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

Medical Aspects of Chemical Warfareto phosgene compared to levels in controls. 185 Levelsof IL-6 were 16-fold higher 4 hours after the phosgeneexposure, peaked at 12 hours, and were still over 100-fold higher than in controls 72 hours after phosgeneexposure. Macrophage inflammatory protein was alsoaffected in the rodents exposed to phosgene, showing a10-fold increase compared to the control rodents 8 and10 hours after the exposure, but macrophage inflammatoryprotein levels returned to near-normal levels24 hours after the phosgene exposure. 185 Sciuto et alreported that changes in IL-4, IL-10, tumor necrosisfactor, and IL-1β levels were minimal after phosgeneexposure as compared to changes in IL-6 levels. 185Sciuto et al also studied changes in fluid electrolytelevels in blood and bronchoalveolar lavagefluid from mice following exposure to phosgene. 187Blood levels of sodium, chloride, and calcium wereunchanged after exposure to phosgene compared tocontrols, but the levels of potassium increased drasticallyand approached physiologically dangerouslevels. In the bronchoalveolar lavage fluid, chloridelevels were unchanged, sodium dropped between 4and 12 hours, and both potassium and calcium levelsincreased significantly after 4 hours and by a factorof 3 after 8 hours, compared to nonexposed controls.The simplicity of determining electrolyte levels offerspromise for suggesting exposure to phosgene, but isnot specific for phosgene exposure and requires supportinganalyses.Because phosgene reacts rapidly with GSH, it isexpected that enzymes responsible for maintainingGSH levels may also be affected, and their levels canbe monitored to suggest phosgene exposure. Sciutoet al found levels of GSH peroxidase and GSH reductasesignificantly increased in the bronchoalveolarlavage fluid of mice exposed to 160 to 220 ppm/minphosgene. 171 The levels of GSH peroxidase and GSHreductase were measured by ELISA and were elevatedup to 72 hours after exposure. 171The amount of total protein in bronchoalveolarlavage fluid may also be a marker for the extentof lung damage after a phosgene exposure. Sciutofound that levels of total protein in the lavage fluidof mice was dramatically increased following phosgeneexposure and remained significantly elevatedup to 7 days postexposure. Other reports by Sciutohave indicated similar increases in protein levels inbronchoalveolar lavage fluid and have suggestedthey are due to increased permeability of the bloodairbarrier. 170 In an earlier study, Currie et al foundsignificant increases in the concentration of bronchoalveolarlavage fluid protein immediately aftera relatively low exposure (60 ppm/min). 188 Totalprotein levels in bronchoalveolar lavage fluid are notspecific for phosgene exposure, but may be helpfulto determine the extent of lung damage caused byit. A simple spectrophotometric assay is suitableto determine protein levels because the amount ofprotein in lavage fluid is nonspecific and measuresonly total protein levels.3-QUINUCLIDINYL BENZILATEBackgroundCommonly termed “QNB,” 3-quinuclidinyl benzilate(BZ) is an anticholinergic glycolate that has beendesignated “agent BZ” by the military. BZ is the onlyknown incapacitating agent that has ever been weaponizedfor use by the US military. That occurred in theearly 1960s when BZ was produced at the Pine BluffArsenal between 1962 and 1965. BZ was subsequentlydropped from the chemical arsenal for several reasons,including concerns about variable and unpredictableeffects.BZ’s action is very similar to other anticholinergicssuch as atropine and scopolamine, differing mainlyin potency and duration of effect. The lethal dose ofan infectious organism required to produce infectionin 50% of the population (ID 50) for BZ is about 6.2µg/kg (about 500 ng/person). BZ is about 25 timesas potent as atropine, but only about 3-fold moreactive than scopolamine. However, BZ’s durationof action is typically much longer, and the uptakeby an oral route is about 80% that of intravenous orintramuscular routes. Under optimum conditions,BZ is also about 40% to 50% as effective by inhalationas by injection. Initial symptoms typically occur 30minutes to 4 hours after exposure. Full recovery mayrequire 3 to 4 days.BZ has a molecular weight of 337 g/mol and amelting point of 168°C. It is solid at room temperatureand has a negligible vapor pressure. BZ is relativelystable and moderately resistant to air oxidation andmoderate temperatures, and it undergoes hydrolysisin aqueous solution to produce benzylic acid and 3-quinuclidinol.3-Quinuclidinyl Benzilate in the Human BodyInformation on BZ in the body is limited. It can take3 to 4 days before symptoms of BZ intoxication resolve.Apparently, most BZ is excreted by the kidneys andurine is the preferred analysis matrix. Benzylic acidand 3-quinuclidinol are the probable main metabolites738