JOURNAL OF COSMETIC SCIENCE 102 differences observed in the RIFT, and to evaluate the signifi cance of these new results. It is worth considering the value of additional measures in future studies, or recruiting in- dividuals with very sensitive skin (e.g., the elderly or those with diagnosed atopy) (51,52). Clearly, as demonstrated from the RIFT results, in vivo studies are critical for a full evalu- ation of detergent formulation mildness. Yet, other work (16,17) proposes using a specifi c set of in vitro methods (zein protein denaturation test, cell culture cytokine release, and corneosurfametry measure of protein and lipid degradation) as suffi cient to assess and compare the mildness of different laundry detergents. In that testing, the AFC product was reported to be milder than TFG (16). Yet, the RIFT clinical results reveal the oppo- site: TFG is signifi cantly milder than AFC in a model mimicking exposure of the skin to laundry detergents during hand-laundering of clothes. Although in vitro methods can be useful tools for rapid screening of large numbers of surfactants and product formulations for skin mildness profi les, they can be limited in scope. It is particularly important to recognize that false negatives do occur with in vitro and other laboratory models (53–58), most likely because such methods do not replicate all the possible skin properties and reactions to treatments (erythema, allergy, hydration, barrier damage, skin surface pH, alteration of the surface microbial community, environ- mental effects, etc.). Thus, inclusion of the appropriate real-life human studies, using a battery of skin end points, is recommended for precisely defi ning mildness of surfactant- containing formulations, such as laundry detergents (5,24,53,54). As a fi nal note, in addition to using a milder detergent, consumers can improve the mild- ness of clothing on skin by using fabric softeners. Studies with softened fabrics have re- vealed less friction, better skin hydration, and gentler effects on sensitive and infant skin (51,59–61). ACKNOWLEDGMENTS The authors wish to thank Dan Yu, Yin Li, Xu Liu, and Yueqing Niu at P&G’s Beijing Technical Center in Beijing, China, for their technical contributions to the RIFT George Jerdack, Ning Ji, and Ann Lawrence for their clinical and statistical guidance on the clinical methods described in this article Deb Schoborg for clinical support for the 21DCIT and Don Bissett for assistance with the manuscript preparation. Declaration of Interest: This work evaluated products marketed by the Procter & Gamble Company (P&G). The work was funded entirely by P&G, and all authors are employees of P&G. REFERENCES (1) R. Kami de, L. Misery, N. Perez-Cullell, V. Sibaud, and C. Taïeb, Sensitive skin evaluation in the Japanese population, J. Dermatol., 40, 177–181 (2013). (2) L. Miser y, V. Sibaud, C. Merial-Kieny, and C. Taïeb, Sensitive skin in the American population: preva- lence, clinical data, and role of the dermatologist, Int. J. Dermatol., 50, 961–967 (2011). (3) L. Misery , S. Boussetta, T. Nocera, N. Perez-Cullell, and C. Taïeb, Sensitive skin in Europe, J. Eur. Acad. Dermatol. Venereol., 23, 376–381 (2009). (4) F. Xu, S. Yan, M. Wu, F. Li, Q. Sun, W. Lai, X. Shen, N. Rahhali, C. Taïeb, and J. Xu, Self-declared sensitive skin in China: a community-based study in three top metropolises, J. Eur. Acad. Dermatol. Venereol., 27, 370–375 (2013).

MILDNESS OF LAUNDRY DETERGENTS DIFFERING IN pH 103 (5) C. Crawford and M. J. Zirwas, Laundry detergents and skin irritancy—a comprehensive review, Skinmed, 12, 23–31 (2014). (6) M. A. Farag e, Does sensitive skin differ between men and women? Cutan. Ocul. Toxicol., 29, 153–163 (2010). (7) M. A. Farag e, Perceptions of sensitive skin: changes in perceived severity and associations with environ- mental causes, Contact Dermatitis, 59, 226–232 (2008). (8) M. A. Farag e, A. Katsarou, and H. I. Maibach, Sensory, clinical and physiological factors in sensitive skin: a review, Contact Dermatitis, 55, 1–14 (2006). (9) G. C. Morri son, C. J. Weschler, G. Bekö, H. M. Koch, T. Salthammer, T. Schripp, J. Toftum, and G. Clausen, Role of clothing in both accelerating and impeding dermal absorption of airborne SVOCs, J. Expo. Sci. Environ. Epidemiol., 26, 113–118 (2016). (10) G. Bekö, G. Morrison, C. J. Weschler, H. M. Koch, C. Palmke, T. Salthammer, T. Schripp, J. Toftum, and G. Clausen, Measurements of dermal uptake of nicotine directly from air and clothing, Indoor Air, 27, 427–433 (2017). (11) M. Brandt, C . Brown, J. Burkhart, N. Burton, J. Cox-Ganser, S. Damon, H. Falk, S. Fridkin, P. Garbe, M. McGeehin, J. Morgan, E. Page, C. Rao, S. Redd, T. Sinks, D. Trout, K. Wallingford, D. Warnock, and D. Weissman, Mold prevention strategies and possible health effects in the aftermath of hurricanes and major fl oods, MMWR Recomm. Rep., 55, 1–27 (2006). (12) M. Gong, C. J. Weschler, and Y. Zhang, Impact of clothing on dermal exposure to phthalates: observa- tions and insights from sampling both skin and clothing, Environ. Sci. Technol., 50, 4350–4357 (2016). (13) T. Kiriyama, H. Sugiura, and M. Uehara, Residual washing detergent in cotton clothes: a factor of win- ter deterioration of dry skin in atopic dermatitis, J. Dermatol., 30, 708–712 (2003). (14) D. V. Belsit o, A. F. Fransway, J. F. Fowler, E. F. Sherertz, H. I. Maibach, J. G. Mark, C. G. Mathias, R. L. Rietschel, F. J. Storrs, and J. R. Nethercott, Allergic contact dermatitis to detergents: a multicenter study to assess prevalence, J. Am. Acad. Dermatol., 46, 200–206 (2002). (15) S. Kwon, D. Holland, and P. Kern, Skin safety evaluation of laundry detergent products, J. Toxicol. Environ. Health A, 72, 1369–1379 (2009). (16) J. F. Fowler , M. J. Zirwas, L. Napolitano, J. Coope-Epstein, and M. Russell, A new approach to formu- lating a milder laundry detergent for patients with sensitive skin, J. Am. Acad. Dermatol., 76(Suppl. 1), AB17 (2017). (17) J. F. Fowler , M. J. Z. Zirwas, L. Napolitano, M. Russell, and J. Coope-Epstein, A novel multifactorial approach to developing mild laundry detergents and assessing their relative mildness, J. Drugs Derma- tol., 16, 1235–1239 (2017). (18) K. Kulthanan , P. Maneeprasopchoke, S. Varothai, and P. Nuchkull, The pH of antiseptic cleansers, Asia Pac. Allergy, 4, 32–36 (2014). (19) W. Boonchai and P. Iamtharachai, The pH of commonly available soaps, liquid cleansers, detergents and alcohol gels, Dermatitis, 21, 154–156 (2010). (20) M. Bock, B. Wulfhorst, and S. M. John, Site variations in susceptibility to SLS, Contact Dermatitis, 57, 94–96 (2007). (21) R. Warren, K . D. Ertel, T. G. Bartolo, M. J. Levine, P. B. Bryant, and L. F. Wong, The infl uence of hard water (calcium) and surfactants on irritant contact dermatitis, Contact Dermatitis, 35, 337–343 (1996). (22) J. R. Young, M. J. How, A. P. Walker, and W. M. H. Worth, Classifi cation as corrosive or irritant to skin of preparations containing acidic or alkaline substances, without testing on animals, Toxicol. In Vitro, 2, 19–26 (1988). (23) A. G. Craan, G. Sanfaçon, and R. H. Walker, The use of pH and acid/alkaline reserve for the classifi ca- tion and labeling of household cleaning products: data from a poison control center, Int. J. Consum. Prod. Saf., 4, 191–213 (1997). (24) K. Rizi, R. J . Green, M. X. Donaldson, and A. C. Williams, Using pH abnormalities in diseased skin to trigger and target topical therapy, Pharm. Res., 28, 2589–2598 (2011). (25) T. Fujimura, Y. Shimotoyodome, T. Nishijima, K. Sugata, H. Taguchi, and S. Moriwaki, Changes in hydration of the stratum corneum are the most suitable indicator to evaluate the irritation of surfactants on the skin, Skin Res. Technol., 23, 97–103 (2017). (26) H. M. Gunathilake, G. M. Sirimanna, and N. Y. Schürer, The pH of commercially available rinse-off products in Sri Lanka and their effect on skin pH, Ceylon Med. J., 52, 125–129 (2007). (27) R. Gfatter, P. Hackl, and F. Braun, Effects of soaps and detergents on skin surface pH, stratum corneum hydration, and fat content in infants, Dermatology, 195, 258–262 (1997). (28) H. C. Korting, K. Hübner, K. Greiner, G. Hamm, and O. Braun-Falco, Differences in the skin surface pH and bacterial microfl ora due to the long-term application of synthetic detergent preparations of pH