354 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Table I Percutaneous Absorption and TEWL Values According to Anatomic Site Percutaneous Absorption of Benzoic Acid Urinary Excretion Total Penetration 0-24 h In 4 Days (nmoles ß cm- 2) (nmoles ß cm- 2) TEWL Anatomic Site (a) (b) (gm ' m -2 ' h-•) Back 6.41 8.55 4.51 (c) (0.99) (1.32) (0.57) Arm 7.06 9.41 4.34 (0.77) (1.02) (0.07) Chest 8.78 11.70 4.73 (0.98) (1.30) (0.26) Thigh 9.38 12.50 4.39 (1.07) (1.43) (0.32) Abdomen 11.44 15.26 4.99 (1.44) (1.93) (0.38) Forehead 20.74 27.65 8.12 (2.71) (3.61) (0.64) (a) (b) calculated values from (a): -- O.75 (c) S.D. thigh and the chest, it is worth noting that these values do fall on the correlation plot obtained and thus confirm it. The cutaneous permeability of benzoic acid varied according to the site in the following manner: back arm chest thigh abdomen forehead. These results are in excellent agreement with previous studies (13,18) involving various molecules of different chemical structures, and confirm that the forehead displays the greatest permeability. The laws describing diffusion through a membrane accord a major role to membrane thickness. These general laws have been applied to several biophysical phenomena, including TEWL and percutaneous absorption. However, examination of the literature shows that it is not unusual for these laws, predictated by pure mathematical logic, to be found wanting when applied to a discontinuous membrane of great physicochemical complexity such as the stratum corneum. Similarly, our results show that the forehead is about two to three times more perme- able to water and to benzoic acid than the other sites studied here, despite the fact that the SC thicknesses are comparable in all cases (12 [x on average for 18 layers) (22,23). This example seems, therefore, to run counter to the inverse relation which should exist between permeability and membrane thickness. Hence, simple consideration of the thickness of the SC cannot of itself explain the differences in TEWL and penetration observed between anatomic sites. Other criteria must be considered. By virtue of its density of active sebaceous glands, the forehead is the richest of all those studied in terms of sebum, which forms an uneven film of thickness varying form 0.4 to

SKIN PERMEABILITY AND WATER LOSS 355 30- 25- 20- z LI.I z 10- o 1 a : A : C : T : AB : F : BACK ARM / CHEST / THIGH / ABDOMEN / FOREHEAD / /•B r = 0.97 i i i i I I i I I 2 3 4 5 6 7 8 T, E.W.L. (g. m-2. h -1 ) Figure 2. In vivo relationship between total penetration of benzoic acid and TEWL according to anatomic site. 4 bt. Although the real influence of this film on molecular percutaneous absorption is poorly understood, it is established that its removal, or artificial thickening of it, in no way modified TEWL (24,25). In adults (26,27), the flat surface of forehead stratum corneum cells is approximately 30% less in area than those for cells from the arm, abdomen, or thigh. Moreover, as a function of the anatomic site, it has been demonstrated that there exists an inverse relation between the area of the horny layer cells and the value of the TEWL (27). What