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

Riot Control Agentsand increased lipid peroxidation. Hepatic acid phosphataseincreased after the 5-day CN exposure, andthe glutathione levels decreased after the 10-day CNexposure. CN-induced elevation in acid phosphataselevels reflected the release of lysosomal enzyme fromthe liver, which is indicative of tissue injury. CR exposuredid not produce any significant alteration of thebiochemical parameters. Additionally, hyperglycemiawas observed after exposure to CN, an effect previouslyreported by Husain et al. 133 It was suggested thatthe hyperglycemia was induced by the stress-mediatedrelease of epinephrine, which is known to elevate glucoselevels. Significant decreases in body weight gainwere also noted on exposure to these compounds, withCN having a more prominent effect on body weight.The acute mammalian inhalation toxicity of CN was3 to 10 times greater than CS toxicity in rats, rabbits,guinea pigs, and mice. Lung pathology in the CNexposedanimals was also severe, consisting of patchyacute inflammatory cell infiltration of the trachea andbronchioles, as well as of more edema and more evidenceof early bronchopneumonia than with CS. 134Ocular effects. In a variety of studies, mice and ratsexposed to CN aerosols for 13 weeks had no findingsof gross clinical signs except for irritation of the eyes,including opacity. No microscopic lesions were notedcompared to controls. Avoidance and the intense lacrimationand blepharospasm are indicative of defensivemechanisms caused by CN ocular irritation. High concentrationsof CN may result in chemical injury to theeyes, with corneal and conjunctival edema and erosion,or ulceration, chemosis, and focal hemorrhage. 135–137CN-induced ocular effects on the rabbit eye havebeen investigated by Ballantyne et al 138 and Gaskinset al. 139 The effects included lacrimation, chemosis,iritis, blepharitis, and keratitis, and the severity wasdependent on the formulation.Sublethal effects observed on exposure to CNconsisted of lacrimation, conjunctivitis, copious nasalsecretions, salivation, hyperactivity, dyspnea, andlethargy, which occurred in all animals. At high concentrationsCN has caused corneal epithelial damageand chemosis. Like CS and CR, CN causes almostinstant pain in the eyes along with excessive flow oftears and closure of the eyelids. 71 The ocular effect ofconjunctivitis and dermal erythema persisted for 3to 7 days postexposure in animal studies. 71 Lacrimationpersisted for about 20 minutes postexposure;conjunctivitis and blepharospasm persisted for up to24 hours. 27Cutaneous effects. Exposure to CN has been associatedwith primary irritation and allergic contactdermatitis. 140–142 CN is a potent skin irritant and ismore likely to cause serious injury to the skin than CS.Exposure to high doses of CN results in skin injury thatmay consist of severe generalized itching, diffuse andintense erythema, severe edema, and vesication. CNis also considered to be a more potent skin sensitizerthan CS. 140Carcinogenicity testing. The National Institutesof Health conducted a carcinogenicity bioassay inrats and mice with CN, finding no indication ofcarcinogenetic activity of CN in male rats exposedby inhalation. The evidence was equivocal in femalerats based on the findings of an increase in mammarygland fibroadenomas. The 2-year inhalation study inboth male and female mice did not suggest any carcinogenicactivity. 143Human Studies and EffectsThe effects caused by CN in humans are similar tothose of CS, but more severe. The harassing dose andtoxicity of CN are also greater than for CS. The effectsof exposure to low concentrations usually disappearwithin 20 to 30 minutes. Based on animal toxicology ofCN, the initial LCt 50estimated for humans was 7,000mg•min/m 3 , which was subsequently revised andestablished as 14,000 mg•min/m 3 . Persistence of theseeffects (rhinorrhea, lacrimation, blurred vision, conjunctivitis,and burning of the throat) was negligible,with no clinical signs and symptoms noted approximately10 minutes following cessation of exposure.Values for the ICt 50of CN range from 25 to 50 mg•min/m 3 . These ICt 50values are comparable to those of DM.The estimated LCt 50for CN dispersed from solventin grenades is 7,000 mg•min/m 3 , although some researchershave reported estimates between 8,500 and25,000 mg•min/m 3 . 144Volunteer acute exposure studies. In human volunteerstudies, the immediate effects of exposure to CNwere a burning sensation or stinging in the eyes, nose,throat, and exposed skin, followed by lacrimation,salivation, rhinorrhea, and dyspnea. Common signsobserved were rhinorrhea, lacrimation, and conjunctivitis,and reported symptoms included blurred vision,burning of the throat, and some less frequent but moresevere symptoms of difficulty in breathing, nausea, andburning in the chest. 55 Punte et al 55 studied the effectsof CN on human subjects exposed to aerosols at Ctsbelow 350 mg•min/m 3 . This dosage is considered themaximum safe inhaled aerosol dosage for humans.Punte et al 55 also studied CN dispersed from solvent ingrenades and found the maximum safe inhaled dose tobe 500 mg•min/m 3 . Other estimates range from 8,500to 25,000 mg•min/m 3 .Respiratory effects. Exposed individuals may experiencelacrimation, conjunctivitis, conjunctival edema,461