Diethylene glycol monoethyl ether is a chemical compound, hydroxypolyether, an ether glycol, primary alcohol derived from ethylene oxide.

It occurs as a colourless transparent liquid with a mild, ethereal odour. High boiling point solvent, soluble in water.

What it is used for and where

Pharmaceuticals. Diethylene glycol monoethyl ether is used as a solvent excipient and transdermal permeation enhancer in a number of injectable, transdermal and oral products in the pharmaceutical industry and, in particular, has the prerogative of improving skin deposition with poorly soluble drugs such as corticosteroids and griseofulvin (1). 

An intermediate chemical compound used in the preparation of organic compounds and analytical chemical reagents.

Cosmetics. Monoethyl ether diethylene glycol is an excipient approved by the FDA (Food and Drugs Administration) for use in cosmetics where it is generally used as a solvent.

Other uses

Textiles. Solvent and emulsion stabiliser in fibre dyeing processes.

Solvent in industrial processes of leather, synthetic resins, paints, spray paints, wood, petroleum sulphonic acid.

Safety

In this 2019 evaluation aimed at clarifying the doubts of the Scientific Committee on Consumer Products (SCCP) which, having examined Diethylene Glycol Monoethyl Ether (DEGEE) had found the toxicological reports submitted at the time to be unsatisfactory, the researchers found that the nephrotoxic potential of DEGEE cannot be excluded. Tests were carried out on single acute exposure of DEGEE intraperitoneally in Swiss albino mice and, in addition, a 28-day subchronic exposure study was conducted in which DEGEE was administered orally, once daily (2).

Diethylene glycol monoethyl ether studies

Typical optimal commercial product characteristics Diethylene Glycol Monoethyl Ether

• Molecular Weight  C₆H₁₄O₃      CH₃CH₂OCH₂CH₂OCH₂CH₂OH
• Linear Formula    C₂H₅OCH₂CH₂OCH₂CH₂OH
• Molecular Weight    134.17
• Exact Mass    134.094299
• CAS  111-90-0
• UNII    A1A1I8X02B
• EC Number   203-919-7
• DSSTox Substance ID     DTXSID2021941
• IUPAC  2-(2-etossietossi)etanolo
• InChI=1S/C6H14O3/c1-2-8-5-6-9-4-3-7/h7H,2-6H2,1H3  
• InChl Key      XXJWXESWEXIICW-UHFFFAOYSA-N
• SMILES   CCOCCOCCO
• MDL number  MFCD00002872
• PubChem Substance ID    329757987
• Beilstein    1736441
• ChEBI  40572
• ICSC    0039
• NSC   408451
• RTECS   KK8750000
• NACRES  NA.21   

Synonyms:

• Diethylene glycol ethyl ether
• Ethyldiglycol
• Carbitol ™
• Transcutol^®
• 2-(2-Ethoxyethoxy)ethanol
• Ethoxy diglycol

References____________________________________________________________________

(1) Ritschel WA, Panchagnula R, Stemmer K, Ashraf M. Development of an intracutaneous depot for drugs. Binding, drug accumulation and retention studies, and mechanism of depot. Skin Pharmacol. 1991;4(4):235-45. 

(2) Srivastava S, Mishra S, Dewangan J, Divakar A, Gupta N, Kalleti N, Mugale MN, Kumar S, Sharma S, Rath SK. Safety assessment of the pharmacological excipient, diethylene glycol monoethyl ether (DEGEE), using in vitro and in vivo systems. Daru. 2019 Jun;27(1):219-231. doi: 10.1007/s40199-019-00264-5. 

Compendium of the most significant studies with reference to properties, intake, effects.

Mura P, Faucci MT, Bramanti G, Corti P. Evaluation of transcutol as a clonazepam transdermal permeation enhancer from hydrophilic gel formulations. Eur J Pharm Sci. 2000 Feb;9(4):365-72. doi: 10.1016/s0928-0987(99)00075-5. 

Abstract. Such a result is explained on the basis of the particular mechanism of action demonstrated for transcutol which associates the increase of drug solubility to the potent effect of a depot in the skin.

Shu J, Zhao J, Guo F. Systematically optimized topical delivery system for Loperamide hydrochloride: Formulation design, in vitro and in vivo biopharmaceutical evaluation. Asian J Pharm Sci. 2018 May;13(3):255-264. doi: 10.1016/j.ajps.2017.08.009.

Abstract. This study aimed to develop a suitable topical delivery system containing diethylene glycol monoethyl ether (DGME) for Loperamide hydrochloride (Lop). 

Hardin BD, Goad PT, Burg JR. Developmental toxicity of four glycol ethers applied cutaneously to rats. Environ Health Perspect. 1984 Aug;57:69-74. doi: 10.1289/ehp.845769.

Abstracts. In the present study ethylene glycol monoethyl ether acetate (EGEEA), ethylene glycol monobutyl ether (EGBE), and diethylene glycol monoethyl ether (diEGEE) were tested in the same experimental model, using distilled water as the negative control and EGEE as a positive control....Visceral malformations and skeletal variations were significantly increased in EGEE and EGEEA groups over the negative control group. No embryotoxic, fetotoxic, or teratogenic effects were detected in the EGBE- or diEGEE-treated litters.

Pireddu R, Sinico C, Ennas G, Schlich M, Valenti D, Murgia S, Marongiu F, Fadda AM, Lai F. The effect of diethylene glycol monoethyl ether on skin penetration ability of diclofenac acid nanosuspensions. Colloids Surf B Biointerfaces. 2018 Feb 1;162:8-15. doi: 10.1016/j.colsurfb.2017.11.012.

Abstract. In this work, the penetration enhancer diethylene glycol monoethyl ether was included in novel diclofenac acid nanocrystal formulations, developed using the wet media milling technique and Poloxamer 188 as stabilizer. 

Zhang Y, Hu H, Jing Q, Wang Z, He Z, Wu T, Feng NP. Improved Biosafety and Transdermal Delivery of Aconitine via Diethylene Glycol Monoethyl Ether-Mediated Microemulsion Assisted with Microneedles. Pharmaceutics. 2020 Feb 17;12(2):163. doi: 10.3390/pharmaceutics12020163.

Abstract. In the current study, diethylene glycol monoethyl ether-mediated microemulsions were combined with microneedles for enhanced transdermal aconitine delivery. 

 Levi-Schaffer F, Dayan N, Touitou E. Diethylene glycol monoethyl ether (Transcutol) displays antiproliferative properties alone and in combination with xanthines. Skin Pharmacol. 1996;9(1):53-9. doi: 10.1159/000211390.

Abstract. In conclusion, we have shown that Transcutol has antiproliferative effects on 3T3 murine, human normal and psoriatic fibroblasts and tumour cell lines. In addition it enhances xanthine antiproliferative effects on 3T3 fibroblasts. Therefore it might be a useful topical drug alone or in combination with xanthines in the treatment of skin hyperproliferative disorders.