Carbon Nanotube Structure-Activity Relationships for Predictive Toxicology

The long-term goal of our multidisciplinary approach is to develop a predictive toxicological approach to CNT safety screening premised on the identification of physicochemical properties that pose pro-inflammatory and pro-fibrogenic hazard potential and that could also be used for safer design. The overall objective of this application, as the next step towards attainment of our long-term goal, is to develop a series of single-wall (SW) and multi-wall carbon nanotube (MWCNT) libraries that can be used in combination with robust cellular assays to establish semi-quantitative SARs and hazard ranking of the tubes’ potential to induce granulomatous inflammation and fibrosis in vivo. Our central hypothesis is that tube length, state of dispersal, surface chemistry, purity and electronic properties play key roles in determining cellular bioavailability and perturbation of cellular redox status, organelle damage and inflammasome activation. These interactions determine pro-inflammatory and pro-fibrogenic effects in the lung and the liver. This hypothesis is premised on our preliminary data demonstrating that the state of tube agglomeration, dispersion and surface functionalization determine bioavailability and initiation of pro-inflammatory and pro-fibrogenic effects at the level of target cells that also contributes to organ damage in vivo. The rationale for the proposed research is that once the major physicochemical properties contributing to in vitro and in vivo hazard outcome are known, it will be possible to implement predictive safety testing and safe design to assist widescale implementation of this technology