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

Medical Aspects of Chemical Warfaretearing and uncontrollable closure of the eyelid. Insome cases, the subject experiences an aversion tolight. As the agent enters the respiratory tract, it causesirritation and burning in the nose and mouth as wellas excessive nasal discharge and salivation. It causespain and discomfort in the throat and chest, resultingin sometimes violent coughing spasms and difficultybreathing. 35 The respiratory effects are the most pronouncedand most capable of causing individuals toflee from the exposure. 51 Irritation and reddening ofexposed skin is quite common and is more pronouncedwith increased temperature, humidity, and concentrationof the agent. 52Animal StudiesAcute oral toxicology studies. Acute oral studiesinvolving CS in alcohol or water administered byesophageal catheter to rabbits and rats yielded medianlethal doses (LD 50s) of 401 mg/kg and 822 mg/kg,respectively. 53 When CS was administered in polyethyleneglycol to various animal species, the LD 50swere determined to be 231 mg/kg in male rabbits, 143mg/kg in female rabbits, 1,366 mg/kg in male rats,1,284 mg/kg in female rats, and 262 mg/kg in femaleguinea pigs. 40Acute eye toxicology studies. Solutions of up to10 mg CS in methylene dichloride placed into theeyes of rabbits did not produce permanent oculardamage. 54,55 Immediate effects observed followingadministration were conjunctivitis that lasted for 30to 60 minutes and erythema of the eyelid. CS administeredinto the eyes of rabbits via solutions of 0.5%to 10% CS caused conjunctivitis, chemosis, keratitis,and corneal vascularization, as well as denudation ofthe corneal epithelium and neutrophilic infiltration.When administered via thermal dispersion, the solidcaused tearing at all doses, uncontrolled closure of theeyelids that increased with dose, and mild chemosisat the high doses that persisted for up to 3 days. Thesmoke also caused excessive tearing and swelling ofthe conjunctiva lasting 24 hours. All tissues were normalwithin 7 days. 54Acute skin toxicology studies. When 12.5 mg of CSin corn oil or acetone was applied to the dorsal skin ofrabbits, guinea pigs, and mice, the effects were erythemaand edema. These effects resolved within 7 days. 40Mutagenic potential studies. The mutagenicpotential of CS and CS2 was investigated in microbialand mammalian bioassays. 56–59 The results wereequivocal, but the Committee on Toxicology of theNational Research Council reported in 1984 that, takenin their totality, the test of CS for gene mutation andchromosomal damage provides no clear evidenceof mutagenicity. 60 Most of the evidence is consistentwith nonmutagenicity, and in the committee’s judgment,it is unlikely that CS poses a mutagenic hazardto humans.Acute inhalation toxicology studies. Acute inhalationstudies of CS were conducted in several animalspecies with CS generated as a smoke. 40,61 The acuteinhalation (vapor exposure) median lethal doses(LCt 50s) are presented in Table 13-2. Studies by Weimarand associates 62 indicated that toxicity of CS variesdepending upon the method of dispersion, arrivingat the following order of toxicity: molten dispersion >dispersion in methylene dichloride > dispersion viathermal grenade.Repeat exposures. Repeat exposures to thermallydispersed CS were conducted in rats and dogs for25 days. The cumulative doses received were 91,000mg•min/m 3 and 17,000 mg•min/m 3 , respectively.No lethality occurred in the dogs, while 5 of the 30rats exposed died, 2 at the cumulative dose of 25,000mg•min/m 3 , and 3 at 68,000 mg•min/m 3 . No grosspathology was observed in the rats that died, norin the six other rats sacrificed following the 25 daysof exposure. During the exposure, the rats becamehyperactive and aggressive, although no changeswere found in the blood chemistry. The exposedrats lost almost 1% of their body weight, whereasthe unexposed rats gained 20% during the 5-weekperiod, although there was no difference in organto body weight ratios. It was concluded from thesestudies that repeated exposures did not make theanimals more sensitive to the lethal effects of CS.The animals that died during the exposures showedincreased numbers of goblet cells in the respiratoryand gastrointestinal tracts and conjunctiva, necrosis inthe respiratory and gastrointestinal tracts, pulmonaryedema, and occasional hemorrhage in the adrenals.The deaths appeared to be caused by poor transfer ofTable 13-2ACUTE INHALATION TOXICITY of CS inAnimalslCt 50(mg•min/m 3 )Species CS Smoke CS AerosolGuinea pig 35,800 67,000Rabbit 63,600 54,090Rat 69,800 88,480Mouse 70,000 50,110LCt 50: the vapor or aerosol exposure that is lethal to 50% of theexposed population448