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

The objective of this study was to determine the characterization of the developmental toxicity of di-n-butyl phthalate (DBP) in rats. Pregnant rats were given DBP by gastric intubation at a dose of 0.75, 1.0 or 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 increase in the postimplantation loss was found in dams given DBP at doses of 0.75 and 1.0 g/kg regardless of the days of treatment. No evidence of teratogenicity was detected when DBP was given on days 10-12. Treatment on days 7-9 with DBP at doses of 0.75 and 1.0 g/kg caused a significant increase in the number of skeletal malformations such as deformity of the vertebral column in the cervical and thoracic regions and of the ribs, but neither external nor internal malformations. Treatment 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 skeletal malformations such as cleft palate and fusion of the sternebrae. The frequency of malformations increased as the dose of DBP was increased. The highest incidence of malformed fetuses occurred after treatment with DBP on days 13-15. It could be concluded that susceptibility to the teratogenicity of DBP varies with the developmental stage at the time of administration.