PEGs-6,-8,-32,-75,-150,-14M, and 20M are polymers of ethylene oxide used as humectants, solvents, binders, emulsion stabilizers, and viscosity-increasing agents in cosmetics. In metabolism studies with rats, rabbits, dogs, and humans, the lower molecular weight PEGs were absorbed by the digestive track and excreted in the urine and feces.
PEGs have low oral and dermal toxicity, and are not irritating to the skin of rabbits or guinea pigs; PEG-75 was not a sensitizer. PEGs caused mild, transient ocular irritation in rabbits. PEG-8 was negative in the Chinese hamster ovary cell mutation test, the sister chromatid exchange test, and the unscheduled DNA synthesis assay. PEG-150 was not mutagenic in the mouse TK+/TK-/- forward mutation assay.
PEG-8 was not carcinogenic when administered orally, intraperitoneally, or subcutaneously to various test animals. No adverse reproductive effects occurred during subchronic and chronic oral toxicity studies of PEG-6–32 and PEG-75. In clinical studies, PEG-8, PEG-6–32, and PEG-75 were not sensitizers.
On the basis of the individual and combined data on PEGs-6,-8,-32,-75,-150,-14M, and-20M, it is concluded that these ingredients are safe for use at the concentrations reflected in the Cosmetic Use section and in the product formulation safety test data included in this report. However, cosmetic formulations containing these PEGs should not be used on damaged skin.
References
1.
Arcus, MF., Arcos, JC., and Hoch-Ligeti, C. (1965). Studies on the carcinogenic activity of protein-denaturing agents: hepatocarcinogenicity of dioxane. J. Natl. Cancer Inst.35:949–58.
2.
Bartoliklugmann, F., Decorti, G., Candussio, L, and Baldini, L. (1986). Anticonvulsant activity of two polyethylene glycols in mice. Pharmacol. Res. Commun.18(2):149–54.
3.
Bartsch, W., Sponer, G., Dietmann, K., and Fuchs, G. (1976). Acute toxicity of various solvents in the mouse and rat. Arzneimittelforsch.26:1581–3.
4.
Berenblum, I. and Haran, N. (1955). The influence of croton oil and of polyethylene glycol-400 on carcinogenesis in the forestomach of the mouse. Cancer Res.15:501–6.
5.
Bessler, WG., Schimmelpfeng, L, and Peters, JH. (1977). Potentiation of mitogen-induced lymphocyte stimulation by polyethylene glycols. Biochem. Biophys. Res. Commun.76(4): 1253–60.
6.
Blow. AMJ., Botham, GM., Fisher, D., Goodall, AH., Tilcock, CPS., and Lucy, JA. (1978). Water and calcium ions in cell fusion induced by polyethylene glycol). FEBS Lett.94(2):305–10.
7.
Boyland, E., Carter, RL., Gorrod, JW., and Roe, FJ.C. (1968). Carcinogenic properties of certain rubber additives. Eur. J. Cancer4:233–9.
8.
Braun, W. (1969). Contact allergies to polyethylene glycols. Z. Hautkr.44:385. (Secondary referee from Fisher, 1978.)
9.
Bruns, DE., Herold, DA., Rodeheaver, GT., and Edlich, RF. (1982). Polyethylene glycol intoxication in burn patients. Burns9:49–52.
10.
Budden, R., Kuhl, UC., and Bahlsen J. (1979). Experiments on the toxic, sedative and muscle relaxant potency of various drug solvents in mice. Pharmacol. Ther.5:467–74.
11.
BUSHY RUN RESEARCH CENTER. (1980). Submission of unpublished data by CTFA. Polyethylene glycol-400 Carbowax. In vitro mutagenesis studies: 3-test battery. (15 pages).*
12.
BUSHY RUN RESEARCH CENTER. (1987). Submission of unpublished data by CTFA. Carbowax PEG-1450 NMW. Acute toxicity and primary irritancy studies. (3 pages).*
13.
BUSHY RUN RESEARCH CENTER. (1988a). Submission of unpublished data by CTFA. Tergitol and Carbowax samples. Assessment of toxicity and pulmonary effects in the rat following single endotracheal injection. (13 pages).*
14.
BUSHY RUN RESEARCH CENTER. (1988b). Submission of unpublished data by CTFA. Carbowax PEG 600, PEG 3350 and MPEG 2000. Assessment of pulmonary effects in the rat following single endotracheal injection. (5 pages).*
15.
Carpenter, CP. and Shaffer, CB. (1952). A study of the polyethylene glycols as vehicles for intramuscular and subcutaneous injection. J. Am. Pharm. Assoc. Sci. Ed.41:27–9.
16.
Carpenter, CP. and Smyth, HF. (1946). Chemical burns of the rabbit cornea. Am. J. Ophthalmol.29:1363–72.
17.
Carpenter, CP., Woodside, MD., Kinkead, ER., King, JM., and Sullivan, LJ. (1971) Response of dogs to repeated intravenous injection of polyethylene glycol 4000 with notes on excretion and sensitization. Toxicol. Appl. Pharmacol.18:35–40.
18.
Carter, RL. (1969). Early development of injection site sarcomas in rats: A study of tumors induced by a rubber additive. Br. j. Cancer.23:408–16.
19.
Chadwick, VS., Phillips, SF., and Hofmann, AF. (1977) Measurement of intestinal permeability using low molecular weight polyethylene glycols (PEG 400). I. Chemical analysis and biological properties of PEG 400. Gastroenterology73(2):241–6.
20.
Cori, CF. (1925). The fate of sugar in the animal body. I. The rate of absorption of hexoses and pentoses from the intestinal tract. J. Biol. Chem.66:691–75.
21.
Cosmetic, Toiletry, AND FRAGRANCE ASSOCIATION (CTFA). (1980). Submission of unpublished data by CTFA. Allergic contact sensitization test. 14A/16427-14 containing 3.0% PEG-8 (Rl 0639). (11 pages).*
22.
CTFA (1981). Submission of unpublished data by CTFA. The safety evaluation of 14A/16427-14 containing 3.0% PEG-8 Rl 0639/Group 6.13 week subchronic dermal toxicity study using male and female albino rats. Study project: AT0173. (15 pages).*
23.
CTFA (1982a). Submission of unpublished data by CTFA. Allergic contact sensitization test. 12A/23379-04 containing 1.0% PEG-8 (Rl 0639). (8 pages).*
24.
CTFA (1982b). Submission of unpublished data by CTFA. Allergic contact sensitization test. 12J/22879-07 containing 1.0% PEG-8 (RI 0639). (8 pages).*
25.
CTFA (1982c). Submission of unpublished data by CTFA. Allergic contact sensitization test. 12J/12829-19 containing 1.0% PEG-8 (RI 0639). (7 pages).*
26.
CTFA (1982d). Submission of unpublished data by CTFA. Allergic contact sensitization test. 12J/25402-16 containing 1.0% PEG-8 (Rl 0639). (7 pages).*
27.
CTFA (1983a). CTFA List of Japanese Cosmetic Ingredients. Washington, DC: Ctfa, pp. 60–2.
28.
CTFA (1983b). Submission of unpublished data by CTFA. Allergic contact sensitization test. 12C/25613-05 containing 1.0% PEG-8 (Rl 0639). (7 pages).*
29.
CTFA (1983c). Submission of unpublished data by CTFA. Allergic contact sensitization test. 12F/27764-06 containing 1.0% PEG-8 (Rl 0639). (8 pages).*
30.
CTFA (1984). Submission of unpublished data by CTFA. Allergic contact sensitization test. 12F/30612-03 containing 1.0% PEG-8 (Rl 0639). (9 pages).*
31.
CTFA (1985a). Submission of unpublished data by CTFA. The safety evaluation of 14A/25363-17 containing 5.0% PEG-8 (Rl 0639)/Group 6. 13 week subchronic dermal toxicity study using male and female albino rats. Study project code 219. (14 pages).*
32.
CTFA (1985b). Submission of unpublished data by CTFA. Allergic contact sensitization test. 12G/34562-12 containing 1.0% PEG-8 (Rl 0639). (10 pages).*
33.
Delahunty, T. and Hollander, D. (1986). New liquid-chromato-graphic method for measuring polyethylene glycol in urine. Clin. Chem.32(2):351–3.
34.
Elder, R.L. (Ed.). (1983). Final report on the safety assessment of PEG-2,-6,-8,-12,-20,-32,-40,-50,-100, and-150 Stearates. J. Am. Coll. Toxicol. 2(7):17-34.
35.
Estrin, N.F., Crosley, PA., and Haynes, C.R. (Editors). (1982). CTFA Cosmetic Ingredient Dictionary. Third Edition.Washington, DC: The Cosmetic, Toiletry and Fragrance Association, pp. 202–3.
36.
FAO. (1983). Polyethylene glycols. FAO Food and Nutrition Paper No. 28.
37.
FEDERAL REGISTER. (1992). Modification in voluntary filing of cosmetic product ingredient and cosmetic raw material composition statements. Final rule.57(18):3128–30.
38.
Fisher, AA. (1977). Contact urticaria due to polyethylene glycol. Cutis19(4):409–12.
39.
Fisher, AA. (1978). Immediate and delayed allergic contact reactions to polyethylene glycol. Contact Derm.43(3):135–8.
40.
FOOD AND DRUG ADMINISTRATION (FDA). (1981). Cosmetic product formulation data. FDA computer printout.Washington, DC: FDA.
41.
FDA. (1984). Cosmetic product formulation data: ingredients used in each product category. FDA computer printout. Washington, DC: FDA.
Fort, FL., Heyman, I. A., and Kesterson, J.W. (1984). Hemolysis study of aqueous polyethylene glycol 400, propylene glycol and ethanol combinations in vivo and in vitro.). Parenter. Sci. Technol.38:82–7.
45.
Guillot, JP., Martini, MC., Giauffret, JY., Gonnet, JF., and Guyot, JY. (1982). Safety evaluation of some humectants and moisturizers used in cosmetic formulations. Int. J. Cosmet. Sci.4:67–79.
46.
Hamburger, R., Azaz, E., and Dondrow, M. (1975). Autoxidation of polyoxyethylenic non-ionic surfactants and of polyethylene glycols. Pharm. Acta Helv.50:10–7.
47.
Hannuksela, M., Pirila, V., and Salo, OP. (1975). Skin reactions to propylene glycol. Contact Derm.1:112–6.
48.
Hartveit, F. (1967). In-vitro potentiation of immune oncolysis by polyethylene glycol and by polyvinylpyrrolidone. J Pathol. Bacteriol.94(1):200–4.
49.
Hartveit, F. (1969a). Oral polyethylene glycol's inhibitory effect on the subcutaneous growth of Ehrlich's carcinoma in mice, and on the local inflammatory responses to the tumor. Acta Pathol. Microbiol. Scand.77:623–38.
50.
Hartveit, F. (1969b). Inhibition of the subcutaneous growth of Ehrlich's ascites carcinoma in female mice by polyethylene glycol 4000. J. Pathol.97(1):145–8.
51.
Hawley, G.G. (Editor). (1971). The Condensed Chemical Dictionary.8th Edition. New York: Van Nostrand Reinhold Company, p. 706.
HILL TOP Research, INC. (1979). Unpublished data submitted by CTFA. The study of cumulative irritant properties of a series of test materials. 14A/16427-09 containing 3.0% PEG-8 (Rl 0639). (14 pages).*
54.
HILL TOP Research, INC. (1982). Unpublished data submitted by CTFA. Repeated insult patch test. 12J/25402-09 containing 1.0% PEG-8 (Rl 0639). (13 pages).*
55.
HILL TOP Research, INC. (1983). Unpublished data submitted by CTFA. Repeated insult patch test. 12J/25402-16 containing 1.0% PEG-8 (Rl 0639). (20 pages).*
56.
Hoch-Ligeti, C., Argus, MF., and Arcos, JC. (1970). Induction of carcinomas in the nasal cavity of rats by dioxane. Br. J. Cancer.24:164–7.
57.
Hunting, AL.L. (1983). Encyclopedia of Shampoo Ingredients.Cranford, NJ: Micelle Press Inc., pp. 308–10, 321.
58.
JOURNAL OFFICIEL DE LA RÉPUBLIQUE FRANÇAISE DU 21/4/71 (Ed. Lois de Décrets). (1971a). Arrêté du 5/4/71 relatif aux méthodes officielles d'analyses des cosméliques et produits de beauté. Annexe I: Détermination de I'indice d'irritation primaire.
59.
JOURNAL OFFICIEL DE LA RÉPUBLIQUE FRANÇAISE DU 21/4/71. (1971b). Arrêté du 5/4/71 relatif aux méthodes officielles d'analyses des cosmétiques et produits de beauté. Annexe II: Détermination de I'indice d'irritation oculaire.
60.
JOURNAL OFFICIEL DE LA RÉPUBLIQUE FRANÇAISE DU 5/6/73. (1973a). Arrêté du 16/4/73 relatif aux méthodes officielles d'analyses des cosmétiques et produits de beauté. Annexe I: Determination de I'indice d'irritation primaire.
61.
JOURNAL OFFICIEL DE LA RÉPUBLIQUE FRANÇAISE DU 5/6/73. (1973b). Arrêté du 16/4/73 relatif aux méthodes officielles d'analyses des cosmétiques et produits de beauté. Annexe II: Détermination de I'indice d'irritation oculaire.
62.
JOURNAL OFFICIEL DE LA RÉPUBLIQUE FRANÇAISE DU 29/1/1980. (1980). Arrêté du 18/12/79, relatif à la méthode officielles pour l'appréciation de I'aggressivité superficielle cutanée par applications itératives pendant 6 semaines d'un produit cosmetique ou d'hygiène corporelle.
63.
Klonne, DR., Dodd, DE., Losco, PE., and Troup, CM. (1989). Two-week aerosol inhalation study on polyethylene glycol (PEC) 3350 in F-344 rats. Drug Chem. Toxicol.12(1):39–48.
64.
Kociba, RJ., Mccollister, SB., Park, C., Torkelson, TR., and Gehring, PJ. (1974). 1,4-Dioxane. I. Results of a 2-year ingestion study in rats. Toxicol. Appl. Pharmacol.30:275–86.
65.
Krugliak, P., Hollander, D., Ma, TY., Tran, D., Dadufalza, VD., Katz, KD., and Le, K. (1989). Mechanisms of polyethylene glycol 400 permeability of perfused rat intestine. Gastroenterology97:1164–70.
66.
Laillier, J., Plazonnet, B., and Le Douarec, J.C. (1976). Evaluation of ocular irritation in the rabbit: development of an objective method of studying eye irritation. Proc. Eur. Soc. Toxicol.17(Predict. Chronic. Toxic. Short Term Stud., Proc. Meet., 1975):336–50.
67.
Lockard, JS. and Levy, RH. (1978). Polyethylene glycol 400: Solvent and anticonvulsant?Life Sci.23(25):2499–502.
68.
Lockard, JS., Levy, RH., Congdon, WC., and Ducharme, LL. (1979). Efficacy and toxicity of the solvent polyethylene glycol 400 in monkey model. Epilepsia20(1):77–84.
Mcginity, JW., Hill, JA., and La Via, A.L. (1975). Influence of peroxide impurities in polyethylene glycols on drug stability. J. Pharm. Sci.64(2):356–7.
71.
MELLON INSTITUTE OF INDUSTRIAL RESEARCH. (1956). Unpublished data submitted by CTFA. Gross results of 90-day feeding of Carbowax compound 20-M to rats and of 30-dose rabbit inunction and single skin penetration of 20-M and Carbowax compound 4000. (5 pages).*
72.
Mokyr, MB., Przepiorka, D., and Dray, S. (1982). Mode of action of polyethylene glycol 6000 in potentiating the in vitro generation of antitumor cytotoxicity by MOPC-315 tumor bearer spleen cells. Cancer Res.42(7):2537–43.
73.
Nikitakis, J.M. (Editor). (1988). CTFA Cosmetic Ingredient Handbook.First Edition.Washington, DC: The Cosmetic, Toiletry and Fragrance Association, pp. 149–50. 281-2, 289-91, 293-4, 297-8, and 304.
74.
Patty, F.A. (Editor). (1963). Industrial Hygiene and Toxicology.Second Revised Edition. Vol. II. New York: Interscience Publishers, p. 1511.
75.
Ponzio, NM. (1980). Lymphocyte responses to syngeneic antigens. I. Enhancement of the murine autologous mixed lymphocyte response by polyethylene glycol. Cell. Immunol.49:266–82.
76.
Reed, KW. and Yalkowsky, SH. (1985) Lysis of human red blood cells in the presence of various cosolvents. J. Parenter. Sci. Technol.39:64–9.
77.
Robinson, JJ. and Ciurczak, EW. (1980). Direct gas chromatographic determination of 1,4-dioxane in ethoxylated surfactants. J. Soc. Cosmet. Chem.31:329–37.
78.
Roe, FJ.C., Ross, WC.J., and Mitchley, BC.V. (1966). Carcinogenicity of certain glycidal derivatives. Fd. Cosmet. Toxicol.4:365–7.
79.
Sax, NI. (1979). Dangerous Properties of Industrial Materials.5th Edition.New York: Van Nostrand Reinhold Company, p. 921.
Shaffer, CB. and Critchfield, FH. (1947b). The absorption and excretion of the solid polyethylene glycols (Carbowax compounds). J. Am. Pharm. Assoc. Sci. Ed.36:152–7.
82.
Shaffer, CB., Critchfield, FH., and Carpenter, CP. (1948). Renal excretion and volume distribution of some polyethylene glycols in the dog. Am. J. Physiol.152:93–9.
83.
Shaffer, CB., Critchfield, FH., and Nair, J.H. III. (1950). The absorption and excretion of a liquid polyethylene glycol. J. Am. Pharm. Sci. Ed.39:340–4.
84.
Shideman, FE. and Procita, I. (1951). Some pharmacological actions of polypropylene glycols of average molecular weight 400, 750, 1200 and 2000. Pharmacol. Exp. Ther.103:293–305.
85.
Silverstein, BD., Furcinitti, PS., Cameron, WA., Brower, JE., and White, O., Jr. (1984). Biological effects summary report–polyethylene glycol. Government Reports Announcements & Index. Issue 15. NTIS/DE84007984. 27 pp.
86.
Smith, BL. and Cadwaller, DE. (1967). Behavior of erythrocytes in various solvent systems III. Water–polyethylene glycols. J. Pharm. Sci.56:351–5.
87.
Smyth, HF., Jr., Carpenter, CP., and Shaffer, CB. (1945). The subacute toxicity and irritation of polyethylene glycols of approximate molecular weights of 200, 300, and 400. J. Am. Pharm. Assoc.34:172–4.
88.
Smyth, HF., Jr., Carpenter, CP., and Shaffer, CB. (1947). The toxicity of high molecular weight polyethylene glycols; chronic oral and parenteral administration. J. Am. Pharm. Assoc. Sci. Ed.36:157–60.
89.
Smyth, HF., Jr., Carpenter, CP., Shaffer, CB., Seaton, J., and Fischer, L. (1942). Some pharmacological properties of polyethylene glycols of high molecular weight (“Carbowax” compounds). J. Ind. Hyg. Toxicol.24:281–4.
90.
Smyth, HF. Jr., Carpenter, C. P., and Weil, CS. (1950). The toxicology of the polyethylene glycols. J. Am. Pharm. Assoc. Sci. Ed.39:349–54.
91.
Smyth, HF., Jr., Carpenter, CP., and Weil, CS. (1955). The chronic oral toxicology of the polyethylene glycols. J. Am. Pharm. Assoc. Sci. Ed.44:27–30.
92.
Smyth, HF., Jr., Seaton, J., and Fischer, L. (1941). The single dose toxicity of some glycols and derivatives. J. Ind. Hyg. Toxicol.23:259–68.
93.
Sturcill, BC., Herold, DA., and Bruns, DE. (1982). Renal tubular necrosis in burn patients treated with topical polyethylene glycol. Lab. Invest.46:81 A (abstract).
94.
Tusinc, T. W., Elsea, J.R., and Sauveur, AB. (1954). The chronic dermal toxicity of a series of polyethylene glycols. J. Am. Pharm. Assoc.43:489–90.
95.
Wangenheim, J. and Bolcsfoldi, C. (1988). Mouse lymphoma L5178Y thymidine kinase locus assay of 50 compounds. Mutagenesis3(3): 193–206.
96.
Windholz, M. (Editor). (1983). The Merck Index.10th Edition.Rahway, NJ: Merck & Co., Inc. p. 1092.
97.
Zaldivar, RS.D. (1963). Precancerous lesions in guinea-pigs after intramural injections of 3-methylcholanthrene. Naturwissenschaften50:380–1.
