title: In vitro phototoxicity and hazard identification of nano-scale titanium dioxide.
abstract: Titanium dioxide nanoparticles (nano-TiO(2)) catalyze reactions under UV radiation and are hypothesized to cause phototoxicity. A human-derived line of retinal pigment epithelial cells (ARPE-19) was treated with six samples of nano-TiO(2) and exposed to UVA radiation. The TiO(2) nanoparticles were independently characterized to have mean primary particle sizes and crystal structures of 22nm anatase/rutile, 25nm anatase, 31nm anatase/rutile, 59nm anatase/rutile, 142nm anatase, and 214nm rutile. Particles were suspended in cell culture media, sonicated, and assessed for stability and aggregation by dynamic light scattering. Cells were treated with 0, 0.3, 1, 3, 10, 30, or 100μg/ml nano-TiO(2) in media for 24hrs and then exposed to UVA (2hrs, 7.53J/cm(2)) or kept in the dark. Viability was assessed 24hrs after the end of UVA exposure by microscopy with a live/dead assay (calcein-AM/propidium iodide). Exposure to higher concentrations of nano-TiO(2) with UVA lowered cell viability. The 25nm anatase and 31nm anatase/rutile were the most phototoxic (LC(50) with UVA<5μg/ml), while the 142nm anatase and 214nm rutile were the least phototoxic. An acellular assay ranked TiO(2) nanoparticles for their UVA photocatalytic reactivities. The particles were found to be capable of generating thiobarbituric acid reactive substances (TBARS) under UVA. Flow cytometry showed that nano-TiO(2) combined with UVA decreased cell viability and increased the generation of reactive oxygen species (ROS, measured by Mitosox). LC(50) values under UVA were correlated with TBARS reactivity, particle size, and surface area.
authors: Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
authors: Kristen
authors: K
authors: Sanders
authors: Laura L
authors: LL
authors: Degn
authors: William R
authors: WR
authors: Mundy
authors: Robert M
authors: RM
authors: Zucker
authors: Kevin
authors: K
authors: Dreher
authors: Baozhong
authors: B
authors: Zhao
authors: Joan E
authors: JE
authors: Roberts
authors: William K
authors: WK
authors: Boyes
mesh_terms: D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D007928:Lethal Dose 50; D008027:Light; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D017382:Reactive Oxygen Species / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D012542:Scattering, Radiation; D014025:Titanium / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D017382:Reactive Oxygen Species; C009495:titanium dioxide; D014025:Titanium