DEVELOPMENTAL EFFECTS OF DI-N-BUTYL PHTHALATE AFTER A SINGLE ADMINISTRATION IN RATS

The objective of this study was to determine the susceptible day for t he developmental toxicity of din-butyl phthalate (DBP), Pregnant rats were given a single dose of DBP by gastric intubation at 1500 mg kg(-1 ) on one of days 6-16 of pregnancy, A significant increase in the inci dence of postimplantation loss was found in pregnant rats given DBP on one of days 6-16, except for days 7 and 11, Significant increases in the incidences of fetuses with skeletal malformations, of fetuses with skeletal and internal malformations and of fetuses with external and skeletal malformations were noted after a single dosing of DBP on day 8, on day 9 and on day 15, respectively, Deformity of the cervical ver tebrae was frequently observed after administration of DBP on day 8, D eformity of the cervical and thoracic vertebrae and ribs and dilatatio n of the renal pelvis were predominantly found in fetuses of dams trea ted with DBP on day 9, Cleft palate and fusion of the sternebrae were exclusively detected after administration of DBP on day 15, It could b e concluded that the manifestation of deviant development induced by D BP varies with the developmental stage at the time of administration a nd that DBP induces two discrete responses from embryos to teratogenic ity on days 8 and 9 and on day 15 of pregnancy. (C) 1997 John Wiley & Sons, Ltd.