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

Riot Control AgentsClinical EffectsAcute effects. The acute effects in laboratory animalsand human volunteers following inhalation ofDM are strikingly variable. 27,161 Numerous factors cancontribute to variability in laboratory studies (eg, differencesin agent preparation, delivery method, dose,endpoint of interest). Clinical observations followingexposure to DM have been reported as immediate ordelayed; the delay in onset of pulmonary and systemiceffects following DM exposure was considered advantageousbecause the delay meant that significant exposurecould occur before the individual was warnedto don a protective mask. 27,153,160In laboratory animals, clinical signs of toxicity immediatelyfollowing exposure to high doses of DMhave been studied in several species. 27 Immediatelyfollowing exposure, the clinical signs of toxicity in mice(LCt 50: 46,245 mg•min/m 3 ); rats (LCt 50: 12,710–66,856mg•min/m 3 , depending on method of dispersion);and pigs (LCt 50: 6,599–29,888 mg•min/m 3 , dependingon the method of dispersion) included transienthyperactivity and followed within a few minutesby lacrimation and salivation. Lethargy and laboredbreathing were observed within 5 to 15 minutes andpersisted for 1 to 2 hours.In dogs (LCt 50: 13,945–28,428 mg•min/m 3 , dependingon the method of dispersion), immediate clinicalsigns of toxicity included extreme restlessness (jumpingand barking) accompanied by salivation, retching,vomiting, and ataxia. Postexposure dogs also becamehypoactive, with gagging and vomiting occurringperiodically for 24 hours and lasting for about 1 week.Following lethal doses, most deaths in dogs occurredwithin the first week.During exposure, clinical signs of toxicity in monkeys(LCt 50: 13,866–22,814 mg•min/m 3 , dependingon the method of dispersion) included salivation,vomiting, rhinorrhea, ataxia, and difficulty breathing.Postexposure monkeys exhibited wheezing, ptosis, andlethargy. Coughing and vomiting persisted for 24 to 48hours, and depressed breathing preceded death.During exposure to a toxic dose of DM, goats (LCt 50:8,076–12,072 mg•min/m 3 , depending on the methodof dispersion) displayed hyperactivity, shaking of thehead, rearing on hind legs, licking, chewing, frothing atthe mouth, ataxia, convulsions, and bloating. Clinicalsigns postexposure included hypoactivity, kneeling,gagging, and vomiting. All goats were bloated upondeath.Lastly, in swine (LCt 50: 35,888–56,361 mg•min/m 3 ,depending on the method of dispersion), salivation,frothing at the mouth, ataxia, and irregular breathingwere observed during exposure. During the first 2weeks postexposure, pigs had difficulty breathing, lostweight, and appeared emaciated.The acute lethal inhalation dose of pure DM in humansis not known but was estimated by the ChemicalResearch and Development Laboratories, EdgewoodArsenal, in 1959. 153 This risk assessment was basedlargely on lethality data collected in mice, pigs, anddogs from studies that used highly purified DM. Thesedata were combined to produce a composite lethalitydose–response curve for mammals, which was thoughtto capture the dose-lethality relationship in humans.From this curve, an LCt 50value of 14,000 mg•min/m 3was established. Based on subsequent studies conductedbetween 1959 and 1965, which further characterizedthe lethal dose in seven species of laboratory animalsand addressed different methods of dispersion, thepredicted human LCt 50following exposure to highlypurified DM was reduced to 11,000 mg•min/m 3 .Given the variability in the dose–response curves inlaboratory animal studies depending on the methodof exposure or dissemination (as outlined above)and purity of the agent, the predicted human LCt 50was determined to be 44,000 mg•min/m 3 and 35,000mg•min/m 3 for DM dispersed from the M6A1 andcommercial thermal grenades, respectively.Inhalation of DM has been linked to at least onehuman fatality. 153 In this incident, 22 sleeping maleswere exposed to the agent via a DM generator for 5or 30 minutes at an estimated concentration of 1,130to 2,260 mg/m 3 . In the single fatality, postmortemexamination revealed emphysema of the subcuataneoustissues of the neck, mediastinum, plura, andpericardium. Emphysematous bullae were scatteredover the lungs, which were springy and had a bluishdiscoloration. Histological examination revealedpathology in the entire respiratory tract, edema andcongestion of the epiglottis, superficial ulceration andacute diffuse inflammation of the trachea and bronchi,pseudomembrane formation in the trachea andbronchi, lung congestion, edema, hemorrhage, andbronchopneumonia.The immediate incapacitating effects (irritationeffects, local effects) and the delayed incapacitatingeffects (systemic effects) of DM in humans have beenexamined using volunteers. The incapacitating dose ofDM following a 1-minute exposure ranged from 22 to220 mg/m 3 (22–220 mg•min/m 3 ). 153 The concentrationrange spans an order of magnitude because intolerabilityis defined as the desire to leave a contaminatedarea, which is due, in part, to the population’s degreeof motivation to resist. Other researchers suggest thatthe effective immediate incapacitating dose of DM isas low as 0.14 mg/m 3 for a 1-minute exposure. 162 Theclinical signs of immediate irritation included a burn-465