Pennanen S, Tuovinen K, Huuskonen H, Komulainen H
National Public Health Institute, Division of Environmental Health, Kuopio, Finland.
Fundam Appl Toxicol. 1992 Nov;19(4):505-11. doi: 10.1016/0272-0590(92)90088-y.
The developmental toxicity of 2-ethylhexanoic acid (2-EHA), a wood preservative and a mammalian metabolite of di-(2-ethylhexyl) phthalate was examined in Wistar rats (20-21 pregnant females/dose). Mated animals were exposed to 2-EHA in their drinking water at doses of 100, 300, or 600 mg/kg/day on Days 6-19 of gestation. Control animals received vehicle water. The fetuses were examined (on Gestational Day 20) for external, visceral, and skeletal malformations and variations. 2-EHA was marginally toxic to the dams at 600 mg/kg, but not at lower doses, since the mean near term body weight was reduced by 11%. This dose level was also slightly fetotoxic as indicated by a 5 to 8% decrease in the mean fetal body weight both in males and females. No treatment-related effects were observed in the number of implantations or live fetuses. At doses of 100 mg/kg and above, 2-EHA caused skeletal malformations (clubfoot, absence of fibula, polydactyly), while the development of visceral tissues was less affected. The number of affected fetuses increased in a dose-dependent way (4.9, 8.9, and 15.3% of treated offspring at 100, 300, and 600 mg/kg/day, respectively, vs 2.4% control). These results indicate that 2-EHA is teratogenic in rats already at doses which are not yet maternally toxic. The skeleton appears to be the main target of 2-EHA in developing rats.
2-乙基己酸（2-EHA）是一种木材防腐剂，也是邻苯二甲酸二（2-乙基己基）酯的哺乳动物代谢产物，研究人员在Wistar大鼠（每组20 - 21只怀孕雌性大鼠）中检测了其发育毒性。在妊娠第6至19天，将交配后的动物通过饮用水分别给予剂量为100、300或600 mg/kg/天的2-EHA。对照动物饮用溶剂水。在妊娠第20天检查胎儿的外部、内脏和骨骼畸形及变异情况。600 mg/kg剂量的2-EHA对母鼠有轻微毒性，而较低剂量则无此毒性，因为接近足月时的平均体重降低了11%。该剂量水平对胎儿也有轻微毒性，表现为雄性和雌性胎儿的平均体重均下降了5%至8%。在着床数或活胎数方面未观察到与处理相关的影响。在100 mg/kg及以上剂量时，2-EHA导致骨骼畸形（马蹄内翻足、腓骨缺失、多指畸形），而内脏组织的发育受影响较小。受影响胎儿的数量呈剂量依赖性增加（在100、300和600 mg/kg/天的处理后代中分别为4.9%、8.9%和15.3%，而对照组为2.4%）。这些结果表明，2-EHA在尚未产生母体毒性的剂量下就已对大鼠具有致畸性。在发育中的大鼠中，骨骼似乎是2-EHA的主要靶标。
