Change of embryotoxic susceptibility to di-n-butyltin dichloride in cultured rat embryos.

Abstract

Di-n-butylin dichloride (DBTCl), which is commonly used as heat and light stabilizer for polyvinyl chloride (PVC) plastics, is a teratogen in vivo. In the present study, the toxic effects were investigated of DBTCl on cultured rat embryos during three different stages of organogenesis. Rat embryos explanted on gestational day (GD) 8.5, GD 9.5, and GD 11.5 were cultured for 68, 46, and 48 h and were exposed to a range of DBTCl concentrations for the first 24, 46, and the last 46 h of culture, respectively. Significant decreases in the placental diameter at > or = 10 ng/ml and in the number of somite pairs and the morphological score at 30 ng/ml were noted in embryos cultured from GD 8.5. Significant decreases in the yolk sac diameter and the crown-rump length at 100 ng/ml, in the number of somite pairs at > or = 50 ng/ml, and in the morphological score at > or = 30 ng/ml were found in embryos cultured from GD 9.5. No adverse effects on these parameters were detected in embryos cultured from GD 11.5 even at 300 ng/ml. Dysmorphogenesis in embryos cultured from GD 8.5, GD 9.5, and GD 11.5 was observed at > or = 10, > or = 50, and 300 ng/ml, respectively. Incomplete turning and craniofacial defects in embryos cultured from GD 8.5 and GD 9.5 and defects of the forelimb buds and tail in embryos cultured from GD 11.5 were frequently observed. These results show that in vitro exposure to DBTCl interferes with normal development of embryos during three different stages of organogenesis and that susceptibility to the embryotoxicity, including the dysmorphogenic potential of DBTCl, varies with developmental stage.