The action of five zwitterionic surfactants on the barrier function of hairless mouse skin has been studied in vitro. The surfactants considered were dodecylbetaine and hexadecylbetaine (C12BET and C16BET, respectively), hexadecylsulfobetaine (C16SUB), N,N-dimethyl-N-dodecylamine oxide (C12AO), and dodecyltrimethylammonium bromide (C12TAB). Excised skin was pretreated with each surfactant, at various concentrations, for 16 hr, following which the permeation of a model compound, nicotinamide, was measured. The action of the surfactants was assessed by comparing nicotinamide flux through surfactant-pretreated skin with that across control membranes which were exposed to buffer alone for 16 hr. All surfactants decreased skin barrier function to some extent. The degree of nicotinamide penetration enhancement induced was correlated with the ratio of the surfactant pretreatment concentration to the surfactant critical micelle concentration, suggesting that solubilization of stratum corneum lipids may be an important mechanism in explaining the effects observed. More detailed studies with 14C-radiolabeled C12BET and C16BET showed that the dodecyl analog was itself well absorbed, whereas the C16 compound partitioned into the skin favorably but then transferred only very slowly into the receptor phase. These observations were consistent with toxicity studies (albeit at much higher concentrations in a different animal model, the rat) which indicated that the dermal LD50 of C12BET was significantly less than that of C16BET (the value for which was so large that it could not be reliably determined). Overall, this study provides, we believe, useful information pertinent to the potential dermal toxicity of the surfactants considered following occupational or environmental exposure.
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