Safety Assessment of Monoalkylglycol Dialkyl Acid Esters as Used in Cosmetics Status: Tentative Report for Public Comment Release Date: June 22, 2017 Panel Meeting Date: September 11-12, 2017 All interested persons are provided 60 days from the above date to comment on this safety assessment and to identify additional published data that should be included or provide unpublished data which can be made public and included.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 All unpublished data submitted to CIR will be discussed in open meetings, will be available at the CIR office for review by any interested party and may be cited in a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 Interim Director, Dr. Bart Heldreth. The 2017 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 Interim Director is Bart Heldreth Ph.D. This report was prepared by Lillian C. Becker, Scientific Analyst/Writer. © 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 (CIR) Expert Panel (Panel) reviewed data relevant to assessing the safety of 28 monoalkylglycol dialkyl acid esters as used in cosmetics. The reported functions of these ingredients include: film former, hair conditioning agent, opacifying agent, plasticizer, skin-conditioning agents (emollient, miscellaneous, and occlusive), slip modifier, solvent, surface modifier, and viscosity increasing agent – nonaqueous. The Panel concluded that 25 of these monoalkylglycol dialkyl acid esters are safe in cosmetics in the present practices of use and concentration described in this safety assessment and that the available data are insufficient to make a determination that Diethylpentanediol Dineopentanoate, Dioctadecanyl Didecyltetradecanoate, and Dioctadecanyl Ditetradecyloctadecanoate are safe under the intended conditions of use in cosmetic formulations. INTRODUCTION This is a safety assessment of 28 monoalkylglycol dialkyl acid esters as used in cosmetics (Table 1). The ingredients in this report are structurally related to each other as alkyl esters of monoalkyl diols (i.e. not polyalkyldiols such as polyethylene glycols (PEGs)) that vary by type of diol and lengths of the fatty acid residues. The ingredients in this report include: Trimethyl Pentanyl Diisobutyrate Glycol Ditallowate Butylene Glycol Dicaprylate/Dicaprate Hexanediol Distearate Butylene Glycol Diisononanoate Neopentyl Glycol Dicaprate Diethylpentanediol Dineopentanoate Neopentyl Glycol Dicaprylate/Dicaprate Dioctadecanyl Didecyltetradecanoate Neopentyl Glycol Dicaprylate/Dipelargonate/Dicaprate Dioctadecanyl Ditetradecyloctadecanoate Neopentyl Glycol Diethylhexanoate Glycol Dibehenate Neopentyl Glycol Diheptanoate Glycol Diethylhexanoate Neopentyl Glycol Diisononanoate Glycol Dilaurate Neopentyl Glycol Diisostearate Glycol Dioleate Neopentyl Glycol Dilaurate Glycol Dipalmate/Palm Kernelate/Olivate/Macadamiate Propanediol Dicaprylate Glycol Dipalmate/Rapeseedate/Soyate Propanediol Dicaprylate/Caprate Glycol Dipivalate Propanediol Diisostearate Glycol Distearate Propanediol Dipelargonate According to the International Cosmetic Dictionary and Handbook, the reported functions of these ingredients include: film former, hair conditioning agent, opacifying agent, plasticizer, skin-conditioning agents (emollient, miscellaneous, and occlusive), slip modifier, solvent, surface modifier, and viscosity increasing agent – nonaqueous (Table 1).1 Some of these ingredients have been previously assessed for safety by the Panel. Glycol Distearate has been previously reviewed by the Panel and was found to be safe as used; the conclusion was reaffirmed in 2001 (Table 2).2,3 Neopentyl Glycol Dicaprylate/Dipelargonate/Dicaprate and Neopentyl Glycol Diisononanoate have also been reviewed by the Panel and were found to be safe as used in 2011.4 The Panel has reviewed related ingredients, moieties, and component parts of these ingredients (Table 2). These CIR safety assessments have been utilized herein, in part, to inform the safety of the monoalkylglycol dialkyl acid esters. Please see the original reports for details (http://www.cir-safety.org/ingredients). Pertinent data were discovered in the European Chemicals Agency (ECHA) database for Glycol Distearate, Neopentyl Glycol Dicaprylate/Dicaprate, Neopentyl Glycol Diethylhexanoate, Neopentyl Glycol Diheptanoate, and Trimethyl Pentanyl Diisobutyrate.5-9 The ECHA website provides summaries of information submitted by industry. ECHA is cited in this assessment to identify the source of the data obtained from these summaries. Summaries from the original reports on Glycol Distearate, Neopentyl Glycol Dicaprylate/Dipelargon- ate/Dicaprate, and Neopentyl Glycol Diisononanoate are included in the appropriate sections in italics.3,4 Please see the original reports for further details (http://www.cir-safety.org/ingredients). CHEMISTRY Definition and Structure The ingredients in this report are structurally related to each other as alkyl diesters of monoalkane diols. These ingredients vary by the type of diol and the size of the carboxylic acid residues (Figure 1). For example, Neopentyl Glycol Dicaprate is a diol (neopentyl glycol) esterified at both hydroxyl groups with a carboxylic acid (capric acid) (Figure 2). Figure 1. Monoalkylglycol Dialkyl Acid Esters in which “ORO” is the residue of a diol and “R’C(O)” and “R”C(O)” are the residues of a fatty acids. Figure 2. Neopentyl Glycol Dicaprate, wherein “ORO” from Figure 1 is the residue of neopentyl glycol, and both R’C(O)” and “R”C(O)” are the residues of capic acid. Physical and Chemical Properties Physical and chemical properties for several of the monoalkylglycol dialkyl acid esters in this safety assessment are presented in Table 3. Some of the monoalkylglycol dialkyl acid esters (e.g., Neopentyl Glycol Diethylhexanoate and Propanediol Dicaprylate) are clear or yellow liquids that are insoluble in water.8,10-12 However, longer-chain diesters, such as Glycol Distearate, can be white to cream-colored waxy solids.3 The physical properties of these ingredients may vary within specified limits according to the proportions of mono- and diesters, and other components (e.g., variations in how many of the glycol residues in Glycol Distearate are mono- or di-substituted with stearic acid). Depending on the intended use, these variations can be set during manufacturing to achieve the desired physical characteristics. Diethylpentanediol Dineopentanoate is stable at 25°C under storage conditions.13 The average residual ash on ignition for Neopentyl Glycol Dicaprate is 0.05%.14 Trimethyl Pentanyl Diisobutyrate is stable at pH 4.0 and 7.0.15 The half-life in water at pH 9 is 178 days. UV Absorption Data provided by a manufacture indicated that Neopentyl Glycol Diisononanoate did not significantly absorb light in the 250 to 400 nm range.4 The structures of these ingredients lack chromophores that would result in UV absorption above 210 nm. Method of Manufacture In general, alkyl esters can be produced via the esterification of carboxylic acids with the corresponding glycols (with or without a metal catalyst).16 These carboxylic acids and glycols are often derived from plant or animal sources (e.g., Glycol Dipalmate/Rapeseedate/Soyate and Glycol Ditallowate). Acids from these sources are often mixtures; accordingly, the resulting esters are also mixtures (e.g., Glycol Dipalmate/Palm Kernelate/Olivate/ Macadamiate and Glycol Dipalmate/Rapeseedate/Soyate). Impurities/Constituents Ethylene glycol and/or ethylene oxide are used as starting material for the synthesis of Glycol Stearate. These starting materials are expected to be used as starting materials for Glycol Distearate, a related ingredient. Because the former is known to be contaminated with traces of 1,4-dioxane, it is possible that such traces also appear in the final synthesized material.17 A safety data sheet on a product mixture containing Glycol Distearate recited that 1,4-dioxane was not detected.18 A batch of Neopentyl Glycol Diheptanoate was reported to be > 99% pure; the impurities were not named.6 One batch of Trimethyl Pentanyl Diisobutyrate was reported to be > 99% pure, and another batch was reported to be 98.95% pure.7 The impurities were not named. Another source also reported that Trimethyl Pentanyl Diisobutyrate was > 99% pure and the major impurity was 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate.15 A product data sheet for a product mixture containing Glycol Distearate (88% - 5%), ethylene glycol monostearate (5% - 15%), and ethylene glycol (< 4%) reported that this product contained < 1 ppb toluene.18,19 According to this product data sheet, this product mixture contains < 10 ppm of the following: cadmium, mercury, antimony, arsenic, chromium, cobalt, nickel, lead, or silver. It was also reported to not contain ethylene oxide or propylene oxide. USE Cosmetic The safety of the cosmetic ingredients included in this assessment is evaluated based on data received from the U.S. Food and Drug Administration (FDA) and the cosmetic industry on the expected use of these ingredients in cosmetics.