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

Medical Aspects of Chemical Warfarecapillary damage, as evidenced by ballooning of theendothelium. The authors concluded that these veryhigh dosages of CR aerosols produced only minimalpulmonary damage.Dermatological effects. CR was reported by Ballantyneand Swanston 134 and by Holland 173 to producetransient erythema, but it did not induce vesicationor sensitization and did not delay the healing of skininjuries. The burning sensation on exposure to CR persistedfor 15 to 30 minutes, and the erythema lasted 1to 2 hours. 134,173 Repeated dermal administration of CRwas conducted in mice by Marrs et al 177 and in rabbitsand monkeys by Owens et al. 178 In the latter study, CRwas applied to the skin 5 days per week for 12 weeks.Both teams of investigators concluded that repeateddermal applications of CR had little effect on the skin.They further postulated that in view of the absence ofany specific organ effects, absorption of even substantialamounts of CR would have little effect.Ophthalmologic effects. Higgenbottom andSuschitzky 179 were first to note the intense lacrimationand skin irritation caused by CR. Mild and transitoryeye effects such as mild redness and mild chemosiswere observed in rabbits and monkeys after a singledose of 1% CR solution. Multiple doses over a 5-dayperiod of the same solution to the eye produced onlyminimal effects. 179 Biskup et al 180 reported no signs of eyeirritation in animals following single or multiple doseapplications of 1% CR solutions. Moderate conjunctivitisfollowing the application of 5% CR solution to the eyesof rabbits was reported by Rengstorff et al, 181 althoughhistological examination revealed normal corneal andeyelid tissues. Ballantyne and Swanston 134 also studiedthe ocular irritancy of CR and arrived at a thresholdconcentration for blepharospasm in several species.Ballantyne et al 138 studied the effects of CR as a solid, anaerosol, and a solution in polyethylene glycol. Aerosolexposures of 10,800 and 17,130 mg•min/m 3 resultedin mild lacrimation and conjunctival injection, whichcleared in 1 hour. When applied in solution, it producedreversible dose-related increases in corneal thickness.The authors concluded that CR produced considerablyless damage to the eye than CN and is much safer.Gastrointestinal disturbances. Although humandata is not readily available in this area, animal studiesby Ballantyne and Swanston 134 showed the repeateddose effects of orally administered CR on variousanimal species. The animals that died following intravenousand oral administration demonstrated congestionof the liver sinusoids and alveolar capillaries. Atnecropsy, the surviving animals did not show any grossor histological abnormalities. The toxic signs followingintraperitoneal administration included muscle weaknessand heightened sensitivity to handling. Theseeffects persisted throughout the first day followingexposure. Some animals also exhibited central nervoussystem effects. On necropsy, the surviving animals didnot show any gross or histological abnormalities.Other physiological responses. Ballantyne et al 172reported the effects of dilute CR solution on humansfollowing splash contamination of the face, or facialdrench. These exposures resulted in an immediateincrease in blood pressure concomitant with decreasedheart rate. In subsequent studies by Ballantyne et al, 78humans were exposed to whole body drenches thatresulted in the same effects of immediate increase ofblood pressure and bradycardia. The authors concludedthat the cardiovascular effects in both studieswere caused by the CR, theorizing that the amount ofCR uptake was insufficient to produce the systemiceffects on the heart. However, they did not providean explanation for the cardiovascular changes. Lundyand McKay 182 suggested that these cardiovascularchanges resulted from the CR effects on the heart viathe sympathetic nervous system.Several animal species were exposed to acute inhalationof CR aerosols and smokes for various timeperiods. Rats exposed to aerosol concentrations from13,050 to 428,400 mg•min/m 3 manifested nasal secretionsand blepharospasm or uncontrollable closureof the eyelids, which subsided within an hour aftertermination of the exposure. No deaths occurred duringor following these exposures. There were also nodeaths in rabbits, guinea pigs, or mice exposed to CRaerosols of up to 68,000 mg•min/m 3 . Animals exposedto CR smoke generated pyrotechnically had alveolarcapillary congestion and intraalveolar hemorrhage, aswell as kidney and liver congestion.Long-term effects and severe medical complications.Repeated inhalation exposures were conductedby Marrs et al, 183 who exposed mice and hamsters toconcentrations of 204, 236, and 267 mg/m 3 CR for 5days per week for 18 weeks. The high concentrationsproduced death in both species, but no single causeof death could be ascertained, although pneumonitiswas present in many cases. Chronic inflammation ofthe larynx was observed in mice. Although alveologeniccarcinoma was found in a single low-dose anda single high-dose group of mice, the findings andconclusions were questioned because the spontaneousoccurrence of alveologenic carcinoma is high in manymouse strains. 184,185 Furthermore, this tumor type differsin many respects from human lung tumors. Nolung tumors and no lesions were found in hamstersexposed to CR aerosols. Histopathology revealed hepaticlesions in mice, but these were of infectious originand not related to the CR. The authors concluded thatCR exposures at high concentrations reduced surviv-468