Grantee Research Project Results

2005 Progress Report: Responses of Lung Cells to Metals in Manufactured Nanoparticles

EPA Grant Number: R831723
Title: Responses of Lung Cells to Metals in Manufactured Nanoparticles
Investigators: Veranth, John , Reilly, Christopher A. , Yost, Garold S.
Institution: University of Utah
EPA Project Officer: Hahn, Intaek
Project Period: October 1, 2004 through September 30, 2007
Project Period Covered by this Report: October 1, 2004 through September 30, 2005
Project Amount: $332,958
RFA: Exploratory Research to Anticipate Future Environmental Issues: Impacts of Manufactured Nanomaterials on Human Health and the Environment (2003) RFA Text |  Recipients Lists
Research Category: Nanotechnology , Human Health , Safer Chemicals

Objective:

The objective of this research project is to determine if transition metals in particles induce proinflammatory signaling and cell damage through the production of reactive oxygen species. Established cell culture models and toxicology assays are being applied to the analysis of manufactured nanoparticles containing metal and ceramic oxides. Based on the literature and our own data, we expect that the small physical size and high surface area of nanoparticles (d < 30 nm) will increase cellular uptake and increase induction of proinflammatory signaling compared to larger particles with the same elemental composition. In vitro studies with human and rat lung cells are being used to evaluate the effects of manufactured nanoparticles in the as-sold condition and the same materials after the particles have been subjected to surface modification simulating fire and wastewater treatment conditions. The emphasis is on lower-cost nanomaterials that are sold in powder or liquid suspension form because these materials are expected to be produced and ultimately will be released in the largest amount.

Progress Summary:

During Year 1 of the project, in vitro assays with lung epithelial cells were used to compare pairs of micron-sized and nano-sized particles with the same nominal chemical composition for cytotoxicity and induction of the proinflammatory cytokine IL-6. Results suggest that nano-sized particles of metal oxides are not always more potent than micron-sized particles. This is an important result for risk assessments of nanomaterials, and we intend to verify the conclusions in other in vitro models.

We have initial experimental indications that nanoparticles can cause artifacts in some established toxicology assays, presumably because the high surface area results in adsorption of proteins. We are following up on these artifacts as this issue is important for both designing experiments and interpreting published results.

Future Activities:

During Year 2 of the project, we intend to complete the in vitro lung cell study comparing IL-6 induction in response to micron- and nano-sized particles of the same nominal chemical composition and submit a paper for publication. Because nanoparticles are reported to translocate from the lung to other tissues, we have started experiments with other cell types, such as human umbilical vein endothelial cells. We also will be continuing studies of mRNA expression in nanoparticle-treated cells to look at mechanisms by which particles induce inflammatory responses in tissues.

Journal Articles:

No journal articles submitted with this report: View all 7 publications for this project

Supplemental Keywords:

air, bioavailability, dose-response, ultrafine particulate matter, in vitro, mammalian, cellular, metals, toxicology,, Health, Scientific Discipline, Health Risk Assessment, Risk Assessments, Environmental Chemistry, cytokines, particle size, combustion emissions, human exposure, particulate matter, engineered nanomaterials, ambient particle health effects, nanotechnology, inhalation toxicology, human health risk, inhalation study, particle exposure, biochemical research, carbon fullerene

Progress and Final Reports:

Original Abstract

2006

Final Report