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Manufacturing

NORA Manufacturing Sector Strategic Goals

927ZJJRa - Toxicological Effects of Aerosolized MWCNT (NTRC)

Start Date: 10/1/2009
End Date: 9/30/2012

Principal Investigator (PI)
Name: Dale Porter
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

By 2014 the world market for products containing nanotechnology materials, such as multi-walled carbon nanotubes (MWCNT), is estimated to be $2.6 trillion. There is paucity of information about the possible adverse health outcomes resulting from exposure to MWCNT. Thus, we plan to expose mice to aerosolized MWCNT (10 mg/m3, 5 hours per day) for either 2 days or 12 days. Pulmonary and central nervous system toxicity will be evaluated at 1 day, 14 days, 1, 3, 6, and 12 months post-exposure. The results of this study will establish correlation between MWCNT lung deposition and pathophysiological outcomes. The quantification of hazard and determination of dose-responses and time course will support risk assessment, assist in establishing exposure standards and safe handling practices, and guide development of MSDS for users.



Description

In order to predict and reduce the risk of occupational illness associated with carbon nanotubes, it is necessary to study their potential toxicological effects. Hence, our long-term goals are to conduct toxicological investigations of multi-walled carbon nanotubes, a specific form of carbon nanotube that is likely to have significant worker exposure. The aims of this project are to: (1) determine the acute and chronic pulmonary responses to inhaled MWCNT in the pulmonary system, (2) determine the acute and chronic responses to inhaled MWCNT in the central nervous system, and (3) determine the potential for inhaled MWCNT to induce mesothelioma and/or lung cancer. The central hypothesis of this proposal is that multi-walled carbon nanotubes will exhibit dose- and time-dependent toxicity in the pulmonary and central nervous systems.



To accomplish these objectives, mice will be exposed to aerosolized MWCNTs (10 mg/m3, 5 hours per day) for either 2 days or 12 days. Pulmonary and central nervous system toxicity will be evaluated at 1 day, 14 days, 1, 3, 6, and 12 months post-exposure. Pulmonary toxicity studies will examine multi-walled carbon nanotube-induced pulmonary inflammation, damage, and fibrosis. In addition, we will examine the hypothesis that inhaled multi-walled carbon nanotubes penetrate the bronchiolar epithelial and mesothelial cells, cause persistent pulmonary inflammation and lymphatic inflammation (lymphangeitis), impair lymphatic clearance in subsequent multi-walled carbon nanotubes exposure and cause malignant transformation in mice. For central nervous system toxicity studies, we will evaluate the integrity of the blood-brain barrier, neuroinflammatory and oxidative stress responses, and assess neuronal damage by biochemical and histological techniques to determine progressive neurodegenerative changes, i.e. Alzheimer's-like pathology. It is anticipated that all inhalation exposures will be completed during the first 1.5 years of this project; all other aspects of the project occur during the entire 3 year period of the project.



Objectives

This is a new project, thus none of the outputs or outcomes have been started. However, the anticipated outputs are: (i) determine the dose- and time course of pulmonary inflammation and damage induced by inhalation of multi-walled carbon nanotubes, (ii) determine the dose- and time course of pulmonary fibrosis induces by inhalation of multi-walled carbon nanotubes, (iii) determine if inhalation of multi-walled carbon nanotubes induced mesothelioma, (iv) determine if inhalation of multi-walled carbon nanotubes induces lung cancer, (v) determine the dose- and time course of neuroinflammation induced by inhalation of multi-walled carbon nanotubes, and (vi) determine if inhalation of multi-walled carbon nanotubes results in neurodegenerative disease. It is anticipated that all inhalation exposures will be completed during the first 1.5 years of this project; all other aspects of the project occur during the entire 3 year period of the project.



Project success will be judged by:



1) achievement of project aims

2) the number of presentations and publication which result from this project.

3) the number of citations of project manuscripts

4) the impact of results on NIOSH recommendations for prevention strategies

5) the usefulness of results to NTP in planning an inhalation study

6) the usefulness of results to NIOSH, OSHA and EPA in risk assessment and standard setting.



Mission Relevance

In order to predict and reduce the risk of occupational illness associated with carbon nanotubes, it is necessary to study their potential toxicological effects. Hence, our long-term goals are to conduct toxicological investigations of MWCNT, a specific form of carbon nanotube, which is likely to have significant worker exposure.

By 2014 the world market for products containing nanotechnology materials, such as multi-walled carbon nanotubes (MWCNT), is estimated to be $2.6 trillion. There is paucity of information about the possible adverse health outcomes resulting from exposure to MWCNT.

The quantification of hazard and determination of dose-responses and time course will support risk assessment, assist in establishing exposure standards and safe handling practices, and guide development of MSDS for users.



 
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