Environmental Transformation And Biological Fate Of Fresh And Aged Cerium Oxide NanoparticlesEPA Grant Number: R834860
Title: Environmental Transformation And Biological Fate Of Fresh And Aged Cerium Oxide Nanoparticles
Investigators: Jolliet, Olivier , Keeler, Gerald J. , Emond, Claude , Wagner, James , Wooldridge, Margaret , Morishita, Masako
Current Investigators: Jolliet, Olivier , Keeler, Gerald J. , Emond, Claude , Harkema, Jack , Wagner, James , Wooldridge, Margaret , Morishita, Masako
Institution: University of Michigan , Michigan State University
EPA Project Officer: Aja, Hayley
Project Period: March 1, 2011 through June 30, 2013 (Extended to February 28, 2016)
Project Amount: $600,000
RFA: Increasing Scientific Data on the Fate, Transport and Behavior of Engineered Nanomaterials in Selected Environmental and Biological Matrices (2010) RFA Text | Recipients Lists
Research Category: Chemical Safety for Sustainability
The overall objective is to improve our understanding of environmental exposure-dose pathways of Cerium oxide (CeO2) nanoparticles (NPs). Our Specific Aims are: (1) characterize environmental transformation and physicochemical properties of aged CeO2 NPs using their interactions with UV radiation and ambient air co-pollutants, and compare them to freshly-combusted CeO2 NPs; (2) determine the biological fate of freshly-combusted and aged CeO2 NPs, comparing the concentrations in blood and target organs resulting from animal inhalation and intratracheal exposures; and (3) develop and evaluate a Physiologically Based ToxicoKinetic (PBTK) model of CeO2 NPs to identify the main factors affecting translocation and distribution of CeO2 NPs in the body. These Specific Aims are designed to test four hypotheses: (1) the solubility and macrophage uptake of aged CeO2 NPs increase after atmospheric transformation by photochemical reaction occurs; (2) significant translocation from the nasal cavity via olfactory neural paths to the brain will be observed; (3) the inhalation of aged CeO2 NPs will lead to greater distribution in the body than freshly-combusted NPs; and (4) The rapidly perfused organs with higher macrophage reserves will be the organs that will trap the majority of the free NPs.
First we will conduct detailed physicochemical characterization (e.g., solubility, morphology, size distribution) of both freshly-combusted and aged NPs and measure the degree of photochemical transformation following interactions with UV radiation and air co-pollutants including nitric oxides and sulfur dioxide. Second, we will conduct animal inhalation and intratracheal instillation exposure studies, and measure CeO2 NP concentrations in blood and multiple organs via ICP-MS. We will finally develop an 8 compartment multiscale PBTK model, use a mass balance analysis of the in vivo kinetics experiment to parameterize it and carry out a sensitivity study to gain understanding on the main factors affecting biodistribution.
This project will aid in understanding the bioavailability and exposure-dose pathways of environmentally relevant CeO2 NPs. The project will provide new insights into physicochemical transformation of CeO2 NPs in the atmosphere; biological fate and mass balance of CeO2 NP distribution from the inhalation exposure routes; and the first PBTK model of environmentally relevant CeO2 NP inhalation exposure.