Medical Aspects of Chemical Warfare (2008) - The Black Vault

Medical Aspects of Chemical WarfarePhysiological EffectsCapsaicin is a member of the vanilloid family ofchemical compounds and binds to the vallinoid receptorsubtype 1 (VR1) on sensory neurons; the VR1receptor was discovered in 1997 using capsaicin asthe ligand. 98 VR1, now known as TRPV1, is a memberof the transient receptor potential (TRP) superfamilyof receptors. TRPV1 is activated, in part, by excessiveheat (>43°C) or abrasion, which explains whya major sensation following exposure to peppers isburning and heat. Mice deficient in TPRV1 receptorsare defective in nociceptive, inflammatory, and hypothermicresponses. 99 Thus, capsaicin does not causea chemical burn, only the sensation of one. TRPV1is also involved in purinergic signaling by the bladderurothelium, and its activation leads to a bladderdistension sensation. 100Many of the acute respiratory effects induced bycapsaicin in laboratory animals and humans are associatedwith the release of bioactive compoundssuch as substance P, neurokinin A, and calcitoningene-related peptide from sensory nerves innervatingthese tissues. 4,73 The actions of these compounds resultin clinical symptoms associated with exposure to capsaicin:bronchoconstriction, mucous secretion, edemaof the tracheobronchial mucosa, enhanced vascularpermeability, and neutrophil chemotaxis.Clinical EffectsOC, CS, and CN are considered peripheral sensoryirritants that interact with sensory nerve receptors inthe skin or mucosae to produce local sensation (discomfort,itching, burning sensation, or pain) togetherwith related local and some systemic (autonomic) reflexes.The effects subside after removal of the stimulusand do not result in any long-term adverse sequelae.The principle effects of these agents are on the eye, respiratorytract, and skin. On the eyes, depending on theconcentration, the effects are local itching, discomfort,or pain with excessive lacrimation and blepharospasmas local reflexes. 2Pain stimuli can be suppressed through a varietyof mechanisms (eg, medication and alcohol, ignoredthrough discipline, or overcome by anger and aggression).The sensory irritation induced by OC can involveinflammation and swelling in respiratory tissues andthe eyes. The ocular swelling forces the eye to involuntarilyshut, which cannot be overcome or suppressed 95(people who are described as “unaffected” by OC spraystill display involuntary eye closure and temporaryblindness 101 ).Acute EffectsAs with any compound, the physiological andtoxicological effects following acute exposure to OCare a function of the dose and route of exposure. Inhumans, these can range from mild irritant effects thatquickly resolve following removal of the stimulant tolethality, which can occur within 1 hour of exposure.The most immediate affect following exposure to OCin a spray is in the eyes, with lacrimation and blepharospasm.Following inhalation, OC can also inducechanges in the respiratory system, including nasalirritation, severe coughing, sneezing, and shortnessof breath. A burning sensation in the skin is anothercommon effect. Finally, neuromotor dysfunction andaccompanying loss of motor control can result. Highdoses of capsaicin can induce serious and sometimeslethal toxicity on the respiratory, cardiovascular, andsensory nervous system.The LD 50s for capsaicin are 0.56 mg/kg (intravenous),7.6 mg/kg (intraperitoneal), 7.8 mg/kg(intramuscular), 9.0 mg/kg (subcutaneous), 190mg/kg (oral), 512 mg/kg (dermal), and 1.6 mg/kg(intratracheal). 102 The most probable cause of death isrespiratory paralysis. The estimated oral lethal dosein humans ranges from 0.5 to 5.0 g/kg. 102Respiratory EffectsThe respiratory system is a major target followingexposure to OC owing to the highly sensitive TRPV1receptors located in the mucosa of the respiratorytract. These effects have been characterized in severalreviews. 73,95 The initial symptoms of exposure are oftena tingling sensation accompanied by the protectivemechanisms of coughing and decreased inhalationrates. Thereafter, depending on dose, intense irritationaccompanied by severe pain occurs. Profound vasodilatationand secretion occur in the nasal passages, both ofwhich are considered protective mechanisms. In lowerportions of the respiratory tract, capsaicin induces bronchoconstriction,pulmonary edema, and in severe casesof poisoning, apnea and respiratory arrest.Dermatological EffectsAlthough OC is most effective on the eyes andmucous membranes, it does irritate the skin, whichcontributes to the overall unpleasant effects of thecompound. 73 Following contact with skin, OC can induceintense burning pain, tingling, edema, erythema,and occasional blistering, depending on dose. Thesensations usually last less than an hour following454