668 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS microorganism is often more susceptible to antimicrol)ial action in the cosmet- ic than it is in a carefully selected nutrient medium. For these reasons• cos- metic chemists aud microbiologists should test what really •natters: the cos- metic itself. Nonionic emulsifiers are commonly used in eosinerie ereams. Unfortunately, they are also one of the most common causes of preservative failure. When used in low concentrations (e.g., below ca. 1%), they do not significantly in- terfere with preservative action. Usually, they are employed in concentrations higher than the critical mieelle concentration. Above this critical mieelle con- centration, the nonionic emulsifier forms aggregates, called "micelies," which constitute a new phase in the system and actually extract preservatives out of the other phases. If 5% nonionic emulsifier is added to a water-oil enmlsion, as much as 75% of the total methyl paraben preservative will locate in the nonionic emulsifier mieelle, leaving only 25% of the preservative to distribute between the oil and water phases (1). Some organic compounds form a coating around the microorganism and give the cell protection against chemical attack. Many components of cosmet- ics inaetivate or lower the activity of antimierobials by reacting with them, absorbing them, or dissolving them. Although the inaetivation is sometimes complete, often it is not, and some residual activity renmins. In the following comments the term inaetivated is meant to include both complete and partial inaetivation. Thus, anionie surface-active agents inaetivate eationies (i.e., quaternary ammonium compounds), phenolies, and mercurials. Proteins inae- tivate most preservatives: quaternary ammonium compounds, phenolies, mer- curials, and parabens. Antimicrobial agents are inaetivated by many different materials. Quater- nary ammonium compounds lose activity in the presence of lanolin, methyl cellulose, leeithin, tartaric add, silicates, kaolin, zinc oxide, and other com- pounds. Although quaternary ammonium compounds are effective antimicro- bial agents in screening experiments, they are not of general use in cosmetics. Parabens are bound up by various macromolecules, such as methyl cellulose and gelatin. Nonionic emulsifiers, especially those containing polyethyleneoxy groupings (e.g., Tweens ©*, Myrj©*, etc.), and many other coralnon ingredi- ents in cosmetics also tie up parabens and render them less available for anti- microbial action. The lesson to be drawn from all these possible complications is that a pre- servative system must be tested in the specific cosmetic product being studied. A related problem is absorption of preservative by the container used. Rub- her and plastics, especially polyethylene containers or caps, are ahvays suspect because lipid-soluble preservatives are capable of migrating into them. These effects can sometimes be predicted, but only microbiological challenge tests *Registered trademarks of ICI America Inc., Wihnington, Del.

COSMETIC PRESERVATION 669 over prolonged periods will prove the stability and efficacy of the preservative system. Certain components of a for•nulation can enhance the activity of a preserva- tive system. Some common cosmetic ingredients, such as many perfume oils, have antimicrobial properties. Various alcohols, aldehydes, and acids also have antimicrobial activity. Some preservatives are made more effective by the presence in the cosmetic of other ingredients. These enhancing ingredients may have little or no antimicrobial action of their own, but can facilitate antimicrobial activity. Alternatively, enhanced antimicrobial effectiveness may result from the use of two or more preservatives. Synergism in preservation means increased activity resulting from the use of two or more preservatives. In order to constitute synergism, the effect of the combination must be more than additive. Thus, combinations of parabens are superior to the individual parabens. This is generally acknowledged as synergism, although some people maintain that this is strictly a solubility ef- fect, i.e., the parabens are so poorly soluble in water that combinations merely permit a higher total paraben concentration. Another illustration of syner- gism is the combined preservative effectiveness of parabens with Germall©* 115, to be discussed later. Combining parabens with Germall 115 significantly increases the capacity of the preservative system to withstand microbial in- sult, and also widens the range of microorganisms against which the cosmetic is protected. COSMETIC PRESERVATIVES Selection of a suitable preservative or preservative system for a cosmetic must take into account the composition and intended use of the cosmetic. Firstly, the preservative must be compatible with the color and fragrance of the cosmetic, and with all the other components. Above all, there should be no inactivation of the preservative by components of the cosmetic. Secondly, the antimicrobial activity in the specific formulation must be determined. This is done by microbial challenge testing of the cosmetic. Thirdly, antimicrobials are by their nature active against living tissue and must be checked, in the specific formulation, for toxicity, irritation, or sensitization. There is no gain in replacing a microbial hazard with another, possibly worse, problem of toxicity. Fourthly, the preservative must be reasonably stable to storage. A preserva- tive which evaporates, like ethyl alcohol, or breaks down in alkaline medium, or reacts with the components of the cosmetic, as does formaldehyde, might not afford protection a few months later. Lastly, the preservative should not only be soluble in water but also have limited or no tendency to migrate into a nonaqueous phase, where it affords little or no protection. Bruch has listed "some of the more important chemicals which have found general acceptance as preservatives in cosmetic preparations" (9,). For more *Registered trademark of Sutton Laboratories, Inc., Roselie, N.J.