Division of Toxicology and Experimental Medicine, CSIR- Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India.
Daru. 2019 Jun;27(1):219-231. doi: 10.1007/s40199-019-00264-5. Epub 2019 Apr 18.
Diethylene glycol monoethyl ether (DEGEE) is widely used as a solubilizer in cosmetics as well as in oral, topical, transdermal and injectable pharmaceutical formulations. Due to the unavailability of detailed toxicological studies on DEGEE, the Scientific Committee on Consumer Products (SCCP) found its toxicological reports to be unsatisfactory, comprising only summaries. Also, a few reports have raised concern on the use of DEGEE as it might cause damage to the kidneys.
Safety assessment of DEGEE using in vitro and in vivo models.
In vitro effects of DEGEE (0.5-25 mg/ml) were assessed in the HEK293 human embryonic kidney cells. In vivo effects were evaluated after single acute exposure of DEGEE via intraperitoneal route in Swiss albino mice and further, a 28 days subchronic exposure study was conducted where DEGEE was administered orally, once daily.
DEGEE was cytotoxic to HEK293 cells, and an IC of 15 mg/ml was established. An increase in the intracellular levels of ROS and alteration in the mitochondrial membrane potential led to nuclear fragmentation and induction of apoptosis in these cells. Survival rate of animals administered intraperitoneally with a single acute dose of 1000 mg/kg DEGEE was 100% with no significant changes in the behavioural and histological parameters. However, the dose of 3000 mg/kg and above led to total mortality within 14 days of acute exposure. Subchronic oral exposure of 500-2000 mg/kg DEGEE showed no significant changes in the hematological, biochemical and histopathological parameters.
The in vitro findings indicate that the nephrotoxic potential of DEGEE cannot be ruled out. The results of the in vivo studies reveal that the degree of toxic effects shown by DEGEE varies, depending on the dose, duration of exposure and routes of administration. Therefore, the present findings are of relevance and thorough studies should be conducted before using this substance in clinical formulations. Graphical abstract Evaluation of the toxic potential of Diethylene glycol monoethyl ether.
二甘醇单乙醚 (DEGEE) 广泛用作化妆品以及口服、局部、经皮和注射药物制剂的增溶剂。由于缺乏关于 DEGEE 的详细毒理学研究，消费者产品科学委员会 (SCCP) 认为其毒理学报告不令人满意，仅包含摘要。此外，一些报告对 DEGEE 的使用表示担忧，因为它可能会对肾脏造成损害。
使用体外和体内模型评估 DEGEE 的安全性。
在 HEK293 人胚肾细胞中评估 DEGEE（0.5-25 mg/ml）的体外作用。通过腹腔途径单次急性暴露 DEGEE 后评估体内作用，进一步进行 28 天亚慢性暴露研究，DEGEE 经口每日一次给予。
DEGEE 对 HEK293 细胞具有细胞毒性，建立了 15mg/ml 的 IC。细胞内 ROS 水平升高和线粒体膜电位改变导致核片段化和细胞凋亡诱导。腹腔给予单次急性剂量 1000mg/kg DEGEE 的动物存活率为 100%，行为和组织学参数无显著变化。然而，剂量为 3000mg/kg 及以上导致急性暴露后 14 天内全部死亡。DEGEE 的亚慢性口服暴露 500-2000mg/kg 对血液学、生化和组织病理学参数无显著变化。
体外研究结果表明不能排除 DEGEE 的肾毒性。体内研究结果表明，DEGEE 表现出的毒性作用程度因剂量、暴露时间和给药途径而异。因此，在将该物质用于临床制剂之前，应进行深入研究。
