Final Report on the Safety Assessment of Ceteareth-2, -3, -4, -5, -6, -7, -8, -9, -10, -11, -12, -13, -14, -15, -16, -17, -18,-20,-22,-23,-24,-25,-27, -28, -29, -30, -33, -34, -40, -50, -55, -60, -80, and -100

Abstract

Ceteareths, used in a large number of cosmetics as surfactants, are the polyethylene glycol (PEG) ethers of Cetearyl Alcohol (q,v.). To supplement the limited available data on Ceteareths, previous findings from the safety assessment of Polyethylene Glycol (PEG), several fatty alcohols (Cetearyl Alcohol, Cetyl Alcohol, and Stearyl Alcohol), and Steareths were considered. These data indicate little evidence of toxicity. Although various metabolites of monoalkyl ethers of ethylene glycol are reproductive and developmental toxins, given the methods of manufacture of Ceteareth compounds, there is no likelihood of such compounds being present as impurities. Further, there would be only limited ethylene glycol monomer linked by an ether group to the Ceteareth moiety for the PEG-5 compounds, little for the PEG-10 compounds, and virtually none for the PEG-20 and higher compounds. Even if linked to ethylene glycol monomer, it was considered unlikely that the Ceteareth moieties would be metabolized (e,g., via β-oxidation) to simple methyl, ethyl, propyl, or butyl alkyl groups. As the current data indicate, such short alkyl chains are needed in order for the production of toxic alcohol or aldehyde dehydrogenase metabolites. For longer alkyl chains there is evidence of diminishing toxicity, and extrapolation to much longer chains such as expected in the Ceteareth moieties suggests that there is no reproductive or developmental hazard posed by these Ceteareth compounds. The principal clinical finding related to PEGs is based on data in bum patients— PEGs were mild irritants/sensitizers and there was evidence of nephrotoxicity. No such effects were seen in animal studies on intact skin. Cosmetic manufacturers should adjust product formulations containing Polyethylene Glycol to minimize any untoward effects when products are used on damaged skin. In the absence of specific impurities data, the possible presence of 1,4-dioxane and ethylene oxide impurities was of concern. The importance of using the necessary purification procedures to remove these impurities was stressed. Creams containing Ceteareth-20 enhanced drug absorption. Ceteareth-15 (10% in formulation) was minimally irritating to rabbits after a single dermal exposure. In ocular studies, ethoxylated Cetearyl Alcohol solution was a severe irritant to unrinsed rabbit eyes and moderately irritating to rinsed eyes. In clinical studies, Ceteareth-15 (1.5 % in formulation) produced minimal irritation when tested in both a 4- and 21-day patch test, and was not a sensitizer when tested (1.35% in formulation) in a repeat-insult patch test. Based on the limited data on Ceteareths and the extensive data on chemically related ingredients, it was concluded that these ingredients are safe as used in cosmetic formulations. These ingredients, however, should not be used on damaged skin.