0 20 40 60 80 100 0 10 50 100 150 200 % abnormal μg/L Zn ZnO NM Fe-doped ZnO NM UC CEIN: Predictive Toxicology Assessment and Safe Implementation of Nanotechnology in the Environment Principal Investigators: Andre E. Nel, Yoram Cohen, Hilary Godwin, Arturo Keller, Roger Nisbet Mission Education/Outreach Education/Outreach ensures that the research performed in the UC CEIN is conveyed effectively to a broader range of stakeholders, provides growth and mentoring opportunities for students and postdoctoral fellows, and encourages interdisciplinarity and synergism within the Center. Courses, Seminars, Symposia • Nanoecotoxicology Online Course – 13 lecture online course. Provides an introduction to the multidisciplinary research of the Center. Includes lectures on ENM characterization, high throughput studies, ecosystems research, fate and transport, and social and policy implications of nanotechnology. Materials available to institutions across the U.S. • Seminar speakers: Mark Hersam, Northwestern University; Frank von der Kammer, University of Vienna; Amy Wang, US EPA; Vicki Grassian, University of Iowa • Co-hosted 3 rd International Conference on the Environmental Implications of Nanotechnology (ICEIN) at Duke University, May 2011. Nanomaterial Regulatory Policy and Safe Handling • Reviewed & evaluated responses received under AB 289 relating to CNTs for CA DTSC. Assisted DTSC in formulating California’s ENM call in on Metal Oxides. • Developed guidelines for the safe handling of nanomaterials in an academic laboratory setting. These guidelines are currently being pilot tested then will be disseminated first to academic laboratories, then made available to industry. Synergistic Activities • An interdisciplinary Protocols Working Group is working to validate and make publicly available protocols from across our Center’s research. Initial protocols are available on CEIN website (http://www.cein.ucla.edu) • Student/Postdoctoral leadership workshops focus on providing career skills and mentoring across our institutions. This year’s workshops included “the Academic Job Search,” “Communicating Science to the Public,” and “Writing Science” which focused on writing for journals and proposal writing. K-12 and Public Outreach Events, lead by faculty, undergraduate, graduate, postdoc volunteers: • NanoDays 2011, in partnership with NISENet, CA Science Center, and UCLA CA Teach • UCLA CSNI Art/Sci and Nanotechnology Summer Institute for high school students • Nanotechnology: Small is Big! public lecture series, Santa Monica Public Library • “Exploring your universe,” UCLA campus, November 12, 2011 The UC CEIN was established in September 2008 with the mission to ensure that nanotechnology is introduced in a responsible and environmentally compatible manner, thereby allowing the US and international communities to leverage the benefits of nanotechnology for global economic and social benefit. This mission is being accomplished by developing a broad-based series of decision tools based on models of predictive toxicology and risk ranking premised on selected nanomaterial properties that determine fate, transport, exposure, and biological injury mechanisms at cellular, tissue, organism, and population levels. The UC CEIN integrates the expertise of engineers, chemists, colloid and material scientists, ecologists, marine biologists, cell biologists, bacteriologists, toxicologists, computer scientists, biostatisticans, and social scientists into a predictive scientific platform that informs us about possible ENM hazards and how through exposure reduction, life cycle analysis and safe-by-design strategies we can reduce the environmental impact of nanotechnology. The UC Center for Environmental Implications of Nanotechnology (UC CEIN) at UC Los Angeles (UCLA) is in partnership with UC Santa Barbara (UCSB), UC Davis (UCD), UC Riverside (UCR), Columbia University in New York, the Molecular Foundry at Lawrence Berkeley National Laboratory (LBNL), the Lawrence Livermore National Laboratory (LLNL), Nanyang Technological University in Singapore (NTU), University of New Mexico (UNM), Northwestern University, Sandia National Laboratory (SNL), University of Texas in El Paso (UTEP), University of Bremen (Germany), University of British Columbia (UBC), Cardiff University (Wales), University College Dublin (UCD, Ireland), and Universitat Rovira i Virgili in Spain (URV). This material is based upon work supported by the National Science Foundation and the Environmental Protection Agency under Cooperative Agreement Number DBI-0830117. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation or the Environmental Protection Agency. This work has not been subjected to EPA review and no official endorsement should be inferred. NP Stock Solutio n Dispersio n Large Agglomerat es 30 min 30 min 24 hr 24 hr Major Sedimentati on Stable Suspension Medium Alone Medium w/ Dispersing Agent Cells Embryos Organisms Data integration Pattern Recognition (heatmaps, self –organizing etc) Machine Learning Multimedia Analysis In vivo toxicity Nanoparticle structural & physicochemical information Hazard ranking Risk profiling Exposure modeling Property-activity relationships Fate & transport HTS Cell, embryo, biomolecules Predictive toxicology ENM libraries UC CEIN Predictive and Multi-disciplinary Toxicology model Select Accomplishments Organization Research within the UC CEIN is carried out by 44 distinct but interactive projects across seven interdisciplinary research themes: • Theme 1: Compositional and Combinatorial ENM Libraries for Property-Activity Analysis • Theme 2: Molecular, Cellular, and Organism High-Throughput Screening for Hazard Assessment • Theme 3: Fate, Transport, Exposure, and Life Cycle Assessment • Theme 4: Terrestrial Ecosystems Impact and Hazard Assessment • Theme 5: Marine and Freshwater Ecosystems Impact and Toxicology • Theme 6: Environmental Decision Analysis for ENMs • Theme 7: Societal Implications, Risk Perception, and Outreach Activities TiO 2 Fe-TiO 2 h + e + Activation with UV light only Activation with Visible light Electron hole reduction (e.g. biological molecules) Electron hole reduction (e.g. biological molecules) O 2 O 2 O 2 - O 2 - ENM-4, Lutz Mädler, Suman Pokhrel 1%, 2%, 4%, 6%, 8%, 10% Fe doping reduced the TiO 2 bandgap from ~3.2 eV to ~2.8 eV. Reduced bandgap allows lower energy UVA light to be absorbed and leads to increasing cell death HTS-1: Andre Nel, Saji George Themes 1 and 2: Synthesis of metal ion doped titania for mechanistic studies of photo-induced toxicity George, S., et al. J. Am. Chem. Soc., 133(29), 11270-11278, 2011. 50 nm Cube d=10 nm d=30 nm d=130 nm Wire Rod >30 types of compositions Theme 1: Assembly and characterization of an Engineered Nanomaterial Library Commercial So-gel method Hydrothermal technique Flame spray pyrolysis Origin Metal oxides: 25 (TiO 2 , ZnO, CeO 2 , CuO…) Doped metal oxides: 3 (Fe-ZnO, Fe-TiO 2 , Al-ZnO) Metals: 3 (Ag, Pt, Pd) Carbon nanotubes: 2 (SWNT, MWNT) >40 different sizes, typically 5 to 200 nm Shapes: spherical, cubic, rod, wire, tube Crystallinity: amorphous, mesoporous, crystalline Various sizes, shapes, and crystal structures Flame Spray Pyrolysis Hydrothermal Themes 2 and 6: Zebrafish HTS to Perform Hazard Ranking of Metals and Metal Oxides Theme 3: TiO 2 NP Morphology has Major Influence on Mobility and Photoactivity Nanoparticle Stability GW Transport Photoactivity Spheres (P25) Dots Wires Rods Plates TBD • Stable suspensions will result in higher mobility, in open waters and in groundwater (GW) • Photoactivity is highest for spheres (P25 TiO 2 ) and lowest for TiO 2 dots • Highest risk for mobile (bioavailable) and photoactive NPs ZnO NPs were biotransformed Photo: G. de la Rosa CeO 2 XAS results CeO 2 remained Unchanged and taken up in roots ?? Zn(OH) 2 ? Zn 2+ ? ZnO ZnO XAS results Theme 4: Differential Processing of ZnO and CeO 2 in Soybean Plants Gardea-Torresdey (Univ. Texas- El Paso) Theme 6: Development of QSARs and Decision Boundaries for Metal Oxide ENMs • Developed the concept of decision boundaries for a specified cost function • Introduced the concept of logistic regression model for classification QSAR Developed QSARs for toxicity of metal oxides ENMs QSAR for metal oxides (9), based on HTS cytotoxicity data for BEAS-2B cells, with 100% classification accuracy. Expanded QSAR for metal oxides (24) based on new CEIN toxicity for BEAS-2B and RAW cell lines (3 assays) , with ~92% classification accuracy. Web-survey of 424 nano experts on their views of ENM risk and regulation Theme 7: Scientists’ and Regulators’ ENM Risk and Benefit Perceptions What it means: 1) Small but significant differences in risk views by expert affiliation/discipline, with regulators judging risks to be higher [ENM risk assessment subject to affiliation bias] 2) Greatest disagreement in views about workplace risk 3) Most agreement about nano-remediation Fairbairn, E.A., et. al. J. Hazardous Materials 102:1565-71, 2011. Lopez-Moreno et al. 2010. ES&T Lopez-Moreno et al. 2010. J. Ag. & Food Chem. NSE – Nanoscientists and engineers NTOX – Nano EHS researchers NREG – Nano regulators, risk assessors in government agencies Theme 5: Fe-doped ZnO Causes Lower Rate of Developmental Abnormalities in Sea Urchin Embryos than Pure ZnO NM Impacts on National Nanotechnology Research Agenda California 2009 – Nanotech Regulatory Policy Workshop 2010 – ICEIN at UCLA 2010 – Nano VI • Workshops • CA NanoEHS Working Group • DTSC CNT and MeO NM Call-In National International • Protocols Harmonization • Commission on Nanotechnology • Workshops 2009 – ICEIN at Howard 2011 – ICEIN at Duke 2011 – NNI at 10 2010 – Nano 2010 Clemson • Reports 2010 – Nanoinformatics (Chair) Nanotechnology 2020 Nanoinformatics 2020 Roadmap • Nano 2 Commission Thomas, C.R., et al. ACS Nano, 5(1), 13-20, 2011 Zhou, D. et al. Env. Sci. Tech, Submitted Control ZnO Newport Green TiO 2 Cu O neg 0 10 20 30 40 50 Normalized fluorescence intensity (A.U.) NiO ZnO CuO NiO ZnO CuO Co 3 O 4 Ag chelator Hatching interference by Inhibiting a hatching enzyme Heat shock protein 70 Xia et al, ACS Nano, 2011 Lin et al. ACS Nano, 2011