670 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS complete data on specific preservatives, the series by Gueklhorn (3) should be consulted. Ethyl Alcohol Bruch (2) indicates that this compound is active against gram-negative bacteria at concentrations greater than 10%. Most other workers report that at ]east 15% ethyl alcohol is needed in acid solution, and at least 18% in neutral or alkaline media. Actually, even concentrations of 5 or 10% alcohol are use- ful, but these low concentrations are usually only bacteriostatic. Propylene glycol acts in a way similar to ethyl alcohol. Quaternary Ammonium Compounds. These compounds look very good in screening experiments with microbio- logical media although they are relatively ineffective against some gram- negative organisms, including pseudomonads. They have their best activity at about pH 7 to 8, and like hypoehlorites are useful for sanitizing equipment. Unfortunately, quaternary ammonium compounds are irritating to skin and eyes even at concentrations of a few tenths of 1%. They are inaetivated by many ingredients: anionies, nonionies, and proteins. Sorbic Acid Sorbic acid has been used in foods for over 25 years because of its low tox- icity. It discolors somewhat on storage and is only slightly soluble in water (about 0.16% at room temperature). Potassium sorbate, because of its high water solubility, is often used to incorporate sorbic acid. Potassium sorbate it- self, however, causes intense eye irritation. Problems that arise with the use of sorbic acid include: some skin irritation at use dilutions (0.15-0.20%), a pH dependence (half of sorbic acid is ionized at pH 4.8), and poor activity against bacteria. Sorbic acid is often ineffective in the presence of nonionics. It tends to migrate into fats and oils, although not to the extent benzoic acid does. Benzoic acid has a low solubility in water and is therefore usually in- corporated as its sodium salt. Because benzoic acid is a stronger acid, it is limited to use at pH's even lower than those usable with sorbic acid. Benzoic acid has higher activity against bacteria, as well as good activity against yeast and molds, and is less irritating to the skin than sorbic acid. Dehydroacetic acid, as mentioned previously, can be used at somewhat higher pH's than ei- ther sorbic acid or benzoic acid. Hexachlorophene Until recently, hexachlorophene was the most widely used antimicrobial in cosmetics. Its key property is substantivity, the ability to remain on the skin

COSMETIC PRESERVATION 671 after washing. The recent FDA action making hexachlorophene a prescription drug is well known. The disadvantages of hexachlorophene have been recog- nized for some time, and are common to phenolic antimicrobials in general. Phenolics are moderately-to-highly toxic and can be hazardous on damaged skin. In general, the antimicrobial activity of phenolics is limited to gram-pos- itive bacteria. They are poor preservatives for cosmetics, in part because they are often inactivated by nonionics, anionics, or proteins. Phenolics usually have low solubility in water, and are somewhat pH-dependent. With hexa- chlorophene, for example, when the solution pH is raised from 6 to 8, the anti~ microbial activity drops by 75%. Phenolics also tend to develop color in the presence of ferric salts. Although parabens are also phenols, they will be dis- cussed separately. Halogenated Salicylanilides These compounds are derivatives of salicylic acid, which is phenolic. Many of the problems of phenolics are therefore present: sparingly soluble in water, sometimes deactivated by nonionics, etc. The halogenated salicylanilides are substantive to skin and reportedly synergistic with hexachlorophene. They have therefore been used in deodorant soaps. Some of these derivatives are photosensitizers: they become toxic or allergenic when irradiated by ultra- violet light. As with most water-insoluble germicides used in antiseptic soaps, they make poor cosmetic preservatives. Formaldehyde Formaldehyde is cheap and has high antimicrobial activity. Although it has been used for mm)y years, it is now banned in Japan, Sweden, and several other countries. It is being phased out of almost all cosmetics in the United States. deNavarre (4) has pointed out the disadvantages of formaldehyde: "The undesirability of formaldehyde is manifold. It is volatile. It is highly re- active with many perfumery and cosmetic ingredients. It is irritating to skin. Its effectiveness decreases with age. It has an undesirable odor." Formaldehyde is chemically reactive, and it is not likely to remain un- changed over a period of weeks or months. Bryce and Smart (5) reported that when formaldehyde was put into a shampoo base (pH 5.5) at 0.12%, its concentration dropped to 0.031% after 10 weeks at 30øC. The loss of anti- bacterial power at pH 8, where formaldehyde has strong reducing properties, vas even more severe. Bronopol* (2-Bromo-2-nitro-l,3-propanediol) Bronopol, a water-soluble preservative with good antimicrobial activity, has several disadvantages. It is reasonably stable at pH 5.5 and can be used suc- *Trade name, Boots Pure Drug Co. Ltd., Nottingham, England.