148 JOURNAL OF COSMETIC SCIENCE Table II Predicted Total Surfactant Monomer Concentration, C• (mM), for the Mixtures of SDS and C12E6 in 0.1 M NaC! at the Various SDS Concentrations and Solution Compositions (%) Used for the SDS Skin Penetration Experiments (30,31) % 25 mM SDS 50 mM SDS 100 mM SDS 1 0.850 0.864 0.877 0.83 0.683 0.695 0.707 0.50 0.266 0.270 0.276 corresponding to the dose-dependent SDS skin irritation potential observed by other researchers (2,3,8,13,16,18). However, it should be noted that, in this paper, we have not measured the amount of C12E 6 that penetrates into the epidermis. Therefore, we did not ascertain whether the interaction between CliE 6 and the SC is indeed mild. In this respect, experiments by de la Maza et al. have shown that nonionic surfactants can have a strong effect on reducing the barrier properties of SC lipid bilayers (19,40). However, other researchers have observed that nonionic surfactants tend to have a smaller effect on the skin than SDS (3,39,41). Therefore, although the assumption that C12E 6 is benign irritation-wise may not be entirely accurate, it is expected that the skin irritation potential of SDS should overwhelm that of C12E 6. An investigation of the skin irritation potential of C•2E 6 is underway, and the results of this investigation will be reported elsewhere. Based on the premise that the skin irritation induced by SDS is related to the concen- tration of SDS in the epidermis, we measured whether adding C12E6 to a fixed SDS concentration (50 mM) in the contacting solution would reduce the concentration of SDS in the epidermis after five hours of exposure, C•ki,, and consequently, reduce the skin irritation potential of the surfactant solution. The purpose of conducting the experiments at a fixed SDS concentration is to ensure that any observed decrease in Cski, upon the addition of C•2E 6 would not result from the decrease in the total SDS con- centration in the contacting solution, but instead would be related to changes in the solution behavior of SDS. Figure 1 shows that as o• s is decreased by adding more C12E6 to the contacting solution, C•i, decreases. The observed decrease in C,•, as o•s decreases is consistent with reported observations of the reduced skin irritation potential of surfactant mixtures, provided that Cs•, is related to the observed skin irritation (6,24,26). EFFECT OF INCREASING % ON THE ABILITY OF MICELLAR SDS TO PENETRATE INTO THE EPIDERMIS There are two plausible mechanisms responsible for the decrease in C,•i, observed in Figure 1: (i) the addition of C12E6 reduces the SDS monomer concentration, as predicted by the monomer penetration model, and (ii) the addition of C12E6 reduces the ability of the miceliar SDS to penetrate into the epidermis, as predicted by our recently proposed micelie penetration model (28). It is entirely possible for both mechanisms to act simultaneously. In view of that, we conducted the following experiments to clarify whether mechanism (ii) was involved in the reduction of C•k•, observed in Figure 1. We tested whether mixed micelles present in the SDS/C•2E 6 surfactant mixtures could

PENETRATION OF MIXED MICELLES INTO THE EPIDERMIS 149 •5 1.00 0.83 0.50 Solution Composition of SDS, as Figure 1. The effect of decreasing the composition of SDS, %, in the contacting solution on the concen- tration of SDS in the epidermis after a five-hour exposure (Cj/•,,,) to solutions containing 50 mM SDS and increasing concentrations of C12E6 . The error bars reflect a 95% confidence interval based on six samples of each composition. penetrate into the epidermis by maintaining a constant o• s value and increasing the total surfactant concentration in the contacting solution. In general, the ability of micelies to penetrate into the skin can be determined by measuring how increasing the total surfactant concentration beyond the CMC, at a fixed (x s value, affects the amount of surfactant penetrating into the epidermis (28). If the surfactant concentration in the epidermis is found to increase, then surfactant in miceliar form contributes to surfactant penetration into the epidermis. Conversely, if the surfactant concentration in the epi- dermis is found to remain constant, then surfactant in miceliar form does not contribute to surfactant penetration into the epidermis, in which case the surfactant penetration should obey the monomer penetration model. The SDS/C•2E 6 surfactant mixtures that were investigated had solution compositions of % = 1, 0.83, and 0.50. Figure 2 shows the effect of increasing the total SDS concen- tration in the contacting solution (from 25 mM to 100 mM) on C,,•i , at these three fixed % values. As shown in Tables I and II (30,31), for each value of % over the range of surfactant concentrations examined, %n = O•s, O• is constant and C• is approximately constant. Therefore, any observed increase in C.,3.i, as the total SDS concentration in- creases for each % value examined can only be attributed to the penetration of miceIlar SDS into the epidermis, because only the micelle concentration is increasing. (Recall that the SDS monomer concentration is equal to oqC•, which remains constant, while the concentration of SDS in miceIlar form is equal to %n(Ct - C•), where C• is the total surfactant concentration, which increases in this case.)