Skin Penetration and Tissue Distribution of Radioactive Butyl 2-Chloroethyl Sulfide in the Rat

Abstract

Skin contact with butyl 2-chloroethyl sulfide (BCS), a volatile and highly reactive alkylating agent, produces an acute inflammatory response, including erythema and edema, and necrosis of the skin in more serious cases. We conducted a series of experiments to determine dermal penetration and tissue distribution of radioactivity in the rat following a topical application of [¹⁴C]BCS. Up to 70% of the topical BCS was lost by evaporation. At 24 hr the epidermis contained about 25 % and the dermis 75 % of the skin radioactivity. In the skin only a portion of BCS was extracted with ethanol. At 1 hr about 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 experimental period. Topical BCS was absorbed into the circulation and incorporated into various organs and tissues. The liver, kidneys, heart, lungs, skeletal muscle, brain, eyes, and bone marrow were radioactive. Over 2% of the dose appeared in expired air. No radioactivity was detected in expired carbon dioxide. In 24 hr up to 70% of radioactivity was excreted in the urine. Four urinary metabolites of BCS were found. This study demonstrates that BCS does penetrate skin and that the dermis acts as a barrier or reservoir for this highly lipophilic compound.