J. Cosmet. Sci., 69, 213–228 (May/June 2018) 213 The Blend of Taurine and Aloe Vera Extract Boosts Action Against Skin Irritation: In Vitro and Clinical Evaluations JUNG M. SEO, SUZIE CHENG, NADIA SOLIMAN, ZEENAT NABI, and LONG PAN, Colgate-Palmolive Company, Piscataway, NJ (J.M.S., S.C., N.S., Z.N., L.P.) Accepted for publication May 10, 2018. Synopsis Regular usage of cosmetic products and drugs in dermatological vehicles may cause irritant contact dermatitis. For example, aluminum chloride (AlCl3), the most effi cacious antiperspirant salt to treat hyperhidrosis, shows high irritancy potential. To mitigate the irritant contact dermatitis caused by topical application of products containing AlCl3, we investigated the anti-irritating effects of aloe extract and taurine in vitro and in vivo. In an in vitro experiment, reconstructed human epidermis model, EpiDerm, was tested with AlCl3 in the presence or absence of taurine and aloe extract. In a human clinical study, 12 adult subjects were tested with two products, a commercial AlCl3 antiperspirant product and a prototype 12% AlCl3 formulation containing 0.1% taurine and 0.1% aloe extract. Skin irritation potential in vitro and in vivo was measured by the release of pro-infl ammatory cytokine, IL-1α, and chemokine, IL-8. Taurine and aloe extract signifi cantly (p 0.05) reduced IL-lα and IL-8 production in vitro and in vivo after topical application of formulations containing AlCl3. The blend of taurine and aloe extract demonstrated boosted anti-irritation benefi ts on AlCl3 irritated skin both in vitro and in vivo. These results suggest that the combination of these anti-irritating actives may possibly be effective in mitigating irritant contact dermatitis caused by other dermatological vehicles containing irritating agents, but further research is warranted to assess their effects. INTRODUCTION In the United States alone, approximately 15.2 million people are affected by dermatitis (1) and 50% of the population has sensitive skin with reduced irritation threshold (2). Application of cosmetics and drugs in dermatological vehicles can induce skin dryness and irritation of the uppermost layer of the epidermis (3). Irritation and sensitization of the stratum corneum can lead to the development of irritant contact dermatitis, which limits the usage of products containing such compounds. Irritant contact dermatitis is the in- fl ammation of the skin which leads to erythema, dryness, itching, burning, and stinging and is caused by a physical or chemical agent that damages the stratum corneum. It is, therefore, important to identify compounds that can reduce skin irritation to develop effi cacious formulations that mitigate irritant contact dermatitis in consumers. However, the biochemical mechanisms and triggers of skin irritation are complex and not fully Address all correspondence to Long Pan at long_pan@colpal.com.

JOURNAL OF COSMETIC SCIENCE 214 understood. Current data and models have shown that irritants trigger infl ammatory processes by inducing the release of pro-infl ammatory cytokines and chemokines, such as IL-1α, PGE2, IL-6, and IL-8 (4). Commonly used cosmetic products or topical prescrip- tion drugs can upregulate the expression of these pro-infl ammatory cytokines. Thus, identifi cation of compounds that inhibit the production of these cytokines is crucial in mitigating irritant contact dermatitis. Aluminum chloride is a highly effective active ingredient used to treat hyperhidrosis, a medical condition in which a person sweats excessively and uncontrollably, but regular usage results in irritant contact dermatitis (5). Aluminum chloride is well-known to cause skin irritation because of its low pH range of 2–3 and topical application leads to the release of cytokines. Aluminum (Al3+) ion also generates reactive oxygen species (ROS) and induces cytotoxic lipid peroxidation in human skin fi broblasts, which leads to cell damage (6,7). Thus, the addition of anti-irritating compounds, such as taurine and aloe extract, into formulations containing aluminum chloride has become necessary to protect against irritation and maintain skin homeostasis. Taurine, 2-aminoethanesulfonic acid, is an amino sulfonic acid that is sometimes con- sidered as amino acid that is synthesized in the liver from cysteine and methionine. Taurine is a β-amino acid and exists mainly as the zwitterion taurine species at biological pH values. Because of the predominance of the zwitterion species, it contributes immensely to the overall lipophilicity of taurine and allows for it to be absorbed through biological membranes (8). It serves important physiological roles, such as membrane stabilization, regulation of calcium levels, and acts as an osmoregulator and a neuromodulator in the brain (9). In the skin, taurine has been previously found to inhibit infl ammation and irrita- tion responses triggered by irritating compounds, such as sodium lauryl sulfate, and it has been added to many topical formulations in recent years (10). It is known that keratinocytes in the outermost granular layer of the stratum spinosum accumulate taurine through the taurine transporter to exert its antioxidant, anti-infl ammatory, and cell-proliferating ef- fects in the skin (11–13). Although taurine alone has been previously found to exhibit anti-irritating effects, supplementation of additional anti-irritating agents into formula- tions with high irritation potential will improve taurine’s effi cacy in mitigating irritant contact dermatitis. Aloe extract is already widely used in many cosmetic and personal care products because of its ability to reduce irritation and promote skin repair. Aloe extract contains various natural ingredients, essential amino acids, minerals, and vitamins that are known to in- hibit COX-1 activity, a major enzyme that plays an important role in the production of prostaglandins (14,15). Aloe is also known for its skin-penetrating enhancement effects and has been found to increase the skin permeation of transdermal drugs in formulations (16,17). Our study aims to investigate the boost in anti-irritating effects that the blend of taurine and aloe extract exhibit with regard to aluminum chloride–induced skin irritation while maintaining the acidic pH necessary for high effi cacy. Although both of these compounds are known to exhibit anti-irritating effects and benefi cial effects on skin health, investiga- tion into their combined effects has been limited. We hypothesize that aloe extract in- creases the permeation and penetration of taurine into the skin, which may explain the signifi cant boost in anti-irritating effects observed in vitro. A multilayered human kera- tinocyte skin model, EpiDerm (MatTek Corporation, Ashland, MA), was used to assess