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Manufacturing

NORA Manufacturing Sector Strategic Goals

927Z1LV - Evaluation of the Pulmonary Deposition and Translocation of Nanomaterials

Start Date: 10/1/2005
End Date: 9/30/2010

Principal Investigator (PI)
Name: Robert Mercer
Phone: 304-285-6157
E-mail: rpm7@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

Recent years have seen an exponential growth in the development and production of nanomaterials. These materials have unique physical, chemical and electrical properties due to specially forged arrangements of atoms on a nanometer scale that do not occur in natural systems. Because of the unique properties and small size of nanoparticles, issues have been raised as to their potential adverse effects on the lung upon inhalation and whether they can translocate to systemic sites. This project will identify where in the lungs inhaled nanomaterials might deposit, the health risks that might arise from nanomaterial deposition, and to what extent the nanomaterials might translocate to other organs of the body after depositing in the lungs. Results of this study will address critical issues of Respiratory Disease identified by the NIOSH Nanotechnology Research Center and assist in hazard identification and risk assessment in the Manufacturing sector.



Description

This project will determine the pulmonary deposition of nanospheres or nanofibers after exposure and evaluate the fate of these deposited nanomaterials. Single walled carbon nanotubes (SWCNT) will be used as a nanofiber and the following issues evaluated: the association of nanoropes and nanotubes to form larger aggregates and/or dissociation of such aggregates, the effect that aggregate size has on toxicity and the translocation to systemic sites after pulmonary deposition. It is expected that this project will characterize the pulmonary deposition pattern of nanomaterials (quantum dots and SWCNT) with two sets of distinct physical properties, determine the extent to which they enter the interstitial space of the lungs, and evaluate resultant pulmonary inflammation and or damage. It will also provide unique data on the ability of nanospheres versus nanofibers to enter the blood and migrate to systemic organs.



To evaluate the deposition and translocation to systemic sites of nanospheres, "quantum dots" will be used. Quantum dots are 4-50 nm spheres containing encapsulated cadmium/ selenium which results in high intensity fluorescence. The distribution of these ultrafine spheres immediately after intratracheal instillation of rats and mice will be evaluated by regional dissection of the lung and quantitation of fluorescent particles by confocal microscopy. Translocation of pulmonary nanospheres will be monitored as a function of time in the blood, lymph nodes, and major systemic organs by precise quantitative measurements using neutron activation analysis of organ cadmium content.



The deposition and translocation to systemic sites of SWCNT will be evaluated as for the nanospheres based on detailed study of the pulmonary distribution and systemic delivery. Preliminary results demonstrate that pharyngeal aspiration of SWCNT by mice results in two types of lesions: (1) fibrotic nodules at sites of aggregates of SWCNT that can be seen in light microscopic sections, and (2) diffuse interstitial fibrosis in areas where visible SWCNT aggregates are absent. The question is whether nanotubes or nanoropes are present at these sites of diffuse interstitial fibrosis. To test this possibility, the SWCNT nanotubes will be labeled with 10nm gold particles. Lungs will be dissected, sectioned, and stained to identify fibrotic tissue. The gold labeled SWCNT will be visualized in sections by silver-enhancement and related to the locations of pathological changes in lung tissues. Systemic delivery of the SWCNT will be determined by neutron activation analysis of organs following instillation of gold-labeled SWCNT.



Results of the project will be disseminated by presentation at scientific conferences and publication in journals. Results will also be included in the NIOSH Nanotechnology Safety and Health Research Program annual reports and in reports by the Nanotechnology Research Center for distribution through NIOSH e-News and the NIOSH Nanotechnology Web site. It is anticipated that results will impact the direction of research by the scientific community and the development of hazard identification and prevention strategies.



Objectives

The Project Objectives will be established by completing elements of the five basic objectives of the project:

• Determine the pulmonary deposition and fate of nanospheres (quantum dots) that are hypothesized to distribute as individual nanoparticles.

• Test the hypothesis that pulmonary deposition of fiber-like nanomaterials (SWCNT) are a significant route for translocation to systemic sites.

• Determine the pulmonary deposition and fate of a fiber-like nanomaterial (SWCNT) which distribute in a wide range of aggregate sizes and determine if individual nanotubes/nanoropes are distributed during deposition and/or produced by dissociation of aggregates following deposition.

• Test the hypothesis that diffuse interstitial fibrosis from SWCNT exposure is due to the presence of sub-micron quantities of nanotubes or nanoropes in the alveolar walls.

• Determine the translocation efficiency of spherical forms of nanomaterials (quantum dots) versus aggregated/fibrous forms (SWCNT) to systemic sites.

Achievement of project goals will be determined by: 1) completion of project milestones, 2) number of presentations and publications, 3) number of times these outputs are cited by the scientific community and/or mentioned in the lay press, 4) influence in hazard identification and development of recommendations for "good workplace practices," and 5) usefulness in modeling dose-response for application to risk assessment efforts.

Achievement of project goals will be determined by: 1) completion of project milestones, 2) number of presentations and publications, 3) number of times these outputs are cited by the scientific community and/or mentioned in the lay press, 4) influence in hazard identification and development of recommendations for "good workplace practices," and 5) usefulness in modeling dose-response for application to risk assessment efforts.



Mission Relevance

The number of workers (estimated to reach 1 million U.S. in the next decade) producing or using nanomaterials is expected to grow dramatically. The NIOSH Nanotechnology Safety and Health Research Center has developed a list of "Critical Occupational Safety and Health Issues Arising from Nanotechnology." This project directly addresses the critical issue of determining the fate and persistence of nanomaterials in the body. Specifically, the goal of this project is to determine the pulmonary deposition of nanomaterials after exposure and their fate, dissociation of aggregates, and translocation to systemic sites after pulmonary deposition. These aims will be accomplished by developing techniques to label carbon nanotubes and trace their deposition in the lung and translocation to extra pulmonary organs at various times post-exposure. The outcome of this project will be use of results by regulatory agencies and industry in determining strategies for control measures and work practices to protect the worker. Information dissemination will be by direct communication of results to OSHA and EPA, communication with the scientific community, and distribution of findings to industry via the activities of the NIOSH Nanotechnology Research Center, the NIOSH website, and meetings with partners.



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) Respiratory Disease Cross-Sector (100%) Goal 5: "Prevent respiratory and other diseases potentially resulting from occupational exposure to nanomaterials"; Intermediate Goal 5.1 (09PPRDRIG5.1) "Determine the potential toxicity of nanomaterials" Activity/Output Goal 5.1.1 (09PPRDRAOG5.1.1) "Perform basic in vitro and in vivo toxicological research" Goal 2 "Prevent and reduce work-related interstitial lung diseases." Intermediate Goal 2.3 (09PPRDRIG2.3) Prevent and reduce fiber induced respiratory disease" Activity/Output Goal 2.3.5 (09PPRDRAOG2.3.5) "Perform basic toxicological research" 3) Nanotechnology (100%) "Determine if nanoparticles and nanomaterials pose risks for work-related injuries". Intermediate Goal 2.4 (09PPNANIG2.4) "Internal dose" Performance Measure 2.4 "Develop methods to label carbon nanotubes and track their deposition and fate".



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

 

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