(217b) A Novel Technique for In-Vivo Toxicological Characterization of Engineered Nanomaterials

How do we balance the potential hazards from new and inadequately characterized engineered nanomaterials with the potential and power of nanotechnology?  It has become apparent, that potential environmental health   effects are critical factors in the likely success or failure of new nanotechnologies.  The current nanotoxicology approach of evaluating the toxic properties of the large universe of existing and emerging ENMs at one material at the time, places a significant financial burden to an emerging industry and may slow down significantly the development of this emerging industry. Alternatively,  a promising approach will be to examine families of engineered and rigorously characterized particles, and to study the role of such factors as particle size, composition, shape, charge and surface chemistry and their link to specific biological outcomes.

Here, a novel method is explored which is suitable for ENM in-vivo inhalation and in-vitro toxicological characterization studies. ENMs are produced continuously in the gas phase using industry relevant flame spray pyrolysis reactors, allowing their continuous transfer to inhalation chambers, without altering their state of agglomeration. Important properties of the generated aerosols (i.e. particle size, concentration, shape, state of agglomeration, surface chemistry) can be modified allowing for both in-vitro and in-vivo investigations of toxicity. The ability of the developed technique to generate a variety of industry relevant, property controlled exposure atmospheres for inhalation studies was systematically investigated. The suitability of the technique to characterize the toxicity of inhaled ENMs in intact animal models was also shown in an in-vivo study involving Sprague-Dawley rats, using freshly generated nano-iron oxide (Fe₂O₃) as a test aerosol. We demonstrated both pulmonary and systemic toxicity using a variety of toxicological assays under acute exposure conditions. The future use of this novel method will improve our understanding in terms of the health and safety of ENMs and help us to investigate further our central hypothesis that physical and chemical characteristics of ENMs determine their bioavailability, redistribution, and toxicity in the lungs.