242 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Table I Summary of Permeability Coefficients of Water as a Function of Mouse Age and Anatomical Site P X 10 3 (cm/hr) + S.D. a Mouse Anatomical Location Age Overall (Days) Abdominal Dorsal Average 4 0.6 + 0.1(3) 2.0 - 0.3(4) 1.3 - 0.2 5 0.8(2) 2.2(2) 1.5 ñ 0.2 20 1.6 _ 0.5(3) 2.8 ñ 0.4(3) 2.2 _ 0.2 25 1.9 ñ 0.1(5) 4.4 ñ 0.5(5) 3.2 ñ 0.2 51 1.3 ñ 0.3(4) 1.6 ñ 0.6(4) 1.5 ñ 0.5 53 1.4 _ 0.2(5) b - - 59 1.4 ñ 0.4(9) b - - 85 1.1 + 0.3(10) • - - 102 1.5 ñ 0.4(6) • - - 110 1.3 ñ 0.3(10) • - - 114 1.4 ñ 0.4(3) • - - 134 1.0 + 0.5(3) b - - 158 0.9(2) • - - 210 0.7 - 0.2(4) 0.9 ñ 0.2(4) 0.8 +_ 0.2 270 1.1 ñ 0.1(5) 0.8 ñ 0.3(5) 0.9 ñ 0.2 360 0.6 -+- 0.1(5) 0.6 ñ 0.2(5) 0.6 ñ 0.2 Numbers in parentheses indicate numbers of animals used. From reference 15 and other works. DISCUSSION GENERAL PERMEABILITY BEHAVIOR Profiles of permeability as a function of age for water, methanol, ethanol, and butanol are qualitatively about the same (Figure 3). Permeation rates rise sharply to a peak seen at 25 days of age and then, just as abruptly, they decline over the next 25 or so days. There follows a period in which permeability coefficients are more or less stable. For some solutes the 25-day permeability coefficient is upwards of five-fold greater than seen as the stabilized value in mature animals. The rate of decline from the peak permeability at 25 days for hexanol and octanol appears slower than with the other permeants. One common feature of the data of all compounds is that a larger perme- ability coefficient is consistently found at the dorsal site than at the abdominal site for mice less than 50 days old. Past this age, the values for the dorsum and abdomen essentially come into coincidence. The only ages for which the permeability coefficients of all six permeants were evaluated both dorsally and abdominally are 4, 5, 20, 25, 53, 210, 270, and 360 days. These data are plotted semilogarithmically versus alkyl chain length in Figure 4 for each age. A common feature of these profiles is a sigmoidal shape with an exponentially increasing middle region between two plateaus. The exponentially increasing region results from an alkyl chain length partitioning dependency of the permeability coefficients which is mildly dampened by decrementally varying diffusivities as the molecules become larger. The methylene (-CH2-) sensitivity of permeability, dP/dn, is referred to as a Q-value. The estimated Q-values are plotted as a function of the age separately for the abdominal

ALKANOL PERMEATION OF HAIRLESS MOUSE SKIN 243 Table II Summary of Permeability Coefficients of Methanol as a Function of Mouse Age and Anatomical Site P X 103 (cm/hr) + S.D. • Anatomical Location Mouse Age Overall (Days) Abdominal Dorsal Average 4 1.0 ñ 0.1(3) 2.7 ñ 0.3(4) 1.8 ñ 0.1 5 1.2(2) 3.5(2) 2.3 ñ 0.3 20 2.6 ñ 1.0(4) 4.3 --- 0.9(4) 3.3 ñ 0.2 25 3.4 ñ 0.3(5) 6.8 ñ 0.9(5) 5.1 ñ 0.5 39 2.5(1) b 2.3(1) b 2.4 41 2.2 ñ 0.5(4) • 2.5 ñ 0.6(4) • 2.4 ñ 0.6 42 2.9(2) • 3.3(2) • 3.1 ñ 0.5 44 2.4(1) b - - 45 2.4(2) • 2.9(2) • 2.7 ñ 0.0 46 2.6 ñ 0.2(4) • 1.9 ñ 0.5(4) • 2.3 ñ 0.3 47 2.7 ñ 10.(5) b - - 53 2.2 ñ 0.5(15) • - - 57 1.6 ñ 0.3(4) • 2.2 _+ 1.1(20) • 1.9 ñ 0.7 59 2.0 ñ 0.7(20) • 2.3 ñ 1.0(20) b 2.4 ñ 0.8 68 1.7 ñ 0.3(5) • - - 77 1.9 ñ 0.5(4) • 1.3 ñ 0.3(4) • 1.6 + 0.2 85 1.6 ñ 0.4(15) • - - 109 1.9 ñ 0.8(5) b - - 110 2.0 ñ 0.5(10) • - - 134 1.9 ñ 1.2(11) • - - 165 1.2 (1) • - - 210 1.0 ñ 0.3(4) • 1.4 ñ 0.3(4) b 1.2 ___ 0.3 270 1.3 ñ 0.3(5) 1.1 ñ 0.4(5) 1.2 ñ 0.3 360 0.8 ñ 0.2(5) 1.0 _+ 0.3(5) 0.9 ñ 0.2 Numbers in parentheses indicate numbers of animals used. From reference 15 and other works. and the dorsal skins in Figure 5. x-values appear constant between the ages of 53 and 360 days. However, there may be a slight irregularity in the x-values during the hair cycle. Such irregularity is consistent with other evidence which shows the skin functions differently as a transport barrier during the period of dynamic follicular activity. The exact placements of the homolog profiles on the log P axis differ for the different aged skins but all curOes evidence a stereotypical sigmoidal shape. This general pattern is a physicochemical expression of a barrier system in which the permeation of solutes is controlled by three different, interactive events, each with different sensitivity to chemical structure. Water and the two most polar alcohols, methanol and ethanol, permeate with comparable velocities. Since their permeability coefficients evidence no o/w-type partitioning sensitivity, one is left to conclude that these three substances are preferentially passing through some watery pores or channels within the membrane. The exponentially increasing region of the profile (moderate chain lengths) signals a shift in rate-determining pathway to a lipoidal phase in parallel with the aqueous shunt. As hydrophobicity is further increased and o/w partition coefficients become very large, permeation by way of the lipoidal regime of the stratum corneum becomes facile due to its expanding capacity. In this circumstance, aqueous strata both external to a skin