TERATOGENIC PHASE SPECIFICITY OF BUTYL BENZYL PHTHALATE IN RATS

Pregnant rats were given butyl benzyl phthalate (BBP) by gastric intubation at a dose of 0.6, 0.75 or 1.0 g/kg on days 7-9, 10-12 or 13-15 of pregnancy. While treatment with BBP on days 7-9 or 13-15 at doses of 0.75 and 1.0 g/kg was significantly teratogenic, no evidence of teratogenicity was detected when BBP was given on days 10-12. The incidence of malformed fetuses was proportional to the dose of BBP. Treatment on days 7-9 with BBP at doses of 0.75 g/kg and above caused a significant increase in the number of skeletal malformations, such as fusion of the cervical vertebral arches and deformity of the thoracic vertebrae, but neither external nor internal malformations. Treatment on days 13-15 with two higher doses of BBP resulted in a significantly increased incidence of fetuses with external and skeletal malformations such as cleft palate and fusion of the sternebrae. The highest incidence of malformed fetuses occurred after treatment with BBP on days 13-15. It could be concluded that the susceptibility to the teratogenicity of BBP varies with the developmental stage at the time of administration.