Shiota K, Nishimura H
Environ Health Perspect. 1982 Nov;45:65-70. doi: 10.1289/ehp.824565.
Di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DBP) were mixed with diet at graded levels of 0.05, 0.1, 0.2. 0.4 and 1.0 wt-% and given to pregnant ICR mice throughout gestation. Maternal weight gain was suppressed and fetal resorption increased at 0.2, 0.4 and 1.0% levels of DEHP and 1.0% level of DBP. All the implanted ova died early in rats fed 0.4 and 1.0% levels of DEHP. External malformations increased significantly by 0.2% DEHP, and 1.0% DBP showed borderline significance. The major malformations in treated groups were neural tube defects (exencephaly and myeloschisis), suggesting that the phthalic acid esters (PAEs) affect neural tube closure in developing embryos. Treatment with the compounds caused intrauterine growth retardation and delayed ossification with an apparently dose-related response pattern. These results indicate that a high dose of DEHP and DBP might be embryotoxic and teratogenic in mice. The maximum nonembryotoxic doses of PAEs in mice were more than 2000 times the estimated level of human intake through the food chain. Thus it is assumed that the current "normal" exposure level of PAEs dose not pose an imminent threat to human fetal development.
邻苯二甲酸二（2-乙基己基）酯（DEHP）和邻苯二甲酸二正丁酯（DBP）按0.05%、0.1%、0.2%、0.4%和1.0%（重量百分比）的分级水平与饲料混合，并在整个妊娠期给予怀孕的ICR小鼠。在DEHP含量为0.2%、0.4%和1.0%以及DBP含量为1.0%时，母体体重增加受到抑制，胎儿吸收增加。在喂食DEHP含量为0.4%和1.0%的大鼠中，所有植入的卵子均早期死亡。DEHP含量为0.2%时，外部畸形显著增加，DBP含量为1.0%时具有临界显著性。治疗组的主要畸形为神经管缺陷（无脑畸形和脊髓裂），表明邻苯二甲酸酯（PAEs）影响发育中胚胎的神经管闭合。用这些化合物进行治疗会导致子宫内生长迟缓以及骨化延迟，呈现出明显的剂量相关反应模式。这些结果表明，高剂量的DEHP和DBP可能对小鼠具有胚胎毒性和致畸性。PAEs在小鼠中的最大无胚胎毒性剂量比通过食物链估计的人类摄入量水平高2000多倍。因此，可以认为目前PAEs的“正常”暴露水平不会对人类胎儿发育构成紧迫威胁。
