Bailey Melissa M, Jernigan Peter L, Henson Megan B, Sturdivant John, Rasco Jane F, Lovich Ashley N, Lockhard Jarrett E, Hough Whitney L, Di Bona Kristin R, Beaird Janis, Sherrill Jonathan, Swatloski Richard P, Rogers Robin D, Hood Ronald D
Department of Biological Sciences, Emporia State University, Emporia, Kansas 66801, USA.
Birth Defects Res B Dev Reprod Toxicol. 2010 Jun;89(3):233-8. doi: 10.1002/bdrb.20251.
Ionic liquids (ILs; salts with melting points below 100 degrees C) exhibit wide liquid ranges, non-flammability, and thermal stability among other properties. These unique salts are best known as "green" alternatives to traditional volatile organic solvents, which are utilized in both academia and industry. Our current study compares the developmental toxicity potential of three representative ionic liquids, with various chain lengths: 1-ethyl-3-methylimidazolium chloride ([C(2)mim]Cl), 1-butyl-3-methylimidazolium chloride ([C(4)mim]Cl), and 1-decyl-3methylimidazolium chloride ([C(10)mim]Cl).
From gestation days (GD) 6-16, mated CD-1 mice were orally dosed with one of the following: 1,000, 2,000, or 3,000 mg/kg/day [C(2)mim]Cl; 113, 169, or 225 mg/kg/day [C(4)mim]Cl; 50, 75, or 100 mg/kg/day [C(10)mim]Cl; or the vehicle only. Dams were sacrificed on GD 17, and their litters were examined for adverse effects.
Fetal weight was significantly decreased in the two highest dosage groups exposed to [C(4)mim]Cl and [C(10)mim]Cl in comparison with their controls, but the [C(2)mim]Cl treated groups were not affected. An apparent teratogenic effect was associated with both [C(4)mim]Cl and [C(10)mim]Cl, as the offspring exhibited certain uncommon morphological defects. However, the incidences of malformations were low and no correlation between incidence and dosage could be made. No morphological defects were observed in any of the [C(2)mim]Cl-treated groups, despite maternal morbidity at the highest dosage level.
This study indicates that [C(4)mim]Cl and [C(10)mim]Cl may have adverse effects on development at high maternal exposures and strongly supports the supposition that the toxicity of imidazolium-based ILs is influenced by alkyl chain length.
离子液体(ILs;熔点低于100摄氏度的盐)具有宽液体范围、不可燃性和热稳定性等特性。这些独特的盐作为传统挥发性有机溶剂的“绿色”替代品而广为人知,在学术界和工业界均有应用。我们当前的研究比较了三种具有不同链长的代表性离子液体的发育毒性潜力:1-乙基-3-甲基咪唑氯盐([C(2)mim]Cl)、1-丁基-3-甲基咪唑氯盐([C(4)mim]Cl)和1-癸基-3-甲基咪唑氯盐([C(10)mim]Cl)。
从妊娠第6天至第16天,给交配后的CD-1小鼠口服以下物质之一:1000、2000或3000毫克/千克/天的[C(2)mim]Cl;113、169或225毫克/千克/天的[C(4)mim]Cl;50、75或100毫克/千克/天的[C(10)mim]Cl;或仅给予赋形剂。在妊娠第17天处死母鼠,并检查其窝仔有无不良反应。
与对照组相比,暴露于[C(4)mim]Cl和[C(10)mim]Cl的两个最高剂量组的胎儿体重显著降低,但[C(2)mim]Cl处理组未受影响。[C(4)mim]Cl和[C(10)mim]Cl均与明显的致畸作用相关,因为后代出现了某些罕见的形态缺陷。然而,畸形发生率较低,且发生率与剂量之间无相关性。尽管在最高剂量水平出现了母体发病情况,但在任何[C(2)mim]Cl处理组中均未观察到形态缺陷。
本研究表明,在母体高暴露情况下,[C(4)mim]Cl和[C(10)mim]Cl可能对发育产生不利影响,并有力支持了基于咪唑鎓的离子液体的毒性受烷基链长度影响的假设。