Sulfur mustards accidental exposure

TDG and TDGO (after reduction to TDG) were detected retrospectively in urine samples taken from three of the same casualties, collected 8 days after the exposure and after storage at — 20 °C for 5 years. Concentrations were in the range 27-72 ng/ml, compared to a concentration of 11 ng/ml in a control sample. In two casualties accidentally exposed to sulfur mustard from a WW I munition, concentrations in urine collected 2-3 days after the exposure were TDG 2 ng/ml (in both), TDGO 69 ng/ml and 54 ng/ml (mean of 3 determinations) (12). These are shown in Table 1. 

Jakubowski et al. (13) were able to monitor the excretion of TDG in a subject accidentally exposed to sulfur mustard in a laboratory. The casualty developed blisters on hands and arms (< 1% of body area) and erythema on his face and neck (< 5 % of body area). Urine was collected over a 10-day period. A maximum excretion rate of TDG of 20 ug per day was observed between days 3 and 4, the highest concentration being 65 ng/ml. It was noted that the total amount of urine produced for analysis during the first three days was low. Concentrations >10 ng/ml were detected in urine for 7 days after the exposure. The half-life of excretion was estimated as 1.18 days. The total amount of TDG excreted over the 10-day period was 243 ug. There was mass spectrometric evidence of oligomers of TDG (e.g. 

E.M.Jakubowski Read, F.R. SideU, R.A. Evans, M.A. Carter, J.R. Keeler, J.D. McMonagle, A. Swift, J.R. Smith and T.W. Dolzine, Quantification of thiodiglycol in human urine after an accidental sulfur mustard exposure, Toxicol. Methods, 10, 143-150 (2000). 

Following two simultaneous cases of accidental human exposure to sulfur mustard, Smith et al. (2008) investigated the concentration of the cysteine-34 adduct to albumin and adducts to glutamic and aspartic acids of plasma proteins. In the case of a more severely exposed patient who required hospitalization, both adducts were detected over a 42 day period, though decreasing by approximately 75% towards... 

Smith, J.R., Capacio, B.R., Korte, W.D., Woolfitt, A.R., Barr, J.R. (2008). Analysis for plasma protein biomarkers following an accidental human exposure to sulfur mustard. J. Anal. Toxicol. 32 17-24. 

Since WWI, a large body of information on sulfur mustard toxicity has been reported from wartime accounts, accidental laboratory and industrial exposures, and animal experiments. Deliberate volunteer exposures of skin to minute amounts of mustard were commonplace in many countries through WWII however, realiza-... 

Jakubowski EM, Sidell ER, Evans RA, et al. Accidental human sulfur mustard exposure Verification and quantification by monitoring thiodiglycol levels. J. Toxicol. Methods 2000 10 143-150. 

In 1990, urine samples from an accidental laboratory exposure to sulfur mustard were obtained (Jakubowski et al., 2000). The erythematous and vesication areas of the individual were estimated to be less than 5% and 1%, respectively, of the total body surface area. The assay measured both free and conjugated TDG using GC-MS (Jakubowski et al., 1990). The maximum TDG urinary excretion rate was 20 (pg/day on day 3. TDG concentrations of 10 ng/mL or greater were observed in some samples for up to a week after the exposure. A first-order elimination was calculated from days 4 through 10 and found to be 1.2 days. A great deal of intraday variability was noted for the TDG urine concentrations. Attempts were made to estimate the total amount of sulfur mustard on the skin of the patient. The estimate was based on two assumptions (1) that the assay for the free and conjugated TDG represents approximately 5% of the total amount of sulfur mustard related products in the blood, and (2) that the bioavailability factor from skin to blood is 10. A total of 0.243 mg of TDG was recovered over a 2 week period. This would represent 4.86 mg in the blood or 48.6 mg on the skin. 

Application to Human Exposure (Blood Samples). Blood samples following a suspected human exposure to sulfur mustard have only rarely become available for laboratory analysis. Three of the five known reports involve the analysis of samples that were taken from casualties of the Iran-Iraq War, frozen for several years and then analyzed to verify exposure as methods were developed. The other two published reports are on the analysis of blood samples obtained from three individuals that were casualties of accidental exposures to WWI munitions. 

Barr JR, Young CL, Woolfit AR, et al. Comprehensive quantitative tandem MS analysis of urinary metabolites and albumin adducts following an accidental human exposure to sulfur mustard. In Proceedings ofthe 53rd Conference ofthe American Society of Mass Spectrometry, San Antonio, TX, June 2005. 

Jakubowski EM, Sidell FR, Evans RA et al. (2000). Quantification of thiodiglycol in human urine after an accidental sulfur mustard exposure. Toxicol Methods, 10, 143-150. 

Chemical warfare agents were not used in World War n, although both sides had the capability. Reports have surfaced that chemical agents were used in experiments conducted on concentration camp prisoners, by both the Third Reich and Japan. An accidental exposure to mustard did occur during World War II when a tanker was sunk and mustard leaked and contaminated the waters of an Italian port. Survivors rescued from the sinking ship developed classic skin lesions associated with sulfur mustard. 

Sulfur mustard (SM) is unique among chemical warfare agents because of the large number of reports of its effects in man. The majority of these reports are of its effects after release on the battle field, and give a description of the types of effect and their time course from exposure to resolution of the injury. However, SM is also one of the few chemicals that have been the subject of tests on humans to determine how toxic they are in terms of the doses or dosages that produce toxic effects. Unlike reports of accidental or battlefield exposures, these trials were carried out in chambers under controlled, or at least carefully recorded, conditions, usually with analytical confirmation of chamber concentrations. Many of the reports of these trials, which were elassified at the time they were produced, have now been released into the public record and are available for scientific review. This chapter reviews those reports that are now available to the general public in addition to the work already published. Volunteer trials were carried out in the USA, UK, India and Australia. The reports of these trials that have been released to the public record are held by the Defense Technical Information Service... 

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