Article International Journal of Toxicology 2017, Vol. 36(Supplement 1) 17S-56S ª The Author(s) 2017 Safety Assessment of Amino Acid Alkyl Reprints and permission: sagepub.com/journalsPermissions.nav Amides as Used in Cosmetics DOI: 10.1177/1091581816686048 journals.sagepub.com/home/ijt Christina L. Burnett1, Bart Heldreth2, Wilma F. Bergfeld3, Donald V. Belsito3, Ronald A. Hill3, Curtis D. Klaassen3, Daniel C. Liebler3, James G. Marks Jr3, Ronald C. Shank3, Thomas J. Slaga3, Paul W. Snyder3, and F. Alan Andersen4 Abstract The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the product use, formulation, and safety data of 115 amino acid alkyl amides, which function as skin and hair conditioning agents and as surfactants—cleansing agents in personal care products. Safety test data on dermal irritation and sensitization for the ingredients with the highest use concentrations, lauroyl lysine and sodium lauroyl glutamate, were reviewed and determined to adequately support the safe use of the ingredients in this report. The Panel concluded that amino acid alkyl amides are safe in the present practices of use and concentration in cosmetics, when formulated to be nonirritating. Keywords amino acid alkyl amides, safety, cosmetics Introduction Chemistry This safety assessment summarizes the available data relevant The amino acid alkyl amides in this report are comprised of to assessing the safety of 115 amino acid alkyl amides as used amino acids acylated with acids or acid chlorides at the amino in cosmetics. These ingredients mainly function as skin and acid nitrogen to form amides (except for lauroyl lysine, which hair conditioning agents and as surfactants—cleansing agents is formed by acylation at the epsilon nitrogen). For example, in personal care products. The list of ingredients in this report is capryloyl glycine is the N-acylation product of glycine with found in Table 1. caprylic acid chloride. By and large, the ingredients in this report will not rap- A likely metabolic pathway for these ingredients includes idly dissociate (beyond zwitterion formation) in the pres- reactions catalyzed by amidases, should the ingredients pene- ence of water, but action by amidases is the most likely trate the skin. The net result would be the release of the amino first step of metabolism if dermal penetration occurs. The acid (glycine in the example above) and a fatty acid (caprylic relative exposure, hence, would also include amino acids acid in the example). The definitions of the amino acid alkyl and fatty acids. The Cosmetic Ingredient Review Expert amides can be found in Table 1, and the structures can be found Panel (Panel) previously has reviewed the safety of in Table 3. a-amino acids and animal- and plant-derived amino acids and concluded that these ingredients are safe for use as 1,2 cosmetic ingredients. The Panel also reviewed the fol- 1 Cosmetic Ingredient Review Scientific Analyst/Writer, Cosmetic Ingredient lowing fatty acid constituents and concluded that these fatty Review, Washington, DC, USA 2 acids are safe for use as cosmetic ingredients: coconut acid, Cosmetic Ingredient Review Chemist, Cosmetic Ingredient Review, Washington, DC, USA olive acid, sunflower seed acid, palm acid, acetic acid, 3 Cosmetic Ingredient Review Expert Panel Member, Cosmetic Ingredient lauric acid, oleic acid, palmitic acid, stearic acid, and myr- Review, Washington, DC, USA 3-9 istic acid. The Panel concluded that malic acid was safe 4 Former Director, Cosmetic Ingredient Review, Cosmetic Ingredient Review, for use as a pH adjuster, but the data were insufficient to Washington, DC, USA determine safety for any other functions.10 The maximum Corresponding Author: concentrations of use along with summaries of the data Lillian J. Gill, Cosmetic Ingredient Review, Suite 1200, 1620 L Street, NW, included in those existing safety assessments are provided Washington, DC 20036, USA. in Table 2. Email: [email protected] 18S International Journal of Toxicology 36(Supplement 1) Table 1. Definitions and Functions of the Amino Acid Alkyl Amides in This Safety Assessment.20,69,a Ingredient CAS No. Definition Function Acetyl arginine Acetyl arginine is the substituted amino acid that conforms Humectants; skin conditioning agents—emollient 210545-23-6 to the formula. Acetyl arginine is the amide formed from the reaction of acetic acid chloride and arginine. Acetyl cysteine Acetyl cysteine is the organic compound that conforms to Antioxidants; skin conditioning agents—misc 616-91-1 the formula. Acetyl cysteine is the amide formed from the reaction of acetic acid chloride and cysteine. Acetyl glutamic acid Acetyl glutamic acid is the substituted amino acid that Skin conditioning agents—misc 1188-37-0 conforms to the formula. Acetyl glutamic acid is the amide formed from the reaction of acetic acid chloride and glutamic acid. Acetyl glutamine Acetyl glutamine is the organic compound that conforms to Skin conditioning agents—misc 2490-97-3 the formula. Acetyl glutamine is the amide formed from the 35305-74-9 reaction of acetic acid chloride and glutamine. Acetyl histidine Acetyl histidine is the organic compound that conforms to Skin conditioning agents—emollient; skin conditioning 39145-52-3 the formula. Acetyl histidine is the amide formed from the agents—humectant reaction of acetic acid chloride and histidine. Acetyl methionine Acetyl methionine is the substituted amino acid that Skin conditioning agents—misc 1115-47-5 conforms to the formula. Acetyl methionine is the amide 65-82-7 formed from the reaction of acetic acid chloride and methionine. Acetyl proline Acetyl proline is the substituted amino acid that conforms Skin conditioning agents—emollient 68-95-1 to the formula. Acetyl proline is the amide formed from the reaction of acetic acid chloride and proline. Acetyl tyrosine Acetyl tyrosine is the organic compound that conforms to Skin conditioning agents—misc 537-55-3 the formula. Acetyl tyrosine is the amide formed from the reaction of acetic acid chloride and tyrosine. Capryloyl collagen amino Capryloyl collagen amino acid is the condensation product Hair conditioning agents; surfactants—cleansing acids of caprylic acid chloride with collagen amino acids. agents Capryloyl glycine Capryloyl glycine is the acylation product of glycine with Hair conditioning agents; surfactants—cleansing 14246-53-8 caprylic acid chloride. agents Capryloyl gold of pleasure Capryloyl gold of pleasure amino acid is the condensation Cosmetic biocides; deodorant agents amino acids product of caprylic acid chloride and the amino acids derived from the complete hydrolysis of the protein fraction obtained from the seeds of Camelina sativa. Capryloyl keratin amino Capryloyl keratin amino acid is the condensation product Hair conditioning agents; surfactants—cleansing acids of caprylic acid chloride with keratin amino acids. agents Capryloyl pea amino acids Capryloyl pea amino acid is the product obtained by the Hair conditioning agents; skin conditioning agents— condensation of caprylic acid chloride and pea amino misc acids. Capryloyl quinoa amino Capryloyl quinoa amino acid is the condensation product of Hair conditioning agents; skin conditioning agents— acids caprylic acid chloride and amino acids obtained from the misc complete hydrolysis of the protein obtained from the seeds of Chenopodium quinoa. Capryloyl silk amino acids Capryloyl silk amino acid is the product obtained by the Hair conditioning agents; surfactants—cleansing condensation of caprylic acid chloride with silk amino agents acids. Cocoyl glutamic acid Cocoyl glutamic acid is the coconut acid amide of glutamic Hair conditioning agents; skin conditioning agents— acid that conforms to the formula. misc; surfactants—cleansing agents Dipalmitoyl cystine Dipalmitoyl cystine is the product obtained by acylation of Hair conditioning agents 17627-10-0 cystine with palmitoyl chloride. Dipotassium capryloyl Dipotassium capryloyl glutamate is the organic compound Deodorant agents; surfactants—cleansing agents glutamate that conforms to the formula. Dipotassium capryloyl glutamate is the dipotassium salt of the amide formed from the reaction of capryloyl chloride and glutamic acid. Dipotassium undecylenoyl Dipotassium undecylenoyl glutamate is the substituted Hair conditioning agents; skin conditioning agents— glutamate amino acid that conforms to the formula. Dipotassium misc; surfactants—cleansing agents undecylenoyl glutamate is the dipotassium salt of the amide formed from the reaction of undecenoyl chloride and glutamic acid. (continued) Burnett et al 19S Table 1. (continued) Ingredient CAS No. Definition Function Disodium capryloyl Disodium capryloyl glutamate is the organic compound that Deodorant agents; surfactants—cleansing agents glutamate conforms to the formula. Disodium capryloyl glutamate is the disodium salt of the amide formed from the reaction of capryloyl chloride and glutamic acid. Disodium cocoyl Disodium cocoyl glutamate is the disodium salt of the Surfactants—cleansing agents glutamate coconut acid amide of glutamic acid. It conforms 68187-30-4 generally to the formula. Disodium hydrogenated Disodium hydrogenated tallow glutamate is the disodium Hair conditioning agents; skin—conditioning agents— tallow glutamate salt of the hydrogenated tallow acid amide of glutamic misc; surfactants—cleansing agents acid. It conforms generally to the formula. Disodium N-lauroyl Disodium N-lauroyl aspartate is the organic compound that Surfactants—cleansing agents aspartate conforms to the formula.