A Rapid In Vivo System for Determining Toxicity of Manufactured NanomaterialsEPA Grant Number: R833320
Title: A Rapid In Vivo System for Determining Toxicity of Manufactured Nanomaterials
Investigators: Tanguay, Robert L. , Harper, Stacey
Institution: Oregon State University
EPA Project Officer: Hahn, Intaek
Project Period: September 1, 2006 through August 30, 2009
Project Amount: $400,000
RFA: Exploratory Research: Nanotechnology Research Grants Investigating Environmental and Human Health Effects of Manufactured Nanomaterials: a Joint Research Solicitation-EPA, NSF, NIOSH, NIEHS (2006) RFA Text | Recipients Lists
Research Category: Health Effects , Nanotechnology , Health , Safer Chemicals
Rapid growth of the nanotechnology industry is resulting in increased exposure of humans and the environment to nanomaterials prior to the scientific investigation of potential risks. It is clear that there is a need to develop rapid, relevant and efficient testing strategies to assess these emerging materials of concern. Here we propose an in vivo system for rapidly assessing the toxicity of nanomaterials at multiple levels of biological organization (i.e. molecular, cellular, systems, organismal). Early developmental life stages are often uniquely sensitive to environmental insult, due in part to the enormous changes in cellular differentiation, proliferation and migration required to form the required cell types, tissues and organs. Molecular signaling underlies all of these processes. Most toxic responses result from disruption of proper molecular signaling, thus, early developmental life stages are perhaps the ideal life stage to determine if chemicals or nanomaterials are toxic. Our hypothesis is that the inherent properties of some engineered nanomaterials make them potentially toxic. To test this hypothesis we specifically propose to (1) further develop our in vivo zebrafish toxicity assay to define the in vivo responses to nanomaterials, and (2) begin to define structural properties of nanomaterials that lead to adverse biological consequences.
We propose a three-tier approach exploiting the advantages of the embryonic zebrafish model to assess the toxicity of nanomaterials. Tier 1: Rapid screening experiments will be conducted to assess the toxicity of a wide range of structurally well-characterized nanomaterials commercially available or produced by researchers of the Oregon Nanoscience and Microtechnologies Institute (ONAMI). Nanomaterials found to elicit significant adverse effects will proceed to Tier 2 testing. Tier 2: Potential cellular targets and modes of action will be defined in vivo using a suite of transgenic fluorescent zebrafish and indicators of cellular oxidative state. Nanomaterials will be grouped according to structural indices and effects. Representative nanomaterials from each group will be selected for Tier 3 testing. Tier 3: Global gene expression profiles will be used to define the genomic responses to nanomaterials. Data from these studies will be used to define structure-activity relationships using a Nanomaterials Effects Database we have created to collate, organize and analyze data on nanomaterial effects across species and exposure scenarios.
The successful completion of these studies will fill important gaps in our understanding of the human health risk posed by exposure to nanomaterials. The proposed research will deliver (1) a validated in vivo system for rapidly assessing existing and future novel nanomaterials, and (2) data on nanomaterial structure effects relationships.