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

Santhanam, P., J.G. Wagner, A. Elder, R. Gelein, J.M. Carter, K.E. Driscoll, G. Oberdörster, J.R. Harkema. 2008. Nasal Toxicity in Laboratory Rats After Subchronic Inhalation Exposure to Carbon Black Nanoparticles. International J. Nanotechnology 5(1): 30-54.

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.

Elder A, Gelein R, Finkelstein JN, Driscoll KE, Harkema J, Oberdörster G. 2005. Effects of Subchronically Inhaled Carbon Black in Three Species. I. Retention Kinetics, Lung Inflammation, and Histopathology. Toxicol Sci. Dec;88(2):614-629

Elder A, Johnston C, Gelein R, Finkelstein J, Wang Z, Notter R, Oberdörster G. 2005 Lung inflammation induced by endotoxin is enhanced in rats depleted of alveolar macrophages with aerosolized clodronate. Exp Lung Res. Jul-Aug;31(6):527-546.

Johnston CJ, Williams JP, Elder A, Hernady E, and Finkelstein JN. 2004. Inflammatory cell recruitment following thoracic irradiation. Exp Lung Res. Jul-Aug;30(5):369-382.

Silva VM, Corson N, Elder A, Oberdörster G. 2005. The rat ear vein model for investigating in vivo thrombogenicity of ultrafine particles (UFP). Toxicol Sci. Jun;85(2):983-989.

Oberdörster, G., Z. Sharp, V. Atudorei, A. Elder, R. Gelein, W. Kreyling, and C. Cox. 2004. Translocation of Inhaled Ultrafine Particles to the Brain. Inhal. Toxicol. Jun;16(6-7):437-445.

Elder, A.C.P., R. Gelein, M. Azadniv, M. Frampton, J. Finkelstein, and G. Oberdörster. 2004. Systemic Effects of Inhaled Ultrafine Particles in Two Compromised, Aged Rat Strains. Inhal. Toxicol. Jun;16(6-7):461-471.

Kittelson DB, Watts WF, Johnson JP, Remerowki ML, Ische EE, Oberdörster G, Gelein RM, Elder A, Hopke PK, Kim E, Zhao W, Zhou L, and Jeong CH. 2004. On-Road Exposure to Highway Aerosols. 1. Aerosol and Gas Measurements. Inhal. Toxicol. 16 Suppl 1:31-39.

Elder A, Gelein R, Finkelstein J, Phipps R, Frampton M, Utell M, Kittelson DB, Watts WF, Hopke P, Jeong CH, Kim E, Liu W, Zhao W, Zhuo L, Vincent R, Kumarathasan P, and Oberdörster G. 2004. On-Road Exposure to Highway Aerosols. 2. Exposures of Aged, Compromised Rats. Inhal Toxicol. 2004;16 Suppl 1:41-53.

Elder AC, Gelein R, Oberdörster G, Finkelstein J, Notter R, and Wang Z. 2004. Efficient depletion of alveolar macrophages using intratracheally inhaled aerosols of liposome-encapsulated clodronate. Exp Lung Res. Mar;30(2):105-120.

Gallagher J, Sams R 2nd, Inmon J, Gelein R, Elder A, Oberdörster G, and Prahalad AK. 2003. Formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine in rat lung DNA following subchronic inhalation of carbon black. Toxicol Appl Pharmacol. Aug 1;190(3):224-231.