730 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Ointments and oils As these are anhydrous materials, in theory they do not support the growth of micro-organisms. However, in practice they are often filled into jars or other containers with large air-spaces and this introduces the possibility of mould spoilage, as for creams, because these organisms can utilize atmospheric moisture. Whereas creams can supply moisture by evaporation, oils and ointments require the accidental ingress of water or the presence of a humid atmosphere. Fortunately a much smaller incidence of this kind of spoilage therefore occurs but we have seen a few examples of mould colonies on the surfaces of ointments, including white petroleum jelly, and ironically, fungicidal ointment. Oils are at a slightly greater risk than ointments as, being more fluid, they allow condensed water to carry organisms to the bottom of the con- tainer and remain trapped. Moulds have been reported to metabolize arachis oil and liquid paraffin (18, 19) and obnoxious odours, tastes and slimy deposits have been found in liquid paraffin while clumps of moulds, yeasts or bacteria have been seen in maize and olive oil. Without exception traces of water are found in these spoiled samples and the detection of foreign substances, such as food particles, often indicates the origin of the contamination. Shampoos Shampoos are particularly susceptible to contamination by a range of Gram-negative waterborne bacteria (20). Although they may support the growth of large numbers of bacteria without visible spoilage, slimy sedi- ments, pellicles, discolouration and odours are sometimes found and the loss of lathering properties has also been noted. Medicated shampoos are not immune from spoilage because the antimicrobial ingredients they contain often possess only a narrow spectrum of antimicrobial activity. It is almost impossible to keep shampoos away from the eyes of the user and con- tamination by invasive bateria such as pseudomonads must also render products of this type unfit for use, whether other spoilage has occurred or not. Syrups The sugar content of syrups inhibits the growth of many micro-organ- isms by virtue of its high osmotic pressure but osmotolerant moulds and yeasts are a source of trouble. Fermentation of the sugar by these organisms causes foul flavours due to the production of alcohol, lactic acid and other

MICROBIOLOGICAL SPOILAGE IN PHARMACEUTICALS AND COSMETICS 73l organic acids while the production of carbon dioxide leads to gassing and troublesome pressure increases (21). In addition, these products, including syrup B.P. and various syrup-containing cough remedies, can be spoiled by the presence of suspended or deposited osmophilic moulds. As with other products spoilage in syrup can be accelerated by an excessive air space in the container. Fluctuating storage temperatures then cause sufficient con- densation of water vapour to dilute the syrup at its surface so that growth can occur. Cork closures, now happily uncommon, have in the past provided the necessary inoculum of mould spores. Osmophilic organisms may also cause trouble in malt extracts which largely depend on their high con- centration of low molecular weight saccharides for preservation. The effect of a number of environmental factors on fermentation caused by Sac- charomyces rouxii in malt extract has been studied (22). Compounds formulated in syrup may be metabolized with the pro- duction of toxic substances. For instance Wills (23) isolated a species of Penicillium from a sample of Syrup of Tolu which smelled of toluene. He showed that this organism could grow on benzoic or cinnamic acid as a sole carbon source and that a toluene-like odour was produced from the latter. The toluene-like product was not characterized because of the presence of interfering substances but rupture of the unsaturated linkage in the cin- namic acid molecule could have yielded toluene itself. Tinctures, elixirs and linctuses In general, these formulations do not allow microbial survival because of their high concentrations of alcohol, sugars or glycerol. For instance, even in concentrations as low as 5•o, alcohol will kill most bacteria and moulds in time, while yeasts are generally killed at concentrations above 15}/o . Nevertheless isolated incidents of spoilage due to suspensions or deposits of dead mould have occurred. The organisms presumably grow in the container for a while before becoming immersed by the formulation and succumbing. Solids Raw materials Solid raw materials may serve as a source of contaminants which will later spoil a formulated product. Natural earths such as kaolin, bentonite, Fuller's earth or french chalk contain anaerobic spore-bearing rods, moulds or Gram-negative bacteria which can render a product objectionable or