THERAPEUTIC POTENTIALITIES OF TRIGLYCERIDES 313 mycotic disorders it would be interesting to see if formulations of glycerol triacetate would provide at least symptomatic relief. The toxicity, or rather lack of toxicity, of glycerol triacetate is note- worthy and undoubtedly accounts for part of its acceptability as a chemo- therapeutic agent. The LD50, subcutaneously in rats, is 2.8 ml. per ks. (8). Likewise oral toxicity is low rats fed a diet containing 55 per cent glycerol triacetate for sixty days increased 90 grams in weight whereas controls increased 140 grams (9). The ester was not stored as such in body fat but was converted first to longer chained, unsaturated fatty acids. Irrigation of the rabbit eye for six minutes with triacetin caused no apparent irritation or damage. There is an area in the hydrolysis of glycerol triacetate in which some work should be done that is, the spontaneous hydrolysis by water when catalyzed by unknown substances. We have some observations here rather than real experiments. Some of us have made solutions of 25 per cent triacetin in 50 per cent isopropanol and have found them to be stable for at least three years others have noted considerable hydrolysis in a matter of a few months. Two dermatologists have stated that triacetin when formulated in a base of their choice underwent spontaneous hydrolysis yet another has formulated it extensively with no notice of hydrolysis. It is likely that there are nonenzyme catalysts, organic, inorganic or both, which when present with available water can cause hydrolysis. Another piece of information that might be useful is the extent and rapidity of penetration into the skin. We have always assumed that penetration was good because glycerol triacetate is very soluble in lipids and about 7 per cent soluble in water this belief has been fortified by the statement of Rothman (10) to the effect that lipid soluble substances pene- trate quickly especially if they are somewhat soluble in water. Is it likely that triglycerides of higher fungistatic fatty acids will not be as good chemo- therapeutic agents because they do not have such fortunate solubility characteristics ? We hope to know the answer in the near future. CONCLUSION On the basis of the hydrolysis kinetics by esterases, its toxicological properties and the results of clinical trials, it would seem that glycerol tri- acetate and perhaps related compounds offer considerable promise as chemotherapeutic agents, especially in superficial mycotic infections and where a lowered skin pH is desired. SUMMARY Preliminary clinical trials showed that formulations of glycerol triacetate were useful in the treatment of soperficial mycotic infections. Laboratory work showed the compound to be inhibitory to a number of dermatophytes

314 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS and evidence was obtained that it was hydrolyzed by esterases from fungi, serum and skin the hydrolysis rate became vanishingly small as the freed acid created a pH in the region of 4 to 5. Clinical reports and a limited literature on the subject suggest a very low order of toxicity for glycerol triacetate. REFERENCES (1) Ochs, Irving L.,/lrch. Otolaryngol., 52, 1 (1950). (2) Ludwig, F. E., Surgery, 19, 486 (1946). (3) Adkins, H., Royals, H. E., and Wilds, A. L., O•ce of Scientific Research and Development Report No. •t•t19, Dec. 2 (1944). (4) Nicolaides, N., and Wells, George C., •7. Invest. Dermatol., 29, 423 (1957). (5) Rothman, Stephen, "Physiology and Biochemistry of the Skin," 1st edition, Chicago, University of Chicago Press (1954), p. 224. (6) Burack, Adele M., and Knight, S. G., •7- Invest. Dermatol., 30, 197 (1958). (7) Bernstein, Eugene Traugott, and Herrmann, Franz, N.Y. State y. Med., 42, 436 (1942). (8) Li, R. C., Sah, P. P. T., and Anderson, H. H., Proc. $oc. Exptl. Biol. Med., 46, 26 (1941). (9) Cox, W. M., Jr., •7. Biol. Chem., 103, 777 (1933). (10) Rothman, Stephen, op. cit., 38. DRUGS IN COSMETICS--SHOULD THEY MIX? By A. J. LEHM^* Presented February ¾, 1959, New York Chapter DURINO THE PAST thirty or forty years cosmetics have become almost a necessity and are probably no longer considered as a luxury. Synthetic chemistry has aided greatly in popularizing cosmetics, and the demand for incorporating the newer materials into cosmetic products has outstripped research in the fundamentals of skin physiology and related problems in skin pharmacology and toxicology. Claims for the new products frequently have taken them beyond the realm of cosmetics into the category of drugs. The terms "cosmetic" and "drug" as defined in the law are not mutually exclusive. An article may be both a cosmetic and a drug. The Food, Drug, and Cosmetic Act states that the term "cosmetic" means: (1) arti- cles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body or any part thereof for cleans- ing, beautifying, promoting attractiveness, or altering the appearance and (2) articles intended for use as a component of any such articles, except that soap is excluded. * Div. Pharmacology, Bureau of Biological and Physical Sciences, Food and Drug Ad- ministration, U.S. Dept. of Health, Education, and Welfare, Washington 25, D.C.