Deducing in vivo Toxicity of Combustion-Derived Nanoparticles from a Cell-Free Oxidative Potency Assay and Metabolic Activation of Organic Compounds

• Published in: Environmental health perspectives 2009-01, Vol.117 (1), p.54-60
• Main Authors: Stoeger, Tobias, Takenaka, Shinji, Frankenberger, Birgit, Ritter, Baerbel, Karg, Erwin, Maier, Konrad, Schulz, Holger, Schmid, Otmar
• Format: Article
• Language: English
• Subjects: Activation; Air pollution; Animals; Betting; Biocompatibility; Biomedical materials; Biotransformation; Carbon; Causes of; Cell-Free System; Chemical hazards; Correlation; Environmental aspects; Enzymes; Female; Gene expression; Genes; Health; Health aspects; In vitro testing; In vivo testing; In vivo tests; Inflammatory response; Lungs; Mathematical models; Mice; Mice, Inbred BALB C; Nanoparticles; Neutrophils; Organic Chemicals - pharmacokinetics; Oxidation-Reduction; Oxidative stress; Particle mass; Polyallylamine hydrochloride; Shielding; Stresses; Surface area; Surface areas; Surgical implants; Toxicity
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.11370

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 (${\rm{Ox}}_{{\rm{Pot}}} $) of particles. Results: For six types of CDNPs with widely varying particle diameter (10-50 nm), organic content (OC; 1-20%), and specific Brunauer, Emmett, and Teller (BET) surface area (43-800 m²/g),${\rm{Ox}}_{{\rm{Pot}}} $correlated strongly with the in vivo inflammatory response (pulmonary polymorphonuclear neutrophil influx 24 hr after intratracheal particle instillation). However, for CDNPs with high organic content,${\rm{Ox}}_{{\rm{Pot}}} $could not explain the observed inflammatory response, possibly due to shielding of the${\rm{Ox}}_{{\rm{Pot}}} $of the carbon core of CDNPs by an organic coating. On the other hand, a pathway-specific gene expression screen indicated that, for particles rich in polycyclic aromatic hydrocarbon (PAHs), cytochrome P450 1A1 (CYP1A1) enzyme-mediated bio transformation of bio-available organics may generate oxidative stress and thus enhance the in vivo inflammatory response. Conclusion: The compensatory nature of both effects (shielding of carbon core and biotransformation of PAHs) results in a good correlation between inflammatory response and BET surface area for all CDNPs. Hence, the in vivo inflammatory response can either be predicted by BET surface area or by a simple quantitative model, based on in vitro${\rm{Ox}}_{{\rm{Pot}}} $and Cyp1a1 induction.