Guenter Oberdoerster, D.V.M., Ph.D.

Biokinetics, Effects and Mechanisms of Inhaled Micro- and Nano- Particles: Dosimetry, Risk Extrapolation and Risk Assessment

Numerous epidemiological studies have shown that acute adverse health effects are associated with exposures to ambient airborne particles. These effects occur mostly in sensitive parts of the population such as the elderly with a compromised cardiorespiratory system. We hypothesize that ultrafine particles (particle size below 0.1 µm) are one potential source causing these effects. Such particles occur in fumes generated by heating and combustion processes and are also normal constituents of the ambient aerosol, specifically in urban areas generated from numerous sources (e.g., internal combustion engines, power plants, incinerators). In addition, a new source of exposure to particles below 100 nm in size - engineered nanoparticles - has become a cause for concern, giving rise to the emerging field of nanotoxicology (see below).

Our studies with laboratory-generated ultrafine particles have shown that these particles have a significantly greater potency to induce inflammatory lung injury than larger-sized particles with the same chemical composition. Our studies are aimed at investigating cellular and molecular mechanisms of ultrafine particle-induced lung injury as well as secondary effects on the cardiovascular and the central nervous systems. An important component of this research is to develop rodent models with a compromised target organ system to evaluate cellular mechanisms of effects following inhalation exposure. Evaluating translocation pathways of inhaled nano-sized particles after deposition in the respiratory tract to other organ systems is an important part of our studies.

A more recent area of activity involves nanotoxicology, investigating the unique biokinetics and the toxicological potential of engineered nanoparticles. We investigate the propensity of these particles of different shapes (e.g., spheres, tubes, rods), different chemistries (e.g., metals, semiconductors, carbon) and different surface characteristics (coating, charge, porosity) to translocate from the site of deposition in the respiratory tract to extrapulmonary organs such as heart, liver, bone marrow and brain is being studied. Examination of the influence of physicochemical properties of nanoparticles on their effects and biokinetics is the ultimate objective of these studies. We engage in multidisciplinary team efforts to determine effects and underlying mechanisms of translocated nanoparticles (e.g., cellular oxidative stress).