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

Medical Diagnosticsmonosulfoxide MSMTESE was only detected from oneof the casualties and was near the limit of detectionfor the assay. The bissulfoxide SBMSE was detectedin the urine from both casualties, but for each sampleit was near the limit of detection of the assay (0.1–0.5ng/mL).Some of the most extensive testing of urine samplesfor sulfur-mustard–related metabolites involved twoindividuals who were accidentally exposed to a WorldWar I munition containing sulfur mustard. The injurieswere described as predominately cutaneous exposures,with both individuals exhibiting extensive skin blistering.Urine samples were collected 2 to 3 days after theindividuals were exposed. Black and Read analyzedthe urine using three different methods to detect metabolitesof sulfur mustard hydrolysis. 91 In addition,the urine samples were examined for products of areaction between sulfur mustard and GSH. The first assaymeasured TDG (free and conjugated together) andfound concentrations of 2 ng/mL for each individual.The second assay targeted only free TDG-sulfoxide,and concentrations of 69 ng/mL and 45 ng/mL werefound for the two individuals. Concentrations of 77ng/mL and 54 ng/mL were found using a GC-MS-MS assay that measures TDG and TDG-sulfoxide as asingle analyte. Control samples analyzed along withthe patient samples for the second and third assaysgave levels of 4 to 5 ng/mL, therefore the patientresults were significantly higher than control values.The β-lyase metabolites were measured using both theGC-MS-MS method 91 and the LC-MS-MS method. 96When the β-lyase metabolites were analyzed individuallyby LC-MS-MS, their concentrations rangedfrom 15 to 17 ng/mL and from 30 to 34 ng/mL for themonosulfoxide and bissulfoxide, respectively. Whenanalyzed as the single, reduced form of SBMTE usingGC-MS-MS, observed concentrations were 42 ng/mL and 56 ng/mL. Samples were also analyzed for abis-(N-acetylcysteine) conjugate using LC-MS-MS. 97This biomarker is also a reaction product of sulfurmustard and GSH. Although the biomarker is a majormetabolite in rats exposed to sulfur mustard, it had notbeen reported in urine samples from exposed humans.The metabolite was found in urine samples from bothexposed individuals, but concentrations were near thelower limit of detection (0.5–1 ng/mL).The most recently reported exposure incident involvedtwo explosive ordnance technicians who werepart of a team tasked with destroying a suspectedWorld War I 75-mm munition. The munition had beendiscovered in a clamshell driveway and was believedto have originated from material dredged from aseafloor dumping area. Following demolition procedures,two individuals came into contact with a brownoily liquid that was found leaking from the remnantsof the munition. During the disposal operation, noneof the ordnance team members complained of eye orthroat irritation or breathing difficulties. The clinicalsequence of events for one of the individuals haspreviously been reported, 103,104 but will be describedin brief here. Within 2 hours of the munition destruction,one of the individuals (patient D1, a 35-year-oldmale) noticed a tingling sensation on one arm and thenshowered. The next morning (approximately 14 hoursafter the liquid contact), painful areas had developedon his hand, along with noticeable reddening and smallblisters. He went to a local emergency room where theblisters were observed to grow and coalesce. He wassubsequently transferred to a regional burn center.Blisters developed on the patient’s arm, hand, ankle,and foot. The erythema and blistered area on the patientwas estimated to be 6.5% of his body surface area(Figure 22-8). The patient never developed ocular orrespiratory complications; consequently it appearedthat his injuries were only the result of a cutaneousliquid exposure. The second individual (patient D2)had a small, single blister and was not hospitalized.Urine samples from patient D1 were collected on days2 through 11 and 29, 35, and 42 days after exposureand from patient D2 on days 2, 4, and 7 after exposure.Reports containing preliminary analysis results mistakenlyindicated that the first samples collected were1 day post exposure. 104,105 Urine from both individualswas analyzed for hydrolysis metabolites and GSHreaction products. 104,105 Hydrolysis metabolites weredetermined using several different methods. Using aFig. 22-8. Aspiration of blister fluid from accidental exposureto sulfur mustard.717