In vivo and in vitro percutaneous absorption of [C-14]di-n-butylphthalate in rat

This study evaluated the toxicokinetics of [C-14]di-n-butylphthalate ([C-14 ]DBP) after an intravenous administration (1 and 10 mg/kg, in Cremophor) or a topical application (10 mul/cm(2); 10 cm(2), neat) in haired male Spragu e-Dawley rats. Additional in vivo and in vitro percutaneous penetration stu dies of [14C]DBP were conducted on male and female haired rats and male hai rless rats. After intravenous administration, unchanged DBP disappeared rap idly from the plasma, following a two-exponential function (T1/2 beta = 5-7 min). The peak levels of monobutylphthalate (MBP) and its glucuronide conj ugate (MBP-Gluc) occurred 1 to 2 and 20 to 30 min after administration, res pectively, These metabolites were intensively and rapidly excreted in urine (57% of the dose), However, about 35% of the dose recovered in urine was p rimarily excreted in bile (mainly as MBP-Gluc) and underwent hepatobiliary recycling, Unchanged DBP was barely detectable in excreta. DBP rapidly pene trated the skin, which constituted a reservoir. The absorption flux determi ned for 0.5 to 8 and 8 to 48 h of exposure were 43 and 156 mug/cm(2)/h, res pectively, The higher flux may be due to radial diffusion of DBP in the str atum and/or epidermis. The in vivo and in vitro experiments revealed that D BP was intensively metabolized into the skin. In vivo percutaneous absorpti on flux was very similar in male and female haired rats, In contrast, the p ercutaneous absorption determined in vivo and in vitro was higher in hairle ss than in haired male rats. Absorption flux was accurately estimated from urinary excretion rate of MBP or MBP-Gluc.