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Metal nanoparticles can potentially contact human skin during their manufacture and use in commercial products. This study examined the potential of metal nanoparticles to elicit irritant contact dermatitis in a human skin equivalent model (HSEM) derived from keratinocytes. Ag (10-100nm), TiO2 (22-214nm), and CeO2 (15-40nm) nanoparticles were studied. The Ag particles were either coated/shelled with silica or capped with citrate or polyvinylpyrrolidone and were in water. The TiO2 and CeO2 particles were suspended in media containing 10% fetal bovine serum. The particles (1mg/ml) were applied to the epidermal surface of the HSEM. Positive (5% sodium dodecyl sulfate (SDS)) and negative controls (saline or media) were included. After 1-h exposure at 37 degrees C, the HSEM was washed with saline to remove the nanoparticles. Following a 42-h incubation (37 degrees C), HSEM viability was assessed using the MTT assay. A test substance is considered a dermal irritant if the HSEM viability is<50%. The mean viability for the SDS-treated HSEM was 7.8%. The viabilities of the nanoparticle-treated HSEM were 91% or greater. The Ag, TiO2, and CeO2 nanoparticles examined were not dermal irritants under the conditions used in this study. The stratum corneum of the HSEM may limit penetration of metal nanoparticles to induce toxicity.