EPA Perspectives on Nanoinformatics: Prioritization Based on Potential for Exposure and ToxicityNanoinformatics

The U.S. Environmental Protection Agency’s (EPA) Office of Research and Development (ORD) is investigating the environmental health and safety implications of engineered nanomaterials. Research activities as outlined in ORD’s Nanomaterial Strategy address four main themes in: 1) identifying sources, fate, transport, and exposure; 2) understanding human health and ecological effects; 3) developing risk assessment approaches; and 4) preventing and mitigating risks. Under the second theme, EPA's National Center for Computational Toxicology (NCCT) is working to include evaluation of nanomaterials in its ToxCast™ chemical prioritization program. ToxCast is a battery of in vitro, high-throughput screening (HTS) assays that the EPA is using to develop methods to predict potential for toxicity of environmental chemicals. Design and conduct of the ToxCast pilot for screening nanomaterials requires selection of testing concentrations, characterization of materials, and analysis of resulting HTS data. Material testing concentrations are being selected by using the open-source Multiple-Path Particle Dosimetry (MPPD) model (from Applied Research Associates, Inc. (ARA)) to calculate nanomaterial mass retained in the alveolar region of the human lung based on occupational-setting aerosol levels curated from the literature. In collaboration with the Center for the Environmental Implications of NanoTechnology (CEINT) at Duke University, nanomaterial physicochemical properties are being characterized to aid in interpretation of test results. Data collection, curation, and analysis for the ToxCast nanomaterial pilot as well as for ORD-wide research on implications of nanomaterials will be facilitated using several databases developed within the NCCT. These include the Aggregated Computational Toxicology Resource (ACToR), ToxMiner, ExpoCast-DB, and the virtual tissues knowledgebase (VT-KB). Results of nanomaterial ToxCast screening and physicochemical characterization will be publicly accessible through ACToR.