Toxicology of Inhaled Ultrafine Particles and Engineered Nanomaterials

Our laboratory has focused for several years on the toxicology of inhaled ultrafine particles (UFPs), the most numerous size fraction of particulate air pollution. Interests include the impacts of age, gaseous co-pollutant exposure, and health status on the response(s) to inhaled UFPs. We are also interested in determining the basis for potential adverse effects of inhaled particles in the cardiovascular and central nervous systems.

This research focus has naturally led to our work with engineered nanomaterials. The research commonalities between UFP and nanomaterials are numerous, including the kinetics of tissue distribution following exposure, mechanisms of response related to oxidative stress, particle-protein interactions, and the physicochemical characteristics of the particles that determine response. Our research aims are met by using a combination of animal and cell culture models as well as detailed particle characterization.

In addition to looking for nanosized particles in tissues via chemical and microscopic means, responses are determined by measuring markers of inflammation and oxidative stress in the lung lining fluid, lung tissue, blood, circulating inflammatory cells, and extrapulmonary tissues (e.g. heart, liver, spleen, kidney, brain regions). We also have specific projects focused on cardiovascular stability and neurodegeneration following exposures to UFPs and nanomaterials.

Selected Publications

Han X, Gelein R, Corson N, Wade-Mercer P, Jiang J, Biswas P, Finkelstein JN, Elder A, and Oberdšrster G. Validation of an LDH assay for assessing nanoparticle toxicity. Toxicology. 2011 Sep 5;287(1-3):99-104. Epub 2011 Jun 23.

Elder AN, Dangelo NM, Kim SC, Washburn NR. Conjugation of beta-sheet peptides to modify the rheological properties of hyaluronic acid. Biomacromolecules. 2011 Jul 11;12(7):2610-2616.

Elder A, McManus C, McAlpine L, Dacre J. What skills are tested in the new PACES examination? Ann Acad Med Singapore. 2011 Mar;40(3):119-125.

Anderson A, Boyd K, Christie B, Claridge C, Currie P, Doherty T, Dorward D, Elder A, Hadley-Brown M, Hughes D, Jackson M, Jung R, Marshall S, MacKinnon M, Pollock A, Ritchie L.M RCPE UK consensus statement on diabetes. J R Coll Physicians Edinb. 2010 Jun;40(2):130-131.

Elder AS, Saccone GT, Bersten AD, and Dixon DL. L-Arginine-induced acute pancreatitis results in mild lung inflammation without altered respiratory mechanics. Exp Lung Res. 2011 Feb;37(1):1-9.

Elder AS, Saccone GT, Bersten AD, and Dixon DL. Caerulein-induced acute pancreatitis results in mild lung inflammation and altered respiratory mechanics. Exp Lung Res. 2011 Mar;37(2):69-77.

Gil, P.R., G. Oberdörster, A. Elder, V. Puntes, W.J. Parak. Correlating Physico-Chemical with Toxicological Properties of Nanoparticles: The Present and the Future. ACS Nano. 2010 Oct 26;4(10):5527-5531

Gillespie, P.A., G.S. Kang, A. Elder, R. Gelein, L. Chen, A.L. Moreira, J. Koberstein, K.M., Tchou-Wang, T. Gordon, L.C. Chen. Pulmonary response after exposure to inhaled nickel hydroxide nanoparticles: short and long-term studies in mice. Nanotoxicol. 4(1): 106-119, 2010.

Kim, S.C., D. Chen, C. Qi, R.M. Gelein, J.N. Finkelstein, A. Elder, K. Bentley, G. Oberdörster, D.Y.H. Pui. A Nanoparticle Dispersion Method of In Vitro and In Vivo Nanotoxicity Study. Nanotoxicol. 4(1): 42-51, 2010.

Rushton, E.K., J. Jiang, S.S. Leonard, S. Eberly, V. Castranova, P. Biswas, A. Elder, X. Han, R. Gelein, J. Finkelstein, G. Oberdörster. Concept of Assessing Nanoparticle Hazards Considering Nanoparticle Dosemetric and Chemical/Biological Response Metrics. J. Toxicol. Environ. Health Part A 73: 445-461, 2010.

VanWinkle, B.A., K.L. de Mesy Bentley, J.M. Malecki, K.K. Gunter, I.M. Evans, A. Elder, J.N. Finkelstein, G. Oberdörster, T.E. Gunter. Nanoparticle (NP) uptake by type I alveolar epithelial cells and their oxidant stress response. Nanotoxicol. 3(4): 307-318, 2009.

Elder, A. Nanotoxicology: How Do Nanotubes Suppress T Cells? Nat. Nanotechnol. 4(7): 409-410, 2009. Commentary.

Elder, A., S. Vidyasagar, L. DeLouise. Physicochemical Factors that Affect Metal and Metal Oxide Nanoparticle Passage Across Epithelial Barriers. WIREs Nanomed. Nanobiotechnol. 1(4): 434-450, 2009.

Oberdörster, G., A. Elder, A. Rinderknecht. Nanoparticles and the Brain:Cause for Concern? J. Nanosci. Nanotechnol. 9: 4996-5007, 2009. Review.

Jiang, J., G. Oberdörster, A. Elder, R. Gelein, P. Mercer, P. Biswas. Does Nanoparticle Activity Depend On Size and Crystal Phase? Nanotoxicol. 2(1): 33-42, 2008

Elder, A., H. Yang, R. Gwiazda, X. Teng, S. Thurston, H. He, G. Oberdörster. 2007. A Testing Strategy for Nanomaterials of Unknown Toxicity: An Example using Platinum Nanoparticles of Different Shapes. Adv. Materials. 19: 3124-3129.

Elder A, Couderc J-P, Gelein R, Eberly S, Cox C, Xia X, Zareba W, Hopke P, Kittelson D, Frampton M, Utell M, Oberdörster G. 2007. Effects of On-Road Highway Aerosol Exposures on Autonomic Responses in Aged, Spontaneously Hypertensive Rats. Inhalation Toxicol. Jan; 19: 1-12.

Elder A, Oberdörster G. 2006. Translocation and effects of ultrafine particles outside of the lung. Clin Occup Environ Med. 5(4):785-796. Review.

Carter JM, Corson N, Driscoll KE, Elder A, Finkelstein JN, Harkema JR, Gelein R, Wade-Mercer P, Nguyen K, Oberdörster G. 2006. A Comparative Dose-Related Response of Several Key Pro- and Anti-inflammatory Mediators in the Lungs of Rats, Mice and Hamsters after Subchronic Inhalation of Carbon Black. J Occup Environ Med. Dec; 48(12): 1265-1278.

Elder A, Gelein R, Silva V, Feikert T, Opanashuk L, Carter J, Potter R, Maynard A, Ito Y, Finkelstein J, Oberdörster G. 2006. Translocation of Inhaled Ultrafine Manganese Oxide Particles to the Central Nervous System. Environ Health Perspect. Apr; 114 (8): 1172-1178.