title: TiO2 nanoparticle exposure and illumination during zebrafish development: mortality at parts per billion concentrations.
abstract: Photoactivation of titanium dioxide nanoparticles (TiO2NPs) can produce reactive oxygen species (ROS). Over time, this has the potential to produce cumulative cellular damage. To test this, we exposed zebrafish (Danio rerio) to two commercial TiO2NP preparations at concentrations ranging from 0.01 to 10,000 ng/mL over a 23 day period spanning embryogenesis, larval development, and juvenile metamorphosis. Fish were illuminated with a lamp that mimics solar irradiation. TiO2NP exposure produced significant mortality at 1 ng/mL. Toxicity included stunted growth, delayed metamorphosis, malformations, organ pathology, and DNA damage. TiO2NPs were found in the gills and gut and elsewhere. The two preparations differed in nominal particle diameter (12.1 ± 3.7 and 23.3 ± 9.8 nm) but produced aggregates in the 1 μm range. Both were taken up in a dose-dependent manner. Illuminated particles produced a time- and dose-dependent increase in 8-hydroxy-2'-deoxyguanosine DNA adducts consistent with cumulative ROS damage. Zebrafish take up TiO2NPs from the aqueous environment even at low ng/mL concentrations, and these particles when illuminated in the violet-near UV range produce cumulative toxicity.
authors.affiliation: Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, Madison, Wisconsin 53706, USA.
authors.forename: Ofek
authors.initials: O
authors.lastname: Bar-Ilan
authors.forename: Connie C
authors.initials: CC
authors.lastname: Chuang
authors.forename: Denise J
authors.initials: DJ
authors.lastname: Schwahn
authors.forename: Sarah
authors.initials: S
authors.lastname: Yang
authors.forename: Sanjay
authors.initials: S
authors.lastname: Joshi
authors.forename: Joel A
authors.initials: JA
authors.lastname: Pedersen
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hamers
authors.forename: Richard E
authors.initials: RE
authors.lastname: Peterson
authors.forename: Warren
authors.initials: W
authors.lastname: Heideman
mesh_terms: D000818:Animals; D053768:Metal Nanoparticles; D046529:Microscopy, Electron, Transmission; D014025:Titanium / Q000032:analysis / Q000633:toxicity*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics
chemical_list: C009495:titanium dioxide; D014025:Titanium