Skin Penetration and Tissue Distribution of [14C]Butyl 2-Chloroethyl Sulfide in the RAT

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Abstract
In vivo percutaneous penetration and tissue distribution of radioactivity following a topical application of 14C-labeled butyl 2-chloroethyl sulfide (BCS) were determined in the laboratory rat. Up to 70% of the topical BCS was lost by evaporation. Only a portion of BCS in the skin was extracted with ethanol. At 1 hr, approximately two-thirds of the applied BCS was ethanol-extractable. This level decreased to about 6% at 24 hr. Radioactivity in blood was detected 5 min after application. Thereafter, a linear increase in blood radioactivity was observed throughout the entire 4 hr experimental period. Topical BCS was absorbed into the circulation and was incorporated into various organs and tissues. The liver, kidneys, heart, lungs, skeletal muscle, brain, eyes, and bone marrow were radioactive. On an equal weight basis, the kidneys and lungs contained the highest level of radioactivity. Following a subcutaneous injection of BCS, over 2% of the dose appeared in expired air. No radioactivity was detected in expired carbon dioxide. In 24 hr, up to 70% of the applied radioactivity was excreted in the urine. Four urinary metabolites of BCS were found. This study demonstrates that skin contact with BCS forms an extensive reservoir of ethanol-extractable labeled BCS and/or its metabolites in the affected skin site.

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