FUNDAMENTAL AND APPLIED TOXICOLOGY 10, 730-735 (1988) Metabolic Alterations Induced by Topical Dimethylacetylenedicarboxylate1

of topical dimethylacetylenedicarboxylate (DMAD) in tissue and its effect on glucose metabo-lism were studied in vivo, using skin grafted athymic nude mice, and in vitro, using excised pig skin. [I4C]DMAD that penetrated skin grafts was distributed throughout the body. At 24 hr, the liver contained 15.62 % of the applied dose. The kidneys, lungs, brain, and the heart contained 12.73, 5.61,0.36, and 3.24 % of the dose, respectively. One hour postapplication, DMAD mark-edly decreased [U-l4C]glucose oxidation and the syntheses of fatty acids and glycogen in the livers and skin grafts. Similar effects were observed in excised pig skin. In addition, the activities of hepatic glucose-6-phosphate dehydrogenase, isocitric and NADP-mahc dehydrogenase, and acetyl-CoA carboxylase were significantly reduced in DMAD-treated mice. In contrast, no effect was observed on the activity of glucokinase. The data indicate that DMAD rapidly penetrates the skin and causes aberrations in the activities of the glycogenic. lipogenic, and tricarboxylic acid metabol ic pathways. © 1988 Society of Toxicology Skin contact with dimethylacetylenedicarboxy-late (DMAD, 2-butynedioic acid dimethyles-ter), a highly toxic unsaturated compound widely used in the chemical industry, causes skin irritation and may lead to severe, delayed burns if skin contact is maintained for a pro-longed period of time (Slovak and Payne, 1984). Toxic symptoms observed in experi-mental animals include well-defined erythema, lethargy, and gasping respiration, followed by ' In conducting the research described in this report, the investigators adhered to the "Guide for the Care and Use of Laboratory Animals, " as promulgated by th