246 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Polythene occlusion lowers the threshold concentration of topical corticosteroids producing vasoconstriction on normal skin about one hundred fold (4). There can be no doubt of the importance of occlusion induced by ointment bases in increasing percutaneous absorption, irrespec- tive of whether the penetrant is water-soluble or not. The precise effect now needs to be measured for a variety of important penetrants in the various vehicles. The effects of vehicles on the stratum corneum, other than by hydration, have largely been neglected except for such substances as detergents and salicylic acid. The experiments described above show clearly that whether this effect is major or minor, this is a function which has to be measured under a variety of experimental conditions before conclusions can be drawn concerning the mode of action of any new clinically favoured vehicle. ACKNOWLEDGEMENTS Figs. 1-4 are published by kind permission of the Editor of the Journal of Investigative Dermatology. (Received: 19th September 1968) REFERENCES (1) Grice, K. A. and Bettley, F. R. Brit. J. Dermatol. 78 458 (1966). (2) Baker, H. and Kligman, A.M. Arch. Dermatol. 96 441 (1967). (3) Sarkany, I., Hadgraft, J. W., Caron, G. A. and Barrett, C. W. Brit. J. Dermatol. 77 569 (196s). (4) McKenzie, A. W. and Stoughton, R. B. Arch. Dermatol. 86 608 (1962). DISCUSSION DR. D. SrRVYT: The "complete suppression" of TEWL by soft white paraffin (SWP) is very impressive. As I doubted whether the occlusivity of SWP could have been caused by its own resistance against water permeation, I have carried out the same experiment as you and, in addition, I measured the specific resistance of SWP against evaporation according to the theories and measurements of Langmuir and Schaefer (5), Archer and La Mer (6), and La Mer (7) on monomolecular layers. The water vapour loss through a layer of SWP depends on temperature and is repre- sented in Figure 6. Even a very thin layer of SWP has a highly effective occlus- ivity. Therefore I estimated the probable thickness of the layer of SWP as applied upon 5x 10----50 cm2 forearm skin. It was applied in the way you have described, liberally in a therapeutic manner in a 0.3 mm thick layer, left for 15 rain and then scraped off the stretched surface with the flat side of a wooden spatula so as to leave a film on the (5) Langmuir, I. and Schaefer, V. J. J. Franklin Inst., 2115 119 (1943). {6) Archer, R. J. and La Mer, V. K. Ann. N.Y./Icad. Sci., 58 807 (1954). (7) La Mer, V. K. Retardation of evaporation by monolayers (1962) (Academic Press, New York).

EXPERIMENTAL STUDIES ON PERCUTANEOUS ABSORPTION 247 ioo o •o 0 50- OOl 4o L•• Forearm Forearm J Isoft white '• • I paraffin N I lo.Ommj x k o N j •j O'?mm j•øJo'JO j mm •5 50 25 20 Temperature, øC Figure 6. surface. Only a 0.06 mm thick layer remained on the skin, as estimated from the weight of the recovered SW'P. Perhaps the SWP had meanwhile spread over the skin surface to about 8 x 13 -- 100 cm 2 so that the layer had been reduced to about 0.03 mm SWP. In order to estimate the resultant retardation of the evaporation, indicated by you as occlusivity, I would like to propose the resistance of the skin and the resistance of the SWP layer against water permeation as parameters, because the resistances of both layers can be added while the permeabilities cannot. The resistance (r) is found in analogy to Ohm's law: (C ,--C 2) M/At (C •--C2) represents the difference of the xvater concentrations at both sides of the membrane M represents the amount of water permeated through an area of A cm-2 per unit of time (t). The value of (C •--C 2) at 33øC skin temperature, carrying dry air over the skin in our experiments, is 35.3x 10 -3 mg cm -3. The value of M/At is found