SURFACTANT-SKIN INTERACTIONS 81 toward liposomal membranes. An aggressive component may be taken up into a mixed micelie and thus be prevented from interacting with the membrane, while the deter- gency of the surfactant mixture may be maintained. Lang and Spengler mathematically described the changing synergism of very simple surfactant/cosurfactant mixtures (9). More complex mixtures have so far eluded math- ematical treatment. The effect of a surfactant alone may differ greatly from its syner- gistic effect in a surfactant mixture. Modification of the action of one surfactant can often be achieved by the addition of a second. Figure 11 depicts a reduction in aggressiveness of sodium lauryl sulfate by the addition of increasing amounts of lauryl ether sulfosuccinate. Unexpected results were obtained from mixtures of SLES and Pluriol PE6400, a PO/EO block co-polymer. The interaction of the surfactant blend with the liposomes increased as the ratio of the nonionic com- ponent was stepped up from 20% to 50% (Figure 12). This may be due to the changing character of the surfactant-mixed micelies, i.e., the surfactant mixture takes on a more nonionic character and the correlation breaks down. DISCUSSION For the personal care and cosmetic industries it is very important to be able to offer the consumer the least irritating products and to be able to substantiate claims to this effect. A variety of in vivo and in vitro tests have, therefore, been developed (24) that range from the survival time of goldfish in surfactant solutions (25), chemical and biophysical changes in skin and isolated skin components (8,26,27), and damage to rabbit eyes in vivo (the Draize test) (2) to correlating irritancy with surface tension of surfactant solutions (28). Several other in vivo and in vitro methods have been described and assessed ......... SLS+O.B•SUCC .... ß .... SLS+4•SUCC I I I I I I I I I I I I X ourfactant Figure 1 l. Effect of surfactant mixtures (SLS/di-Na lauryl ether sulfosuccinate).

82 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS 2 -- toO-' 14 o.tl I I I I I I I I I I I I 0.0 O. o 0.4 0.8 0,8 I,,O t. o t.4 t.8 t.8 o.0 o.o o.4 • SLES/PLUR[OL 5: t .... ß .... SLES/PLUR[OL 3: t • SLES/PLUR[OL •: t --&----SLES/PLUR[OL •: t ß SURFACTANT Figure 12. Effect of surfactant mixtures (SLES/Pluriol PE6400). by Kastner and Frosch (29). None of them have been found to be entirely comprehensive and accurate. The Draize test has also aroused the ire of concerned consumers and laboratory personnel on humanitarian grounds. Skin irritancy has been correlated with the ability of a surfactant system to solubilize skin lipids (8,9), and damage to the lipid components of membranes has been shown to precede the involvement of proteins. Binding of detergent to protein is generally weaker than its binding to lipids, i.e., protein is solubilized only at detergent concentrations above the CMC (12). These facts indicate that phospholipid liposomes may, indeed, be a suitable model membrane system for the study of surfactant irritancy. It was, there- fore, important to develop a numerical index for the surfactant irritancy determined by the liposome assay, and this leads to the development of the "c-value" (see above) (Fig- ure 3). The irritancy ranking of most of the anionic surfactants and anionic blends tested in this study by the liposome method essentially parallels in vivo observations obtained for the same compounds by Toxicol Laboratories, U.K. (Figure 13). The data underlying Figure 13 are listed in Table I. The possible reasons for the poor correlation obtained for magnesium lauryl sulfate have been discussed above (see Counterion Effects). The correlation is generally poor or lacking for most nonionic surfactants, whereby one has to consider that in vivo scores are simplifications of extremely complex phenomena that may also be expressed with some subjectivity and are no longer universally con- sidered to be a comprehensive assessment of irritancy (10). Table II lists "c-values" for a variety of anionic and nonionic surfactants and mixtures that do not correlate with soap chamber scores. It may well be that the liposome technique does not measure primary irritation potential but total aggressivity. Surfactant aggressivity is composed of two factors, namely pri-