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Veterans at Risk: The Health Effects of Mustard Gas and Lewisite (1993)
Institute of Medicine (IOM)

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. "3 History and Analysis of Mustard Agent and Lewisite Research Programs in the United States." Veterans at Risk: The Health Effects of Mustard Gas and Lewisite. Washington, DC: The National Academies Press, 1993.

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Veterans at Risk: The Health Effects of Mustard Gas and Lewisite

product was identified as a compound [(C2H4)2S2Cl2] different from sulfur mustard; however, the observed severe skin blistering, latent period of several hours, and subsequent slow healing are all typical of skin exposure to sulfur mustard. At about the same time, Guthrie (1859, 1860) published investigations describing yet another variant compound (thought to be C4H4S2Cl2), also produced from sulfur chloride in reaction with ethylene. The odor was "pungent," resembling that of "oil of mustard." Guthrie noted destruction of the epidermis when the thin skin between the fingers and around the eyes was exposed to the ''vapour" of this compound. When the liquid was allowed to remain on the skin, blister formation was observed. Finally, in 1886, a process to produce significant quantities of pure sulfur mustard was described by Meyer using sodium sulfide, ethylene chlorohydrin, and hydrochloric gas (Jackson, 1936; Meyer, 1886; Prentiss, 1937; West, 1919). This process was the one eventually used by the German war factories to fill the shells fired at Ypres (Haber, 1986).

Lewisite

Lewisite (C2H2AsCl3) is a vesicant that contains organic arsenic. During WWI, a U.S. chemical warfare research laboratory investigating arsenic compounds as potential war gases developed the potent vesicant, subsequently named "Lewisite" after the research group director. Purified Lewisite is a colorless, oily liquid at room temperature with a faint "geranium-like" odor. More volatile than sulfur mustard, this agent can be used as a vapor over large distances and has been mixed with sulfur mustard to achieve greater effectiveness in combat. With a freezing point between -18°C and 0°C, Lewisite is effective over a wider temperature range than sulfur mustard.

Lewisite is also a cellular poison, but works via a different mechanism than sulfur mustard. It is readily absorbed through the skin and respiratory tract, but moist tissues are particularly vulnerable and eyes exhibit the greatest sensitivity (Trammell, 1992; Watson and Griffin, 1992). In contrast to sulfur mustard, Lewisite exposure is characterized by immediate onset of pain. The agent is lethal at sufficient doses, produces chromosomal aberrations in some mammalian cellular assays, and is a systemic poison when absorbed into the bloodstream. Finally, some evidence suggests that Lewisite might be a carcinogen (Centers for Disease Control, 1988).

The development of Lewisite as a war gas was made by W. Lee Lewis in 1918, while working at the Chemical Laboratory of the Catholic University of America in Washington, D.C. (Lewis and Perkins, 1923). The thrust of the work in this laboratory during WWI was the evaluation of substituted arsines (arsenic-containing chemicals) as potential chem-

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Front Matter (R1-R20)
Executive Summary (1-8)
1 Introduction (9-13)
2 Methods of Literature Collection and Survey (14-20)
3 History and Analysis of Mustard Agent and Lewisite Research Programs in the United States (21-60)
4 Findings from the Public Hearing Process (61-70)
5 Chemistry of Sulfur Mustard and Lewisite (71-80)
6 Relationship of Mustard Agent and Lewisite Exposure to Carcinogenesis (81-111)
7 Nonmalignant Respiratory Effects of Mustard Agents and Lewisite (112-130)
8 Ocular Effects of Mustard Agents and Lewisite (131-147)
9 Dermatological Effects of Mustard Agents and Lewisite (148-178)
10 Other Physiological Effects of Mustard Agents and Lewisite (179-198)
11 Relationship of Mustard Agent and Lewisite Exposure to Psychological Dysfunction (199-213)
12 Summary of Findings and Recommendations (214-226)
Bibliography (227-330)
A. Scientific and Background Presentations Made to the Committee (331-334)
B. Excerpt from The Residual Effects of Warfare Gases (335-337)
C. Involvement of the National Academy of Sciences Complex in World War II Research Programs: A Summary (338-339)
D. Excerpts from Chamber Tests with Human Subjects I, II, and IX. Naval Research Laboratory Reports Nos. P-2208 and P-2579 (340-369)
E. Interim Report and Addendum: Feasibility of Developing a Cohort of Veterans Exposed to Mustard Gas During WWII Testing Programs (370-377)
F. Summary of the Department of the Army Report: Use of Volunteers in Chemical Agent Research (378-381)
G. Public Hearing Announcement (382-385)
H. Letter from Dr. Jay Katz to Dr. David P. Rall (386-389)
I. Risk Assessment Considerations for Sulfur Mustard (390-398)
J. Examination of the Effects of Certain Acute Environmental Exposures on Future Respiratory Health Consequences (399-416)
List of Acronyms and Abbreviations (417-420)
Index (421-428)