Low Doses of Iron-Oxide Nanoparticles have a Detrimental Effect on Reproduction and Development. Benjamin W. Henderson¹, Rami R. Ajjuri¹, Sarah Boyd¹, Gavin Daigle¹, Yuping Bao², Janis M. O'Donnell¹. 1) Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35401; 2) Department of Chemical and Biological Engineering, The University of Alabama, Tuscaloosa, AL.

   Nanoparticle applications are becoming increasingly used in the biomedical fields, with applications ranging from target drug delivery systems to medical imaging technologies. Toxicity analysis in cell culture has been the principle means of determining their safety. With rapidly increased use, there is need for in-depth toxicological analysis of nanoparticles in whole organisms to determine whether their use has deleterious side effects. We have developed toxicological assays to assess the biological consequences of nanoparticle exposure in Drosophila melanogaster. The current study focuses on the effects of transient exposure to polyacrylic acid-coated iron oxide nanoparticles. Larvae were fed on yeast paste containing varying concentrations of nanoparticles for 24hrs. Concentrations of 10-100 g/ml had no discernable effect on larval survival or development to the adult stage. However, we noted slight elevations in larval lethality at concentrations below 10 g/ml. Subsequently, we exposed larvae to nanoparticle concentrations below 10 ug/mL and then assayed the effects on development to pupation, eclosion rates, fertility of males and females that had been dosed as larvae, and the fertility rates of their progeny. We detected a narrow concentration window for elevated larval toxicity. Pupation rates of survivors were nominal. However, both male and female survivors that had ingested nanoparticles within the toxicity window had a significant long-term effects resulting in diminished fertility. Moreover, the surviving progeny of treated females had elevated sterility. Higher nanoparticle concentrations appear to induce a protective innate immune response. We hypothesize that transient exposure to concentrations within the toxicity window are insufficient to induce this response, but is sufficient to cause cellular damage.