726 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS smells of the fatty acids, the 'fishy' odours of the amines and the astringency of ammonia. Often these are combined to produce the 'off' odours of a spoiled product. Changes in the aroma of a product due to contaminants vary from the production of a nauseating smell to a slight change in the bouquet but all can be disastrous, particularly to cosmetic and toiletry preparations which depend so much upon their specific perfumes. One of the most common olfactory warnings of spoilage is the typical smell of mould. The responsible aromatic elements have not been clearly identified but some actinomycetes which taint water with undesirable earthy odours have recently been shown to produce geosmin, a strongly earth-smelling, neutral oil (10). An alcoholic odour, produced from fermentable substrates, is typical of spoilage by yeasts. Taste Reports that products taste 'peculiar' are often the first indications that they may be spoiled. The sense of taste varies widely between individuals and these reports do not invariably indicate microbial contamination. For this reason, and because of the hazards involved, taste is not a practicable control procedure with which to detect spoilage at an early stage. Never- theless, the combined senses of smell and taste are highly perceptive to changes in flavour, particularly in bland, unflavoured, preparations where the presence of microbial metabolites is not masked. Margalith and Schwartz (11) have listed over 100 organic compounds involved in the pro- duction of flavour by micro-organisms. These consist mainly of alcohols, aldehydes, ketones, acetals, acids, amines, esters and phenols. Texture The feel of topical preparations, particularly cosmetic and toiletry ones, is vital to their acceptability but texture may be marred by contaminants. For instance, creams can become lumpy or 'gritty' and changes in viscosity of liquid preparations, which can be detected when applied to the skin, may occur. Audible effects Apart from immediate manifestations of toxicity, which happily appear to be rare, audible manifestations of spoilage are the most dramatic. If visible effects of spoilage are obscured by the pack, an explosion can be the

MICROBIOLOGICAL SPOILAGE IN PHARMACEUTICALS AND COSMETICS 727 first indication that a gas-producing micro-organism has successfully adapted itself to what may have been considered inimical conditions. TYPES OF SUSCEPTIBLE PRODUCT The range and composition of pharmaceutical and cosmetic products is so varied and the species, and even strains, of micro-organism capable of causing spoilage are so multifarious that, as we have already emphasized, each spoilage incident tends to be unique. Generalizations about sus- ceptible products are therefore likely to be inaccurate and are made more difficult today because of the inclusion, particularly in cosmetics, of in- creasingly sophisticated and often highly. biodegradable ingredients. Never- theless some types of product are more susceptible than others to spoilage by specific organisms and those of which we have experience are described below. Liquids Water Water is a major constituent of living material and participates in many metabolic reactions. Bacteria, in particular, require high concentrations of water in their immediate environment and may be regarded as aquatic organisms. Hence, all products containing large amounts of free water can be particularly susceptible to spoilage by bacteria. Water supplied by water undertakings in this country is of high micro- biological quality and is generally suitable for the manufacture of pharma- ceuticals and cosmetics. Low-conductivity water, whether prepared by distillation or deionization, may be chemically purer but can constitute a greater microbiological hazard. Distilled water leaving the still can readily pick up organisms from pipes and tubing and ion-exchange columns may actually serve as a reservoir of organisms because nutrient organic residues are not removed by the process. Without effective treatment to minimize contamination, water can, within a few days, contain large numbers of initially Gram-negative and Gram-positive bacteria, and subsequently a wide variety of bacteria, moulds and yeasts. At this stage visible and ol- factory spoilage occurs and a foul taste may develop. Indeed contaminated deionized water has often been incriminated as the original source of spoilage in a formulation. Often the responsible organisms are pseudo- monads which are not only highly resistant to preservatives but are also able to use the widest range of organic compounds as substrates.