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

Belsito, M., Hill, R. A., Klaassen, C. D., Liebler, D., Marks Jr, J. G., & Ronald, C. (2012). On the Safety Assessment of Ethanolamides as Used in Cosmetics. Final Amended Report.

Abstract. The CIR Expert Panel re-reviewed the safety of isostearamide, myristamide, and stearamide MEA as used in cosmetics, and included 25 additional ethanolamides that are secondary carboxamides comprised of the amidation products of alkyl carboxylic acids and ethanolamine, concluding that these ingredients are safe in the present practices of use and concentration when formulated to be non-irritating, and that these ingredients should not be used in cosmetic products in which N-nitroso compounds may be formed. Most of the ethanolamides are reported to function in cosmetics as hair conditioning agents, skin conditioning agents, and surfactant – foam boosters; a few are reported to have other uses. The Panel reviewed available animal and clinical data, as well as information from previous CIR reports.

Martiryan, A. I., Shahinyan, G. A., & Vardapetyan, V. V. (2022). Antiradical activity, base-catalyzed hydrolysis and partition coefficients of some surfactants. Colloid and Interface Science Communications, 50, 100653.

Abstract. Antiradical activity and some environmental characteristics such as biodegradability and bioavailability of several coconut oil derived surfactants have been studied by photometry and UV–Vis absorption spectroscopy. The effects of polar group size and type were revealed using non-ionic surfactants cocamide monoethanolamine, cocamide diethanolamine, amphoteric surfactant cocamidopropyl betaine, and anionic surfactants sodium lauryl sulfate and sodium alfa olefin sulfonate. Free radical scavenging properties were examined by determination of rate constant of the reaction with hydroxyl radicals. To calculate the rate constant the competitive reaction between hydroxyl radicals and p-nitroso-N,N-dimethyl aniline was investigated. The results show pronounced antioxidant activity of surfactants. To confirm the environmentally friendly character of mentioned surfactants the biodegradability and accumulation were studied using base-catalyzed hydrolysis and partition coefficient between n-octanol/water layers. The obtained results show that type of head group and the carbon chain structure have major effect on these properties.

Mertens S, Gilissen L, Goossens A. Allergic contact dermatitis caused by cocamide diethanolamine. Contact Dermatitis. 2016 Jul;75(1):20-4. doi: 10.1111/cod.12580. Epub 2016 May 3. PMID: 27144883.

Hoeman KW, Culbertson CT. A novel, environmentally friendly sodium lauryl ether sulfate-, cocamidopropyl betaine-, cocamide monoethanolamine-containing buffer for MEKC on microfluidic devices. Electrophoresis. 2008 Dec;29(24):4900-5. doi: 10.1002/elps.200800463.

Abstract. A new buffer has been developed for fast, high-efficiency separations of amino acids by MEKC. This buffer was more environmentally friendly than the most commonly used surfactant-containing buffers for MEKC separations. It used a commercially available dishwashing soap by Seventh Generation (Burlington, VT, USA), which contained three micelle-forming agents. The mixed micelles were composed of sodium lauryl ether sulfate (anionic), cocamidopropyl betaine (zwitterionic), and cocamide monoethanolamine (non-ionic). The optimized buffer contained 5.0% w/w Seventh Generation Free & Clear dishwashing soap, 10 mM sodium borate, and was completely void of organics. The lack of organics and the biodegradability of the surfactant molecules made this buffer more environmentally friendly than typical SDS-containing buffers. This new buffer also had a different selectivity and provided faster separations with higher separation efficiencies than SDS-based buffers. Fast separations of BODIPY FL labeled amino acids yielded peaks with separation efficiencies greater than 100,000 in less than 20 s.

Yavrukova VI, Radulova GM, Danov KD, Kralchevsky PA, Xu H, Ung YW, Petkov JT. Rheology of mixed solutions of sulfonated methyl esters and betaine in relation to the growth of giant micelles and shampoo applications. Adv Colloid Interface Sci. 2020 Jan;275:102062. doi: 10.1016/j.cis.2019.102062.

Forsby A, Norman KG, El Andaloussi-Lilja J, Lundqvist J, Walczak V, Curren R, Martin K, Tierney NK. Using novel in vitro NociOcular assay based on TRPV1 channel activation for prediction of eye sting potential of baby shampoos. Toxicol Sci. 2012 Oct;129(2):325-31. doi: 10.1093/toxsci/kfs198.

Abstract  The transient receptor potential vanilloid type 1 (TRPV1) channel is one of the most well-characterized pain-inducing receptors. The purpose of this study was to predict human eye stinging of 19 baby bath and shampoo formulations by studying TRPV1 activity, as measured by increase in intracellular free Ca(2+). The NociOcular test, a novel recombinant neuronal in vitro model with high expression of functional TRPV1 channels, was used to test formulations containing a variety of surfactants, preservatives, and fragrances. TRPV1-specific Ca(2+) influx was abolished when the TRPV1 channel antagonist capsazepine was applied to the cells prior to shampoo samples. The positive control, an adult shampoo that contains cocamide monoethanolamine (CMEA), a known stinging ingredient, was the most active sample tested in the NociOcular test. The negative control, a marketed baby shampoo, was negative in the NociOcular and human tests. Seven of the formulations induced stinging in the human test, and of those six were positive in the NociOcular test. Twelve formulations were classified as nonstinging in the human test, and of those ten were negative in the NociOcular test. There was no correlation between the clinical stinging results for the baby formulations and the data generated from other in vitro eye irritation assays (cytosensor microphysiometer, neutral red uptake, EpiOcular, transepithelial permeability). Our data support that the TRPV1 channel is a principal mediator of eye-stinging sensation induced by baby bath and shampoo formulations and that the NociOcular test may be a valuable in vitro tool to predict human eye-stinging sensation.

Wu HY, Shih CL, Lee T, Chen TY, Lin LC, Lin KY, Chang HC, Chuang IC, Liou SY, Liao PC. Development and validation of an analytical procedure for quantitation of surfactants in dishwashing detergents using ultra-performance liquid chromatography-mass spectrometry. Talanta. 2019 Mar 1;194:778-785. doi: 10.1016/j.talanta.2018.10.084.

Diethanolamine | FDA 

PEG-20 Cocamide MEA (Cocamide Monoethanolamine ) is a chemical compound, diethanol-amide, non-ionic surfactant, belongs to the family of cocamides (MEA, DEA, TEA, MIPA) and is a non-ionic surfactant (has the function of removing dirt particles), emulsifier, viscosifier, foaming agent, stabilizer, thickener. It is easily biodegradable.

The name describes the structure of the molecule:

• PEG-20. PEG stands for polyethylene glycol. It is a polyether compound that is used in a variety of applications, from industrial production to medicine. "20" refers to the average molecular weight of polyethylene glycol units. In cosmetics and personal care products, pegs work in three ways: as emollients, as emulsifiers, and as vehicles that help deliver other ingredients deeper into the skin.
• Cocamide is a mixture of amides of fatty acids found in coconut oil. Cocamide is used in many types of liquid soaps, shampoos and bath oils because it helps to increase their foaming capacity and liquid thickness.
• MEA stands for Monoethanolamine , an organic chemical compound that is both a primary amine and a primary alcohol. MEA is used in the production of detergents, emulsifiers and polishers, and is often used in cosmetics and personal care products to help maintain the pH balance of a product.

The synthesis process takes place in different steps:

• Preparation. Cocamide MEA produced by reacting coconut fatty acids with monoethanolamine (MEA). This forms a mixture of ethanolamines.
• PEGilation. Cocamide MEA reacts with polyethylene glycol (PEG) in a process known as pegylation. This process binds PEG chains to Cocamide MEA, increasing their solubility in water and improving their surfactant properties. The number "20" in PEG-20 Cocamide MEA refers to the average number of ethylene glycol units in the PEG chain.

PEG-20 Cocamide MEA is typically produced as an amber yellow liquid. 

What it is for and where

It is used in cosmetics for liquid soaps, shampoos, dishwashing detergents and as the main raw material for surfactants of the alkanolamide series. In particular in soaps it acts as a preservative, improves fragrance and increases shine.

Cosmetics

Surfactant - Emulsifying agent. Emulsions are thermodynamically unstable and are used to soothe or soften the skin and emulsify, so they need a specific, stabilising ingredient. This ingredient forms a film, lowers the surface tension and makes two immiscible liquids miscible. A very important factor affecting the stability of the emulsion is the amount of the emulsifying agent. Emulsifiers have the property of reducing the oil/water or water/oil interfacial tension, improving the stability of the emulsion and also directly influencing the stability, sensory properties and surface tension of sunscreens by modulating the filmometric performance.

Other uses

Used as a diluent for oily solutions in perfumes.

Safety

Can give allergic reactions and some of its related DEA components have an association between topical application and cancer in laboratory animals. The study that did the research did not establish a link between DEA and cancer risk in humans.

Ph from 7.0 to 10.5 depending on the components added.

Cocamide MEA studies

Molecular Formula: 

Molecular Weight: 

UNII: 

CAS: 68425-44-5

EC Number: 

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And a premise on PEG.

Since the PEG (1) family is numerous and is found in many cosmetic, cleaning and medicinal products and others, we need a cognitive premise on the subject that is rather complex from the point of view of safety because these products not only come into contact with the skin but, as in the case of medicine, they are also ingested.

PEG or polyethylene glycols polymerise the condensed ethylene oxide and water and are called polyethylene glycols, but in reality, they are complex chemical components, polymers bound together. For example,  plastic is polyethylene and has a hard consistency, while  polyethylene aggregated to the glycol forms a liquid.

The number that appears after the initials PEG represents the molecular weight and the higher this number is, the less it penetrates  the skin. 

Here below are some studies in Medicine that refer to the use of PEG Polyethylene glycol in various fields.

Intestine

Polyethylene glycol with or without electrolytes is effective for the treatment of functional constipation, both in adults and in paediatric patients, with great safety and tolerability. These preparations are the most effective osmotic laxatives (more than lactulose) and are the first-line treatment for functional constipation in the short- and long-term. They are as effective as enemas in faecalomas, avoid the need for hospitalisation and are well tolerated by patients (especially when given without electrolytes) (2).

In the preparation  for colonoscopy,  polyethylene glycol tablets confirmed efficacy, acceptability, tolerance and safety similar to those of sodium phosphate (3).

For peripheral nerve repair (4).

Eyes

Dry eye syndrome is a disorder that affects 5-34% of the world's adult population with reduced quality of life. Artificial or lubricating tears are the most used therapy for treating this condition due to their low side effects profile, which attempt to modify the properties of the tear film. Polyethylene glycol has demonstrated clinical efficacy in the treatment of this condition (5).

Brain

Polyethylene glycol facilitates the neuroprotective effects of magnesium in head injuries (6).

Tumors

For transarterial chemoembolization, Polyethylene glycol is effective and safe for the treatment of liver cancer, as indicated by good tolerability, quality of life and high tumour response (7). 

Cosmetics

Many types of PEG are hydrophilic and are used as creams, topical dermatological preparations and in cosmetic products such as surfactants, emulsifiers, detergents, humectants and skin conditioners.

Safety varies from type to type given the structural complexity (8).

References___________________________________________________________________

(1) Fruijtier-Pölloth C. Safety assessment on polyethylene glycols (PEGs) and their derivatives as used in cosmetic products. Toxicology. 2005 Oct 15;214(1-2):1-38. doi: 10.1016/j.tox.2005.06.001.

(2) Mínguez M, López Higueras A, Júdez J. Use of polyethylene glycol in functional constipation and fecal impaction. Rev Esp Enferm Dig. 2016 Dec;108(12):790-806. doi: 10.17235/reed.2016.4571/2016.

Santos-Jasso KA, Arredondo-García JL, Maza-Vallejos J, Lezama-Del Valle P. Effectiveness of senna vs polyethylene glycol as laxative therapy in children with constipation related to anorectal malformation. J Pediatr Surg. 2017 Jan;52(1):84-88. doi: 10.1016/j.jpedsurg.2016.10.021.

(3) Chaussade S, Schmöcker C, Toulemonde P, Muñoz-Navas M, O'Mahony V, Henri F. Phosphate tablets or polyethylene glycol for preparation to colonoscopy? A multicentre non-inferiority randomized controlled trial. Surg Endosc. 2017 May;31(5):2166-2173. doi: 10.1007/s00464-016-5214-1.
Tsunoda T, Sogo T, Iwasawa K, Umetsu S, Oikawa-Kawamoto M, Inui A, Fujisawa T. Feasibility and safety of bowel cleansing using low-volume polyethylene glycol with ascorbic acid before pediatric colonoscopy: A pilot study. Dig Endosc. 2017 Mar;29(2):160-167. doi: 10.1111/den.12756.

(4) Hoffman AN, Bamba R, Pollins AC, Thayer WP. Analysis of polyethylene glycol (PEG) fusion in cultured neuroblastoma cells via flow cytometry: Techniques & optimization. J Clin Neurosci. 2017 Feb;36:125-128. doi: 10.1016/j.jocn.2016.10.032.

(5) Pérez-Balbuena AL, Ochoa-Tabares JC, Belalcazar-Rey S, Urzúa-Salinas C, Saucedo-Rodríguez LR, Velasco-Ramos R, Suárez-Sánchez RG, Rodríguez-Carrizalez AD, Oregón-Miranda AA. Efficacy of a fixed combination of 0.09 % xanthan gum/0.1 % chondroitin sulfate preservative free vs polyethylene glycol/propylene glycol in subjects with dry eye disease: a multicenter randomized controlled trial. BMC Ophthalmol. 2016 Sep 20;16(1):164. doi: 10.1186/s12886-016-0343-9.

Labetoulle M, Messmer EM, Pisella PJ, Ogundele A, Baudouin C. Safety and efficacy of a hydroxypropyl guar/polyethylene glycol/propylene glycol-based lubricant eye-drop in patients with dry eye. Br J Ophthalmol. 2017 Apr;101(4):487-492. doi: 10.1136/bjophthalmol-2016-308608.

(6) Busingye DS, Turner RJ, Vink R. Combined Magnesium/Polyethylene Glycol Facilitates the Neuroprotective Effects of Magnesium in Traumatic Brain Injury at a Reduced Magnesium Dose. CNS Neurosci Ther. 2016 Oct;22(10):854-9. doi: 10.1111/cns.12591.

(7) Aliberti C, Carandina R, Sarti D, Mulazzani L, Catalano V, Felicioli A, Coschiera P, Fiorentini G. Hepatic Arterial Infusion of Polyethylene Glycol Drug-eluting Beads for Primary and Metastatic Liver Cancer Therapy. Anticancer Res. 2016 Jul;36(7):3515-21.

(8) Jang HJ, Shin CY, Kim KB. Safety Evaluation of Polyethylene Glycol (PEG) Compounds for Cosmetic Use. Toxicol Res. 2015 Jun;31(2):105-36. doi: 10.5487/TR.2015.31.2.105.