246 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Table VI Summary of Permeability Coefficients of Octanol as a Function of Mouse Age and Antomical Site P X 103 (cm/hr) _ S.D. a Mouse Anatomical Location Age Overall (Days) Abdominal Dorsal Average 4 29.6 ñ 4.4 (3) 23.3 - 6.4 (4) 27.4 ñ 4.8 5 52.5 (2) 47.2 (2) 49.8 ñ 6.3 20 58.9 ñ 16.5(4) 92.6 - 4.9 (4) 75.8 ñ 6.1 25 118.4 ñ 20.9(5) 128.4 ñ 32.5(5) 123.4 ñ 24.5 39 90.0 (1) b 102.8 (1) b 96.4 46 77.7 (2) b 67.2 (1) b 78.7 53 88.9 (2) b 105.6 (2) b 97.2 ñ 12.1 59 94.6 ñ 8.6 (3) b 85.5 ñ 4.1 (4) b 92.1 ñ 7.5 71 85.3 ñ 12.3(5) b - - 72 68.5 ñ 10.3(15) - - 85 51.4 (2) b - - 103 67.8 ñ 2.5 (3) - - 106 68.0 ñ 4.1 (3) - - 134 49.9 (1) b - - 210 14.0 ñ 0.9 (4) 11.7 ñ 0.9 (4) 12.7 ñ 0.8 270 18.3 ñ 4.2 (5) 21.3 ñ 4.0 (5) 19.7 ñ 2.5 360 24.6 ñ 7.4 (4) 20.2 ñ 10.4(4) 24.0 ñ 9.1 Numbers in parentheses indicate numbers of animals used. From reference 15 and other works. The question can be posed whether increases in permeation rates during the skin's early metamorphosis are directly due to the increased follicular presence. Certainly the fol- licles enlarge and grow and the opportunity for transfollicular passage is expanded. A 3-5-fold rise in rates is not entirely unreasonable. This possibility requires aqueous as well as lipid media to exist within the follicular channels as the polar solutes, water, methanol and ethanol, are as affected as the intermediate-chain length alkanols. As an emulsion, sebum could function in this fashion. Unfortunately the nature of the sebum in hairless mouse skin immersed in saline is not known. Moreover, there may be concurrent changes in the stratum corneum accompanying the follicular developments which cause it either to be thinner or of diminished barrier competency. Decreased lipogensis by the keratinocytes as the epidermis sprouts hair, with a general loss in integrity of the horny tissue, is plausible. As in the follicular explanation, lipoidal and aqueous pathways would have to be similarly affected, considering that increases in permeability are seen for both polar and semipolar solute groups. The nature of the aqueous shunt is ill-defined by either mechanism. A combination of both mechanisms may be involved. The very gradual decline in the permeability coefficient apparent for octanol (and possibly to a lesser extent for hexanol) past 25 days of age seems related to changes taking place in phases of the tissue other than the stratum corneum. Octanol's per- meability is obviously not strictly stratum corneum-controlled, and since the overall thickness of the full skin gradually increases with mouse age, except of course for the first 25 days of life, steady decreases in permeability coefficients of permeants sensitive

ALKANOL PERMEATION OF HAIRLESS MOUSE SKIN 247 6 water 8[ methanol 40 [ butanol 20 10 i i i i i i 100 hexanol 60 40 ß 20 i I i i i i i i i 160 [ octanol ß 40 i i i i i i i i • i 40 80 120 160 200 240 280 320 360 MOUSE AGE (days) _ Figure 3. Plots of permeability coefficients (P-values) of the abdominal and the dorsal skins of hairless mouse as a function of age. Data are graphed for water (plot 3-a), methanol (plot 3-b), ethanol (plot 3- c), butanol (plot 3-d), hexanol (plot 3-e), and octanol (plot 3-f). The closed triangles, •, are data from dorsal skin sections while the closed circles, O, are data obtained with abdominal sections. to mass transfer across strata beneath the horny tissue, as observed with octanol, are to be expected. While the membrane as prepared is thus behaving predictably on this score, this influence of skin thickening on hydrophobic permeants would either not exist or would not be anywhere near as exaggerated in the living animal where per- meation presumably terminates at the interface of the systemic blood in the upper reaches of the dermis. In all young animals the ratio of the body surface area to the body weight gradually