Grantee Research Project Results
2007 Progress Report: Impacts of Manufactured Nanomaterials on Human Health and the Environment - A Focus on Nanoparticulate Aerosol and Atmospherically Processed Nanoparticulate Aerosol
EPA Grant Number: R831717Title: Impacts of Manufactured Nanomaterials on Human Health and the Environment - A Focus on Nanoparticulate Aerosol and Atmospherically Processed Nanoparticulate Aerosol
Investigators: Grassian, Vicki H. , Thorne, Peter S. , O'Shaughnessy, Patrick
Institution: University of Iowa
EPA Project Officer: Aja, Hayley
Project Period: October 1, 2004 through September 30, 2007
Project Period Covered by this Report: October 1, 2006 through September 30, 2007
Project Amount: $335,000
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:
In this research, the potential effects of manufactured nanoparticle aerosol on human health are being investigated. This research is being conducted to satisfy three main objectives. These objectives are to:
- fully characterize a variety of manufactured nanomaterials in terms of their size, shape, bulk and surface properties;
- determine if engineered nanomaterials are particularly deleterious to health compared toparticles from combustion processes that have been more extensively studied; and
- evaluate the relative health effects caused by different surface coatings on the nanoparticle.
To carry out these objectives a variety of different chemical classes of nanomaterials are to beinvestigated. Surface coatings, or capping groups, are often used to control particle size inmanufacturing. Thus, the effects of surface coatings from both the manufacturing process in thetoxicity of manufactured nanomaterials. We have focused our attention on metal and metal oxide based nanomaterials as these materials have wide ranging applications and are being used in consumer products.
Progress Summary:
In the past year, the potential effects of manufactured nanoparticles on human health have beeninvestigated. In particular, a series of acute and sub-chronic exposures of TiO2 nanoparticles with a primary particle size of 5 nm have been completed. Although there have been earlier inhalation studies on TiO2 ultrafine particles, these have been done on particles with a particlesize of 20 nm and above, there is some evidence that particles with a primary particle size lessthan 10 nm may behave differently than particles with a primary particle size greater than 10 nm.Titanium dioxide (TiO2) nanoparticles with a primary size of 2-5 nm have not previously been studied in inhalation exposure models and represent some of the smallest manufactured nanoparticles. The properties of TiO2 nanoparticles as well as the characteristics of aerosols ofthese particles were evaluated. The purpose of this study was to assess the toxicity of these nanoparticles using a murine model of lung inflammation and injury. Mice were exposed to TiO2nanoparticles in a whole-body exposure chamber acutely (4 hr) or sub-acutely (4 hr/day for 10 days). (See Figure 1 showing the schematic of the exposure chamber). Toxicity in exposed micewas assessed by enumeration of total and differential cells, determination of total protein, LDHactivity and inflammatory cytokines in bronchoalveolar fluid. Lungs were also evaluated forhistopathological changes. Mice exposed acutely to 0.77 or 7.22 mg m-3 of nanoparticles demonstrated minimal lung toxicity or inflammation. Mice exposed sub-acutely (8.88 mg m-3)and necropsied immediately, 1 or 2 wks post exposure had higher counts of total cells and macrophages in the broncheoalveolar lavage fluid compared to sentinels. However, mice recovered by 3rd wk post exposure. Other indicators were negative. From this study, , we concluded that mice sub-acutely exposed to 2-5 nm TiO2 nanoparticles showed a significant but moderate inflammatory response among animals 0, 1 or 2 wks after exposure that resolved 3 wkspost exposure.
In another study, instillation and acute inhalation exposures of different size TiO2 particles to mice are run to examine how nanoparticle size and exposure method affect inflammatory response. Through the use of a whole body exposure chamber and nasal instillation techniquealong with bulk and surface characterization techniques, it was found that the smaller 5 nmparticles did not create a larger inflammatory response than 20 nm particles. The aggregation states of the particles were shown using TEM to behave very different in the instillation solutioncompared to the powder delivery in the acute inhalation exposure. One conclusion from this study is that the aggregation state of the particles, along with other surface and physicalcharacteristics, is an important factor in the toxicity of nanoparticles.
Figure 1. The powder XRD pattern of iron nanoparticles is shown along with reference spectra of Fe metal, Fe3O4 and γ-Fe2O3. (B) The powderXRD pattern of copper nanoparticles is shown along with reference spectra of Cu metal, Cu2O and CuO. Based on the XTD data as well as TEM measurements and surface analysis using X-ray photoelectron spectroscopy, pictorial representationsof the iron and copper nanoparticles with these different phases are shown.
Finally, we have completed a study of acute and sub-acute exposures of 25 nm iron and copper nanoparticles. Based on the physicochemical characterization data which includes powder X-ray diffraction, TEM (from whole body chamber, vide infra) and X-ray photoelectron spectroscopyfor these commercially materials, these nanoparticles consist of a metallic core and an oxide coating that contains two phases with the most oxide phase being on the surface of thenanoparticles (see Figure 1 which shows XRD data). The toxicity data shown below in Figure 2 gives a comparison of the total number of cells and differential cell counts in the bronchoalveolar lavage fluid for control mice and for mice sub-acutely exposed to Fe and Cu nanoparticles. It can be seen from these data that Cu nanoparticles produce the greatest response and give rise tothe highest cell count and the greatest percentage of neutrophils. Copper nanoparticle exposedmice showing significantly larger response as well as signs of perivasculitis and aveolitis in lungs. After 3 weeks post-exposure, all inflammatory markers decreased and lungs were evaluated as normal for both iron and copper nanoparticle-exposed mice. In vitro dissolution studies showed that copper nanoparticles displayed enhanced propensity for dissolution compared to iron nanoparticles at biologically relevant pHs. Nanoparticle dissolution results in both dissolved ions and nanoparticles of decreased size. As such, it is surmised that both theformation of dissolved ions and the concomitant production of smaller nanoparticles below 10 nm that form during the dissolution process following inhalation of copper nanoparticles, may bethe cause of the increased inflammatory response in exposed mice.
Figure 2. Number of cells in BAL fluid from animals acutely sub-acutely exposed to Fe and Cu nanoparticles.
People Working on the Project
Vicki Grassian, PI, Department of Chemistry, Patrick O’Shaughnessy, co-PI, Department of Environmental and Occupational Health, Peter Thorne, co-PI, Department of Environmental and Occupational Health, John Pettibone, Ph.D. candidate, Department of Chemical and Biochemical Engineering, Dr. Andrea Adamcakova-Dodd, Research Scientist, Department of Environmental and Occupational Health.
Future Activities:
We are currently finishing up experiments that will be included in the publication Pettibone (et al 2008). We are investigating the solubility and dissolution properties of these mental nanoparticleto better understand the inhalation toxicology results that show copper nanoparticles give rise to a much larger inflammatory response than other nanoparticles investigated thus far.
Journal Articles on this Report : 4 Displayed | Download in RIS Format
| Other project views: | All 21 publications | 6 publications in selected types | All 5 journal articles |
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Grassian VH, Adamcakova-Dodd A, Pettibone JM, O'Shaughnessy PI, Thorne PS. Inflammatory response of mice to manufactured titanium dioxide nanoparticles: comparison of size effects through different exposure routes. Nanotoxicology 2007;1(3):211-226. |
R831717 (2007) |
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Grassian VH, O'Shaughnessy PT, Adamcakova-Dodd A, Pettibone JM, Thorne PS. Inhalation exposure study of titanium dioxide nanoparticles with a primary particle size of 2 to 5 nm. Environmental Health Perspectives 2007;115(3):397-402. |
R831717 (2005) R831717 (2006) R831717 (2007) |
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Pettibone JM, Adamcakova-Dodd A, Thorne PS, O’Shaughnessy PT, Weydert JA, Grassian VH. Inflammatory response of mice following inhalation exposure to iron and copper nanoparticles. Nanotoxicology 2008;2(4):189-204. |
R831717 (2007) |
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Pettibone JM, Cwiertny DM, Scherer M, Grassian VH. Adsorption of organic acids on TiO2 nanoparticles: effects of pH, nanoparticle size, and nanoparticle aggregation. Langmuir 2008;24(13):6659-6667. |
R831717 (2007) |
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Supplemental Keywords:
Health, Scientific Discipline, PHYSICAL ASPECTS, Health Risk Assessment, Physical Processes, Risk Assessments, Environmental Chemistry, Biochemistry, cytokines, particle size, human exposure, particulate matter, engineered nanomaterials, exposure, ambient particle health effects, nanotechnology, respiratory impact, inhalation toxicology, human health risk, inhalation study, particle exposure, biochemical researchProgress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.