Campbell J, Holt D, Webb M
J Appl Toxicol. 1984 Feb;4(1):35-41. doi: 10.1002/jat.2550040108.
The rat foetus, in contrast with the maternal liver and placenta, has little or no ability to hydrolyse di-(2-methoxyethyl)-phthalate (DMEP) to mono-2-methoxyethyl)-phthalate (MMEP). At short times after the administration of DMEP to the dam on the 14th day of gestation, however, both the di- and mono-ester are present in the foetus. Clearance of total phthalate from the foetus and placenta, is rapid and the foetal burden is reduced by 96% between 45 min and 4 h. Although MMEP, when injected into the dam at the same molar dose level, crosses the placenta, its concentration in the foetus is lower than the after the injection of DMEP, MMEP (2.49 mmol kg-1), is no teratogenic when administered as an aqueous solution of the sodium salt on day 8, 10, 12 or 14 of gestation, in contrast with the same molar dose of the liquid DMEP. The alcohol, 2-methoxyethanol (ME), when administered as a single injection at this dose level (2.49 mmol kg-1), however, is highly teratogenic and its effects cannot be differentiated clearly from those of DMEP. These results, which indicate the possibility that ME, derived by metabolism of DMEP, may be the teratogenic agent, suggest that both the rate of hydrolysis to the monoester and the chemical properties of the liberated alcohol, could be important determinant factors in the teratogenic activities of different phthalate diesters.
与母体肝脏和胎盘相比，大鼠胎儿水解邻苯二甲酸二（2 - 甲氧基乙基）酯（DMEP）生成邻苯二甲酸单（2 - 甲氧基乙基）酯（MMEP）的能力很小或几乎没有。然而，在妊娠第14天给母鼠施用DMEP后的短时间内，胎儿体内同时存在二酯和单酯。胎儿和胎盘内总邻苯二甲酸酯的清除速度很快，在45分钟至4小时之间胎儿体内的负担减轻了96%。尽管以相同摩尔剂量水平注入母鼠体内时MMEP会穿过胎盘，但其在胎儿体内的浓度低于注入DMEP后的浓度。与相同摩尔剂量的液态DMEP相比，当在妊娠第8、10、12或14天以钠盐的水溶液形式施用时，MMEP（2.49 mmol kg-1）没有致畸性。然而，当以该剂量水平（2.49 mmol kg-1）单次注射施用醇类2 - 甲氧基乙醇（ME）时，它具有高度致畸性，其作用无法与DMEP的作用清楚地区分开来。这些结果表明，由DMEP代谢产生的ME可能是致畸剂，这表明水解为单酯的速率和释放出的醇的化学性质，可能是不同邻苯二甲酸二酯致畸活性的重要决定因素。
