Phase specificity of developmental toxicity after oral administration of mono-n-butyl phthalate in rats.

The objective of this study was to further characterize the developmental toxicity of mono-n-butyl phthalate (MBuP), which is one of the major metabolites of n-butyl benzyl phthalate (BBP) and di-n-butyl phthalate (DBP). Pregnant rats were given MBuP by gastric intubation at a dose of 500, 625 or 750 mg/kg on days 7-9, days 10-12, or days 13-15 of pregnancy. A significantly increased incidence of postimplantation loss was noted in pregnant rats given MBuP on days 7-9 and days 10-12 at doses of 625 mg/kg and above and on days 13-15 at doses of 500 mg/kg and above. No evidence of teratogenicity was found when MBuP was given on days 10-12 of pregnancy. A significantly increased incidence of fetuses with external malformations was found after treatment with MBuP on days 7-9 and days 13-15 at doses of 625 and 750 mg/kg. A significantly increased incidence of fetuses with skeletal malformations was observed after treatment with MBuP on days 7-9 at doses of 500 mg/kg and above and on days 13-15 at doses of 625 mg/kg and above. Deformity of the cervical vertebrae was predominantly observed following treatment with MBuP on days 7-9. Cleft palate and fusion of the sternebrae were exclusively found following treatment with MBuP on days 13-15. It could be concluded that the manifestation of deviant development induced by MBuP varies with the developmental stage at the time of administration.