Bartnik F G, Reddy A K, Klecak G, Zimmermann V, Hostynek J J, Kunstler K
Fundam Appl Toxicol. 1987 Jan;8(1):59-70. doi: 10.1016/0272-0590(87)90100-x.
A series of studies was conducted to examine the percutaneous absorption, distribution, excretion, and hemolytic activity of n-butoxyethanol (BE). Rats receiving a subcutaneous dose of 14C-labeled BE excreted the radioactivity in the urine (79%), expired air (10%), and feces (0.5%) within 72 hr. Of the organs analyzed, thymus and spleen showed elevated specific radioactivities as compared with blood. A percutaneous application of BE on rats, under nonocclusive conditions, showed 25-29% absorption within 48 hr. Peak blood levels of BE occurred at 2 hr after application; butoxyacetic acid (BAA) was found to be the major metabolite. Comparison of in vitro skin penetration data showed the following absorption pattern of BE: hairless rat much greater than pig greater than human skin. Hemolysis and associated hematological changes were noted in the rats which received single dermal applications of 260-500 mg/kg of BE. In vitro, BAA showed markedly greater hemolytic ability on rat erythrocytes than did BE. Human erythrocytes showed no hemolysis when incubated with BE or BAA at concentrations that are hemolytic to rat erythrocytes. An intravenous dose of 62.5 mg/kg of BE does not result in hemolysis or hemoglobinuria in the rat. The rat may be an animal model with increased susceptibility to the effects of BE compared with humans because of its rapid percutaneous absorptive ability and its greater hemolytic sensitivity.
进行了一系列研究以检测正丁氧基乙醇（BE）的经皮吸收、分布、排泄及溶血活性。皮下注射14C标记BE的大鼠在72小时内，放射性物质经尿液排出（79%）、经呼出气体排出（10%）、经粪便排出（0.5%）。在所分析的器官中，胸腺和脾脏的比放射性高于血液。在非封闭条件下，对大鼠经皮涂抹BE，48小时内吸收量为25%-29%。涂抹后2小时BE血药浓度达峰值；发现主要代谢产物为丁氧基乙酸（BAA）。体外皮肤渗透数据比较显示BE的吸收模式如下：无毛大鼠＞猪＞人皮肤。单次经皮涂抹260-500mg/kg BE的大鼠出现溶血及相关血液学变化。体外实验中，BAA对大鼠红细胞的溶血能力明显强于BE。当与对大鼠红细胞有溶血作用的浓度的BE或BAA孵育时，人红细胞未出现溶血。静脉注射62.5mg/kg BE未导致大鼠溶血或血红蛋白尿。由于大鼠经皮吸收能力强且溶血敏感性高，与人类相比，大鼠可能是对BE作用更敏感的动物模型。
