Final report of the amended safety assessment of PEG-5, -10, -16, -25, -30, and -40 soy sterol.

PEGs Soy Sterol are polyethylene glycol (PEG) derivatives of soybean oil sterols used in a variety of cosmetic formulations as surfactants and emulsifying agents, skin-conditioning agents, and cleansing and solubilizing agents. When the safety of these ingredients were first reviewed, the available data were insufficient to support safety. New data have since been received and the safety of these ingredients in cosmetics has been substantiated. Current concentration of use ranges from a low of 0.05% in makeup preparations to 2% in moisturizers and several other products. PEGs Soy Sterol are produced by the reaction of the soy sterol hydroxyl with ethylene oxide. In general, ethoxylated fatty acids can contain 1,4-dioxane as a byproduct of ethoxylation. The soy sterols include campesterol, stigmasterol, and beta-sitosterol. The distribution of sterols found in oils derived from common plants is similar, with beta-sitosterol comprising a major component. Impurities include sterol hydrocarbons and cholesterol (4% to 6%) and triterpine alcohols, keto-steroids, and other steroid-like substances (4% to 6%). No pesticide residues were detected. PEGS: Because PEGs are an underlying structure in PEGs Soy Sterols, the previous assessment of PEGs was considered. It is generally recognized that the PEG monomer, ethylene glycol, and certain of its monoalkyl ethers are reproductive and developmental toxins. Given the methods of manufacture of PEGs Soy Sterol, there is no likelihood of ethylene glycol or its alkyl ethers being present. Also, the soybean oil sterol ethers in this ingredient are chemically different from the ethylene glycol alkyl ethers of concern. PEGs are not carcinogenic, although sensitization and nephrotoxicity were observed in burn patients treated with a PEG-based cream. No evidence of systemic toxicity or sensitization was found in studies with intact skin. Plant Phytosterols: Intestinal absorption of ingested plant phytosterols is on the order of 5%, with 95% of the material entering the colon. Absorbed plant phytosterols are transported to the blood. Although there are some data suggesting that sulfates of beta-sitosterol can act as abortifacients in rats and rabbits, other studies of well-characterized plant phytosterols and phytosterol esters demonstrated no effect in an estrogen-binding study, a recombinant yeast assay for estrogen or estrogen-like activity, or a juvenile rat uterotrophic assay for estrogen or estrogen-like activity. In a two-generation reproduction study using rats, plant phytosterol esters in the diet had no effect on any parameter of reproduction or fertility. Subcutaneous injections of beta-sitosterol did reduce sperm concentrations and fertility in rats. Sitosterol inhibited tumor promoting activity of 12-O-tetradecanoylphorbol-13-acetate (TPA) in mice after initiation with 7,12-dimethylbenz[a]anthracene (DMBA), and reduced the tumors produced by N-methylnitrosourea in rats. Phytosterols were not genotoxic in several bacterial, mammalian, and in vitro assay systems. Phytosterols decreased epithelial cell proliferation in the colon of mice and rats, and were cytotoxic for human epidermoid carcinoma of the nasopharynx. PEGs Soy Sterols: The acute oral LD50 in rats of PEG-5-25 Soy Sterol was >10 g/kg. The acute dermal LD50 of a liquid eyeliner containing 2%PEG-5 Soy Sterol was >2 g/kg in rabbits. PEG-5-25 Soy Sterol was not a primary irritant in rabbits when applied undiluted. Undiluted PEG-5 Soy Sterol did not cause sensitization in guinea pigs. PEGs Soy Sterol did not produce ocular toxicity in rabbits. PEG-5 Soy Sterol was negative in the Ames mutagenicity test, with or without metabolic activation. PEG-5 Soy Sterol, at concentrations up to 2%in formulation, did not cause dermal or ocular irritation, dermal sensitization, or photosensitization in clinical studies. Because of the possible presence of 1,4-dioxane reaction product and unreacted ethylene oxide residues, it was considered necessary to use appropriate procedures to remove these from PEGs Soy Sterol before blending them into cosmetic formulations. Based on the systemic toxicity and sensitization seen with PEGs applied to damaged skin, it was recommended that PEGs Soy Sterol should not be used in cosmetic products applied to damaged skin. Although no dermal absorption data were available, oral studies demonstrate that phytosterols and phytosterol esters are not significantly absorbed and do not result in significant systemic exposure. Some small amounts did appear in the ovaries, however. This raises a concern about the potential presence of free phytosterols and beta-Sitosterol, which could have antiestrogenic, antiprogestational, gonadotrophic, antigonadotrophic, and antiandrogenic effects in PEG sterols. These concerns are alleviated by the extensive data showing that well-defined phytosterols and phytosterol esters are not estrogenic and do not pose a hazard to reproduction. Likewise, the absence of impurities in plant phytosterols and phytosterol esters and extensive data demonstrating the absence of any genotoxicity in bacterial and mammalian systems mitigate against the possibility of any carcinogenic effect with those same well-characterized materials. The Cosmetic Ingredient Review (CIR) Expert Panel concluded that the PEGs Soy Sterol are safe as used in cosmetic products.