Pulmonary Toxixity

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    Nanotoxicology : pulmonary toxicity studies on self-assembling

    rosette nanotubes

    A growing demand for information on the human health and environmental

    effects of materials produced using nanotechnology has led to a new area of

    investigation known as nanotoxicology. Research in this field has widespread

    implications in facilitating the medical applications of nanomaterials but also in

    addressing occupational and environmental toxicity concerns. Improving our

    understanding of these issues also has broad appeal in the stewardship of

    nanotechnology and its acceptance by the public. This work represents some of

    the early research in burgeoning field of nanotoxicology. Using a variety of in vivo

    and in vitro models, as well as cellular and molecular techniques I first studied a

    possible role for the novel cytokine endothelial monocyte activating polypeptide-

    II (EMAP-II) in acute lung inflammation in rats (Chapter 2). This work

    demonstrated a significant increase in total EMAP-II concentration in

    lipopolysaccharide inflamed lungs as early as 1h post-treatment (P

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    cell line since the macrophage is one of the key defense mechanisms to

    encounter RNT in the lung environment. The data indicate that this cell line lacks

    a robust inflammatory response upon exposure to RNT and that when RNT length

    is changed by altering the conditions of nanotube self-assembly, cytokine release

    into the supernatant is not affected profoundly. Although, EMAP-II is upregulated

    in a lipopolysaccharide model of lung inflammation, it does not serve as a good

    marker of RNT exposure. The data indicate that RNT have a favourable toxicity

    profile and these experiments provide a framework upon which rosette

    nanotubes can be investigated for a range of biomedical applications.

    Furthermore, in light of media and scientific reports of nanomaterials showing

    signs of toxicity, this work demonstrates that a biologically inspired nanostructure

    such as the RNT can be introduced to physiological environments without acute

    toxicity.