Ema M, Kurosaka R, Amano H, Ogawa Y
National Institute of Health Sciences, Osaka, Japan.
Arch Environ Contam Toxicol. 1995 Feb;28(2):223-8. doi: 10.1007/BF00217620.
n-Butyl benzyl phthalate (BBP) and di-n-butyl phthalate (DBP) were evaluated and compared for their developmental toxic potential. Pregnant rats were given either BBP or DBP by gastric intubation at a dose of 0.75, 1.0 and 1.25 g/kg on days 7-9, days 10-12 and days 13-15 of pregnancy. Regardless of the days of treatment, a significantly increased incidence of postimplantation loss was found at all doses of BBP and DBP. While treatment with BBP and DBP at doses of 0.75 g/kg and above on days 7-9 or days 13-15 resulted in a significant increase in the incidence of fetuses with malformations, no increase in the incidence of malformed fetuses was found after treatment with BBP and DBP on days 10-12. The incidences of postimplantation loss and malformed fetuses increased as the doses of BBP and DBP were increased. Deformity of the vertebral column and ribs commonly occurred after treatment with BBP and DBP on days 7-9. Cleft palate and fusion of the sternebrae were predominantly observed after treatment with BBP and DBP on days 13-15. The similarity in dependence of gestational days of treatment on the manifestation of developmental toxicity and on the spectrum of fetal malformations caused by BBP and DBP suggests that they may act by the same mechanism, possibly via a common metabolite of these two parent compounds.
对邻苯二甲酸正丁酯苄酯(BBP)和邻苯二甲酸二正丁酯(DBP)的发育毒性潜力进行了评估和比较。在妊娠第7 - 9天、第10 - 12天和第13 - 15天,通过胃管给怀孕大鼠分别给予剂量为0.75、1.0和1.25 g/kg的BBP或DBP。无论治疗天数如何,在所有剂量的BBP和DBP下,着床后丢失的发生率均显著增加。虽然在第7 - 9天或第13 - 15天用0.75 g/kg及以上剂量的BBP和DBP治疗导致畸形胎儿的发生率显著增加,但在第10 - 12天用BBP和DBP治疗后未发现畸形胎儿的发生率增加。着床后丢失和畸形胎儿的发生率随着BBP和DBP剂量的增加而增加。在第7 - 9天用BBP和DBP治疗后,脊柱和肋骨畸形常见。在第13 - 15天用BBP和DBP治疗后,主要观察到腭裂和胸骨融合。治疗的妊娠天数对BBP和DBP引起的发育毒性表现以及胎儿畸形谱的依赖性相似,这表明它们可能通过相同的机制起作用,可能是通过这两种母体化合物的共同代谢产物。