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Title: Particokinetics In Vitro: Dosimetry Considerations for In Vitro Nanoparticle Toxicity Assessments

Abstract

The rapid growth in the use of in vitro methods for nanoparticle toxicity assessment has proceeded with limited consideration of the unique kinetics of these materials in solution. Particles in general and nanoparticles specifically, diffuse, settle and agglomerate in cell culture media as a function of several systemic and particle factors: media density and viscosity, particle size, shape and density. Cellular dose then is also a function of these factors as they determine the rate of transport of nanoparticles to cells in culture. Here we develop and apply the principles of particokinetics and dosimetry in vitro and outline an approach for simulation of nanoparticle particokinetics in cell culture systems. We illustrate that where equal mass concentrations (μg/ml) imply equal doses for dissimilar materials, the corresponding particle number or surface area concentration doses differ by orders of magnitude. When rates of diffusional and gravitational particle delivery are accounted for, the trends and magnitude of cellular dose as a function of particle size and density differ significantly from those implied by NMC doses. Fifteen nm Ag nanoparticles appear ~4000 times more potent than micron sized cadmium oxide particles on a cm2/ml media basis, but are only ~50 times more potent when differencesmore » in nanoparticle delivery to adherent cells are considered. We conclude that simple surrogates of dose can cause significant misinterpretation of response and uptake data for nanoparticles in vitro. Incorporating particokinetics and principles of dosimetry would significantly improve the basis for or nanoparticles toxicity assessment, increasing the predictive power and scalability of such assays.« less

Authors:
; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)
Sponsoring Org.:
USDOE
OSTI Identifier:
898095
Report Number(s):
PNNL-SA-55055
25390; 30504; TRN: US200705%%406
DOE Contract Number:
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicological Sciences, 95(2):300-312
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; CADMIUM OXIDES; CELL CULTURES; DOSIMETRY; IN VITRO; KINETICS; PARTICLE SIZE; SHAPE; SURFACE AREA; TOXICITY; nanomaterial; kinetics; dosimetry; in vitro; risk assessment; settling; agglomeration; diffusion; Environmental Molecular Sciences Laboratory

Citation Formats

Teeguarden, Justin G., Hinderliter, Paul M., Orr, Galya, Thrall, Brian D., and Pounds, Joel G. Particokinetics In Vitro: Dosimetry Considerations for In Vitro Nanoparticle Toxicity Assessments. United States: N. p., 2007. Web. doi:10.1093/toxsci/kfl165.
Teeguarden, Justin G., Hinderliter, Paul M., Orr, Galya, Thrall, Brian D., & Pounds, Joel G. Particokinetics In Vitro: Dosimetry Considerations for In Vitro Nanoparticle Toxicity Assessments. United States. doi:10.1093/toxsci/kfl165.
Teeguarden, Justin G., Hinderliter, Paul M., Orr, Galya, Thrall, Brian D., and Pounds, Joel G. Thu . "Particokinetics In Vitro: Dosimetry Considerations for In Vitro Nanoparticle Toxicity Assessments". United States. doi:10.1093/toxsci/kfl165.
@article{osti_898095,
title = {Particokinetics In Vitro: Dosimetry Considerations for In Vitro Nanoparticle Toxicity Assessments},
author = {Teeguarden, Justin G. and Hinderliter, Paul M. and Orr, Galya and Thrall, Brian D. and Pounds, Joel G.},
abstractNote = {The rapid growth in the use of in vitro methods for nanoparticle toxicity assessment has proceeded with limited consideration of the unique kinetics of these materials in solution. Particles in general and nanoparticles specifically, diffuse, settle and agglomerate in cell culture media as a function of several systemic and particle factors: media density and viscosity, particle size, shape and density. Cellular dose then is also a function of these factors as they determine the rate of transport of nanoparticles to cells in culture. Here we develop and apply the principles of particokinetics and dosimetry in vitro and outline an approach for simulation of nanoparticle particokinetics in cell culture systems. We illustrate that where equal mass concentrations (μg/ml) imply equal doses for dissimilar materials, the corresponding particle number or surface area concentration doses differ by orders of magnitude. When rates of diffusional and gravitational particle delivery are accounted for, the trends and magnitude of cellular dose as a function of particle size and density differ significantly from those implied by NMC doses. Fifteen nm Ag nanoparticles appear ~4000 times more potent than micron sized cadmium oxide particles on a cm2/ml media basis, but are only ~50 times more potent when differences in nanoparticle delivery to adherent cells are considered. We conclude that simple surrogates of dose can cause significant misinterpretation of response and uptake data for nanoparticles in vitro. Incorporating particokinetics and principles of dosimetry would significantly improve the basis for or nanoparticles toxicity assessment, increasing the predictive power and scalability of such assays.},
doi = {10.1093/toxsci/kfl165},
journal = {Toxicological Sciences, 95(2):300-312},
number = ,
volume = ,
place = {United States},
year = {Thu Feb 01 00:00:00 EST 2007},
month = {Thu Feb 01 00:00:00 EST 2007}
}
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