134 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS LINE EQUATION = 3.203 't- O.04X -I- 0.0144X r =0.93 100/0 75/25 50/50 25/75 0/100 Ratio LAS/AEOS-3EO Figure 5. Crosswise swelling of human stratum corneum by mixtures of LAS and AEOS-3EO. Ratios shown are weight ratios of LAS to AEOS-3EO. Total surfactant concentration of the mixtures was 0.15% (w/w), while ratios of the two surfactants varied as shown. Incubation time was 1 hour. Swelling values are percent increases from hydrated lengths and are means + S.D. Reduction in swelling was statistically significant, P • 0.05. DISCUSSION IMPORTANCE OF CONCENTRATION DEPENDENCE AND REVERSIBILITY The shape of the concentration curve for the stratum corneum swelling response to SLS (Figure 1) suggests saturation of binding sites or of the stratum corneum surface area. The fact that apparent saturation for SLS occurs around 8 raM, which is the CMC of this

SURFACTANT SWELLING OF STRATUM CORNEUM 135 Table IV Effects of Ethoxylated Alcohol Sulfates and Amphoterics on SLS-Induced Stratum Corneum Swelling Stratum Corneum Swelling** (% increase from hydrated length) Experiment No. Treatment* 1 hr. 3 hr. 6 hr. 1 1% SLS 31.0 ñ 3.9 43.5 ñ 3.2 46.1 _+ 3.6 1 1% SLS + 1%AEOS-3EO* 14.0 ñ 1.0 18.0 -+ 1.8 21.6 ñ 1.3 1 1% SLS + 1%AEOS-6EO* 13.5 ñ 3.7 16.7 ñ 3.4 19.1 ñ 3.6 2 1% SLS 29.4 -+ 4.4 39.0 - 4.9 46.8 ñ 4.1 2 1% SLS + 1% LDAO* 5.7 ñ 0.9 7.6 ñ 1.4 7.7 -+ 1.7 2 1% SLS + 0.5% LDAO* 13.0 ñ 3.5 21.0 --- 6.8 25.8 ñ 8.4 2 1% SLS + 1% Betaine* 10.9 - 2.4 17.0 ñ 3.8 21.0 ñ 4.4 2 1% SLS + 0.5% Betaine* 20.0 ñ 4.8 29.0 ñ 4.0 34.5 ñ 4.2 * Values are means ñ S.D. AEOS-3EO, AEOS-6EO, lauryl dimethyl amine oxide (LDAO), and coco amidopropyl betaine when tested alone at 1% w/w all produced small or negligible increases in swelling above the hydrated lengths (i.e. equal to or less than 5% increase in 6 hours). All treatments caused a significant reduction in swelling compared to 1% SLS treatment alone (P • 0.01). ** Times shown are incubation times after which readings were taken. surfactant, also suggests that the swelling response may be primarily due to surfactant monomer (or submicellar species) as discussed by others (3). This is reasonable since SLS micelies would presumably be too large (aggregation number is approximately 80) to penetrate the membrane. Observed increases in surfactant-induced swelling with time suggest continuous disruption of the secondary and tertiary structure of keratin proteins resulting in expo- sure of new binding sites. Reversibility of the swelling supports this view. Reversible interactions with skin lipids may occur, although one would expect that the lipids would be extracted by the surfactant and that this type of reaction should render the system irreversible, which is not the case under these conditions. Disruption of protein structure by surfactants as part of the swelling mechanism was also suggested by Scheu- plin and Ross (13) and Putterman eta/. (3) and may explain the edge curling phenom- enon observed by Tavss eta/. (4). Examination of the effects of systematic variation of surfactant structure on stratum corneum swelling allows some conclusions regarding the parameters controlling swelling and the mechanism of irritation by surfactants. These are discussed in the following sections. EFFECT OF INCREASING THE EXTENT OF ETHOXYLATION Increasing the extent of ethoxylation of alkyl (C12-C14 average) sulfate reduced swelling. This may be explained by several factors. Increasing the degree of ethoxyla- tion increases the molecular size of the penetrating species. Thus rate of penetration of the larger molecules into the matrix will be more difficult. Along with this, the critical micelie concentration decreases with increasing ethoxylation thus the submicellar levels of surfactant are lower for the higher ethoxylates. These factors taken together are con- sistent with the results.