title: Assessing the relevance of in vitro studies in nanotoxicology by examining correlations between in vitro and in vivo data.
abstract: There is an urgent need for in vitro screening assays to evaluate nanoparticle (NP) toxicity. However, the relevance of in vitro assays is still disputable. We administered doses of TiO(2) NPs of different sizes to alveolar epithelial cells in vitro and the same NPs by intratracheal instillation in rats in vivo to examine the correlation between in vitro and in vivo responses. The correlations were based on toxicity rankings of NPs after adopting NP surface area as dose metric, and response per unit surface area as response metric. Sizes of the anatase TiO(2) NPs ranged from 3 to 100 nm. A cell-free assay for measuring reactive oxygen species (ROS) was used, and lactate dehydrogenase (LDH) release, and protein oxidation induction were the in vitro cellular assays using a rat lung Type I epithelial cell line (R3/1) following 24 h incubation. The in vivo endpoint was number of PMNs in bronchoalveolar lavage fluid (BALF) after exposure of rats to the NPs via intratracheal instillation. Slope analyses of the dose response curves shows that the in vivo and in vitro responses were well correlated. We conclude that using the approach of steepest slope analysis offers a superior method to correlate in vitro with in vivo results of NP toxicity and for ranking their toxic potency.
authors.affiliation: Department of Environmental Medicine, University of Rochester, Rochester, NY 14642, USA. XHan2100@gmail.com
authors.forename: Xianglu
authors.initials: X
authors.lastname: Han
authors.forename: Nancy
authors.initials: N
authors.lastname: Corson
authors.forename: Pamela
authors.initials: P
authors.lastname: Wade-Mercer
authors.forename: Robert
authors.initials: R
authors.lastname: Gelein
authors.forename: Jingkun
authors.initials: J
authors.lastname: Jiang
authors.forename: Manoranjan
authors.initials: M
authors.lastname: Sahu
authors.forename: Pratim
authors.initials: P
authors.lastname: Biswas
authors.forename: Jacob N
authors.initials: JN
authors.lastname: Finkelstein
authors.forename: Alison
authors.initials: A
authors.lastname: Elder
authors.forename: Günter
authors.initials: G
authors.lastname: Oberdörster
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity*; D010316:Particle Size; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014025:Titanium / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods
chemical_list: D017382:Reactive Oxygen Species; C009495:titanium dioxide; D014025:Titanium