ENZYME INHIBITORS FOR DENTIFRICES 277 rapidity of penetration should be tested for their duration of action beyond the one-hour period which is the safe limit of extrapolation from the primary screening method. Inhibitors for use in dentifrice should have an action which lasts for twelve hours, the usual interval between the customary morning and evening brushing, and inhibition can be studied for twelve hours with the procedure we have described. With these two screening principles the ten most active compounds could be selected from the original hundred. The ten would certainly deserve initial study of toxicity. Any toxic substance could be replaced by com- pounds that rank next highest by in vitro tests, then the ten could be studied without undue cost by means of plaque pH drop tests used by Stephan (12) and others. The ten compounds might also be used for evaluation on dental caries activity with hamsters or rats. The best of the ten could be selected for clinical trial on the basis of a wide variety of data on inhibitory action. SUMMARY The aims, scope, and methods of an Inhibitor Survey Program have been described, and some background has been presented regarding the assump- tions that dental investigators make in their search for inhibitors for denti- frice use. Examples have been given of the findings with amines. Twenty active amines were selected from a group of 156 tested. Compounds ca- pable of inhibiting acid production were generally alkylated amines, ethylene diamines, imidazolines, or piperazines. It is recommended that these and other chemicals be examined next for their effectiveness during short contact with a synthetic dental plaque, and for the duration of their action. The substances which show rapid penetra- tion and good retention deserve to be investigated by toxicity and other in vivo studies. This approach is suggested as an efficient means of selecting one compound from a large group of substances that appear promising from primary screening methods. REYERENC•S (1) Fosdick, L. S., •. Am. Dent. Assoc., 40, 133 (1950). (2) Zander, H. A., Ibid., 40, 569 (1950). (3) Hill, T. J., Rasch, C., and Wollpert, B., •7. Dent. Res., 32, 453 (1953). (4) Stephan, R. M., Ibid., 22, 63 (1943). (5) Bibby, B. G., Ibid., 24, 297 (1945). (6) Muhler, J. C., Nebergall, W. H., and Day, H. G., Ibid., 33, 33 (1954). (7) Nevin, R. B., Walsh, J.P., and King, R. M., N. Z. Dent. 7., 49, (July, 1953). (8) Manly, R. S., and Bibby, B. G., •. Dent. Res., :18, 160 (1949). (9) Bruckner, R. J., Hill, T. J., and Wollpert, B. J., Ibid., 31, 105 (1952). (10) Manly, R. S., and Hargreaves, G., Presented at the International Association for Dental Research, French Lick, Ind., March 21, 1954. (11) Fosdick, L. S., Calandra, J. C., Blackwell, R. Q., and Burrill, J. H., 5 e. Dent. Res., 32, 486 (1953). (12) Stepban• R. M, and Miller• B. F.• Ibid., 22, 53 (1943).

RANCIDITY IN SOAPS* By W. W. MYDDLETON, D.Sc., F.R.I.C. County Laboratories, Ltd., Stanmore, Middlesex, England To is•'RoI)vCV. a discussion on rancidity in soap, I put forward four propositions which I shall describe and explain in turn. My first proposition is as follows: That any theory of rancidity more than twelve years old should be put upon the shelf with the Theory of Phlogiston. Rancidity in soap is recognised by the appearance of discoloured patches on the surface and by the odour better known as the odour of rancid fat. A so-called tasteless soap also develops a strong flavour when it becomes rancid. As to what goes on in the soap, little is known by direct observa- tion on soap as such little more perhaps than that atmospheric oxygen is absorbed and, as one would expect, flake or powdered soap, presenting a larger surface to the air, becomes rancid more rapidly than bar or tablet soap under similar conditions of storage. The process is described as autoxidation because it takes place at room temperature and the operative agent is molecular oxygen. For other clues as to what happens in soap we must turn to the analogous phenomena in fatty acids and their esters. It Js in this field that most of the fundamental work on rancidity has been carried out. This is partic- ularly fortunate because, in the highly purified acids and esters, impurities which act in the natural oils and fats and in the soaps made from them as pro- or antioxidants have been eliminated. From this work we know that the saturated acids and their esters are stable at room temperature unless attacked by microbrganisms. On the other hand, oleic, linoleic, linolenic, and the more highly unsaturated fatty acids and their esters, oxidise with increasing ease in the order given. Let us consider the case of methyl oleate. It has one double bond at the middle of the carbon chain and its iodine value is normal for that condition. The molecule can be broken at the double bond by disruptive oxidation with potassium permanganate in acetone and Jt then gives a mixture pro- viding the monobasic nonoic acid and the dibasic acid. * Presented at the April 9, 1954, Meeting, London, England. 278