SUBSTANTIVITY OF COSMETIC INGREDIENTS 29 pitfalls. There is, for example, a possibility of the tracer becoming detached from the parent substance. Tracers other than isotopes are often suspect for this reason. For example, if an oil-soluble dye is used as a means of demonstrating the substantivity of an oil to the skin, one must always consider whether the dye is preferentially taken up by the skin. Indeed, it could well be argued that tracer studies will only be convincing if we are able to demonstrate the continued association of the tracer with the parent substance. If this view is taken, the effort might just as well be devoted to developing good assay procedures for the parent substance itself. Radio-isotopes are perhaps not so easily separated, or so suspect in consequence. Even so, they can still be misleading, because exchange with a stable atom can have the same effect of dissociating the tracer from the labelled material. An experienced radio-chemist, on the other hand, should be on the look-out for this type of spurious answer. The most promising area for developing in vivo techniques to study substantive behaviour on human tissues is, undoubtedly, the use of non- radioactive or stable isotopes such as carbon-13, nitrogen-15 and oxygen-18. Mass spectrometry makes possible the sensitive monitoring of these isotopes. Since radioactivity is not involved, it is permissible to carry out human studies (14) even with pregnant women and with children, which would be too hazardous using, say, the carbon-14 label. The toxicity of the material labelled with a stable isotope will be no greater and no less than that of the unlabelled material. This is potentially of unique interest for cosmetics, where radiobiological studies cannot usually be justified in terms of a positive benefit-to-risk ratio. One of the main limitations on the development of stable isotope studies is the availability of a wide enough range of suitably labelled compounds. No doubt these will be forthcoming in due course and some very promising investigations will then become feasible which would be virtually impossible by current methods. The need for a positive demonstration of persistence should be em- phasized. Data are sometimes offered showing, for example, the depletion of a compound from a solution in contact with the skin it is then argued that, since the concentration of the solute has decreased, this must have been taken up by the substrate. This type of negative reasoning is unsatis- factory, because it gives no information as to persistence. Although it would be more relevant to demonstrate by chemical assay or tracer technique that a material does persistently associate itself with the appropriate substrate, even this does not give the whole answer. Generally, it must also be shown that the intended property is conferred. For example, it is not enough to

30 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS show the presence on the hair of protein derived from a protein shampoo its ability to effect a so-called 'repair' of split-ends will need to be confirmed. The in vitro demonstration that ingredients of a formulation can be sub- stantive to the skin, hair or teeth is certainly of value to the researcher such a demonstration will indicate whether biological or clinical studies are likely to give a favourable result. To convince others--especially adjudicat- ing bodies-- the biological or clinical evidence will generally have much greater impact. CONCLUSIONS Attention is often drawn to the risk of upsetting the ecology of the skin and of the oral cavity. Recent evidence (15) confirms that certain, relatively harmless, strains of bacteria on the skin may be important as a protection against other bacteria of pathogenic significance. The successful achievement of bactericidal or bacteriostatic activity on the skin, for cosmetic purposes, might conceivably prove quite hazardous it might increase the risk of contracting a serious clinical infection. Substantivity, in other words, is a feature involving benefit and risk and we must be fully aware of both possibilities. Cosmetic science today is facing a powerful challenge. On the one hand, we are accused of charging high prices for products offering little benefit. On the other hand, the use of relatively potent ingredients generates pro- blems on the question of toxicity. There is no easy way out of this dilemma, but it does seem essential to seek ways of genuinely improved product performance, without recourse to powerful pharmacologically-active in- gredients. By way of illustration, this review is intended to suggest that a thorough consideration of substantivity may well open up some promising avenues. (Received: 29th December 1972) REFERENCES (1) de Boever, J. and Muhlemann, H. R. pH ofinterproximal plaque with regard to continuous sucrose application. Helv. Odontol. Acta 13 97 (1969). (2) L6e, H., Mandell, M., Derry, A. and Schiott, C. R. The effect of mouthrinses and topical application of chlorhexidine on calculus formation in man. J. Periodon tal Res. 6 312 (1971). (3) Barnes, G. P., Carter, H. G., Gross, A., Bhaskar, S. N., Schildt, N. N. and Bush, A. G. Dental plaque reduction with an antibacterial mouth rinse. Part I. Oral $urg. Oral Med. Oral Path. 34 553 (1972). (4) Quintana, R. P., Fisher, R. G. and Lasslo, A. Surface-active factors in the efficacy of chlorhexidine against plaque. J. Dent. Res. 51 1687 (1972).