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

Medical Aspects of Chemical WarfareLong-Term EffectsThere are no data on human exposure from whichto predict the long-term effects from lewisite. No substantialevidence exists to suggest that lewisite is carcinogenic,teratogenic, or mutagenic. 256 The NationalAcademy of Sciences committee reported a causalrelationship between lewisite exposure and chronicrespiratory diseases, and also that acute, severe injuriesto the eye from lewisite will persist. 246PHOSGENE OXIMEPhosgene oxime is not a true vesicant because itdoes not produce vesicles. Instead, phosgene oximeis an urticant or nettle agent: it causes erythema,wheals, and urticaria (hives). Its lesions have beencompared with those caused by nettle stings. Becauseit causes extensive tissue damage, phosgene oximehas been called a corrosive agent. Phosgene oximeis not known to have been used on a battlefield, andthere is very little information regarding its effects onhumans. This compound must be distinguished fromphosgene, which exerts effects on the alveolar-capillarymembrane. Phosgene oxime is made from phosgene,hence the name.Military UseGerman scientists first synthesized phosgene oximein 1929, and Russia and Germany had developed itbefore World War II. Both countries may have hadweapons that contained the agent. 260,261 The UnitedStates also studied phosgene oxime before World WarII but rejected it as a possible chemical agent becauseof its biological effects, or lack thereof, and its instability.107 The apparent lack of biological effects was laterfound to result from the low concentrations (1%–2%)used in the pre–World War II studies. Later studiesindicated that concentrations below 8% cause no orinconsistent effects. 261,262Phosgene oxime is of military interest because it• penetrates garments and rubber much morequickly than do other chemical agents and• produces a rapid onset of severe and prolongedeffects.When mixed with another chemical agent (eg, VX),the rapid skin damage caused by phosgene oximerenders the skin more susceptible to the second agent.Also, if unmasked soldiers were exposed to phosgeneoxime before donning a mask, the pain caused by theexposure would prompt them to unmask again.PropertiesPure phosgene oxime (dichloroformoxime) is acolorless, crystalline solid; the munitions grade compoundis a yellowish-brown liquid. Its melting point is35° to 40°C (95° to 104°F). The solid material producesenough vapor to cause symptoms. 252Biochemical Mechanisms of InjuryPhosgene oxime is the least well studied of thechemical agents discussed in this volume, and itsmechanism of action is unknown. It might producebiological damage because of the necrotizing effects ofthe chlorine, because of the direct effect of the oxime,or because of the carbonyl group (Figure 8-16). Theskin lesions, in particular, are similar to those causedby a strong acid. The agent seems to cause its greatestsystemic effects in the first capillary bed it encounters.For example, cutaneous application or intravenousinjection of phosgene oxime causes pulmonary edema;injection into the portal vein produces hepatic necrosisbut not pulmonary edema. 262Direct InjuryMechanism• Enzyme inactivation• Cell death• Corrosive injury• Rapid local destruction of• tissue (eg, vesication)Phosgene OximeCellular TargetsNot KnownIndirect InjuryMechanism• Activation of alveolar• macrophages• Recruitment of neutrophils• Release of H 2 O 2• Delayed tissue injury• (eg, pulmonary edema)Fig. 8-16. The putative mechanisms by which phosgeneoxime causes tissue damage.H202: hydrogen peroxideAdapted from: US Army Medical Research Institute ofChemical Defense. A global picture of battlefield vesicants,I: a comparison of properties and effects. Med Chem Def.1992;5(1):6.294