CHARACTERIZATION OF THE DEVELOPMENTAL TOXICITY OF DI-N-BUTYL PHTHALATE IN RATS

The objective of this study was to determine the characterization of t he developmental toxicity of di-n-butyl phthalate (DBP) in rats. Pregn ant rats were given DBP by gastric intubation at a dose of 0.75, 1.0 o r 1.5 g/kg on days 7-9, 10-12 or 13-15 of pregnancy. Postimplantation loss was 100% for each period of dosing at 1.5 g/kg. A significant inc rease in the postimplantation loss was found in dams given DBP at dose s of 0.75 and 1.0 g/kg regardless of the days of treatment. No evidenc e of teratogenicity was detected when DBP was given on days 10-12. Tre atment on days 7-9 with DBP at doses of 0.75 and 1.0 g/kg caused a sig nificant increase in the number of skeletal malformations such as defo rmity of the vertebral column in the cervical and thoracic regions and of the ribs, but neither external nor internal malformations. Treatme nt with DBP on days 13-15 at doses of 0.75 and 1.0 g/kg resulted in a significant increase in the incidence of fetuses with external and ske letal malformations such as cleft palate and fusion of the sternebrae. The frequency of malformations increased as the dose of DBP was incre ased. The highest incidence of malformed fetuses occurred after treatm ent with DBP on days 13-15. It could be concluded that susceptibility to the teratogenicity of DBP varies with the developmental stage at th e time of administration.