Human Exposures to 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 

Chemical Warfare Toxicology, Volume 1 Fundamental Aspects Edited by Franz Worek, John Jenner, and Horst Thiermann The Royal Society of Chemistry 2016 Published by the Royal Society of Chemistry, www.rsc.org 

Although these trials would be considered unethical today, the reports of them remain an invaluable source of toxicological information and their use in scientific research should be regarded as a tribute to the sacrifices made by those who took part. 

It was clear from early observations, confirmed during more recent conflicts, that dosages normally received during battlefield exposure were not usually sufficient to kill, but produced some very serious incapacitating injuries. Such injuries are very slow to heal and produce a variety of long term efects on health, such as cancer, recurrent skin lesions, keratosis of the eye and respiratory difficulties. The most obvious injuries caused to the skin resemble thermal injury and are often described, perhaps misleadingly, as burns. These effects are described in more detail below. 

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Analytical methods have been reported for unchanged agent and six of the urinary excretion products described above. These are TDG, TDGO, the bis A-acetylcysteine conjugate (1), two 3-lyase metabolites (2) and (3), and the guanine adduct (6). These methods have been applied to animal and/or human exposures to sulfur mustard. 

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. 

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. 

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