title: Distinctive toxicity of TiO2 rutile/anatase mixed phase nanoparticles on Caco-2 cells.
abstract: Titanium dioxide has a long-standing use as a food additive. Micrometric powders are, e.g., applied as whiteners in confectionary or dairy products. Possible hazards of ingested nanometric TiO(2) particles for humans and the potential influence of varying specific surface area (SSA) are currently under discussion. Five TiO(2)-samples were analyzed for purity, crystallinity, primary particle size, SSA, ζ potential, and aggregation/agglomeration. Their potential to induce cytotoxicity, oxidative stress, and DNA damage was evaluated in human intestinal Caco-2 cells. Only anatase-rutile containing samples, in contrast to the pure anatase samples, induced significant LDH leakage or mild DNA damage (Fpg-comet assay). Evaluation of the metabolic competence of the cells (WST-1 assay) revealed a highly significant correlation between the SSA of the anatase samples and cytotoxicity. The anatase/rutile samples showed higher toxicity per unit surface area than the pure anatase powders. However, none of the samples affected cellular markers of oxidative stress. Our findings suggest that both SSA and crystallinity are critical determinants of TiO(2)-toxicity toward intestinal cells.
authors.affiliation: Particle Research, Leibniz Institut für Umweltmedizinische Forschung (IUF) at the Heinrich Heine University Düsseldorf, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Gerloff
authors.forename: Ivana
authors.initials: I
authors.lastname: Fenoglio
authors.forename: Emanuele
authors.initials: E
authors.lastname: Carella
authors.forename: Julia
authors.initials: J
authors.lastname: Kolling
authors.forename: Catrin
authors.initials: C
authors.lastname: Albrecht
authors.forename: Agnes W
authors.initials: AW
authors.lastname: Boots
authors.forename: Irmgard
authors.initials: I
authors.lastname: Förster
authors.forename: Roel P F
authors.initials: RP
authors.lastname: Schins
mesh_terms: D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D005503:Food Additives / Q000737:chemistry / Q000633:toxicity*; D005721:Glutamate-Cysteine Ligase / Q000235:genetics; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D013499:Surface Properties; D014025:Titanium / Q000737:chemistry / Q000633:toxicity*
chemical_list: D005503:Food Additives; D012333:RNA, Messenger; C009495:titanium dioxide; D014025:Titanium; D051547:Heme Oxygenase-1; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione