Wang J S, Busby W F, Wogan G N
Division of Toxicology, Whitaker College of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Toxicol Appl Pharmacol. 1996 Oct;140(2):264-73. doi: 10.1006/taap.1996.0221.
Acute toxicity, absorption, excretion, and tissue distribution of topically administered diacetoxyscirpenol (DAS, anguidine) were studied in Fischer rats and CD-1 mice. Mortality (75%) was observed in rats treated with a single dose of 2.625 mg of DAS to 1.44 cm2 of skin, whereas the proportionate (0.75 mg to 0.42 cm2 of skin) and even higher doses were not lethal to mice. Histopathological lesions induced in the rat were similar to those observed by administration through other routes, mainly involving lymphohematopoietic tissues and the gastrointestinal tract. Although lesions in internal organs were less severe, the skin of the mouse was more severely damaged at the application site than that of the rat. During the 90-min period after topical application of a single dose of [3H]DAS, the rat absorbed and retained more [3H]DAS and excreted less radioactivity through urine and feces than the mouse. By 24 hr after treatment, the rat had absorbed, excreted, and retained about twice as much [3H]DAS as had the mouse (p < 0.05 or < 0.005). At 7 days posttreatment, the rat had absorbed more than four times the amount of [3H]DAS than had the mouse (13.1 vs 57.5%; p < 0.005). However, tissues of the mouse retained a higher proportion of administered radioactivity (4.1%) than those of the rat (1.0%; p < 0.05). Total excretion of radiolabel by the rat was approximately sixfold higher than that of the mouse (56 to 9%; p < 0.005). The ratio of excretion in urine to that in feces in the rat was about 2 to 1 (37 to 18%) and in the mouse was about 3.5 to 1 (7 to 2%). Significant differences in the time course of tissue distribution of [3H]DAS in the rat and mouse were found when data were expressed as the percentage of absorbed dose present in tissues or as specific radioactivity (dpm) per gram tissue. These results demonstrated a significant interspecies difference in acute percutaneous toxicity of DAS and different patterns of absorption, excretion, and tissue distribution of topically administered [3H]DAS in rats and mice.
在Fischer大鼠和CD-1小鼠中研究了局部应用双乙酰氧基镰刀菌烯醇（DAS，安圭定）的急性毒性、吸收、排泄及组织分布。给大鼠1.44 cm²皮肤单次涂抹2.625 mg DAS后观察到有75%的死亡率，而给小鼠按比例（0.75 mg至0.42 cm²皮肤）甚至更高剂量涂抹时未导致死亡。大鼠中诱导的组织病理学损伤与通过其他途径给药所观察到的损伤相似，主要累及淋巴造血组织和胃肠道。虽然内脏器官的损伤较轻，但小鼠皮肤涂抹部位的损伤比大鼠更严重。在局部单次涂抹[³H]DAS后的90分钟内，大鼠吸收并保留的[³H]DAS比小鼠更多，通过尿液和粪便排泄的放射性比小鼠更少。处理后24小时，大鼠吸收、排泄和保留的[³H]DAS约为小鼠的两倍（p < 0.05或< 0.005）。处理后7天，大鼠吸收的[³H]DAS量是小鼠的四倍多（13.1%对57.5%；p < 0.005）。然而，小鼠组织保留的给药放射性比例（4.1%）高于大鼠（1.0%；p < 0.05）。大鼠放射性标记物的总排泄量约为小鼠的六倍（56%对9%；p < 0.005）。当数据以组织中吸收剂量的百分比或每克组织的比放射性（dpm）表示时，发现大鼠和小鼠中[³H]DAS组织分布的时间进程存在显著差异。这些结果表明DAS的急性经皮毒性存在显著种间差异，以及局部应用的[³H]DAS在大鼠和小鼠中的吸收、排泄和组织分布模式不同。
