Ritter E J, Scott W J, Randall J L, Ritter J M
Teratology. 1987 Feb;35(1):41-6. doi: 10.1002/tera.1420350107.
It is hypothesized that the teratogen di(2-ethylhexyl) phthalate (DEHP) acts by in vivo hydrolysis to 2-ethylhexanol (2-EHXO), which in turn is metabolized to 2-ethylhexanoic acid (2-EHXA), the proximate teratogen. Teratological studies were conducted with Wistar rats, with administration of these agents on day 12 of gestation. On an equimolar basis DEHP was least potent, 2-EHXO was intermediate, and 2-EXHA was the most potent of the three agents, which is consistent with the hypothesis. Similarity in the types of defects found with these agents also suggests a common mechanism, with 2-EHXA as the proximate teratogen. All three agents were potentiated by caffeine. Valproic acid, which is an isomer of 2-EXHA, also produced similar defects, and was approximately twice as potent as 2-EHXA.
据推测，致畸剂邻苯二甲酸二（2-乙基己基）酯（DEHP）通过体内水解作用生成2-乙基己醇（2-EHXO），而2-乙基己醇又会代谢为2-乙基己酸（2-EHXA），即直接致畸剂。在妊娠第12天对Wistar大鼠进行了致畸学研究，并给予这些药剂。在等摩尔基础上，DEHP的效力最低，2-EHXO处于中间水平，而2-EXHA是这三种药剂中效力最强的，这与该假设一致。这些药剂所导致的缺陷类型相似，这也表明存在一种共同机制，以2-EHXA作为直接致畸剂。所有这三种药剂的作用都因咖啡因而增强。丙戊酸是2-EXHA的异构体，也会产生类似的缺陷，其效力约为2-EHXA的两倍。
