14 Betty Croshaw any concentration of one preservative alone (v) convenience of use of smaller pre- servative amounts or economic savings may result. The author suggests that the combination of a highly active labile preservative with a less active but more stable one to control prolonged in-use contamination is a further justification for preservative combinations. Mixtures of parabens in place of a single ester have been used for a long time (64) claims for these mixtures, which are available commercially e.g. 2Vipasept, Nipastat, have varied from simple additive effects to potentiation (see 12). Probably the main advantage is that the solubilities of the individual esters in the mixture are independent of each other so that a higher total concentration can be used. More recently, t'henonip, a combination of parabens and t'henoxetol (phenoxy- ethanol), has been evaluated and found to be a potent, wide-spectrum liquid preservative effective in the presence of anionic surfactants and proteins. There is some loss of activity in nonionic surfactants, in which Phenonip is very soluble, but this can be offset by utilizing the solubilization to create higher concentrations of the preservative in the product (65, 66, 67). Examples of extension of the microbial spectrum are the combinations of parabens with compounds showing low antifungal activity such as Dowicil 200 and Bronopol. From our own experience a mixture of Bronopol and parabens can also be useful in some alkaline formulations where the Bronopol is effective as a labile preservative and the paraben will combat in-use contamination. Germall 115 is reported to act synergistically with other preservatives (51) it is certainly useful in combination with parabens but true synergy is a rare occurrence. The use of mercurials with parabens to reduce the toxicity of the former may be useful in some formulations (19). Parker suggested in 1973 that the use of multicomponent preservative systems on a rational basis was probably the only way to preserve the complex formulations in use (62). This is still true today and may well be for some time to come since our knowledge of preservatives and their mode of action is still largely empirical. We cannot, therefore, hope to design an individual preservative or combination of preservatives that will match up to the ideal. References 1 De Navarre, M. G. The Chemistry and Manufacture of Cosmetics, p. 145 (1941) (D. Van Nostrand Co. Inc., New York). 2 Smart, R. and Spooner, D. F. Microbiological spoilage in pharmaceuticals and cosmetics. J. Soc. Cosmet. Chem. 23 721 (1972). 3 Wedderburn, D. L. Preservation of emulsions against microbial attack. Adv. Pharm. Sci. 1 195 (1964). 4 Woodward, C. R. and McNamara, T. F. Microbiological considerations of cosmetic emulsions. Am. Perfum. Cosmet. 85 No. 3 73 (1970). 5 Yablonski, J. I. and Goldman, C. L. Microbiology of shampoos. Cosmet. t'erfum. 90 No. 3 45 (1975). 6 Bean, H. S., Heman-Ackah, S. M. and Thomas, J. The activity of antibacterials in two-phase systems. J. Soc. Cosmet. Chem. 16 15 (1965). 7 Bryce, D. M. and Smart, R. The preservation of shampoos. J. $oc. Cosmet. Chem. 16 187 (1965). 8 Tice, L. F. and Barr, M. Factors to be considered in the preservation of cosmetic emulsions. J. $oc. Cosmet. Chem. 9 171 (1958). 9 Malcolm, S. A. and Woodroffe, R. C. S. The relationship between water-borne bacteria and shampoo spoilage. J. Soc. Cosmet. Chem. 26 277 (1975). 10 Tenenbaum, S. Pseudomonads in cosmetics. J. Soc. Cosmet. Chem. 18 797 (1967).

Preservatives for cosmetics and toiletties 15 11 12 13 14 15 16 17 18 ß 19 McConville, J. F. and Anderson, D. W. Occurrence of t•seudomonas aeruginosa and Staphylococcus aureus in the orbital area. J. Soc. Cosmet. Chem. 26 169 (1975). Manowitz, M. Cosmetic Preservatives in Disinfection, Sterilization and t•reservation (Ed. by C. A. Lawrence and S.S. Block) 555 (1968) (Lea and Febiger, Philadelphia). Gucklhorn, I. R. Antimicrobials in cosmetics series. Manuf. Chem. Aerosol News, 40--42 (1969-1971). Bruch, C. W. Cosmetics: sterility rs. microbial control. Am. t•erfum. Cosmet. 86 No. 4 45 (1971). Gershenfeld, L. Antimicrobial agents in cosmetic preparations. Am. t•erfum. Cosmet. 78 No. 10 55 (1963). Parker, M. S. Microbiologically acceptable cosmetic. Am. Perfum. Cosmet. 86 No. 12 35 (1971). Tronnier, H. (Editorial) The Preservation of cosmetics. Soap, Perfum. Cosmet. 41 871 (1968). Coates, D. Preservatives--microbiological and physical factors. Manuf. Chem. Aerosol News 44 No. 6 35 (1973). Parker, M. S. A new generation of preservatives. Soap. Perfum. Cosmet. 45 621 (1972). Thomas, M. J. and Majors, P. A. Animal, human and 'microbiological safety testing of cosmetic products. J. Soc. Cosmet. Chem. 24 135 (1973). Manowitz, M. Preservation of cosmetic emulsions. Developments in Industrial Microbiology: Proceedings (Ed. by S. Rich) 2 65 (1961) (Plenum Press, New York). Charles, R. D. and Carter, P. J. The effect of sorbic acid and other preservatives on organism growth in typical nonionic emulsified commercial cosmetics. J. Soc. Cosmet. Chem. 10 383 (1959). Schorr, W. F. Allergic skin reactions from cosmetic preservatives. Am. t•erfum. Cosmet. 85 No. 3 39 (1970). Schorr, W. F. Cosmetic allergy--a comprehensive study of the many groups of chemical anti- microbial agents. Arch. Derre. 104 459 (1971). Bart, M. and Tice, L. F. The preservation of aqueous preparations containing nonionic surfactants. II. J. Am. Pharm. Ass. Sci. Ed. 46 445 (1957). Cainan, C. D. Contact dermatitis from drugs. t'roc. R. Soc. M'ed. 55 39 (1962). Marzulli, F. N. and Maibach, H. I. The use of graded concentrations in studying skin sensitizers: experimental contact sensitization in man. Food Cosmet. Toxicol. 12 219 (1974). Berke, P. A. and Rosen, W. E. Germall, a new family of antimicrobial preservatives for cosmetics. Am. t•erfum. Cosmet. 85 No. 3 55 (1970). Lyman, F. L. and Furia, T. Toxicology of 2, 4,4'-trichlorohydroxy-phenyl ether. Ind. Med. Surg. 38 45 (1969). Bean, H. S., Konning, G. H. and Malcolm, S. A. A model for the influence of emulsion formulation on the activity of phenolic preservatives. J. Pharm. Pharmacol. 21 Suppl. 173S (1969). Bean, H. S., Konning, G. H. and Thomas, J. Significance of the partition coefficient of a preserva- tive in cosmetic emulsions. Am. t'erfum. Cosmet. 85 No. 3 61 (1970). Wedderburn, D. L. Preservation of toilet preparations containing nonionics. J. Soc. Cosmet. Chem. 9 210 (1958). Coates, D. Interaction between preservatives and surfactants. Manuf Chem. Aerosol News 44 No. 8 41 (1973). Wedderburn, D. L. Interactions in cosmetic preservation. Am. t'erfum. Cosmet. 85 No. 3 49 (1970). Coates, D. Preservative/colloid interaction. Manuf. Chem. Aerosol News. 44 No. 10 34 (1973). Coates, D. Interaction between preservatives, plastics and rubbers. Manuf. Chem. Aerosol News 44 No. 12 19 (1973). Tuttle, E., Phares, C. and Chiostri, R. F. Preservation of protein solutions with 2-bromo-2-nitro-1, 3-propanediol (Bronopol). Ant. t•erfum. Cosmet. 85 No. 3 87 (1970). Schuster, G., Modde, H. and Riepl, G. Experimental studies on chemical preservation of poly- peptide-containing substances. Am. t'erfum. Cosmet. 81 No. 6 39 (1966). Horn, N. R., McCarthy, T. J. and Price, C. H. Interaction between preservatives and suspension systems. Am. t•erfum. Cosmet. 86 No. 7 37 (1971). Parker, M. S. and Barnes, M. The interaction of non-ionic surfactants with preservatives. Soap t•erfum. Cosmet. 40 163 (1967). Coates, D. and Woodford, R. Methods available for studying antimicrobial interaction in cosmetics. Cosmet. t•erfum. 88 No. 4 43 (1973). Parker, M. S. The activity of preservatives in complex formulations. Soap t•erfum. Cosmet. 47 123 (1974). Anonymous. Dimethoxane, a new preservative effective with nonionic agents. Am. t•erfum. Cosmet. 77 No. 12 32 (1962).