Lewisite metabolism

FIGURE 50.8. Lewisite metabolism, adduct formation, and its reversal. 

No detailed metabolism studies have been reported for lewisite. It is rapidly hydrolyzed to 2-chloro-vinylarsonous acid (CVAA) (13) in the presence of moisture, and Waters and Williams reported that... 

The subcommittee believes the uncertainty factor for data-base adequacy (UFd) should be assigned a value of 10 because no long-term exposure studies involving lewisite are available, only a few studies that address the acute or subchronic toxicity of lewisite are available, and httle or no information about the metabolism of lewisite or its degradation products is available. 

The subcommittee believes the potential enviromnental and metabolic breakdown products of lewisite are not well identified. There is a possibihty that inorganic arsenic and perhaps even vinyl chloride, two known carcinogens, may be break down products. Accordingly, the subcommittee recommends that the environmental degradation and metabolic products of lewisite be determined, and, if those breakdown products are found to be produced, that the carcinogenic potential of those substances, as well as lewisite, be considered in future assessments. 

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. 

Chlorine, phosgene. Lewisite, and SM all react with thiol groups as well as produce oxidants. The arsenic group in Lewisite has a high affinity to the alpha and gamma thiol groups of lipoic acid found in enzymes (e.g., pyruvate oxidase). Oxidants occur as part of the normal metabolism of cells (redox homeostasis). In the diseased state (e.g., exposure to a chemical agent), there is an acute... 

Lewisite shares many biochemical mechanisms of injury with the other arsenical compounds. It inhibits many enzymes in particular, those with thiol groups, such as pyruvic oxidase, alcohol dehydrogenase, succinic oxidase, hexokinase, and succinic dehydrogenase. As is tme with mustard, the exact mechanism by which Lewisite damages cells has not been completely defined. Inactivation of carbohydrate metabolism, primarily because of inhibition of the pymvate dehydrogenase complex, is thought to be a key factor (Trammel, 1992). 

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