Effect of butyl benzyl phthalate on reproduction and zinc metabolism

Butyl benzyl phthalate (BBP) has been shown to be teratogenic. One mechanis m contributing to the teratogenicity of several developmental toxicants, is chemical-induced changes in maternal zinc (Zn) metabolism which result in an increased synthesis of maternal liver metallothionein (Mt), and a subseq uent reduction in Zn delivery to the conceptus. We investigated the effects of maternal BBP exposure on maternal-fetal Zn metabolism in Wistar rats. I n study I, dams were gavaged with BBP (0, 250, 1000,1500 or 2000 mg/kg) on gestation days (GD) 11 through 13, and killed on GD 20. Maternal toxicity w as evident in the three highest dose groups.. Embryo/fetal death and small pup weights and lengths were noted in the 2000 mg BBP/kg group. Fetuses in the 1500 and 2000 mg/kg groups were characterized by poor skeletal ossifica tion, and a high frequency of cleft palate. Rib anomalies were observed in the three highest dose groups. Maternal liver MI concentrations were only s lightly elevated in the 1500 and 2000 mg/kg groups. In study II, dams treat ed as above, were gavaged with Zn-65 and killed 18 h later. While the 2000 mg/kg group had high percentages of 65Zn in some maternal tissues, sequestr ation of Zn-65 in maternal liver was not evident. Thus, BBP is not a strong inducer of Mt, and the teratogenicity of BBP does not appear to be due to alterations in maternal and/or embryonic Zn metabolism. (C) 2001 Elsevier S cience Ireland Ltd. All rights reserved.