98 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS the correct pronunciation of this term. Now, generally it is the di- sodium salt of ethylene diamine tetraacetic acid which would tie up the calcium. After the usual type of a salt reaction, there is a further sharing of electrons between the divalent metal, like calcium, and the two nitro- gens. This results in an inner ring complex which is so stable it is very slightly, if at all, ionized. I believe some definitions are in order so that we may be more specific in our thinking: 1. A chelating agent is one which can inactivate a multivalent ion by making it an integral part of an inner ring structure. 2. A sequestering agent is one which inactivates a metallic ion by form- ing a water-soluble complex in which the metal is held in non-ionizable form. 3. A complexing agent is one which can inactivate a metallic ion. If the resulting complex is soluble, then it is also a sequestering agent. Ethylenediamine tetraacetic acid and its salts are both chelating and sequestering agents and, of course, complexing agents. I shall indicate the reaction between the di-sodium ethylenediamine tetraacetic acid ion and a divalent metal ion such as calcium by the following: Na2Te q- Me + + • MeNa.e Note that no change in valence occurred so that there is no oxidation or reduction reaction here. In fact, this most closely resembles a simple, acid base titration which is represented by: H * q- OH- --• H•O In each case, ions have come together to form a product having slight, if any, ionization and therefore causing the reaction to go to an end. As a matter of fact, this reaction between EDTA and metals is gaining ever increasing analytical usage for purposes of quantitative determination and is readily accomplished by titration methods. The higher valence metallic ions are most strongly chelated and then those of lower valence, for instance, ferric iron is more strongly chelated than is ferrous iron. In fact, iron is one of the most strongly chelated of all the metals. At- tempts have been made to set up a series similar to the electromotive series which will show the order of chelation. This has met with indifferent success since a series arranged under one specific set of conditions may be found to have an altogether different order under another set of conditions. Some of the factors affecting the order of such a series are: (a) Concentration of the metallic ion. (b) pH. (c) Temperature. (d) Other electrolytes present and their concentration. (e) Other complexing agents present. (f) Precipitating anions and their concentrations, etc.

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.