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

Medical Aspects of Chemical Warfareing sensation and pain in the eyes, nose, throat, andrespiratory tract; uncontrollable cough; violent andpersistent sneezing; lacrimation; and copious flow ofsaliva. In addition to irritant effects on tissues at thesite of exposure, DM also has systemic incapacitatingeffects (ie, nausea and vomiting), which persist followingtermination of exposure. Based on studies usinghuman volunteers, the inhalational ICt 50for systemiceffects was determined to be 370 mg•min/m 3 .Postmortem observations in laboratory animalsthat received a lethal dose of DM have been reportedin five species, and the primary cause of death for allspecies was lung damage. 153 In monkeys, pneumonitis;ulcerative bronchiolitis; and tracheitis, edema, andcongestion of the lungs were reported. Bronchiolitisand tracheitis was also observed in guinea pigs. Dogsdemonstrated hyperemia of the larynx and trachea,with signs of edema, congestion of the lung, andbronchopneumonia. In mice and rats, atelectasis,emphysema, reticular cell proliferation, respiratoryepithelial proliferation, and interstitial leucocytic infiltrationof the bile duct were observed. DM has alsobeen shown to alter blood chemistry in laboratoryanimals. 153 Changes include alterations in leukocytes,serum enzymes, hematocrit, and prothrombin time.Respiratory effects. In the respiratory passagesand lungs, DM causes sneezing, coughing, salivation,congestion of the nose and walls of the pharynx, and afeeling of suffocation. 27,55 Viscous nasal discharge, characterizedas a yellowish-orange material in monkeys,has been reported in laboratory animals and humanvolunteers. 156,160 A World Health Organization reportcharacterized the clinical symptoms in the respiratorytract following DM exposure as initial tickling sensationsin the nose, followed by sneezing and mucousdischarge. The irritation spreads into the throat, followedby coughing and choking, with eventual affectsobserved in the lower air passages and lungs. 162Dermatological effects. Direct application of highdoses of DM, 10 to 100 mg suspended in corn oil, ontorabbit skin resulted in necrosis and erythema, butneither effect was reported at a 1-mg dose. 27 Althoughthese results identify DM as a potential skin hazard,several controlled exposures to DM aerosols in humanvolunteers and laboratory animals suggest thatthe dose required to cause acute skin irritation is wellabove that known to induce irritation and toxicity inother tissues. 55,153 One study in monkeys did reportfacial erythema following a moderate dose of aerosolizedDM, but the pathology was likely the result ofthe animals rubbing their faces because of significantnasal discharge. 160 Repeated exposure to DM may leadto sensitization in susceptible persons. 153 Elevated environmentaltemperature, high relative humidity, andfriction of the agent with the skin may be contributoryfactors to skin damage.Ophthalmologic effects. Depending on the doseand method of administration, irritation of the eyeis observed following exposure to DM, but ocularirritation is often not considered the main immediateeffect at low doses. 163 For example, human volunteersexposed to airborne concentrations of DM up to 100mg•min/m 3 (a dose causing nose, throat, and chestirritation) reported no initial eye irritation. 55 Otherreports using human volunteers reported slight irritationof the eyes and lacrimation at doses causing noseand throat irritation and initial weak immediate ocularirritation. 157,162 In rabbits, a suspension of DM in cornoil was administered intraocularly to six groups of animals(0.1–5.0 mg/eye) and observed for 8 to 14 days. 27The low dose (0.1 mg/eye) was determined to be the“no observable adverse effect” level; whereas transientconjunctivitis was observed following administrationof 0.2 mg per eye; transient conjunctivitis and blepharitiswere observed with the 0.5 mg per eye dose; andthe high doses, 1.0 and 5.0 mg per eye, caused cornealopacity that persisted for the entire 14-day observationperiod. DM’s weak ocular irritation at doses knownto induce irritation in other sensory tissue is likely afactor contributing to the incorporation of the tearingagent CN in DM riot control preparations.Gastrointestinal disturbances. DM is classified bythe military as a vomiting agent, and several researchershave characterized that response in both humansand laboratory animals. 73,156,157 Although the humanstudies did not establish the minimal dose of DM requiredto induce these systemic incapacitating effects,the work did lead to an estimated incapacitating doseof 370 mg•min/m 3 . The World Health Organizationdetailed the progression of symptoms resulting fromDM exposure as initial nausea that soon causes violentretching and vomiting. 163 These effects can have anonset after 20 to 30 minutes of exposure.Other physiological responses. Other systemic effectsincluded headache, mental depression, perspiration,chills, abdominal cramps, and diarrhea. 55,147,161,163–166Long-term effects and severe medical complications.Prolonged exposure to DM and/or high-doseacute exposures can cause death by damage tothe respiratory tract and lungs, but in general themargin of safety between irritant dose and lethaldose is great. 27 Repeated dose toxicity studies havebeen conducted in monkeys, dogs, and guinea pigs.Studies of aerosol DM exposures for 10 consecutivedays generated by commercial thermal grenades toLCt 20, LCt 25, and LCt 50doses gave little indication ofcumulative toxicity. The effect of repeated exposurein humans is not known.466