PERCUTANEOUS-ABSORPTION AND TISSUE DISTRIBUTION OF [H-3] DIACETOXYSCIRPENOL (ANGUIDINE) IN RATS AND MICE

Acute toxicity, absorption, excretion, and tissue distribution of topi cally administered diacetoxyscirpenol (DAS, anguidine) were studied in Fischer rats and CD-1 mice. Mortality (75%) was observed in rats trea ted with a single dose of 2.625 mg of DAS to 1.44 cm(2) of skin, where as the proportionate (0.75 mg to 0.42 cm) of skin) and even higher dos es were not lethal to mice. Histopathological lesions induced in the r at were similar to those observed by administration through other rout es, mainly involving lymphohematopoietic tissues and the gastrointesti nal tract. Although lesions in internal organs were less severe, the s kin of the mouse was more severely damaged at the application site tha n that of the rat. During the 90-min period after topical application of a single dose of [H-3]DAS, the rat absorbed and retained more [H-3] DAS and excreted less radioactivity through urine and feces than the m ouse. By 24 hr after treatment, the rat had absorbed, excreted, and re tained about twice as much [H-3]DAS as had the mouse (p < 0.05 or < 0. 005). At 7 days posttreatment, the rat had absorbed more than four tim es the amount of [H-3]DAS than had the mouse (13.1 vs 57.5%; p < 0.005 ). However, tissues of the mouse retained a higher proportion of admin istered radioactivity (4.1%) than those of the rat (1.0%; p < 0.05). T otal excretion of radiolabel by the rat was approximately sixfold high er than that of the mouse (56 to 9%; p < 0.005). The ratio of excretio n in urine to that in feces in the rat was about 2 to 1 (37 to 18%) an d in the mouse was about 3.5 to 1 (7 to 2%). Significant differences i n the time course of tissue distribution of [H-3]DAS in the rat and mo use were found when data were expressed as the percentage of absorbed dose present in tissues or as specific radioactivity (dpm) per gram ti ssue. These results demonstrated a significant interspecies difference in acute percutaneous toxicity of DAS and different patterns of absor ption, excretion, and tissue distribution of topically administered [H -3]DAS in rats and mice. (C) 1996 Academic Press, Inc.