PERCUTANEOUS ABSORPTION OF ANIONIC SURFACTANTS Table V. Permeability constants (gcm min -•) of some anionic surfactants through isolated human epidermis Time of contact with surfactant solution (h) Surfactant 6 24 48 Soaps Cxo: o 5.4 18.6 -- Cx•: o 18.2 25.0 -- Cx4: o 1.6 9.4 -- Cx•: o 0.1 0.2 -- Cxs: o 0.1 0.1 -- SDI 0.7 0.9 1.3 SDS 0.1 1.8 35 DOBS 0.1 0.1 -- The sodium soaps were applied as a 6 mM solution in a model soap solution. The SDS and SDI were applied as 25 mM solutions and the DOBS as a 3 mu aqueous solution. 59 penetration occurred through the stratum corneum in most of the samples but, whereas in the in vivo state it would be removed in the peripheral blood supply, in the in vitro state the dermis has to be traversed. Scala, McOsker and Reller (14) showed a dermal lag effect with tetrapropylene benzene sulphonate which took about 4 h to reach equilibrium. It is thus likely that the dermis may act as a barrier to penetrated surfactant and this probably accounts for much of the differences found between the penetration of these [•C] surfactants through rat skin and human epidermis. Extrapolation of these in vitro results to the use of these surfactants in vivo is difficult. From the rat skin data some deposition of surfactant on the skin surface could be predicted but the amounts of SDS, SDI, DOBS, C•8: 0 and C•6: 0 soaps penetrating from a 15 min wash and rinse would be very small. The C•0: 0, Cx2:0 and C•: 0 soaps had permeability constants of -•- 3 g cm min 4 in vitro so that from a 15 min wash and rinse with a 6 mM solution a penetration of between 0.05 and 0.1 gg cm -2 would be predicted. From the human epidermis studies in vitro only small amounts of the C•0: 0, C•2: 0, C•: 0 soaps and the SDI would be likely to penetrate from a 15 min wash and rinse in vivo. The low penetration rates of the C•6: 0 and Cxs: 0 soaps and DOBS and the very long lag time before SDS penetrates suggests that little or none of these would penetrate from a 15 min wash and rinse in vivo. The turnover of the [•C] surfactants in the rat showed that there was no significant difference in the rate or route of excretion of •C given by

6O JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS intraperitoneal or subcutaneous administration. It was thus thought valid to assume that [•4C] surfactant penetrating the skin and entering the blood stream would be excreted at a similar rate. The turnover of the C•4: 0, Cx6: 0 and C•8: 0 soaps was slow but for the other [•4C] surfactants levels of •4C in the excreta could be used as good indications of percutaneously absorbed material. The in vivo techniques used in this study have been used for a variety of consumer type applications to experimental animals and have been shown to be reproducible for a number of compounds (15). The limit of detection for this type of assay is governed by the specific activity of the isotopically-labelled compound, the dilution in metabolic pools of the test animals and the overall counting efficiency for the isotope in these pools. For [•4C] labelled compounds, routine assays of 24 h collections of urine, faeces and expired CO2 gave limits of accurate measurement of 2.0, 5.0 and 10.0 x 10 a dpm of •4C respectively. For analysis of whole carcass a limit of accurate measurement of 1 x 104 dpm is possible. These limits have been set by taking a count rate of twice background as the limit of sensitivity. Thus, in this #7 vivo study 0.1 gg of [•4C] surfactant penetrating per cm • of skin could be measured. The exception is the [•4C] SDI which had the lowest specific activity [1.7 gCi mg -•] for which the limit of sensitivity was 0.3 [tg cm -2. Penetration of the [•4C] soaps in vivo followed the same order as those obtained with excised human epidermis, i.e. C•2: 0C•0: oC•4: 0 C•6: o-•-C•8: o. The actual amounts of soap which penetrated from the 15 rain wash and rinse applications to untreated skins with the 6 mM soap solutions ranged from0.674-0.34 I•g cm-" for the C•,: 0 to 0.7-+-0.02 !lg for the C•s: o. These amounts are considerably higher than those predicted from the in vitro study with excised rat skin. Prewashing the skin with 300 mM model soap solution--approximately 7.5•o w/v solution which is similar to that found during consumer use, increased the permeability of the skin, especially for the Clo: o and the Ci•: o soaps. With regard to the synthetic detergents, the small amounts of SDS penetrating the skin (0.264-0.09 Isg cm -•) from the application in vivo with a 25 mM solution, was not predictable from the in vitro studies. Blank and Gould (12) also found no measurable penetration in vitro of SDS which is inconsistent with the known irritancy of SDS to skin. Sprott (3) showed that SDS could penetrate rat skin, but in that study, based on urinary levels after washing with [asS] SDS, some of the urinary aaS could have been due to the animal ingesting [aaS] SDS deposited on the skin.