504 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS According to Sprott (96) retention in the skin depends on the ability of the surfactant to interact with proteins the greater this interaction the greater the amount retained locally and the less passes through. At concentrations appreciably higher than those employed in the studies just mentioned, surfactants enhance percutaneous absorption. Studies by Sprott (96) indicated that surfactants promote the penetration of water and sodium iodide in vivo. Using tritiated water and mI sodium iodide he showed that pre-washing the shaved skin of rats with a bar of 'ordinary' soap increased the penetration rate three-fold. When the soap contained a high proportion of sulphonated fatty acids and fatty acid esters of isethionic acid, there was a four-fold increase in the rate of penetration. Similar in- creases in the rate of penetration of •a•iodide were observed after pretreat- ment of the skin with these two types of soap. A similar enhancement of percutaneous absorption following applica- tion of surfactants was obtained in an earlier study (150, 151) on the influence of alkylaryl-sulphonates and soap on the percutaneous absorption of mercuric chloride and methyl mercury dicyandiamide. Both compounds were labelled with •'øaHg. The mercury compounds were dissolved in water, and in a 1•o aqueous solution of soap and alkylaryl sulphonate, respec- tively. The presence of soap did not influence the absorption of the two mercury compounds. The presence of alkylaryl sulphonate increased the absorption of the organo-mercury compound and to a lesser extent that of mercuric chloride. These results confirmed other observations by these authors using the same mercury salts and surfactants (151). The addition of 0.2•o sodium lauryl sulphate or 1.0•o polysorbate 80 to solutions of chloramphenicol doubled the rate of penetration of this drug (98). Even at lower concentrations, surfactants enhance percutaneous absorption. Using a 0.50 nm concentration of the sodium salts of C8-C•8 straight chain fatty acids, Sprott (96) found that the rate of penetration of tritiated water was increased with C8-Cx4 fatty acid salts, the fatty acids with the shorter chain being the more effective. With a chain length of over C•4 no effect on percutaneous absorption was observed. The sodium salts of alkyl aryl sulphonates at the same concentrations also increased per- cutaneous absorption. In this instance the longer the chain length the more effective was the compound. Bettley (45) correlated the surface activity of a series of ionic surfactants in vitro at 0.04 m concentration with their effect on permeability. He found that the potassium salts of caprylic acid and lauric acid, which depress surface tension to an almost equal degree, differed widely in their ability to enhance the permeability of the stratum

PERCUTANEOUS ABSORPTION 505 corneum to Na + and K + and also cetyltrimethyl ammonium bromide and sodium sulphosuccinate lauric mono-iso-propanolamide polyglycol, which show an equally moderate depression of surface tension, have very different effects on permeability. Surfactants differ considerably in their ability to alter the permeability properties of the skin barrier. Unfortunately, the degree of lowering of the surface tension of water is not always given so that it is impossible to say to what extent this difference is related to the surface active property of the solution. The work of Bettley (45) would suggest that lowering the sur- face tension of water is not an important factor in enhancing skin permea- bility despite the possibility of removal of lipids when the surface tension of water is lowered. In vitro observations are obviously necessary before one can be certain on this point. The observations of Blank and Gould (94) and of Sprott (96) would indicate that the protein binding ability of the sur- factant and the consequent alteration of the structure of the stratum corneum has to be taken into account as one of the factors that influence the alteration of the permeability of the skin. Recent studies (146, 152) tend to confirm the importance of protein denaturation in the increased permeability of skin induced by some surfactants. Ointments, pastes and creams Although the mechanisms by which individual organic solvents affect percutaneous absorption are amenable to investigation and data exist on many such solvents, the influence of formulations, containing a mixture of organic substances, on percutaneous absorption is less understood (153) and Williams (154) pointed out that there is no 'solid scientific evidence to guide the prescription of an active ingredient in..., an ointment, or paste or a cream'. It is equally difficult to predict with any degree of certainty the likely influence of formulations of this sort on percutaneous absorption of cosmetic chemicals. A limited amount of information is, however, available which could form the basis of some sort of a guideline. The question of absorption of medicaments from ointment bases through the intact human skin was reviewed by Johnson and Lee (113). Many conflicting reports exist but in general most authorities considered that medicinals were absorbed more readily from animal and vegetable fats than from 'petroleum' bases. Experimentation in this field was hampered by the difficulty of accurately measuring the 'fatty materials and trace substances' in the tissues (113). The use of radio-isotopes considerably simplified these difficulties and Johnston and Lee (113) used NaC1, labelled