Percutaneous absorption, metabolism, and hemolytic activity of n-butoxyethanol

Abstract 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 14 C-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 blook 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 ⪢ pig > 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 hjmans because of its rapid percutaneous absorptive ability and its greater hemolytic sensitivity.