Chemical Fate, Biopersistance, and Toxicology of Inhaled Metal Oxide Nanoscale Materials
|Principal Investigator||Jacob D McDonald|
|Institution||Lovelace Respiratory Research Institute|
|Relevance to Implications||High|
|Class of Nanomaterial||Engineered Nanomaterials|
|Impact Sector||Human Health|
|Broad Research Categories||
Generation, Dispersion, Transformation etc.
|Anticipated Total Funding||$375,000.00|
|Anticipated End Year||2008|
Observations of unpredicted biological disposition, increased biopersistence, and increased toxicity of the same inhaled materials as they decrease in size (and increase in surface area) has sparked interest in the developing field of nanotechnology. There is an immediate need to confirm and extend those observations as they apply to nanoscale materials (NSMs), including NSMs of different composition. This proposed research will directly compare the biological disposition, persistence, and toxicity of two commercial nanoscale and non-nanoscale metal oxide classes. We will determine the impact of particle class, particle size, and surface area on NSMs that are of significant commercial relevance for nanotechnology (SiO2 and Al2O3).
The proposed studies will test the hypothesis that the biological disposition, persistence, and toxicity of metal oxides change with size (comparisons between nanoscale and micron size) and composition (comparisons between SiO2 and Al2O3) of metal oxide powders. Specifically, we will test the hypothesis that metal oxide particles that are manufactured in the nanoscale have (a) longer biological persistence and (b) increased pulmonary and systemic toxicity relative to the same metal oxides of larger sizes.
Two primary objectives will be executed after repeated inhalation studies (F344 rats, 6 hours/day, 5 days/week for 6 weeks to nanoscale- and micron-size materials of the same composition): (1) determine biological disposition (translocation/elimination/persistence) by measurement of residual metal oxide in plasma and six target organs (lung, brain, liver, kidney, spleen, intestine), and (2) determine local (lung/respiratory tract) and systemic toxicity by measurements of sensitive biochemical markers of inflammation and oxidative stress in addition to histopathological analysis. For both (1) and (2), measurements will be made immediately post exposure, 4 weeks post exposure, and 17 weeks post exposure to complement previous studies in our laboratory on micron-size SiO2 (Langley et al., 2004).
We expect to see extrapulmonary disposition of both types and sizes of metal oxide powders. Because both metal oxides will have partial solubility in vivo, we expect some of the retained and eliminated material will be in a soluble form (this not tested directly). We expect that the NSM will have a longer biopersistence and its increased surface area will lead to increased pulmonary and systemic toxicity. However, we expect that the effect will diminish with decreasing dose and that if doses in the range of plausible human exposure (not yet known) are studied, the toxic effects will diminish.