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

Medical Aspects of Chemical Warfaregenerally in the high parts-per-billion range. Therehave also been assays developed that acidify thesolution and then sample the head space for HCNfollowed by GC with a nitrogen-phosphorus detectoror derivatization followed by GC with an electroncapture detector. Detection limits by nitrogen-phosphorusdetection and electron capture detector havebeen in the high parts-per-billion range. Cyanide hasbeen measured in RBCs by high-performance LC afterderivatization with fluorescence detection.Urine, Saliva, and Serum or PlasmaMethods to detect cyanide exposure in human urine,saliva, and either serum or plasma have concentratedon SCN - . These methods include derivatization withhigh-performance LC with ultraviolet detection, derivatizationwith spectrophotometric detection, or GCwith electron capture detection. Some urine methodshave measured the urinary metabolite 2-aminothiozoline-4-carboxylicacid.Reference Range ValuesReference range values for cyanide in variousmatrices tend to vary greatly depending on thestudy and on the method of analysis. Thus, a referencerange needs to be established for any method.In some of the studies, the range of blood cyanidelevels in normal populations is less than 150 partsper billion and urinary SCN - less than 1.0 mg/mL. 131Smokers have much higher cyanide levels thannonsmokers; in some smokers blood cyanide levelsas high as 500 ng/mL have been reported, whichis 50 times higher than that typically reported fornonsmokers (Table 22-13). 131PHOSGENEBackgroundPhosgene, also known as carbonyl chloride, wasused extensively in World War I and caused moredeaths than any other agent. 149 It is now a widely usedindustrial chemical. In 2002 the global production ofphosgene was estimated to be over 5 million metrictons, 150 most of which is consumed at the productionsite. 151 The first synthesis of phosgene was performedin 1812 by exposing a mixture of chlorine and carbonmonoxide (CO) to sunlight. 152 During World War Iphosgene was produced in bulk by the reaction ofchlorine and CO in the presence of activated carboncatalyst. 152 Phosgene is generally produced in thesame way today but with higher efficiency because ofnewer high-surface–area catalysts. 153 Phosgene is animportant intermediate in many industrial products,including insecticides, isocyanates, plastics, dyes, andresins. 150 Additionally, phosgene is formed duringthe combustion of chlorinated hydrocarbons duringfires, 154 and by the photooxidation of chlorinated solventsin the atmosphere. 155At room temperature (20°C) phosgene is a fumingliquid with a vapor pressure of 1180 mm Hg and boilingpoint of 7.6°C. The gas is heavier than air, witha relative density ratio of 4.39 at 20°C. This densityallows phosgene gas to collect in low-lying areas.Phosgene’s odor is somewhat sweet and resembles thatof fresh cut grass or hay. At higher concentrations theodor becomes pungent or burning and causes rapidolfactory fatigue. 156Exposure to phosgene gas causes irritation to theeyes, nose, throat, and respiratory tract. Higher phosgenegas exposures can lead to pulmonary edema anddeath. Exposure to liquid phosgene by direct skin oreye contact is rare but is thought to produce localizedsevere burns. 156 Inhalation is the most toxic exposureroute for phosgene and the route thought to havecaused most of the injuries and deaths during WorldWar I. A patient who has inhaled phosgene requiresadvanced treatment techniques.Phosgene is also a powerful acylating agent thatreacts with nucleophiles such as amines, sulfides, orhydroxyls. Phosgene’s toxicity was originally thoughtto be due to HCl generation during the reaction ofphosgene with moisture in the body. Later, acylationreactions were found to be responsible for a majorityof phosgene’s toxic effects. Phosgene is greater than800 times more toxic than HCl. Free amines protectagainst phosgene poisoning but not against the toxiceffects of HCl, phosgene inhibits coenzyme I and HCldoes not, and chemically similar compounds (suchas ketene) that do not have chlorine to generate HClhave similar toxicity to phosgene. 157 Furthermore,phosgene’s rate of reaction with free amines has beenfound to be much higher than its rate of reaction withwater. In a solution of aniline in water, phosgene reactsalmost exclusively with the aniline. 152Most of the data on health effects from phosgene arefrom inhalation exposures. The regulatory thresholdlimit value (8-hour, time-weighted average) for phosgenehas been established by the National Institute forOccupational Safety and Health, an institute withinthe Centers for Disease Control and Prevention, as 0.1ppm 158 ; the 60-minute and 24-hour emergency exposurelimits are 0.2 ppm and 0.02 ppm, respectively. 155734