Abstract

Abstract : Chemical warfare agents present an obvious risk to individuals suffering acute exposure, but they may also present long-term environmental or occupational health hazards for workers in operations involving these chemical agents. Occupational health standards have not been established for Lewisite (L) dichloro(2-chlorovinyl)arsine a potent vesicant which reacts with sulfhydryl groups of proteins through its arsenic group. The destruction of current stockpiles of Lewisite by the U.S. Army in the near future could create additional environmental and occupational risk. To establish a database for setting environmental and occupational standards, we conducted studies to evaluate the toxicity, mutagenicity, and reproductive effects of Lewisite using in vitro and in vivo study systems. The cytotoxic, clastogenic mutagenic effects of Lewisite in Chinese hamster ovary cells were investigated and are described in this report. One mutation assay and two cytogenetic assays were used in this study. The mutation assay utilized the hypoxanthine-guanine phyosphoribosyl transferase (HGPRT) locus (6-thioguanine resistance). The two cytogenetic analyses were chromosomal aberration analysis, measurement of chromosome damage, and sister chromatid exchange (SCE), a measurement of chromosome rearrangement. The CHO cells were exposed in the test system for 1 hour, then washed and cultured for an additional 20-30 hours, depending on the assay to be used. The total number of mutant colonies were determined and the mutation frequency was calculated. Chromosome aberrations were scored using 100 metaphases per dose and SCE per cell were calculated.

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