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

26 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS example, account should be taken not only of the surface activity of a product but also that of the skin and its secretions. The skin is, in fact, often regarded as being bathed in an emulsion of sebum, sweat and epider- mal remnants. The properties of this substrate will vary from the normal, for example, if a cosmetic is generally applied soon after the skin has been washed with soap and water or if it is used immediately after shaving. As already indicated, a clear example of substantivity is the relative ease with which cationic materials can be deposited on body tissues and retained there. There are many anionic sites available on the substrate with numerous carboxy groups available for interaction. A recent publication, by Janet Woodard (6) of Dow Chemical, describes the substantive properties of the polyethylenimines. These behave as cationics in an aqueous environment, owing to the many amino-nitrogens which become positively charged, especially at a pH of about 4. The addition of a polyethylenimine to a shampoo is claimed to result in uptake on the hair--especially on damaged hair--and to improve combability and manageability. It is of interest to consider also the behaviour of antiperspirants. In order to work at all, they must presumably have a substantive effect some- where in the eccrine sweat gland or duct. Kligman (7) has shown that dimethyl-sulphoxide (DMSO), a well-known agent for enhancing skin penetration, increases the antiperspirant effect of the customary aluminium salts. This finding is of theoretical interest although DMSO is probably too toxic for inclusion in an antiperspirant formulation in practice. In another paper (8), Kligrnan maintains that the aluminium salts inhibit sweating by converting the eccrine sweat duct into a so-called 'leaking hose' this prevents the sweat from reaching the skin surface. Others have tried to explain antiperspirant activity in terms of inhibiting the secretory portion of the eccrine gland, or blocking the opening of the eccrine duct. So, the fundamental nature of antiperspirant activity is still open to question. The lack of theoretical clarity makes it difficult to understand what kind of substantive action is really needed to improve antiperspirant performance, but obviously a long-term effect is desirable. As mentioned already, anticaries action may well depend on the principle of substantivity. Fluoride in the diet or in the drinking water is principally of benefit to infants and children up to about 8 years of age. By this time the enamel of the second dentition is almost fully formed, even though some of the permanent teeth have not yet erupted. Fluoride provided systemically dur- ing the course of enamel formation is built into the enamel as fluorapatite. Topically-applied fluoride, on the other hand, only affects the enamel surface.