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

Medical DiagnosticsabcglobinSOCglobinNNH 2CHCH(CH 3) 2CH 2CH 2SCH 2CH 2OHOSC 6F 5NCSCH(CH 3) 2NC 6F 5OCHFBICH 2CH 2SCH 2CH 2OC(O)C 3F 7Fig. 22-10. Analytical method of Fidder et al (1996) forblood exposed to sulfur mustard. (a) Reaction of N-terminalvaline of globin with sulfur mustard. (b) Modified Edmandegradation of N-terminal valine-sulfur mustard adduct. (c)Derivatization using HFBI.HFBI: heptafluorobutyryl imidazoleData source: Fidder A, Noort D, de Jong AL, Trap HC, deJong LPA, Benschop HP. Monitoring of in vitro and in vivoexposure to sulfur mustard by GC/MS determination of theN-terminal valine adduct in hemoglobin after a modifiedEdman degradation. Chem Res Toxicol. 1996;9:788–792.HNCHN+CH(CH 3) 2CH 2CH 2SCH 2CH 2OHCH(CH 3) 2NC 6F 5O+S(CH 2CH 2Cl) 2globinfor both individuals, 150 to 160 nM. The individualwith the skin injuries consistent with sulfur mustardexposure had observed ELISA DNA adduct levels inthe lymphocytes that were only about half that observedin the individual with injuries that were lesspronounced: 220 nM and 430 nM, respectively.Blood samples obtained in 1986 from a group ofIranian casualties that were treated at a hospital inGhent for injuries believed to have been caused bysulfur mustard were examined years later using MSmethods by Black et al for both valine and histidineadducts of hemoglobin. 114 The four individuals hadblood samples collected at 5 or 10 days following thesuspected exposure event. Levels of the valine adductranged between 0.3 and 0.8 ng/mL. Observedlevels of the histidine adduct were greater than theamount of valine adduct and ranged between 0.7 and2.5 ng/mL. Using the same methods, Black et al alsoexamined blood from one of the two individuals whowere accidentally exposed to a World War I sulfurmustard munition. 114 Several urinary metabolites weredetected in specimens from this individual, indicatingexposure to sulfur mustard (see above). In a bloodsample obtained 2 days after the exposure, the valineand histidine hemoglobin adduct levels were 0.3 ng/mL and 2.5 ng/mL, respectively.Blood samples obtained from nine Iranian casualtiesof sulfur mustard exposure were analyzed forthe N-terminal valine adduct of hemoglobin usingGC-MS 121 and for the albumin cysteine adduct usingLC-MS-MS. 115 All nine individuals were hospitalizedand had skin changes consistent with sulfur mustardexposure. Several of the casualties also had respiratorydifficulties. Blood samples were collected between 8and 9 days after the exposure incident. Exposure levelsof the patient blood samples were correlated with humanwhole blood that was exposed to sulfur mustardin vitro. Adduct levels for both the hemoglobin valineadduct and for the albumin cysteine adduct werein very close agreement with each other. Observedexposure levels were between 0.3 and 2 µm and 0.4and 1.8 µm for the hemoglobin and albumin adducts,respectively.The final exposure incident to be discussed involvedthe two individuals who were accidentally exposedto a World War I munition in 2004. Details of theexposure were given earlier in the urine section. Thisparticular human exposure to sulfur mustard differedfrom nearly all other previously reported incidents inseveral important aspects. The two individuals areonly the second and third casualties of sulfur mustardexposure to have both urine and blood samples madeavailable for laboratory testing. Generally, urine or723