j. Soc. Cosmet. Chem., 42, 105-128 (March/April 1991) The value of multiple instrumental and clinical methods, repeated patch applications, and daily evaluations for assessing stratum corneum changes induced by surfactants j. ZHOU, R. MARK, T. STOUDEMAYER, A. SAKR, J. LEON LICHTIN, and KARL L. GABRIEL, Biosearch, Incorporated, Philadelphia, PA 19101 (J.Z., R.M., T.S., K.L.G.), and Cosmetic Science Program, College of Pharmacy, University of Cincinnati, Cincinnati, OH (J. z., A.S., J.L.L. ). Received July 5, 1990. Synopsis Biophysical, morphometric, and clinical methods were used to evaluate changes in the stratum corneum of human skin following repeated exposure to surfactants. The objectives of this study were to determine the relative efficacy and sensitivity of the various methods for assessing skin changes, particularly moisture content, water loss, and signs of irritation. The surfactants studied were sodium lauryl sulfate (SLS), sodium laureth-3 sulfate (SLES), and PEGo20 glyceryl monotallowate. The test surfactants were applied to the volar surface of the lower arm of healthy volunteer subjects twice a day for 45 minutes each for five consecutive days. The contralateral arm was similarly treated with water. Skin responses were evaluated each day after the second surfactant treatment, and a final evaluation was performed after a two-day rest. The evaluations included 1) instrumental skin moisture measurements of transepidermal water loss (TEWL), high-frequency electrical conductance and moisture factor with attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy 2) morphometric methods, including determination of skin reflectance and color, macrophotography, and image analysis of skin negative replicas and 3) visual scoring of erythema, scaling, and fissuring. These objective and subjective methods provided a spectrum of data documenting the progressive changes of the stratum corneum by the surfactants. Consistent changes were observed within each treatment group of six subjects. SLS caused marked adverse changes and SLES induced slight adverse changes. PEG-20 glyceryl monotallowate treatment resulted in minimal changes in the skin. The various evaluation methods generally showed good correlation but differed in their sensitivity. Repeated studies after three to four months on the same panel showed reasonable reproducibility of all evaluation methods. Seasonal variability was observed in the SLS-treated sites. INTRODUCTION Repeated and cumulative action of weak irritant agents on the skin are well established as factors in causing various skin conditions (1-3). Surfactants play an important role in the majority of cases (2-5). Although the mechanisms of surfactant-induced skin dam- age are not fully understood, skin damage caused by repeated exposure to surfactants is demonstrated by an increase in epidermal permeability (6-8), dryness and roughness 105

106 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS (9-10), and by the development of erythema and fissures (11). Numerous studies have been focused on the irritant effects of surfactants to elucidate the mechanisms of sur- factant-induced skin damage (12-14) and to compare the irritancy potential of different surfactants (15,16). Although visual grading continues to have an important role for evaluation, many recently developed noninvasive techniques provide more sensitive objective data useful in the investigation of irritant effects caused by surfactants (17-19). In this study, a battery of noninvasive techniques was used to assess the hydration conditions of the stratum corneum (transepidermal water loss measurement, high- frequency electrical conductance measurement, and attenuated total reflectance infrared spectroscopy) and the surface conditions of the skin (reflective color measurement, image analysis of skin negative replicas) following repeated exposure to some surfactants. Daily measurements using these methods provided data on the progressive changes of the stratum corneum and on the consistency and sensitivity of different evaluation methods. A repeat study using the same subject panel after a three-month interval provided data on seasonal influences of the irritancy potential of surfactants. This repeat study also confirmed the reproducibility of the evaluation methods. METHODS SUBJECTS The subjects were a group of 18 healthy Caucasian female volunteers, ages 30 to 45 years and free from skin diseases. A signed consent form was obtained from each subject before initiating the experiment. Six subjects were randomly assigned to each of three sub- groups. Each subgroup was treated with one of the surfactants. Information recorded from each subject included a brief history of the subject's skin conditions. Individuals with any of the following were excluded from this study: a) skin disease, b) severe skin dryness, c) ease of sweating, and d) ease of sunburn. Subjects were instructed to avoid hot tubs, swimming, and exposure to natural or artificial sunlight, and to refrain from applying any cleansing products, creams, lotions, or gels to their forearms during the study period. The subjects were otherwise permitted to follow their usual bathing procedures. All subjects in each subgroup completed two test cycles. Each test cycle was comprised of one week (five working days) of repeated exposures to the surfactant and daily evaluations. Each test cycle also included a pretest evaluation and a final follow-up evaluation, which occurred on day 8 (Monday of the following week). The time interval between test cycles was about three months for all subgroups. The first test cycle was performed during October and November 1989, and the second test cycle during January and February 1990. TEST MATERIALS The three surfactants chosen for this study were two anionic surfactants, sodium lauryl sulfate (SLS) and sodium laureth-3 sulfate (SLES), and one nonionic surfactant, PEG-20 glyceryl monotallowate. Both sodium lauryl sulfate (Sipon LSB ©) and sodium laureth-3 sulfate (Sipon ES/