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This article is available online at http://dmd.aspetjournals.org

The developmental toxicity and placental transfer of di-n-butyl phthalate (DBP) were evaluated in Sprague-Dawley rats given a single oral dose 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 weight were observed at 1.5 and 2 g/kg. Higher incidences of skeletal variations were found at doses > or = at 1 g/kg. No embryotoxic or teratogenic effects were observed at a dose of 0.5 g/kg. In the placental transfer study, dams were dosed with 0.5 or 1.5 g [14C]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 embryo were one-third or less of those in maternal plasma. No accumulation of radioactivity was observed in the maternal or embryonic tissues. From HPLC analyses, it was shown that unchanged DBP and its metabolites mono-n-butyl phthalate (MBP) and MBP glucuronide were rapidly transferred to the embryonic tissues, where their levels were constantly lower than those in maternal plasma. MBP accounted for most of the radioactivity recovered in maternal plasma, placenta, and embryo. Unchanged DBP was found only in small amounts. These findings support the hypothesis that MBP, a potent teratogen, largely contributes to the embryotoxic effects of DBP.

Effects of daily injections of pituitary-derived bovine somatotropin (bST) for 6 wk were evaluated in 10 growing heifers and compared to 9 placebo-treated control animals. Bovine somatotropin was injected at 50 micrograms/kg BW each day. Body weight and growth, plasma concentrations of insulin-like growth factor I (IGF-I) and somatotropin (ST) were assessed. To measure plasma concentrations of IGF-I, we validated a RIA in which bovine plasma samples were extracted with acid-ethanol, a method that resulted in greater than 90% recovery of IGF-I. Average daily gain was similar during the first 4 wk of the experiment in both control and bST-treated groups; however, at the end of the experimental period (wk 4 and 6) ADG was greater (P less than .05) in bST-treated heifers (1.24 +/- .21 kg/d vs .75 +/- .25 kg/d). Plasma IGF-I from wk 2 to wk 6 were increased in bST-treated animals (452 +/- 97 ng/ml at wk 2; 683 +/- 106 ng/ml at wk 6) compared with controls (293 +/- 62 ng/ml at wk 2 (P less than .01) and 293 +/- 115 ng/ml at wk 6 (P less than .001). Moreover, ADG over the 6-wk experimental period was correlated with mean IGF-I concentrations determined over the same period (r = .55; P less than .01). As expected, mean plasma ST concentrations were increased in bST-injected animals from wk 1 to 6. Gel chromatographic profiles of bovine plasma exhibit a 150,000 molecular weight ST-dependent binding protein-IGF-I complex and a 30,000 molecular weight non-ST-dependent complex. This study validates a method for measuring IGF-I in cattle, and shows a positive relationship among IGF-I and ADG after ST treatment. No correlation, however, was found between plasma ST and growth performance.

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