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

Medical Aspects of Chemical Warfareunmetabolized sulfur mustard. 85 The victim was anIranian soldier, age 24, who died of complications frompneumonia 7 days after the suspected exposure. Thepatient had been transferred to an intensive care unitin Munich, Germany. Samples were taken during theautopsy and stored at – 20°C for 1 year prior to analysis.Despite very high concentrations of sulfur mustardfound in autopsy tissue specimens, sulfur mustard wasnot detected in the urine samples.In 1990 Jakubowski et al received urine samples froman accidental laboratory exposure to sulfur mustard. 102A liquid flashpoint tester overheated, vaporized amixture that was thought to contain only a deconnedsolution, and exposed a chemist who had attempted toshut down the reaction. Nine hours after the incident,the individual felt a burning sensation on his arms,hands, neck, and face. Medical care was sought themorning after blisters appeared on his hands and arms.The erythematous and vesicated areas were estimatedto be less than 5% and 1% of the total body surfacearea, respectively. The patient collected his total urineoutput for a 2-week period. For the first 3 days, thepatient’s total urine output was only about a third tohalf that of the average adult daily output of 1.5 liters,but the patient had a normal output level over the next10 days. The assay method used measured both freeand conjugated TDG. 87 The maximum TDG urinaryexcretion rate was 20 µg/day on the third day. TDGconcentrations of 10 ng/mL or greater were observedin some samples for up to 1 week after the exposure.A rate constant was calculated for TDG concentrationfrom days 4 through 10 and the half-life was foundto be 1.2 days. A great deal of intraday variabilitywas noted for the TDG urine concentrations. Consequently,the collection of several urine samples perday is recommended. An attempt was also made toestimate the total amount of sulfur mustard on thepatient’s skin. The estimate was based on two assumptions:1) the assay for the free and conjugated TDGrepresents approximately 5% of the total amount ofsulfur-mustard–related products in the blood, and 2)the bioavailability factor from skin to blood is 10 (ie,10% of the sulfur mustard on the skin penetrated intothe blood). A total of 0.243 mg of TDG was recoveredover a 2-week period. This represents 4.86 mg in theblood, or 48.6 mg on the skin.There are currently four instances of human exposureto sulfur mustard in which urine samples weresubjected to several different assays in order to targetmultiple urinary metabolites. The first report describeda small subset of urine samples previously analyzedby Wils et al 83 and were later reanalyzed by Black andRead 88 after storage at – 20°C for a 5-year period. Willemsprovided clinical information on the five individualsand coded them C1 through C5. 101 This groupof individuals was reportedly exposed to explodingbombs that generated black dust and rain. Decontaminationefforts consisted only of clothing removal,although some victims may have also showered. Earlysymptomatology included eye and throat irritationalong with respiration difficulties. Within 1 to 2 days,victims developed erythema and small blisters on theskin, edema of the eyelids, photophobia, coughing,dyspnea, and hemoptysis. The patients were admittedto a hospital 10 days after the suspected sulfur mustardexposure. Urine samples were obtained at that time.Four of the five patients were discharged 26 to 37days after hospitalization. Patient C1 developed adultrespiratory distress syndrome and was given ventilatorysupport, but died in cardiovascular shock 15 daysafter the original exposure event (5 days after hospitaladmission). Wils et al coded the urine sample set fromindividuals C1 to C5 as G1 to G5 in their report and,using the GC-MS assay described above, found concentrationsof TDG at 90 ng/mL, 45 ng/mL, 40 ng/mL,40 ng/mL, and 15 ng/mL for individuals 1 through5, respectively. 83 Using a different method measuringTDG and TDG-sulfoxide as a single analyte followedby GC-MS-MS analysis, Black and Read found TDGand TDG-sulfoxide levels of 69 ng/mL, 28 ng/mL, and33 ng/mL for individuals C1, C2, and C5, respectively.C3 and C4 were not assayed because their sampleswere insufficient. Control urine samples analyzed byBlack and Read produced a background level of 11ng/mL. 88 Urine samples from all five casualties wereanalyzed for β-lyase concentrations, with the highestconcentration found in patient C1. The concentrationsfound in the urine from four of the casualties rangedbetween 0.5 to 5 ng/mL, while the individual who diedhad a β-lyase concentration of 220 ng/mL. 88Once again using the GC-MS-MS method thatmeasures both TDG and TDG-sulfoxide as a singleanalyte, Black and Read analyzed urine samples fromtwo casualties of an alleged sulfur mustard attack onthe Kurdish town of Halabja in 1988. 88 The patientshad been transferred to London for medical treatmentand urine samples were collected 13 days afterthe alleged incident. Black and Read found combinedTDG plus TDG-sulfoxide levels of 11 ng/mL for bothpatients, but also found similar concentration levelsin control samples. Urine samples were also analyzedfor β-lyase concentrations using GC-MS-MS. Althoughthe concentration of the β-lyase metabolites found inboth patients was near the limit of detection for theassay, the analytes were clearly detectable and rangedbetween 0.1 and 0.3 ng/mL. 88 The urine samples werelater analyzed using the LC-MS-MS assay that candistinguish the individual β-lyase metabolites. 96 The716