Computational and Experimental Nanoparticle Dosimetry for nanomaterial Safety
EMSL Project ID
18190
Abstract
Development and deployment of nanomaterial based technologies improving energy and environmental security are high priority research activities for the Department of Energy. Nanomaterial development and manufacturing is expanding rapidly and with it the potential for human exposure to nanoscale particles for which there no health and safety information. The Systems Nanotoxicology focus area of the Pacific Northwest National Laboratory?s Environmental Biomarker Initiative is developing the capabilities to lead the assessment and prediction of health risks associated with human exposure to nanomaterials, meeting a crucial unmet research need. In vitro cell-based systems are the principal tool for screening nanomaterials and larger particles for biological or toxicological activity. Cells are exposed to test nanomaterials solubilized in culture media and the cellular response is measured as a function of time and media concentration. This conventional measure of dose, particle concentration, are widely used for comparing toxicity across particle class and size but are appropriately applied only to particles of similar size and density because they ignore size and density dependencies on agglomeration and settling rates. These measures of dose also lack the biological relevance reflected by the preferred measure, target tissue dose, or in the case of in vitro work, dose-to-the cell.
The work we propose to complete under the EMSL user agreement is part of a proposal to improve the basis for comparative dosimetry and toxicity of nanoparticles by systematically characterizing the nanomaterial dosimetry using Scanning Electron Microscopy and to provide researchers and regulators with a computational tool for transforming convenient measures of dose into more relevant measures of dose-to-the cell. No other published work or funded proposals address this fundamental problem.
We propose to administer several concentrations and sizes of three important classes of nanoparticles, TiO2, polystyrene beads, and single walled carbon nanotubes to media overlaying a plastic coverslip, and remove the media at various times after exposure. The coverslips with attached nanoparticles will then be processed and submitted for SEM analysis. The number and agglomeration state of particles on the coverslip will be determined using automated image analysis and used to validate the predictions of a computational model of nanoparticle diffusion, agglomeration and deposition. These measures of dose-to-the cell will then be correlated with measures of cellular response collected in the same system in a separate part of the grant proposal.
We hypothesize that higher accuracy measures of dose in vitro will reveal new dose-response relationships, improve the basis for comparative toxicity of nanoparticles, and provide greater power in predicting response within and across particle types. The results are expected to be very high impact in the fields of toxicology, and nanomaterial sciences.
The EMSL user agreement is critical to the success of the grant proposal, and to the success of several projects within the Environmental Biomarker Initiative because SEM is the only single method that provides direct measures of particle deposition and agglomeration state.
Project Details
Project type
Exploratory Research
Start Date
2006-08-01
End Date
2007-01-19
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Teeguarden JG, Webb-Robertson BJ, Waters KM, Murray AR, Kisin ER, Varnum SM, Jacobs JM, Pounds JG, Zanger RC, Shvedova AA. Comparative proteomics and pulmonary toxicity of instilled single-walled carbon nanotubes, crocidolite asbestos, and ultrafine carbon black in mice.
Toxicological Sciences (2011), 120 (1), 123-135