Distribution, excretion, and metabolism of butylbenzyl phthalate in the rat

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Abstract
The disposition of butylbenzyl phthalate (BBP), a widely used plasticizer, was evaluated after oral and iv administration to rats. Male Fischer‐344 rats were dosed with [ 14 C]BBP at 2, 20, 200, or 2000 mg/kg po or 20 mg/kg iv to determine the effects of dose on rates and routes of excretion. In 24 h, 61–74% of the dose was excreted in the urine and 13–19% in the feces at 2–200 mg/kg. At the 2000‐mg/kg dose, 16% of the 14 C was excreted in the urine and 57% in the feces. Urinary 14 C was composed of monophthalate derivatives (MP: 10–42% of the dose) and glucuronides of these monophthalate derivatives (2–21% of the dose). At 4 h after iv administration of BBP (20 mg/kg), 53–58% of the dose was excreted in the bile of anesthetized rats. No parent compound was found in the bile, but monobutyl phthalate‐glucuronide and monobenzyl phthalate‐glucuronide (26% and 13% of the dose, respectively) and trace amounts of free monoesters (2% of the dose) and unidentified metabolites (14% of the dose) were present. Although BBP is an asymmetric diester with the potential of forming equal amounts of monobutyl phthalate (MBuP) and monobenzyl phthalate (MBeP), larger quantities of MBuP were formed (MBuP = 44% versus MBeP = 76% of the dose). The half‐lives of BBP, MP, and total 14 C in blood (20 mg/kg, iv) were 10 min, 5.9 h, and 6.3 h, respectively. This study indicates that BBP is rapidly metabolized and that the major route of excretion of metabolites is biliary. These metabolites are reabsorbed and ultimately eliminated in the urine.