24 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Clearly, the duration of effect may be even more important with so-called 'active' constituents. In practice, the need for clear evidence to show a substantive effect often becomes most obvious when the claims for a new cosmetic have to be justified to an adjudicating body. For example, an advertisement for a deodorant may suggest that one application will guard against perspiration odour for several hours evidence to substantiate such a claim will almost certainly be requested. Another example of the need for substantivity is the inclusion of an anticaries agent in a dentifrice. de Boever and Muhlemann (1) have shown that carious damage or dental decay is probably the result of long-term maintenance of a low pH inthe layer of plaque on the enamel. It follows from this that a prophylactic agent to counteract the acidity of the plaque, has to be persistent during a major part of the interval between toothbrushings. An antibacterial system, to control the plaque bacteria, also needs to show persistence in the oral cavity. This might be achieved by way of sub- stantivity to the dental enamel or to its organic coatings or to the oral soft tissues. L6e, Mandell, Derry and Schiott (2) have claimed successful results with chlorhexidine mouthrinses in plaque control and in calculus or tartar prevention. Recently, a clinical study on young adults has also shown significant reduction in dental plaque, using a mouthrinse containing 0.035•o of alexidine, an ethyl hexyl-bisguanide (3). One of the reasons for selecting this compound was its adsorption to dental enamel, which presumably helped to ensure its prolonged antimicrobial action. On the other hand, the usual idea that antimicrobial activity is the main requirement for dealing with the dental plaque has recently been challenged. A group working at the University of Tennessee (4) prepared a series of compounds representing dissected segments of the chlorhexidine molecule. They then proceeded to show that the adsorption of the chlorhexidine congeners on to hydroxy-apatite is closely matched by their surface activity in water or in a hexane-water system. In the view of these authors, anti- microbial activity may be less important than the surface-active effect of chlorhexidine they suggest that this may help to dissipate cohesive and adhesive forces in the dental plaque. The hair, once it has emerged from the scalp, is no longer a living tissue, but the concept of substantivity is still relevant. Hair-dyeing is an obvious example of a substantive process. The distinction between temporary, semi- permanent and permanent hair dyes simply indicates different degrees of substantive effect.

SUBSTANTIVITY OF COSMETIC INGREDIENTS 25 These illustrations may suggest that substantivity is always a desirable property but this does not necessarily follow. If a human tissue selectively removes a component from a topical application, perhaps with some degree of protein-binding or alteration of cell membranes, there is a distinct risk of toxicity. For example, the fact that cationic surfactants are highly sub- stantive to the tissues is undoubtedly responsible, in part, for the severe eye irritation they can cause (5). So it was very surprising to see a recent article in a Sunday newspaper on shampoos. The writer recommended using cetrimide solution, without any reference whatever to the dangers, in preference to the properly-tested shampoo brands on the market. The systemic toxicity of a topical application depends on the quantity applied, skin penetration, distribution in the body, metabolic transformation and excretion, in addition to any specific toxicity at a particular site. Whether toxic signs are actually seen in normal use of a product will depend not only on its inherent toxicity, but also on the balance between factors, such as the rates of skin penetration and excretion. This balance will determine whether toxic substances accumulate in the body. Enhanced retention of cosmetic ingredients on the body surfaces--that is to say, substantivity--will tend to increase the degree of exposure or, in other words, the effective dose-level. On the other hand, if substantivity is achieved in such a way that the 'active' constituent is localized on the skin without promoting absorption, toxicity could be reduced. Such localization will help excretion to keep pace with systemic absorption. The dynamic aspects of safety-in-use cannot usually be forecast on theoretical grounds. Hence there is likely to be a demand for increasingly more detailed toxico- logical evaluation. In fact, the study of absorption, blood levels, tissue distribution and excretion is now seen as being almost as important as the determination of toxicity itself. It should be recognized that, whenever substantive properties are sought by modifying the surface activity of a formulation, there could well be a risk of promoting skin penetration and raising blood levels. This is one reason why it is often contended that the toxicity of a formulation cannot be fully assessed from data concerning the individual ingredients. MEANS OF ACHIEVING SUBSTANTIVITY Substantivity involves mechanisms such as adsorption, ion exchange and chemical interaction. These mechanisms are too well-known to require explanation, but some aspects perhaps call for further discussion. For