title: Evaluation of topically applied copper(II) oxide nanoparticle cytotoxicity in human skin organ culture.
abstract: The increasing use of nano-sized materials in our environment, and in many consumer products, dictates new safety concerns. In particular, adequate experimental models are needed to evaluate skin toxicity of metal oxide ions, commonly found in cosmetic and dermatologic preparations. We have addressed the biological effects of topically applied copper oxide (CuO) nanoparticles in human skin organ cultures, using light and electron microscopy, and biochemical tests. Nanoparticles were more toxic than micro-sized particles, and their effects were stronger when supplied in growth medium than in topical application. Still topically applied CuO nanoparticles induced inflammatory cytokine secretion and necrosis, especially in epidermis deprived of its protective cornea. Since nanoparticle penetration was not seen, we propose that they may adhere to skin surface, react with the local acidic environment, and generate soluble ions that make their way to inner sites. This work illustrates the abilities of skin organ culture to evaluate the biological effects of topically-applied materials on skin in vitro.
authors.affiliation: Ahava - Dead Sea Laboratories, Dead Sea, Israel.
authors.forename: Dror
authors.initials: D
authors.lastname: Cohen
authors.forename: Yoram
authors.initials: Y
authors.lastname: Soroka
authors.forename: Zeev
authors.initials: Z
authors.lastname: Ma'or
authors.forename: Miriam
authors.initials: M
authors.lastname: Oron
authors.forename: Meital
authors.initials: M
authors.lastname: Portugal-Cohen
authors.forename: François Menahem
authors.initials: FM
authors.lastname: Brégégère
authors.forename: Deborah
authors.initials: D
authors.lastname: Berhanu
authors.forename: Eugenia
authors.initials: E
authors.lastname: Valsami-Jones
authors.forename: Noam
authors.initials: N
authors.lastname: Hai
authors.forename: Yoram
authors.initials: Y
authors.lastname: Milner
mesh_terms: D000287:Administration, Topical; D000328:Adult; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000008:administration & dosage / Q000633:toxicity*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000633:toxicity*; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D009924:Organ Culture Techniques; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D016207:Cytokines; D003300:Copper; D053148:Caspase 3; C000520:cuprous oxide