672 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS cessfully at low pH's, but it breaks down at neutral or alkaline pH's to give formaldehyde and one or more bromo compounds. It develops a yellow or brown color on exposure to light, especially in alkaline solution. Solutions of Bronopol should not be heated. Bronopol tends to migrate into certain oil phases. Dowicil©* 200 Dowicil 200 is a water-soluble antimicrobial which is active against bac- teria. It is somewhat less effective against yeast and mold. Solutions of Dowi- cil 200 become yellow on aging and sometimes cause color changes in the cosmetic. The powder decomposes when heated above 60øC, and solutions containing Dowicil 200 should not be held at elevated temperatures. Dioxin©t (6-Acetoxy-2,4,-dimethyl-m-dioxane) Dioxin is soluble in water, and is reported to have good activity against gram-negative organisms as well as gram-positive organisms. Unfortunately, it has a powerful mustard-like odor which is almost impossible to mask. Be- cause of this odor, it is seldom used in cosmetics. Dioxin hydrolyzes slowly in xvater to form acetic acid, which tends to lower the pH. Also, it is quite solu- ble in oils and organic solvents so it can migrate out of the water phase into an oil phase. Organic Mercurials The most common organic mercurials are the phenyl mercuric salts: ace- tate, benzoate, chloride, and nitrate. Mercurials attack both the cell membrane and thiol groupings on enzymes within the cell. The strong affinity of mer- cury for sulfur means that sulfur-containing components of a cosmetic, such as certain proteins, sulfides, amino acids, can inactivate the mercurial. Anionic surfactants diminish the activity of mercurials, and an irritating hydroxide precipitates at pH's above 8.5. Barring such inactivation, mercurials are effec- tive at low concentrations against a broad spectrum of microorganisms. The problem of toxicity (mercury is toxic at 10 mg/kg) has led to its recent elimi- nation as a preservative from all cosmetics except eye cosmetics. A recent survey by the Cosmetic, Toiletries and Fragrances Association found that, except for eye products, virtually no mercurial preservatives are now in use. Parabens (p-Hydroxybenzoatcs) The parabens are the most widely used cosmetic preservatives. They are p- hydroxybenzoic acid esters, and the name of the paraben reflects the alkyl *Registered trademark of Dow Chemical Company, Mid]and, Mich. tRegistered trademark of Givaudan Corporation, New York, N.Y.

COSMETIC PRESERVATION 673 group on the ester: methyl paraben, ethyl paraben, propyl paraben, etc. The solubility of parabens in water is only about 0.25% for methyl paraben, and progressively lower as the alkyl group becomes larger. They are relatively nontoxic and nonirritating although saturated solutions may cause some irri- tation of the eye. A few cases of skin sensitization have been reported, but problems with parabens have generally arisen only where unreasonably high concentrations were used. The authors feel that parabens have a valuable role to play in cosmetic preservation at modest concentrations-that is, at or below a total of 0.3%. Like other phenols, parabens are more active against gram-positive than gram-negative organisms as such, they are poor against pseudomonads. Parabens are less active against bacteria in general than against yeast and molds although the individual parabens differ in this property. Parabens are inactivated by nonionic emulsifiers, proteins, and many other common cosmetic components. It was pointed out above that micelies of cer- tain nonionic emulsifiers absorb most of the paraben, leaving only a small amount to be partitioned between oil and water phases. Because parabens are oil-soluble and water-insoluble, they tend to partition in favor of, or migrate into, the oil phase. Polyethylene containers absorb parabens, and various mac- romolecules, such as PVP, polyethylene glycol, and methylcellulose, bind them and dinfinish their preservative activity. The parabens have become popular because they are only slightly ionized under alkaline conditions. About two-thirds of the paraben is undissociated, and therefore active, at pH 7, and about half is undissociated at pH 8.5. One must remember, however, that in strongly alkaline solution, parabens gradual- ly hydrolyze to their carboxylic acids, which are then almost completely ionized, and therefore inactive. Combinations of esters are more effective than single parabens, and para- ben combinations are offered commercially. It is the authors' opinion that a great potential for parabens lies in their use in combination with Germall 115. Germall 115 (Imidazolidinyl Urea) Germall 115 is nontoxic, nonirritating, and nonsensitizing (6), and is com- patible with almost all cosmetic ingredients. Its water solubility is very high and its oil solubility is very low. It is colorless, odorless, and tasteless, and is not pH-dependent. Germall 115 is more active against bacteria than against yeast and molds. It is active against both gram-positive and gram-negative organisms. Against yeast and molds it is selectively effective, i.e., good against some, poor against others. A key property of Germall 115 is its ability to act synergistically with other preservatives, resulting in a preservative system which gives not only a wider range of protection against microbial insult, but also a greater preservative capacity.