title: Simple in vitro models can predict pulmonary toxicity of silver nanoparticles.
abstract: To study the effects of nanomaterials after inhalation, a large number of in vitro lung models have been reported in literature. Although the in vitro models contribute to the reduction of animal studies, insufficient data exists to determine the predictive value of these in vitro models for the in vivo situation. The aim of this study was to determine the correlation between in vitro and in vivo data by comparing the dose metrics of silver nanoparticles in an in vitro lung model of increasing complexity to our previously published in vivo inhalation study. In vivo, the previously published study showed that the alveolar dose expressed as particle surface area is the most suitable dose metric to describe the toxicity of silver nanoparticles after inhalation. The results of the present study show that particle surface area is a suitable dose metric to describe the effects of silver nanoparticles when using a simple monolayer of lung epithelial cells. The dose metric shifted from particle surface area to particle mass when adding an increasing number of macrophages. In addition, a co-culture of endothelial cells, epithelial cells and macrophages on a Transwell® insert correlated less well to the in vivo results compared to the epithelial monolayer. We conclude that for studying the acute pulmonary toxicity of nanoparticles simple in vitro models using an epithelial monolayer better predict the in vivo response compared to complex co-culture models.
authors.affiliation: a Department of Toxicogenomics , Maastricht University , Maastricht , the Netherlands .|b National Institute for Public Health and the Environment (RIVM) , Bilthoven , the Netherlands , and.
authors.forename: Hedwig M
authors.initials: HM
authors.lastname: Braakhuis
authors.affiliation: a Department of Toxicogenomics , Maastricht University , Maastricht , the Netherlands .|b National Institute for Public Health and the Environment (RIVM) , Bilthoven , the Netherlands , and.
authors.forename: Christina
authors.initials: C
authors.lastname: Giannakou
authors.affiliation: b National Institute for Public Health and the Environment (RIVM) , Bilthoven , the Netherlands , and.|c Centre for Environmental Sciences, University Leiden , Leiden , the Netherlands.
authors.forename: Willie J G M
authors.initials: WJ
authors.lastname: Peijnenburg
authors.affiliation: b National Institute for Public Health and the Environment (RIVM) , Bilthoven , the Netherlands , and.
authors.forename: Jolanda
authors.initials: J
authors.lastname: Vermeulen
authors.affiliation: a Department of Toxicogenomics , Maastricht University , Maastricht , the Netherlands .|b National Institute for Public Health and the Environment (RIVM) , Bilthoven , the Netherlands , and.
authors.forename: Henk
authors.initials: H
authors.lastname: van Loveren
authors.affiliation: b National Institute for Public Health and the Environment (RIVM) , Bilthoven , the Netherlands , and.
authors.forename: Margriet V D Z
authors.initials: MV
authors.lastname: Park
mesh_terms: D002460:Cell Line; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D019570:Inhalation Exposure / Q000032:analysis; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D008954:Models, Biological; D010316:Particle Size; D011237:Predictive Value of Tests; D017382:Reactive Oxygen Species / Q000378:metabolism; D012834:Silver / Q000737:chemistry / Q000633:toxicity*; D013499:Surface Properties
chemical_list: D017382:Reactive Oxygen Species; D012834:Silver
keywords: Dose metrics; in vitro; nanoparticles; pulmonary toxicity