CHELATING AND SEQUESTERING AGENTS IN COSMETICS 99 These factors can change the order but it generally runs something like this: ferric iron, chromium, copper, nickel, zinc, lead, ferrous iron, man- ganese and then the alkaline earth metals: calcium, magnesium, stron- tium, and barium. Because of the situation described above, it must be emphasized that under any specific conditions tests must be made to determine which metal will be chelated first. In general, the stability of the EDTA complex de- creases as the pH is lowered and increases, especially for divalent metals, as the pH is increased. This is not particularly important in application to cosmetic products as they are all in the range of relatively stable pH. It has already been pointed out that there was no oxidation or reduction in the complexing or chelation of metallic ions. However, the Redox potential is greatly affected when polyvalent ions are chelated. The Redox potential of ferric iron is reduced somewhere in the neighborhood of one-half when it is complexed with the EDTA. This reduces its value below the mi,•imum value required to oxidize fats and oils so that the iron EDTA complex is comparatively inert when it is in a fatty material. One of the newer developments in fats and oils refining is the use of EDTA or its salts in the wash water during the refining process. In this way, most of the metallic contamination in the fat and oil is removed and any remaining is inactivated when it is complexed. This brings up the question of toxicity and irritation. Federal food and drug legislation permits the use of ethy- lene diamine tetraacetic acid salts in pharmaceuticals. For example, it is used in ascorbic acid tablets in order to tie up trace metals which cause catalytic oxidation during storage. There is extensive use of EDTA salts in soaps and in the textile field. This practical usage, along with many tests, has shown that EDTA is no more irritating than ordinary soap. The only way in which it is toxic to warm blooded animals is due to the fact that it will chelate calcium in the blood and cause illness or death by calcium tetany. On the other hand, if the calcium complex is used instead of EDTA, there is little, if any, noticeable toxicity. It has several possible medical uses. For instance, lead is chelated and tied up so that it has little toxicity and the body can excrete it. On the other hand, EDTA seems to have no effect on copper in the body. This, apparently, is due to the fact that body chemistry can form stronger complexes with copper than can EDTA, while EDTA forms stronger complexes with lead than can the natural chelating agent in the body. Coming back to a comparison of EDTA salts with polyphosphates, the latter show some of the following limitations: 1. They are not active at extreme dilutions. 2. Polyphosphates retrograde to orthophosphates which are ineffec- -rive especially in dilute solutions. 3. Polyphosphate complexes are less stable than EDTA complexes.

100 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS 4. Polyphosphates do not combine readily with all of multivalent metallic ions. On the other hand, the polyphosphates have the obvious advantage of cheapness and bulk which recommends them for such products as bath salts. But EDTA is effective at extreme dilutions and this is the condition needed in cosmetics. EDTA chelates are stable not only in extreme dilutions but they are stable also in hot acids or bases for indefinite periods of time even in extreme dilutions. EDTA forms stable complexes with all the di- and trivalent metals. Complexes are also stable under all conditions encoun- tered by cosmetics, such as pH range, manufacture and storage, and use. The EDTA complexes are more stable than those of the phosphates since the degree of ionization is nil or exceedingly small. The textile industry has accepted EDTA and its salts with open arms. I want to discuss some of these applications, especially, because of the points of similarity between wool, human hair, and even skin. All are chelating agents for metals by virtue of their amino acid building blocks. In the processing of textiles, the mill may soften water by zeolite softeners. But since wool and cotton both contain calcium, magnesium, and iron, placed there by nature and also due to soil, it is necessary to add something else to the processing waters to act as a scavenger for these trace contaminants. The characteristics of the EDTA salts make them perfect for this scaveng- ing action. Otherwise, these metal ions form insoluble soaps with the scrub- bing soaps or by reaction with fatty soil present if detergents only are used in cleaning. These insoluble hard water soaps interfere with the evenness of dyeing and other processing. Calcium, magnesium, and especially iron, cause serious interference in the dye bath resulting in varying shades of dyeing and uneven dyeing. When using a product like EDTA one of the first questions to arise is: How much will be required? In most cases this can be calculated stoichiometrically. However, in some acid solutions as much as two or three times of the theoretical is required. Also, in chelating iron in strongly alkaline solutions, an amount beyond the theoretical is re- quired. Since these EDTA salts are so very stable, it is not necessary to add an additional quantity to make up for possible decomposition or break- down on standing. On the other hand, it is desirable to add enough EDTA to ensure chelation of the maximum amount of trace metal ions which can be expected to occur. As an example, the molecular weight of calcium car- bonate is 100 while that of ethylene diamine tetraacetic acid is 292. This means that approximately 3 gm of ethylene diamine tetraacetic acid, or of its salt on the EDTA basis, will completely chelate 1 gin. of calcium cal- culated as calcium carbonate. There is one application very close to the cosmetic field. This is the use of a fraction of a per cent of EDTA salt in soap bar stock. The soap. manufacturer will frequently call this an antioxidant. Actually, it is not