Anionic surfactants compromise skin's barrier function by damaging stratum corneum lipids and proteins. The objective of this study was to examine anionic surfactanteinduced changes in the skin's polar and transcellular pathways and the resulting impact on surfactant penetration into the skin. Three anionic surfactant formulations and one control formulation were each applied to split-thickness human cadaver skin in vitro for 24 h. Electrical conductivity of the skin, determined using a four-terminal resistance method, and water permeation across the skin, determined using a radiolabeled water tracer, were simultaneously measured at several points over the experimental period. Surfactant permeation across the skin was similarly measured using a radiolabeled sodium dodecyl sulfate tracer. Anionic surfactants rapidly enhanced skin electrical conductivity and water permeability in the excised human skin, resulting in nonlinear enhancements in surfactant permeation across the skin over time. Surfactant penetration into the skin was found to increase linearly with increasing surfactant monomer concentration. Surfactant zeta potential was found to correlate well with skin conductivity, water permeation across the skin, and surfactant permeation across the skin, particularly with long surfactant exposures. Micelle charge is a significant predictor of anionic surfactanteinduced damage to the human skin, with more highly charged surfactants inducing the most damage. (c) 2019 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.