Deducing in Vivo Toxicity of Combustion-Derived Nanoparticles
from a Cell-Free Oxidative Potency Assay and Metabolic Activation
of Organic Compounds Tobias Stoeger, Shinji Takenaka, Birgit Frankenberger, Baerbel Ritter, Erwin Karg, Konrad Maier, Holger Schulz, and Otmar Schmid Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Inhalation Biology, Neuherberg/Munich, Germany Abstract Background: The inhalation of combustion-derived nanoparticles (CDNPs) is believed to cause an oxidative stress response, which in turn may lead to pulmonary or even systemic inflammation. Objective and Methods: In this study we assessed whether the in vivo inflammatory response—which is generally referred to as particle toxicity—of mice to CDNPs can be predicted in vitro by a cell-free ascorbate test for the surface reactivity or, more precisely, oxidative potency (OxPot) of particles. Results: For six types of CDNPs with widely varying particle diameter (10–50 nm) , organic content (OC ; 1–20%) , and specific Brunauer, Emmett, and Teller (BET) surface area (43–800 m2/g) , OxPot correlated strongly with the in vivo inflammatory response (pulmonary polymorphonuclear neutrophil influx 24 hr after intratracheal particle instillation) . However, for CDNPs with high organic content, OxPot could not explain the observed inflammatory response, possibly due to shielding of the OxPot of the carbon core of CDNPs by an organic coating. On the other hand, a pathway-specific gene expression screen indicated that, for particles rich in polycyclic aromatic hydrocarbon (PAHs) , cytochrome P450 1A1 (CYP1A1) enzyme-mediated biotransformation of bioavailable organics may generate oxidative stress and thus enhance the in vivo inflammatory response. Conclusion: The compensatory nature of both effects (shielding of carbon core and biotransformation of PAHs) results in a good correlation between inflammatory response and BET surface area for all CDNPs. Hence, the in vivo inflammatory response can either be predicted by BET surface area or by a simple quantitative model, based on in vitro OxPot and Cyp1a1 induction. Key words: air pollution, BET, biotransformation, carbonaceous particles, Cyp1a1, dose response, nanoparticles, nanotoxicity, organic compounds, oxidative stress, particle toxicity, soot particles, specific surface area, surface toxicity, ultrafine particles. Environ Health Perspect 117:54–60 (2009) . doi:10.1289/ehp.11370 available via http://dx.doi.org/ [Online 22 August 2008] Address correspondence to T. Stoeger, Ingolstaedter Landstrasse 1, D-85758 Neuherberg/Munich, Germany. Telephone: 49-89-3187-3104. Fax: 49-89-3187-2400. E-mail: tobias.stoeger@helm-holtz-muenchen.de Supplemental Material is available online at http://www.ehponline.org/members/2008/11370/suppl.pdf This work was funded by grant HL 70542 from the National Institutes of Health and by FE-76177 from the German National Genome Network. The authors declare they have no competing financial interests. Received 14 February 2008 ; accepted 22 August 2008. The full version of this article is available for free in HTML or PDF formats. |