ASSESSMENT OF THE DEVELOPMENTAL TOXICITY, METABOLISM, AND PLACENTAL-TRANSFER OF DI-N-BUTYL PHTHALATE ADMINISTERED TO PREGNANT RATS

The developmental toxicity and placental transfer of di-n-butyl phthal ate (DBP) were evaluated in Sprague-Dawley rats given a single oral do se of DBP on Gestational Day 14. In the developmental toxicity study, dams were dosed with 0, 0.5, 1, 1.5, or 2 g DBP/kg and were necropsied on GD21. Increased incidence of resorptions and reduced fetal body we ight were observed at 1.5 and 2 g/kg. Higher incidences of skeletal va riations were found at doses greater than or equal to at 1 g/kg. No em bryotoxic or teratogenic effects were observed at a dose of 0.5 g/kg. Zn the placental transfer study, dams were dosed with 0.5 or 1.5 g [C- 14]DBP/kg. Maternal and embryonic tissues were collected at intervals from 0.5 to 48 h. Embryonic tissues accounted for less than 0.12-0.15% of the administered dose. Levels of radiocarbon in placenta and embry o were one-third or less of those in maternal plasma. No accumulation of radioactivity was observed in the maternal or embryonic tissues. Fr om HPLC analyses, it was shown that unchanged DBP and its metabolites mono-n-butyl phthalate (MBP) and MBP glucuronide were rapidly transfer red to the embryonic tissues, where their levels were constantly lower than those in maternal plasma. MBP accounted for most of the radioact ivity recovered in maternal plasma, placenta, and embryo. Unchanged DB P was found only in small amounts. These findings support the hypothes is that MBP, a potent teratogen, largely contributes to the embryotoxi c effects of DBP. (C) 1998 Society of Toxicology.