Comparative toxicity of nanomaterials in vitro and in vivo

I&EC 14

Anna A Shvedova, ats1@cdc.gov1, Ashley R Murray, zsk1@cdc.gov2, Vic J. Johnson, VCJ6@cdc.gov3, Olga Gorelik4, Sivaram Arepalli4, Ann Hubbs, afh0@cdc.gov5, Robert R. Mercer5, Paul Baron6, Andrew D. Maynard, amaynard@cdc.gov6, Valerian E. Kagan, kagan@pitt.edu7, Alla I. Potapovich7, Vincent Castranova, vic1@cdc.gov1, and Elena Kisin, edk8@cdc.gov5. (1) Pathology and Physiology Research Branch/Department of Physiology and Pharmacology, HELD, NIOSH/West Virginia University, 1095 Willowdale Rd, Morgantown, WV 26505, (2) Department of Physiology and Pharmacology, West Virginia University, Morgantown, WV 26505, (3) TMBB, HELD, NIOSH, 1095 Willowdale rd, Morgantown, WV 26505, (4) Materials and Processes Branch/Nanotube Team, Lockheed Martin Corporation/GBTech, Inc., NASA-JSC, Houston, TX, (5) Pathology and Physiology Research Branch, HELD, NIOSH, 1095 Willowdale Rd. M/S 2015, Morgantown, WV 26505, (6) DART, NIOSH, (7) Environmental and Occupational Health Department, University of Pittsburgh
Society is currently amidst with revolutionary developments of remarkable new technologies based on novel applications of nanomaterials. A comparative in vitro study of nanosized particles revealed dose-dependent cytotoxicity along with ultra-structural and morphological outcomes observed in cells 18h post exposure. In vivo we found that CNT caused dose-dependent formation of granulomatous bronchointerstitial pneumonia, fibrosis, and changed pulmonary function in C57BL/6 mice. Administration of CNT to mice also resulted in a dose-dependent augmentation of biomarkers of inflammation quantified by lavage cell counts, total protein, lactate dehydrogenase and glutamyltranspeptidase activities in BAL fluids and accumulation of pro-inflammatory and pro-fibrotic cytokines. Overall, our data suggest that in vivo exposure to CNT leads to pulmonary toxicity realized through the synergized interactions of inflammatory response and oxidative stress culminating in the development of multifocal granulomatous pneumonia and fibrosis. The value of both approaches will be discussed in line with assessment of adverse outcomes of nanomaterials.