Lewisite distribution

THIS CHAPTER contains a brief description of the methods used by toxicologists at Oak Ridge National Laboratory (ORNL) to derive the U.S. Army s interim reference doses (RfDs) for GA, GB, GD, VX, sulfur mustard, and lewisite. Those methods were based on the procedures outlined by the U.S. Enviromnental Protection Agency for Superfund risk assessment guidelines (EPA 1989) and for reference concentrations (EPA 1994). An alternative method, the benchmark-dose (BD) approach (Crump 1984) is also described. Because uncertainty factors are integral to both approaches, further consideration is also given to the statistical distribution and confidence associated with them. 

Israeli, M., and C.B. Nelson. 1992. Distribution and expected time of residence for U.S. households. Risk Anal. 12 65-72. lOM (Institute of Medicine). 1993. Veterans at Risk The Health Effects of Mustard Gas and Lewisite. Washington, D.C. National Academy Press. 

Snider, T.H., M.G. Wientjes, R.L. Joiner and G.L. Fisher. 1990. Arsenic distribution in rabbits after lewisite administration and treatment with British anti-lewisite (BAL). Fundam. Appl. Toxicol. 14 262—272. 

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. 

Lewisite has extensive tissue distribution (HSDB, 2008). The highest concentrations were found in the hver, lungs. 

Vesicants including sulfin" mustard and lewisite are the subject of the second main part of this contribution. Coherences of invasion and distribution are presented and the major processes of metabolism and elimination caused by binding to proteins and more prominently to DNA are discussed. The part closes with comments on current bioanalytical approaches. 

Axelrod DJ and Hamilton JG (1946). Radio-autographic studies of the distribution of lewisite and mustard gas in the skin and eye tissues. Am J Pathol, 23, 389-411. 

The use of mustard, Lewisite and phosgene in the vast quantities which we are capable of making and distributing offers the only sure way of holding Korea at the present time. We are not playing marbles. We are fighting for our lives. Let s use the best means we have to overwhelm the enemy scientifically and intelligently.123(p3)... 

While the toxicity of Lewisite is roughly the same as mustard, the action of Lewisite on the skin causes an immediate burning sensation, and its odor is readily apparent. Severe damage to the eyes occurs almost immediately after exposure, while Lewisite vapors irritate the mucosa of the nasal and upper respiratory system. Lewisite is subsequently absorbed into the body, and distributed as a systemic poison to various organs. 

Model reactions on [AuCl(PEt3)] with GSH show chloride displacement but no phosphine displacement [40], and intracellular GSH binding to auranofin was also observed by NMR studies on red cells [14]. The presence of the phosphine, necessary for oral administration, may also dictate some of the biochemical differences between auranofin and the injectable gold complexes. The breakdown of auranofin eventually produces Et PO, a reaction interestingly mimicked by 2,3-dimercaptopropanol (or British Anti-Lewisite) in its reactions with gold—phosphine complexes [14]. The phosphine oxide has recently been detected in human serum [41], supporting the theory that, upon cellular distribution, loss of phosphine results in behavior similar to that of non-phosphine containing complexes. 

Axelrod, D.J., Hamilton, J.G., 1947. Radio-autographic studies of the distribution of lewisite and mustard gas in skin and eye tissues. Am. J. Pathol. 23,389-411. Bast, C., Young, R., McGinnis, P.M., et al., 2013. Provisional Advisory Level (PAL) development for Lewisite and sulfur mustard. Toxicologist 132 (1), 473. Boursnell, J.C., Cohen, J.A., Dixen, M., et al., 1946. Studies on mustard gas (2,2-dichlorodiethyl sulphide) and some related compounds. 5. The fate of injected mustard gas (containing radioactive sulphur) in the animal body. Biochem. J. 40, 756-764. 

Lewisite has extensive tissue distribution (HSDB, 2008). The highest concentrations were foimd in the liver, lungs, and kidneys in rabbits (>7 times blood concentration). Arsenic crosses the placenta and is excreted in the milk. Therefore, nursing animals may be at risk (Barlow and Sullivan, 1982). The elimination half-life of arsenic in rabbits is 55-75 h (HSDB, 2008). For further details on toxicity of arsenic and levHsite, see chapter 15. 

Czerwinski et al., 2006). In the case of vesicant agents, such as sulfur mustard and lewisite, the skin is both a target organ, susceptible to severe local effects, and a pathway for absorption of the agent, leading to its distribution and subsequent systemic effects. The protective skin architecture is provided by a sophisticated and effective barrier built of two main components the outer epidermis and the underl3ung inner dermis. 

Distribution by weight of blister chemicals located at the four depots earlier mentioned is as follows Corny, in high-tonnage containers 293 tonnes of Lewisite, 807 tonnes of Mustard, and 157/71 tonnes of Mustard -Lewisite mixtures (the denominator shows the number of tonnes of Mustard -Lewisite mixture in dichloroethane solvent) Kambarka, in high-tonnage containers 6349 tonnes of Lewisite Khizner, in artillery munitions 129 tonnes of Lewisite Maradykovsky, in aerial bombs 149 tonnes of Mustard -Lewisite mixtures. 

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