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NIOSH Program Portfolio

 

Manufacturing

NORA Manufacturing Sector Strategic Goals

927Z6SB - Pulmonary Toxicity of Metal Oxide Nanospheres and Nanowires

Start Date: 10/1/2006
End Date: 9/30/2010

Principal Investigator (PI)
Name: Dale Porter
Phone: 304-285-6320
E-mail: dhp7@cdc.gov
Organization: NIOSH
Sub-Unit: HELD
Funded By: NIOSH

Primary Goal Addressed
9.0

Secondary Goal Addressed
None


Attributed to Manufacturing
100%

Project Description

Short Summary

The experiments in this project will provide fundamental toxicological data on the exposure hazard posed by TiO2 nanospheres and nanowires. The significance of this project is that data obtained will: (i) increase our understanding of how TiO2 nanoparticle shape affects toxicological responses; (ii) determine critical physico-chemical factors that could be exploited to reduce nanoparticle toxicity; and (iii) provide a basis for initial hazard identification. In addition, these data will contribute to risk assessment studies which may ultimately establish exposure standards and recommended handling practices to avert significant human health risks in the future. Ultimately, knowledge obtained in this project will reduce respiratory disease from occupational exposure in the manufacturing sector, specifically nanotechnology.



Description

The central hypothesis of this proposal is that engineered nanomaterials of the same chemical composition, but different shape, i.e., nanospheres versus nanowires, will exhibit different toxicities. The rationale for this project is that once it is known how nanoparticle geometry affects their toxicity, this knowledge may be used to reduce nanoparticle toxicity. The objective of this project is to study the effect of nanoparticle shape on toxicity in the pulmonary and central nervous systems. To accomplish this objective and to test the central hypothesis, three Specific Aims will be conducted.



In Specific Aim 1, TiO2 nanowires and nanospheres will be synthesized and characterized. Successful completion of this Specific Aim will provide necessary materials for studying how shape of manufactured TiO2 nanoparticles affects their toxicity. The characterization of these nanoparticles will allow us to correlate the physical and chemical properties of TiO2 nanoparticles with their toxicology.



Reactive oxygen species (ROS) generation has been suggested to currently be the best-developed paradigm regarding the toxicity of nanomaterials. Thus, data regarding ROS generation is an important component in understanding nanoparticle toxicity, and will allow comparison to other nanoparticles. Thus, in Specific Aim 2, we plan to investigate nanoparticle-dependent ROS generation from TiO2 nanospheres and nanowires.



It is assumed that aerosolization of nanoparticles is likely, and thus potential pulmonary toxicity is a major concern. Furthermore, nanoparticles have been shown to translocate to other major organs, e.g. the brain, after pulmonary deposition, where they may cause nanoparticle-induced toxicity. Thus, in Specific Aim 3, we will determine the differential toxicity of TiO2 nanospheres and nanowires in the pulmonary and central nervous systems, after pulmonary deposition via pharyngeal aspiration in mice. To determine the effect of shape, TiO2 nanosphere- and nanowire-induced toxicity will be compared.



Recently, a panel of experts assembled by EPA proposed some basic principles for the initial hazard identification for nanomaterial risk assessments. The experiments in this project follow the recommendations of this expert panel. If the experiments in this project are conducted, fundamental toxicological data on the exposure hazard posed by TiO2 nanospheres and nanowires will be obtained. The significance of this project is that data obtained will: (i) increase our understanding of how TiO2 nanoparticle shape affects toxicological responses; (ii) determine critical physico-chemical factors that could be exploited to reduce nanoparticle toxicity; and (iii) provide a basis for initial hazard identification. In addition, these data could contribute to risk assessment studies which may ultimately establish exposure standards and recommended handling practices to avert significant human health risks in the future. Ultimately, knowledge obtained in this project will reduce the burden of human illness and dysfunction from occupational or public environmental exposure to manufactured nanoparticles.



Objectives

• The objective of this project is to study the effect of nanoparticle shape on toxicity.



• Outputs from this project will be data presented at scientific meetings and publication in peer-reviewed journals.



• The outputs from this project will: (i) increase our understanding of how TiO2 nanoparticle shape affects toxicological responses; (ii) determine critical physico-chemical factors that could be exploited to reduce nanoparticle toxicity; and (iii) provide a basis for initial hazard identification.



• The outputs from this project may also contribute to risk assessment studies which may ultimately establish exposure standards and recommended handling practices to avert significant human health risks in the future.



Mission Relevance

With the rapid development of nanotechnology, manufactured nanomaterials, which fall into the dimension of 1-100 nm, are receiving intense interest. Nanospheres and one-dimensional nanostructures (nanowires, nanorods, nanobelts and nanotubes), which are prevailing forms of nanomaterials, exhibit different physical and chemical properties from similar bulk or micron-sized material, offering new or improved engineered applications and medical uses. However, owing to the unique physical and chemical characteristics, engineered nanomaterials may have distinctive biological effects that are different from their bulk counterparts.



The tremendous potential for the development and large scale commercialization of a variety of nanoparticles with different physico-chemical properties means that there is increased risk of exposure to such materials. Unfortunately, a paucity of data exists regarding the toxic potential of many nanomaterials, as well as the physico-chemical properties of nanoparticles that affect their toxicity. Workers are at risk for exposure to nano-sized particles during manufacturing and handling.



At this time, no recommendations can be made regarding exposure limits for any engineered nanomaterials. Recently, a panel of experts assembled by EPA proposed some basic principles for the initial hazard identification for nanomaterial risk assessments. The experiments in this project follow the recommendations of this expert panel. Specifically, titanium nanospheres and nanowires will be synthesized and physicochemically characterized at the West Virginia University Nanotechnology Center. The contribution of shape to in vitro and in vivo bioactivity will be determined at the University of Montana and NIOSH, respectively. Dose-response and time course information will be collected. After experiments in this project are conducted; fundamental toxicological data will be obtained which will dramatically increase our understanding of the potential exposure hazard posed by TiO2 nanospheres and nanowires.



Research results will address the following goals: 1) Goal 9 of the Manufacturing Sector (100%): "Enhance the state of knowledge related to emerging risks to occupational safety and health in manufacturing." 2) Goal 5 of the Respiratory Disease Cross-Sector (100%): "Prevent respiratory and other disease potentially resulting from occupational exposure to nanomaterials"; Intermediate Goal 1: (09PPRDRIG1) "Determine the potential respiratory toxicities of nanomaterials" Activity/Output Goal 5.1.1 (09PPRDRAO5.1.1) "Perform basic in vitro and in vivo toxicology studies" 3) Nanotechnology (100%) Goal 1 "Determine if nanoparticles and nanomaterials pose risks for work-related injuries and illnesses." Intermediate Goal 2 (09PPNANIG2) "Toxicity and internal dose".



Page last updated: June 3, 2011
Page last reviewed: May 23, 2011
Content Source: National Institute for Occupational Safety and Health (NIOSH) Office of the Director

 

NIOSH Program:

Manufacturing