Dibutyl terephthalate

Endpoint summary

Additional information

The metabolism of dibutyl terephthalate has been investigated in both in vivo and in vitro studies. In an in vitro hydrolysis study conducted according to generally acceptable scientific principles, dibutyl terephthalate was incubated with rat gut homogenate to determine the rate and extent of enzymatic destruction of the parent compound and the formation of the predicted metabolite terephthalic acid. Samples of treated homogenate were withdrawn at appropriate intervals and analyzed for the presence of parent compound and terephthalic acid. In vitro, dibutyl terephthalate underwent rapid hydrolysis in gut homogenate to produce the expected terephthalic acid. Less than 10% of the starting material remained at the 5-min sampling time while the terephthalic acid levels continued to increase over time. Due to the rapid metabolism, it was not possible to exactly calculate a half-life for dibutyl terephthalate under conditions used in the in vitro study, but the T1/2 was considered to be less than 5 minutes. In an in vivo absorption and metabolism study, male Sprague Dawley rats were administered a single dose of dibutyl terephthalate by oral gavage at a dose level of approximately 100 mg/kg bw. Following dosing, urine was collected at 8 and 24 hours; feces were collected at 24 hours but not analyzed. Blood samples were withdrawn through an indwelling jugular cannula at 1, 4, 8 and 24 hours post dosing. Urine and blood sample were analyzed by gas chromatography/mass spectrometry for the presence of parent compound and terephthalic acid. Dibutyl terephthalate was only found in blood samples at 1 hour post dosing while terephthalic acid was found in the 1 hour sample and levels then decreased over time. Blood terephthalic acid levels were below the limit of detection at the 24-hour sampling time. None of the parent compound was found in any of the urine samples, indicating rapid and extensive metabolism. Terephthalic acid was quantifiable in all the urine samples. Total terephthalic acid recovered in the urine by 24-hours represented <20% of the parent dose, potentially indicating poor bioavailability via the oral route. Both the in vivo and in vitro metabolism studies indicate that dibutyl terephthalate is rapidly metabolized to terephthalic acid by the oral route. In this study butanol was not analyzed, however, the identification of terephthalic acid indirectly indicates that two molecules of butanol were released for every molecule of DBT.