Lewisite, chemical warfare

Other organoarsenicals, most notably lewisite (dichloro[2-chlorovinyl]arsine), were developed in the early twentieth century as chemical warfare agents. Arsenic trioxide was reintroduced into the United States Pharmacopeia in 2000 as an orphan drug for the treatment of relapsed acute promyelocytic leukemia and is finding expanded use in experimental cancer treatment protocols (see Chapter 54). Melarsoprol, another trivalent arsenical, is used in the treatment of advanced African trypanosomiasis (see Chapter 52). 

The world community has its own Scheduled chemical list with regard to agents of chemical warfare. Schedule I refers to those substances used exclusively for warfare such as the nerve gases, sulfur mustards, nitrogen mustards, and Lewisites. These are overtly banned. 

For example, the elucidation of the mechanism of action of the war gas Lewisite (Fig. 1.2), which involves interaction with cellular sulfhydryl groups, allowed the antidote, British anti-Lewisite or dimercaprol (Fig. 1.2), to be devised. Without the basic studies performed by Sir Rudolph Peters and his colleagues, an antidote would almost certainly not have been available for the victims of chemical warfare. 

Arsine Derivatives,Organic. Many arsine derivs were proposed as CWA s. More than 60 of such derivs are listed by Wachtel (Ref, pp 189-92). The most known of these compds is Lewisite or MI, which is f -cbloro-vinyldichloroarsine, C1-CH CH- AsC12, first isolated in 1917 by Dr W. Lee Lewis and developed as a war gas by the US Chemical Warfare Service (Ref, pp 202-6). Another important arsine CWA is Adamsite (Brit) (designated in the US as DM) or diphenylamine-chloroarsine ... 

The foundation of the CWC s inspection activities was based around the declaration by member states of their chemical weapons capabilities and activities. Nations with chemical warfare programmes were required to declare their production, storage and destruction facilities, which would then receive top monitoring priority. Nevertheless, the CWC did allow states to maintain research programmes to ensure the integrity of defensive equipment such as gas masks and gas detectors, but these activities were also to be closely monitored since they involved work with the chemical agents listed on Schedule l.9 Otherwise, all other warfare agents, mustard gas, Lewisite, soman, sarin, tabun, VX and the capability to produce them were to be eliminated under the watchful eyes of international inspectors (Table 8.1).10 The convention thus defined chemical weapons as any toxic chemical, or its precursors, intended for purposes other than those not prohibited under this convention for... 

Figure 8. Chemical structures of 2-chlorovinyldichloroarsine (Lewisite LI), 2-chlorovinylarsonous acid (CVAA), British Anti-Lewisite (BAL) and the CVAA-BAL complex. (Reprinted from Toxicology and Applied Pharmacology, Vol. 184, D. Noort,H.P. BenschopandR.M. Black, Biomonitoring of Exposure to Chemical Warfare Agents A Review, pages 116-126 (2002), with permission from Elsevier Science.)...

Atomic Absorption Spectrometry Acetylcholinesterase British Anti-Lewisite Carboxylesterase Central Nervous System Chemical Warfare Agent 2-chlorovinylarsonous Acid Enzyme-linked Immunosorbent Assay Environmental Protection Agency... 

In this report, the Subcommittee on Chronic Reference Doses for Selected Chemical-Warfare Agents of the National Research Council s (NRC s) Committee on Toxicology reviews the scientific validity of the Army s interim values for the six chemical-warfare agents—GA, GB, GD, VX, sulfur mustard, and lewisite. The NRC report is intended to be useful to the Army in making site-specific cleanup decisions. 

The results of the subcommittee s evaluations are presented in Chapters 2 through 9. Chapter 2 reviews the method used by the Army to derive RfDs, and also inclndes a discussion of the benchmark dose method as a point of departure for calculating RfDs. Chapters 3 throngh 6 evaluate the RfDs for the nerve agents GA, GB, GD, and VX. Chapter 7 evalnates the RfD and slope factor for sulfnr mustard, and Chapter 8 provides an evaluation of the RfD for lewisite. Research recommendations are presented at the end of Chapters 3-8 for each of the specific chemical-warfare agents. 

Stewart, D.L., E.J. Sass, L.K. Fritz and L.B. Sasser. 1989. Toxicology studies on lewisite and sulfur mustard agents Mutagenicity of lewisite in the Salmonella histidine reversion assay. Final Report, Pacific Northwest Laboratory Report, PNL-6872, Richland, WA. Trammell, G.L. 1992. Toxicodynamics of organoarsenic chemical warfare agents. In Somani, S.M., Ed. Chemical Warfare Agents. Academic Press, Inc. New York, pp.255-270. 

ECAO-CIN-538. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Cincinnati, OH. Warden, E.L. 1941. Lewisite (M-1) 1940 Summary of physiologic and toxicologic data. Report. No. EATR 285. Chemical Warfare Service, Edgewood Arsenal, MD (ADB959553L). 

Lindherg, G., Runn, P., Winter, S., Falhnan, A. (1997). Basic information on lewisite - a chemical warfare agent with effects similar to mustard gas. Defense Research Establishment, Division of NBC Defense, Umea, Sweden. 

Silver, S.D., McGrath, F.P. (1943). Lewisite (M-l) the stereoisomers. Investigation of discrepancies between nominal and anal dical concentrations redetermination of LC50 for mice. Chemical Warfare Service, January 29, 1943. AD-B960457L. Unclassified Report/Limited Distribution. 

Young, R.A. (1999). Health Risk Assessment for Lewisite. In Health Risk Assessments for Oral Exposure to Six Chemical-Warfare Agents. National Research Council. National Academy Press, Washington, DC. 

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