Safety assessment on polyethylene glycols (PEGs) and their derivatives as used in cosmetic products

doi:10.1016/j.tox.2005.06.001

Toxicology

Volume 214, Issues 1–2, 15 October 2005, Pages 1-38

https://doi.org/10.1016/j.tox.2005.06.001 Get rights and content

Abstract

This assessment focusses on polyethylene glycols (PEGs) and on anionic or nonionic PEG derivatives, which are currently used in cosmetics in Europe. These compounds are used in a great variety of cosmetic applications because of their solubility and viscosity properties, and because of their low toxicity. The PEGs, their ethers, and their fatty acid esters produce little or no ocular or dermal irritation and have extremely low acute and chronic toxicities. They do not readily penetrate intact skin, and in view of the wide use of preparations containing PEG and PEG derivatives, only few case reports on sensitisation reactions have been published, mainly involving patients with exposure to PEGs in medicines or following exposure to injured or chronically inflamed skin. On healthy skin, the sensitising potential of these compounds appears to be negligible. For some representative substances of this class, information was available on reproductive and developmental toxicity, on genotoxicty and carcinogenic properties. Taking into consideration all available information from related compounds, as well as the mode and mechanism of action, no safety concern with regard to these endpoints could be identified. Based on the available data it is therefore concluded that PEGs of a wide molecular weight range (200 to over 10,000), their ethers (laureths. ceteths, ceteareths, steareths, and oleths), and fatty acid esters (laurates, dilaurates, stearates, distearates) are safe for use in cosmetics. Limited data were available for PEG sorbitan/sorbitol fatty acid esters, PEG sorbitan beeswax and PEG soy sterols. Taking into account all the information available for closely related compounds, it can be assumed that these compounds as presently used in cosmetic preparations will not present a risk for human health. PEG castor oils and PEG hydrogenated castor oils have caused anaphylactic reactions when used in intravenous medicinal products. Their topical use in cosmetics is, however, considered safe as they are not expected to be systemically available. As all PEGs and PEG derivatives, they must not be applied to damaged skin. Manufacturers of PEGs and PEG derivatives must continue their efforts to remove impurities and by-products such as ethylene oxide and 1,4-dioxane. Overall, it is concluded, that the PEGs covered in this review are safe for use in cosmetics under the present conditions of intended use.

Introduction

Polyethylene glycols (PEGs) and their anionic or nonionic derivatives are widely used in cosmetics as surfactants, cleansing agents, emulsifiers, skin conditioners, and humectants. They comprise a class of compounds varying in molecular weights between 200 and over 10,000. Due to their presence in many cosmetics, an evaluation of their safety is critical, the more so, as potential exposure of consumers may be chronic and extensive.

The following assessment focusses on PEGs and on anionic or nonionic PEG derivatives that are currently used in cosmetics in Europe. Relevant compounds are listed in Table 1, together with their CAS numbers, synonyms and their function in cosmetics.

Further to their use in cosmetics, many of the compounds have other applications. Available information from these uses is included in this assessment where relevant. In the pharmaceutical industry, for instance, they are used as vehicles for drugs and as ointment bases, capsules, tablet and pill binders, suppositories, liquid prescriptions, and in veterinary drugs, including parenteral, topical, ophthalmical, oral, and rectal preparations. Further applications include use as ingredients in soaps and detergents, in the textile and leather industry, in plastics and resins, in the paper industry, in printing, in the ceramics and glass industry, in the rubber, petroleum, mining and metal industries, for wood preservation and as chemical intermediates. Polyoxyethylene sorbitan esters (polysorbates) and polyethylene glycol with an average molecular weight of 6000 are permitted as food additives in various foods according to the European Parliament and Council Directive No. 95/2/EC of 20 February 1995. The WHO has set an estimated acceptable daily intake of polyethylene glycols at up to 10 mg/kg bw (FAO/WHO, 1980).

Section snippets

PEGs and PEG derivatives used in cosmetics

Polyethylene glycols (PEGs) are polymers of ethylene oxide with the generalised formula HO single bond (CH₂CH₂O)_n-H, and “n” indicating the average number of oxyethylene groups. They have been assigned the CAS register number 25322-68-3 and the scientific name “poly(oxy-1,2-ethanediyl)-α-hydro-ω-hydroxy”. Common synonyms are listed in Table 1.

PEGs and PEG derivatives do not represent definite chemical entities, but are mixtures of compounds with varying polymer chain lengths. The average number or the

Use levels

PEGs and PEG derivatives are used as humectants, solvents, binders, emulsion stabilizers, and viscosity-increasing agents in a wide variety of personal care products. Most common uses for PEG and PEG derivatives include those in toothpaste, skin lotions, deodorant sticks, shaving creams, hand creams, face makeup, cream rouge, blush, mascara, lipsticks, bath products, and hair care products. Maximum use levels with product type examples are given in Table 1. The information is based on

Absorption

PEGs can be absorbed by the gastrointestinal tract with the fraction absorbed being dependent on the molecular weight of the compound. PEG-8 is well absorbed via the gastrointestinal tract and approximately 50% of the administered dose is excreted via the urine in humans within 24 h (Chadwick et al., 1977, Shaffer et al., 1950). Likewise, an extensive absorption of PEG-4 and PEG-6 via the oral route can be assumed, while less than 10% of PEG-75 and less than 2% of the greater molecular weight

Discussion

The PEGs and most of their derivatives under review here have low mammalian toxicity following single or repeated exposure with generally decreasing toxicity as the molecular weight is increased. The biological activity varies with the size of the hydrophobic and hydrophilic domain and the balance between them.

Low molecular weight PEGs and some of their derivatives may be absorbed by the gastrointestinal tract and may penetrate the skin, whereas all PEGs are capable of penetrating injured skin

Conclusion

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ReviewSafety assessment on polyethylene glycols (PEGs) and their derivatives as used in cosmetic products

Abstract

Introduction

Section snippets

PEGs and PEG derivatives used in cosmetics

Use levels

Absorption

Discussion

Conclusion

Int. J. Pharmacol.

Food Chem. Toxicol.

Food Cosmet. Toxicol.

Toxicol. Appl. Pharmacol.

J. Pharm. Sci.

Eur. J. Cancer

Food Cosmet. Toxicol.

Burns

Mutat. Res.

Toxicol. Lett.

Am. J. Ophthalmol.

Toxicol. Appl. Pharmacol.

Gastroenterology

Eur. J. Pharm. Sci.

Toxicol. Appl. Pharmacol.

Ann. Emerg. Med.

Toxicol. Appl. Pharmacol.

Arch. Biochem. Biophys.

J. Contr. Release

Fd. Chem. Toxicol.

Toxicol. Appl. Pharmacol.

Biochem. Phamacol.

J. Am. Pharm. Assoc.

Sensitization to oleth-3-phosphate and oleth-5 in a hair wax

Contact Dermatitis

Chemische Charakterisierung von Alkylethoxylaten

Configuration and hydrodynamic properties of the polyoxyethylene chain in solution

Toxicology of topical local anesthetics

Skin Pharmacol.

The influence of croton oil and of polyethylene glycol-400 on carcinogenesis in the forestomach of the mouse

Cancer Res.

Formation of formaldehyde and peroxides by air oxidation of high purity polyoxyethylene surfactants

Contact Dermatitis

Final report on the safety assessment of laureths-4 and -23

J. Am. Coll. Toxicol.

Toxicity profile: polyethylene glycol 400

Toxicity profile tetraethylene glycol

Low molecular weight polyethylene glycol induces chromosome aberrations in Chinese hamster cells cultured in vitro

Mutagenesis

The induction of tumors in mice by intravaginal application of chemical compounds

Br. J. Cancer

Relative toxicity of di(2-ethylhexyl) sebacate and related compounds in an in vivo hamster bioassay

Inhal. Toxicol.

Contact allergies to polyethylene glycols

Z. Haut Geschlechtskr.

Balneologische Therapie der Neurodermitis mit polidocanol-haltigem Badezusatz

Akt. Dermatol.

The gonadotoxic activity of glycols

Gig Sanit

Early development of injection site sarcomas in rats: a study of tumors induced by a rubber additive

Br. J. Cancer

Final report on the safety assessment of steareth-2, -4, -6, -7, -10, -11, -13, -15, and -20

J. Am. College Toxicol.

Final report on the safety assessment of polyethylene glycols (PEGs)-6, -8, -32, -75, -150, -14M, -20M

J. Am. College Toxicol.

Final report on the safety assessment of PEG-30, -33, -35, -36, and -40 castor oil and PEG-30 and -40 hydrogenated castor oil

Int. J. Toxicol.

Final report on the safety assessment of PEG-7, -30, -40, -78, and -80 glyceryl cocoate

Int. J. Toxicol.

Final report on the safety assessment of ceteth-1, -2, -3, -4, -5, -6, -10, -12, -15, -16, -20, -24, -25, -30, and -45

Int. J. Toxicol.

Final report on the safety assessment of oleth-2, -3, -4, -5, -6, -7, -8, -9, -10, -11, -12, -15, -16, -20, -23, -25, -30, -40, -44, and -50

Int. J. Toxicol.

Review
Safety assessment on polyethylene glycols (PEGs) and their derivatives as used in cosmetic products