126 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Table IV Mechanistic Studies of DMSO as a Percutaneous Carrier • Expt. Epidermal Chamber Contents Dermal Chamber Contents Absolute l•ate Constant (cm hr -1) 1 Buffer b and picrate (5.93 X Buffer b 6.89 X 10 -4 10 -2M) 2 80% DMSO in buffer • and Buffer • 14.6 X 10 -4 pierate (7.55 X 10 -2M) 3 80% DMSO in buffer • and 80% DMSO in buffer b 16.2 X 10 -4 pictate (7.55 X 10 -2 M) • (The abdomen of a young male guinea pig was wax epilated. The animal was allowed to recover for five days and then sacrificed by a lethal injection of MgSO4. The abdominal skin was immediately excised and frozen. The time between procurement and utilization of the skin was within 24 to 48 hours. The skin was kept frozen until use.) •3 X 10-2 M. Table V Picric Acid-Dimethyl-C 14 Sulfoxide Penetration Studies a Initial Concentration of Picric Acid (M) % C•4-DMSO (v/v) Absolute Rate Constant (cm hr -•) 5.17 X 10 -2 0 8.51 X 10 -2 80 3.29 X 10 -4 a. Picrate 13.1 X 10 -4 b. C14-DMSO 12.7 X 10 -2 • (A male guinea pig was sacrificed by a lethal injection of MgSO4. The abdominal skin was clipped and the abdominal skin was immediately excised and frozen. The length of time between procurement and utilization of the skin was approximately 24 hours. The skin was kept frozen until use.) of penetration of pierate and DMSO were studied. The results of this isotope experiment (Table V) show that the absolute rate constant for the in vitro diffusion of dimethyl sulfoxide through the skin membrane was approximately 100 times greater than that of the pierate ion, thus clearly demonstrating their independent transfer through the skin. ACI•NOWLrDGMENTS The authors wish to thank Mr. Brian Rogers for his initial work in the procurement of the skin membranes. (Received June 13, 1967) Part II will be published in Volume XIX, No. 3, March, 1968.

(1) (2) (3) (4) (5) (6) (7) (s) (9) (10) (11) DIMETHYL SULFOXIDE 127 References Stoughton, R. B., and Fritsch, W., Influence of dimethylsulfoxide (DMSO) on human percutaneous absorption, Arch. Derrnatol., 90, 512 (1964). Rosenbaum, E. E., et al., Dimethyl sulfoxide in musculoskeletal disorders, J. Am. Med. Assoc., 192, 109 (1965). Kligman, A.M., Topical pharmacology and toxicology of dimethyl sulfoxide--Part 1, ibid., 19:t, 796 (1965). Kligman, A.M., Dimethyl sulfoxide--Part 2, Ibid., 19:t, 923 (1965). Stone, O. J., Thiabendazole in dimethyl sulfoxide for Tinea Nigra Palmaris, Arch. Derrnatol., 9:t, 241 (1966). Leake, C. D., Dimethyl sulfoxidc, Science, 152, 1646 (1966). Sweeney, T. M., et al., The effect of dimethyl sulfoxide on the epidermal water barrier, J. Invest. Derrnatol., 46, 300 (1966). Ainsworth, M., Methods for measuring percutaneous absorption, J. Soc. Cosmetic Chemists, 11, 69 (1960). Kligman, A.M., The biology of the stratum corneum, in Montagna, W. and Lobitz, W. C., Jr., The Epidermis, Academic Press, N.Y., 1964, pp. 387-433. Vinson, L. J., et al., The nature of the epidermal barrier and some factors influencing skin permeability, Toxicol. Appl. Pharrnacol., 7, 7 (1965). Trcgear, R. T., The permeability of mammalian skin to ions, J. Invest. Derrnatol., 46, 16 (1966).