'512 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS activity, measured 1-20 h after application, of the blood and urine from the rabbit were six to eight times greater than those of the guinea-pig. These experiments indicated that the rabbit skin was more permeable to Ni and Co ions than guinea-pig skin. This same author found that human skin was impermeable to cobalt and that both human and rabbit skin were imper- meable to sodium. The permeability of rabbit skin was also shown to be greater than that of guinea-pig in the work conducted by McDermot, Murray and Heggie (178). These authors applied a solution of a quaternary oxime (1-methyl-2- hydroximinomethylpyridinium methane sulphonate) in DMSO to the entire area of clipped skin (except head and legs) of rabbits and guinea-pigs. Hourly measurement of the plasma concentration of the oxime revealed a peak at 2 h in both species which was approximately 60 ¾ ml -• in the case of rabbits and 40 ¾ ml -x in the case of guinea-pigs. These differences are greater than they appear since the rabbit received approximately 0.5 g kg -x of the oxime applied topically while the guinea-pigs received double this amount. The relationship of the rate of absorption from human skin to that of rabbit or guinea-pig is not certain. According to Wahlberg (179) human skin is less permeable than that of the guinea-pig to sodium chromate, cobaltous chloride and mercuric chloride when tested in vitro. This author employed radio-active isotopes and calculated the mean absorption rates for labelled compounds. He found that the absorption of 0.034 M Na•COa, 0.085 M CoCI• and 0.005, 0.239 M HgCI• was approximately three times greater through freshly excised guinea-pig skin compared to stored, human abdominal skin. The difference was less but still appreciable when freshly excised human skin was employed. Thus, the mean absorption rate for 0.08 M HgCI• was 1.8 times greater through freshly excised guinea-pig skin when compared with freshly excised human mammary skin. If one excludes results from LD50 studies it would seem that percutaneous absorption takes place much more readily through skin of the rabbit than that of any of the other species studied. Guinea-pig skin appears to be less permeable than that of the rabbits and human skin is less permeable than either. ACTIVE TRANSPORT AND METABOLIC TRANSFORMATION According to Tregear (180) there is no evidence to support the presence of a system in the skin that actively transports water and electrolytes into

PERCUTANEOUS ABSORPTION 513 or out of mammalian organisms. The earlier claims by Folk and Peary (181) and Buettner (182) have been questioned by later workers (59, 180) on the grounds that insufficient attention was given to a number of physico- chemical factors which could account for the results observed by the earlier authors. No claims have been made that active transport affects the per- cutaneous absorption of other substances. A striking example of metabolic transformation within the skin was reported by Fredriksson (54, 183) who showed that parathion (E605, diethyl 4-nitrophenylthionophosphate) is metabolized to paraoxon (E600 or diethyl 4-nitrophenylphosphate) which is then degraded to non-toxic metabolites within the skin of the cat. Another example of chemical trans- formation within the skin is the reduction of hexavalent chromium to the trivalent form (125). It is not known whether these examples represent enzymatic activity or are straight-forward chemical interactions. SUMMARY AND CONCLUSION The principal cutaneous barrier to the absorption of substances from the external environment, in man and other mammals, is the stratum corneum. This barrier is broken by the ducts of sweat glands and hair follicles but percutaneous absorption via these appendages forms a small proportion of the total absorbed so that the major pathway for percutaneous absorption is across the stratum corneum. In fact, removal of the stratum corneum by the adhesive-tape stripping techniques results in a 10- to 12- fold increase in the absorption of any particular substance. Damaging the stratum corneum by abrasion or other means has a similar effect. The stratum corneum allows some substances to pass through it more readily than others. The precise physico-chemical factors that determine this performance are imperfectly understood but the evidence accumulated from in vivo and in vitro work allows some broad generalizations to be formed. Lipids and lipid-soluble substances readily pass through the stratum corneum, organic compounds possessing hydrophilic groups do so less readily, while water and water-soluble substances, in particular if these are in an ionized form, traverse the stratum corneum with difficulty. If the compound is applied topically in a vehicle, the rate of its absorption is considerably influenced by that of the vehicle, by the degree of its partition between the vehicle and the stratum corneum, and by its concentration in the vehicle. If the degree of partition is very small, the compound is absorbed along with the vehicle. If it is considerable, percu-