Ema M, Itami T, Kawasaki H
National Institute of Hygienic Sciences, Osaka Branch, Japan.
Toxicology. 1993 Mar 30;79(1):11-9. doi: 10.1016/0300-483x(93)90202-4.
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.
在妊娠第7至9天、10至12天或13至15天，通过胃内插管给怀孕大鼠分别以0.6、0.75或1.0克/千克的剂量给予邻苯二甲酸丁苄酯（BBP）。虽然在妊娠第7至9天或13至15天给予0.75和1.0克/千克剂量的BBP具有明显的致畸性，但在第10至12天给予BBP时未检测到致畸证据。畸形胎儿的发生率与BBP的剂量成正比。在第7至9天给予0.75克/千克及以上剂量的BBP治疗会导致骨骼畸形数量显著增加，如颈椎弓融合和胸椎畸形，但没有外部或内部畸形。在第13至15天给予两个较高剂量的BBP治疗导致出现外部和骨骼畸形胎儿的发生率显著增加，如腭裂和胸骨融合。畸形胎儿的最高发生率出现在第13至15天给予BBP治疗后。可以得出结论，BBP致畸性的易感性随给药时的发育阶段而变化。
