverse, and it is suggested that doses up to 20 µL of 20 mM CS can be safely administered to human beings. In conclusion, our data support development of a CS human dermal pain model.

Exposure to the riot control agent CS and potential health effects: a systematic review of the evidence.

o-Chlorobenzylidene malononitrile (CS) is one of the most extensively used riot control agents. Our aim was to conduct a systematic review of the potential health effects related to CS exposure. We searched for papers in English between 1991 and 2014. Thirty five (35) studies (25 case reports, seven descriptive studies and three analytical studies) were included in the review. In the twenty five case reports/series 90 cases of exposure to CS and their clinical effects are presented. Their mean age was 25.7 years and 62.0% were males. In addition, 61% of the cases described dermal, 40% respiratory, 57% ocular clinical effects. Life threatening situations as well as long-term health effects were found and were related with exposure to confined/enclosed space. Descriptive and analytical studies have shown attack rates ranging from 12% to 40%. Subjects who were sprayed by the police more often needed special treatment and reported adverse health effects. Apart from transient clinical effects, CS could have lasting and serious effects on human health. Better surveillance of the subjects exposed to CS and completion of cohort studies among exposed populations will illuminate the spectrum of the health effects of exposure to CS.

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.

Tear gasses CN, CR, and CS are potent activators of the human TRPA1 receptor.

The TRPA1 channel is activated by a number of pungent chemicals, such as allylisothiocyanate, present in mustard oil and thiosulfinates present in garlic. Most of the known activating compounds contain reactive, electrophilic chemical groups, reacting with cysteine residues in the active site of the TRPA1 channel. This covalent modification results in activation of the channel and has been shown to be reversible for several ligands. Commonly used tear gasses CN, CR and CS are also pungent chemicals, and in this study we show that they are extremely potent and selective activators of the human TRPA1 receptor. To our knowledge, these are the most potent TRPA1 agonists known to date. The identification of the molecular target for these tear gasses may open up possibilities to alleviate the effects of tear gasses via treatment with TRPA1 antagonists. In addition these results may contribute to the basic knowledge of the TRPA1 channel that is gaining importance as a pharmacological target.

Secondary contamination of emergency department personnel from o-chlorobenzylidene malononitrile exposure, 2002.

In a hazardous materials event in 2002, the unannounced presentation of 3 symptomatic, contaminated patients to an emergency department (ED) resulted in secondary contamination of 2 ED personnel who experienced skin, eye, and respiratory irritation. The material that caused these injuries was o-chlorobenzylidene malononitrile, a white powder with a peppery odor used largely as a tear gas and riot-control agent. Secondary contamination can cause adverse symptoms and injuries in ED personnel, further contaminate the ED, and potentially lead to costly ED closures and evacuations. To prevent secondary exposure, EDs can educate their staff about the potential for secondary contamination, implement a team approach for handling contaminated patients, establish decontamination protocols, ensure proper selection of and training in the use of personal protective equipment, and simulate drills for receiving contaminated patients.

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.

[Medical aspects of the lacrimator CS].

Since the 1960's, CS has become the main riot control agent in use by police and army forces throughout the world. The first post-exposure symptom is a burning sensation in the eyes, nose and throat. At a later stage, lacrimation, rhinorrhea, conjunctivitis, sore throat and salivation appear. These symptoms are followed by chest pain and dry cough, and if the substance is swallowed, it may cause nausea and vomiting. This article reviews the physical properties of CS, the main dispersing techniques, the clinical signs and symptoms of exposure, including information on mutagenicity, carcinogenesis, pregnancy safety, and will introduce guidelines for treatment after exposure.

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.

Effect of oleoresin capsicum (OC) and ortho-chlorobenzylidene malononitrile (CS) on ciliary beat frequency.

Tear gases are largely used to control civil unrest. Their incapacitating effects involve the eyes, skin, and respiratory tract. We aimed to evaluate the effects of ortho-chlorobenzylidene malononitrile (CS) and oleoresin capsicum (OC) on ciliary beat frequency (CBF) of mouse tracheal rings. Addition of 0.05% OC or 0.01% CS induced a progressive decrease in CBF, from 11.5+/-0.5 to 4+/-0.1 Hz (P<0.05) and from 12.5+/-0.5 to 2.5+/-0.1 Hz (P<0.05), respectively, 30 min after exposure to the tear gas. Addition of exogenous ATP inhibited the effect of OC, suggesting that ATP could be used to counteract these adverse effects on CBF. However, ATP was inefficient against CS. Methylene blue and H7 inhibited the effects of OC, whereas indomethacin had no effect. None of these drugs affected the inhibitory action of CS. These results suggest that the inhibitory effect of OC is mediated through the guanylate cyclase-dependent pathway or protein kinase C-dependent phosphorylation. Another mechanism is probably involved in CS-induced inhibitory effect. Histological analysis of the trachea revealed an increase in mucus secretion after exposure to OC, and cytoplasmic vacuoles in epithelial cells after exposure to CS.