title: Human safety review of "nano" titanium dioxide and zinc oxide.
abstract: Based on the current weight of evidence of all available data, the risk for humans from the use of nano-structured titanium dioxide (TiO(2)) or zinc oxide (ZnO) currently used in cosmetic preparations or sunscreens is considered negligible. There is a large body of information that when viewed in its entirety is considered as sufficient to demonstrate that these nano-structured ultraviolet (UV) filters, irrespective of various treatments (coatings) or crystalline structure, can be regarded as safe for use at concentrations up to 25% in cosmetic products to protect the skin from harmful effects of solar UV radiation. "Nano" TiO(2) and ZnO formulated in topically applied sunscreen products exist as aggregates of primary particles ranging from 30-150 nm in size. These aggregates are bonded such that the force of sunscreen product application onto the skin would have no impact on their structure or result in the release of primary particles. Multiple studies have shown that under exaggerated test conditions neither nano-structured TiO(2) nor ZnO penetrates beyond the stratum corneum of skin. Further, the distribution and persistence of these nano-structured metal oxides is the same compared to larger pigment-grade (i.e., >100 nm) particles, demonstrating equivalence in the recognition and elimination of such material from the body. Finally, the in vitro genotoxic and photogenotoxic profiles of these nano-structured metal oxides are of no consequence to human health. Whereas the most logical, straightforward conclusion based on data from internationally-recognized guideline studies and current 20+ year history of human use is that nano-structured TiO(2) and ZnO are safe, there will continue to be questions as "nano" conjures images of technology gone awry. Despite this rather sober view, the public health benefits of sunscreens containing nano TiO(2) and/or ZnO outweigh human safety concerns for these UV filters.
authors.affiliation: International Regulatory & Scientific Consulting, Paul-Lincke Strasse 36, 67304, Eisenberg, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Schilling
authors.forename: Bobbie
authors.initials: B
authors.lastname: Bradford
authors.forename: Dominique
authors.initials: D
authors.lastname: Castelli
authors.forename: Eric
authors.initials: E
authors.lastname: Dufour
authors.forename: J Frank
authors.initials: JF
authors.lastname: Nash
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Pape
authors.forename: Stefan
authors.initials: S
authors.lastname: Schulte
authors.forename: Ian
authors.initials: I
authors.lastname: Tooley
authors.forename: Jeroen
authors.initials: J
authors.lastname: van den Bosch
authors.forename: Florian
authors.initials: F
authors.lastname: Schellauf
mesh_terms: D000818:Animals; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D049329:Nanostructures / Q000737:chemistry* / Q000633:toxicity*; D012869:Skin Absorption; D014025:Titanium / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D018675:Toxicity Tests; D015034:Zinc Oxide / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*
chemical_list: C009495:titanium dioxide; D014025:Titanium; D015034:Zinc Oxide