HYGIENIC MANUFACTURE AND PRESERVATION * 725 2.2 The selection of a preservative system There is no satisfactory way of choosing preservative agents for a particular formulation on a theoretical basis or from a list of available compounds. Experimental determination of the efficiency of a preservative system is essential for satisfactory results. Furthermore, the choice and testing of preservatives should be regarded as an integral feature of pro- duct development it should not be left until formulation work is thought to be complete. The formulation chemist, packaging technologist, physical chemist, and microbiologist will need to reach a compromise, because the ideal product, the ideal preservative, and the ideal pack may well prove to be incompatible with each other. In the course of product development, the following aspects of preserv- ation will be important:-- 2.21 The preservative system should preferably act bactericidally and fungicidally in the actual product formulation concerned against a broad spectrum of possible contaminants. This activity should be achieved at all likely storage temperatures and in low concentration. 2.22 The preservative system should have adequate efficiency at a pH corresponding to that of the product formulation. 2.23 The preservative should have solubility and partition characteristics such that it is available in the aqueous phase of a biphasic system. Complete solubilization in an oily phase or in surfactant micelies can result in loss of bactericidal or fungicidal activity. 2.24 The selection of product ingredients providing carbon, nitrogen or sulphur sources which may be utilized as nutrients by contaminating micro- organisms, will increase the difficulty of achieving preservation. 2.25 Blends of more than one preservative often ensure synergistic or complementary activity certain blends in which only one compound has antimicrobial activity may also be of value, e.g. the saturation of micelies with a non-inhibitory compound having a partition coefficient higher than that of the inhibitor may limit the level of preservative needed. 2.26 Product ingredients tending to carry a significant level of contamin- ation should be avoided unless they are easily sterilized by heating or by a gaseous inhibitor such as ethylene oxide. 2.27 The physical, chemical and biological compatibility of preservatives with the other product constituents must be examined. For example, toxic or irritant effects on skin or mucous membranes might be encountered the

726 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS hazard of photo-sensitization should be taken into account. Other diffi- culties include instability on storage, odour deterioration, loss by volatiliz- ation and spoilage due to corrosion. 2.28 Association with biologically-active product constituents could result in unexpected changes in the antimicrobial properties of the product itself or in its toxicity towards the skin or mucous membranes. 2.29 The packaging should be designed to avoid (a) access of contaminants, (b) inactivation of preservative by the container or the closure, and (c) diffusion of preservative through the container or closure. As indicated above, a preservative agent should be selected for its broad spectrum of antimicrobial activity. The contamination problem can be exacerbated by using a narrow spectrum preservative which is itself susceptible to contamination by insensitive micro-organisms. This hazard must be precluded by appropriate testing. Since "self-sterilizing" capacity is a desirable target, the preservative system should preferably exhibit bactericidal and fungicidal rather than bacteriostatic and fungistatic activity. In practice, the objective is to achieve rapid destruction of a reasonable number of contaminants, the "inoculum" being kept within bounds by sound hygienic manufacturing arrangements. To insist on "self-sterilizing" capacity against all possible degrees of contamination would call for unduly high concentrations of powerful antimicrobial compounds the consequent hazard of eliciting adverse skin reactions would almost certainly exceed the risk of transmitting infection with a non-sterile product. Whilst the suggestions given in this section have been mainly directed towards safety aspects, the same considerations naturally apply to the avoidance of product spoilage (e.g. unsightly mould growth, development of "off"-odour) from an aesthetic or economical standpoint. The techniques required to deal with the problem of preservative selection are described in Appendix B. 2.3 Bacterial contamination of cosmetics subsequent to purchase Products supplied in containers allowing for the intermittent with- drawal of material are exposed to contamination each time the closure is removed in particular, they often acquire contaminants from the user's fingers. The health hazard to an individual user is probably limited but cross-infection could well occur owing to use by different members of a family unless the product has a relatively high level of "self-sterilizing"