SUBSTANTIVITY OF COSMETIC INGREDIENTS 27 Studies on fluoride uptake by Weatherell (9) and his colleagues at Leeds, suggest that soluble fluorides at the levels included in typical fluoride toothpastes only give a negligible uptake into sound enamel. Much greater incorporation seemingly occurs if the enamel has been partially demineral- ized in an acidic buffer. The effectiveness of fluoride toothpastes has been confirmed in numerous clinical trials. Weatherell's findings indicate that they may function mainly by arresting the progress of 'incipient' carious lesions that is, these toothpastes greatly increase the fluoride content of enamel if it has been partly demineralized by acid from the dental plaque. This line of reasoning also suggests that artificial means might be employed to 'condition' the enamel surface, so that its fluoride uptake is enhanced. Katz, Muhler and Beck (10), in fact, have indicated two main ways to attempt this, (a) by formulating a dentifrice with a relatively low pH or (b) by treating the enamel with a sequestering agent for calcium ions. Some doubt is cast on the idea of conditioning the enamel by a recent paper from Aasenden, De Paola and Brudevold (11). In a clinical study on 8-11-year- olds, they observed equal protection against caries by daily rinsing with either a neutral sodium fluoride solution or an acidulated phosphate-fluoride preparation with a similar fluorine content. Enamel biopsies showed a greater uptake of fluoride from the acidified rinse but evidently the difference was not enough to improve the anticaries performance. So it seems rather unlikely that the anticaries effect of a fluoride toothpaste could be greatly improved by formulating an acidic or calcium-chelating preparation. In any event, the deliberate promotion of enamel demineralization in order to enhance fluoride uptake must obviously be employed with discretion, to avoid causing serious damage. Another long-standing attempt to achieve substantivity--namely, with the silicone oils--is aimed at blocking the effects of other substances on the skin or elsewhere. For example, silicones are used in hand creams to counter- act the degreasing effect of detergents. Cosmetic formulators greeted the silicones with high hopes when they first appeared. The results have often been disappointing but the fault may have been due to unsuitable formula- tion, rather than to failings in the silicones as such. The silicones have featured in a number of attempts to deal with the dental calculus problem. The aim here is not so much water-repellancy as the prevention of crystallization on the tooth surface. The two concepts may well be interconnected. However, the tooth surface is always exposed to an aqueous medium, the saliva, which has excellent wetting properties. A bacterial plaque is rapidly formed on the enamel. Extracellular dextrans

28 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS resulting from bacterial metabolism ensure good adhesion of the plaque. If the saliva is supersaturated with respect to calcium and phosphate, the plaque begins to calcify at this stage it is almost impossible to avoid the attachment of crystal nuclei to the enamel. Tamas (12) ingeniously sought to augment the water-repellent effect of the silicones by including an organo-titanium compound, as used in the waterproofing of paper, e.g. o-butyl titanate. He believed this would improve the bond between the enamel and the silicone. It is arguable whether his composition really was capable of inhibiting calculus deposition under practical conditions even so, the concept of using a coupling agent of the organo-titanium type is an attractive one in theory. There would seem to be considerable scope for the synthesis of molecules capable both of adsorbing or otherwise persisting on a tissue substrate and also of 'holding' the active constituent, that is, to serve as a 'bridge'. An illustration of this principle is described in a recent article by Sardo (13). The co-polymerization of an organic titanate, such as tetra-isopropyl titanate, with a dimethyl siloxane at room temperature is said to provide a hair spray resin which offers good curl retention, combing and non-flaking properties. It is also substantive enough to the hair to withstand several shampoos. Many dyestuffs and antiseptics obviously have substantive properties. Their ability to stain tissues and to damage micro-organisms points to their substantivity, often with beneficial results clearly there may also be a toxic hazard, by damaging human cells. The search for skin-substantive germi- cides led to many promising compounds such as hexachlorophene, bithionol, trichlorocarbanilide and the halogenated salicylanilides. In almost every instance, there have been discouraging suggestions of toxic potential, even though harm to man during cosmetic usage may have been rare. Such toxicity cannot be directly attributed to substantivity of the antibacterial but this may well represent a contributory factor. DETECTION AND ASSESSMENT OF SUBSTANTIVITY Because the term 'substantivity' has no precise meaning in terms of a distinctive physico-chemical property, it is hard to generalize with regard to methods of detection and assessment. The use of a radioactive isotope as a tracer ought to be ideal for qualitative and quantitative verification. The technique of autoradiography is specially useful for demonstrating sub- stantivity this is particularly true when a sequence of autoradiographs provides clear evidence of persistence. Tracers, however, are not without