J. Cosmet. Sci., 68, 205–217 (May/June 2017) 205 Two randomized studies to evaluate the cooling sensation, consumer liking, and tolerability of a skin disinfectant spray PEILI GONG, NAN WANG, LEI GUAN, and WEI LAI GlaxoSmithKline (China) Investment Co, Beijing, China (P.G.), GlaxoSmithKline Consumer Healthcare, Brentford, United Kingdom (N.W.), Guangzhou Landproof Testing Technology Co. Ltd., Tianhe District, Guangzhou, China (L.G.), and Department of Dermatology, The Third Affi liated Hospital, Sun Yat-Sen University, Guangzhou, China (W.L.). Accepted for publication March 24, 2017. Synopsis The aim of these two clinical studies was to evaluate the sensory characteristics and irritation potential of a prototype disinfectant spray (containing 0.13% w/v benzalkonium chloride and a cooling agent) in subjects with experimental wounds. The pilot study was a single center, “replicated latinClinicalTrials. ClinicalTrials. square design,” randomized and double-blinded study. The pivotal study was a single center, randomized, controlled, crossover, double-blinded study, following a direct comparison test design of the study products. The experimental wounds were generated using sequential tape strippings of the forearm skin before product application. The test product was compared with the currently marketed BACTROBAN® disinfectant spray, negative control (0.9% w/v saline), and positive control (70% w/v isopropyl alcohol, pilot study only). The pilot study was intended to inform the study design and sample size for the pivotal study. The pilot study demonstrated that the positive control product delivered signifi cantly more irritancy (stinging /burning sensory) than the negative control product on the experimental wound, which verifi ed the integrity of the wound model. The results of the pivotal study suggested that the prototype formulation delivered signifi cantly more cooling sensation than both BACTROBAN® disinfectant spray and negative control at 3 and 5 min after product application, and overall for a 15-min period after application. No statistically signifi cant differences in product liking were observed between the prototype disinfectant spray and the BACTROBAN® disinfectant spray or negative control. The prototype disinfectant spray, BACTROBAN® disinfectant spray, and control products were well-tolerated in these studies. Address all correspondence to Wei Lai at drlaiwei@163.com. GlaxoSmithKline (China) Investment Co., Ltd sponsored this study and was involved in the study design and clinical operation. Prof. Wei Lai has been an advisory board member for GSK. Guangzhou Landproof Testing Technology Co. Ltd. conducted the experiments and initial effi cacy evaluation. All authors report no com- peting interests. ClinicalTrials.gov Identifi er: NCT02106403. ® BACTROBAN® is a registered trademark owned by GSK group of companies.

JOURNAL OF COSMETIC SCIENCE 206 INTRODUCTION The skin is one of the most important parts of the body because it interfaces with the environment and is the fi rst line of defense from external factors. The skin plays a key role in protecting the body against pathogens (1) and excessive water loss (2). Skin wounds are susceptible to infection because of the loss of sterility of the innate bar- rier function of the skin and dermal appendages, facilitating the development of micro- bial communities within the wound environment (3,4). A wound infection can cause delayed healing and if infection is not controlled it may lead to cellulitis, bacteraemia, and septicaemia (5). It is reported that antiseptic solutions can reduce infection in trau- matic lacerations (6) and are commonly recommended in current clinical practices (7). Benzalkonium chloride has been used safely and effectively as an antiseptic for wound management for several decades. Marple et al. reviewed 18 studies on the safety of benzal- konium chloride in nasal solutions and concluded that benzalkonium chloride appeared “safe and well-tolerated for both long- and short-term clinical use” (8). The Food and Drug Administration has found benzalkonium chloride to be generally recognized as safe and effective/Category I for products to clean skin wounds (short duration use) under fi rst-aid antiseptic and consumer antiseptic monographs at concentrations between 0.1 and 0.13% (9). It is a Category III ingredient under health care antiseptic monograph for most other uses because of the lack of enough data to determine safety or effi cacy (10). In China, there are several products including 0.1% benzalkonium chloride approved by the health authorities as wound antiseptics in the market. BACTROBAN® disinfectant spray (GlaxoSmithKline, Nanjing, China), marketed in China since July 2011, is a skin wound disinfectant containing 0.13% benzalkonium chlo- ride in an aqueous solution. Consumer insight into market research identifi ed that deliver- ing a cooling sensory benefi t together with the existing attributes of the current formulation could provide an enhanced product experience for consumers. A prototype wound wash product formulation using a cooling technology was developed to include a cooling agent (menthol derivatives) and a solubilizer into the currently marketed formulation. Menthol and related cooling compounds are widely used in food and pharmaceutical in- dustries (11). It is widely used in dermatologic practice in topical antipruritic, antiseptic, analgesic, and cooling formulations (12). Menthol has been demonstrated to activate the transient receptor potential melastatin type 8, a recognized thermo-receptor expressed in sensory nerves and/or skin cells, the physiological role of which as a transducer of gentle cooling is widely accepted (13–15). The sensory impact of menthol when applied to skin depends on the concentration of menthol. Low concentrations give a cool sensation whereas high concentrations of 2–5% menthol cause irritation. Menthol has also been reported to be associated with allergic contact dermatitis (11,12) therefore, the level of menthol in the formulation was selected to provide optimum cooling versus minimal irritation. A sensory evaluation in an expert panel with healthy skin successfully demonstrated that the prototype disinfectant spray formulation could deliver more cooling sensation than the currently marketed product (a sensory study conducted by MMR Research World- wide, China data on fi le). The sensory study was performed on healthy skin rather than the product’s indication of wounded skin therefore, it is not necessarily indicative of the prototype product’s performance in real use because the penetration of the topically applied product will be faster on wounded skin. Therefore, to understand the sensory