Safety Assessment of Polysaccharide Gums as Used in Cosmetics Status: Tentative Report for Public Comment Release Date: June 26, 2015 Panel Date: September 21-22, 2015 All interested persons are provided 60 days from the above release date to comment on this safety assessment and to identify additional published data that should be included or provide unpublished data which can be made public and included. Information may be submitted without identifying the source or the trade name of the cosmetic product containing the ingredient. All unpublished data submitted to CIR will be discussed in open meetings, will be available at the CIR office for review by any interested party and may be cited in a peer-reviewed scientific journal. Please submit data, comments, or requests to the CIR Director, Dr. Lillian Gill. The 2015 Cosmetic Ingredient Review Expert Panel members are: Chair, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V. Belsito, M.D.; Ronald A. Hill, Ph.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; James G. Marks, Jr., M.D.; Ronald C. Shank, Ph.D.; Thomas J. Slaga, Ph.D.; and Paul W. Snyder, D.V.M., Ph.D. The CIR Director is Lillian J. Gill, D.P.A. This report was prepared by Wilbur Johnson, Jr., M.S., Senior Scientific Analyst and Bart Heldreth, Ph.D., Chemist. © Cosmetic Ingredient Review 1620 L STREET, NW, SUITE 1200 ◊ WASHINGTON, DC 20036-4702 ◊ PH 202.331.0651 ◊ FAX 202.331.0088 ◊ [email protected] ABSTRACT The Cosmetic Ingredient Review Expert Panel (the Panel) reviewed the safety of 106 ingredients, which function as viscosity increasing agents in cosmetic products. The Panel reviewed relevant animal and human data on these ingredients. The Panel concluded that most of the polysaccharide gums are safe in the present practices of use and concentration in cosmetics, as described in this safety assessment, but that the available data are insufficient to make a determination that hydrolyzed carrageenan is safe under the intended conditions of use in cosmetics. Because final product formulations may contain multiple botanicals, each containing similar constituents of concern, formulators are advised to be aware of these constituents and to avoid reaching levels that may be hazardous to consumers. The Panel was concerned about the presence of alkylating and other agents that are used to modify polysaccharide gums in cosmetics. Industry should use good manufacturing practices to limit impurities. INTRODUCTION The safety of 106 polysaccharide gums (see Tables 1 and 2) as used in cosmetics is reviewed in this safety assessment. The polysaccharide gums are each naturally derived materials that comprise polysaccharides obtained from plants or algae. Based on the different chemical structures that are associated with polysaccharide gums, these ingredients can be subdivided into categories such as modified, unmodified, linear, branched, and cyclic. Regardless of how they are structured, all of the “moieties” that comprise the molecular structures of these ingredients are polymers composed of monosaccharides. Although these ingredients could be categorized in multiple ways, all of these ingredients fall into two predominate categories, modified and unmodified. The ingredients in the Modified subgroup have been further subdivided into Linear, Branched, Cyclic, and Unknown Structural Configuration. The ingredients in the Unmodified subgroup have been subdivided into Linear Polysaccharides and Their Salts, Branched - Natural/Unmodified, Cyclic, and Unknown Structural Configuration. Based on chemical similarities, relevant data on the following are included for use in evaluating the safety of ingredients in this review: wheat bran extract (contains ~ 80% arabinoxylan oligopeptides) - for use in the safety assessment of arabinoxylan (branched - natural/unmodified subgroup); pectin-derived acidic oligosaccharides (mixture of linear oligomers and small polymers of galacturonic acid) - for safety assessment of pectin (branched - natural/unmodified subgroup), which consists chiefly of partially methoxylated polygalacturonic acids; and carboxymethyl inulin - for safety assessment of sodium carboxymethyl inulin (branched - modified subgroup). Many of the polysaccharide gums reviewed in this safety assessment function as viscosity increasing agents in cosmetic products.1 Other functions are listed in Table 2. As a group, polysaccharide gums comprise polymers of simple saccharide monomers. Their substantial molecular sizes suggest that skin penetration of these ingredients would be unlikely. Thus, these ingredients are unlikely to have significant systemic accessibility and any major decomposition products are likely to be simple saccharides. In addition, the Cosmetic Ingredient Review (CIR) Expert Panel (Panel) has issued “safe as used” conclusions for the following cosmetic ingredients which are structurally similar to some of the ingredients reviewed in this safety assessment: galactomannans,2 microbial polysaccharide gums,3 astragalus gummifer gum,4,5 aloe barbadensis leaf polysaccharides,6 oryza sativa (rice) starch,7 zea mays (corn) starch,8 acacia senegal gum,9 glyceryl alginate,10 hyaluronic acid,11 and triticum vulgare (wheat) starch.12,13 CHEMISTRY Definition and Structure Polysaccharide nomenclature follows the general principles of established organic and carbohydrate nomenclature. Polysaccharide (glycan) is the name given to a macromolecule consisting of a large number of monosaccharide (glycose) residues joined to each other by glycosidic linkages (Figure 1). The term poly(glycose) is not a synonym for polysaccharide (glycan), because it refers to macromolecules composed of glycose residues joined to each other by non-glycosidic linkages. Polysaccharides may be linear, branched, or cyclic. Definitions, structures, and functions of the polysaccharide gums reviewed in this safety assessment, as used in cosmetics and defined in the International Cosmetic Ingredients Dictionary and Handbook, are presented in Tables 1 and 2.1 OH O HO O H HO O O CH3 n Figure 1. Starch Acetate – an example of a polysaccharide gum The polysaccharide gums are each naturally derived materials that comprise polysaccharides obtained from plants or algae. Their substantial molecular sizes suggest that skin penetration of these ingredients would be unlikely. While, for the sake of clarity and organization, these ingredients can be subdivided into categories such as linear, branched, cylic, modified, and unmodified, these moieties represent a family of structurally similar polymeric materials, composed of simple saccharide monomers. So, in intended cosmetic application, these ingredients are unlikely to have significant systemic accessibility and any major decomposition products are likely to be simple saccharides, albeit chemically modified ones in some instances (vide supra). Physical and Chemical Properties Physical and chemical properties of polysaccharide gums are presented in Table 3. Method of Manufacture Methods of manufacture of polysaccharide gums are presented in Table 3. The manufacturing processes for hydrolyzed furcellaran and starch hydroxypropyltrimonium chloride are presented in the following sections. Linear – Modified Hydrolyzed Furcellaran The manufacturing process for hydrolyzed furcellaran is presented in Figure 2 below. Fresh Seaweed (Furcellaria lumbricalis) ↓ Drying Extraction (water 90˚C) Filtration Sedimentation Drying ↓ Furcellarane Powder (Sulfated Polysaccharide) ↓ Depolymerization by sub-critical CO2 (105˚C, 250 bar) with water (2%) Solubilization of Phenoxyethanol in Water ↓ ↓ Hydrolyzed Furcellaran → Heating until 70˚C under shaking ← Spray Dried Sea Water (Depolymerized Sulfated ↓ Concentrate Polysaccharide; MW: 200 kDa Cooling at room temperature on average) ↓ Water Phenoxyethanol Hydrolyzed Furcellaran Sea salt Figure 2. Manufacturing Process for Hydrolyzed Furcellaran.14 Branched – Modified Starch Hydroxypropyltrimonium Chloride The manufacturing process for starch hydroxypropyltrimonium chloride is presented in Figure 3 below. Figure 3. Reaction to form cationic starch ether.15 Composition/Impurities Composition and impurities data on polysaccharide gums are presented in Table 4. USE Cosmetic Many of the ingredients reviewed in this safety assessment function as viscosity increasing agents in cosmetic products, and the complete list of polysaccharide gum functions in cosmetic products is presented in Table 2.1 According to information supplied to the Food and Drug Administration (FDA) by industry as part of the Voluntary Cosmetic Registration Program (VCRP), and the results from a survey of ingredient use concentrations conducted by the Personal Care Products Council (Council) in 2013, 59 of these polysaccharide gums are being used in cosmetic products and maltodextrin has the highest reported use frequency.16,17,18,19 The Council survey data also indicate that polysaccharide gums are being used in rinse-off cosmetic products at maximum ingredient use concentrations up to 50% (i.e., for algin in paste masks and mud packs), and in leave-on cosmetic products at maximum ingredient use concentrations up to 45.7% (i.e., for corn starch modified in tonics, dressings, and other hair grooming aids).16,18 Frequency of use/use concentration data for polysaccharide gums are summarized in Table 5. Cosmetic products containing polysaccharide gums may be applied to the skin and hair or, incidentally, may come in contact with the eyes (maximum ingredient use concentration in these products = 30%) and mucous membranes