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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 3rd 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
CellsEmbryos
Organisms
Data integration Pattern Recognition (heatmaps,
self –organizing etc) Machine Learning
Multimedia Analysis
In vivotoxicity
Nanoparticle structural & physicochemical information
Hazard ranking Risk profiling Exposure modeling Property-activity
relationshipsFate&
transport
HTS
Cell, embryo, biomolecules
Predictivetoxicology
ENM
libraries
UC CEIN Predictive and Multi-disciplinary Toxicology model
Select Accomplishments
OrganizationResearch 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
TiO2 Fe-TiO2
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)
O2
O2
O2-
O2-
ENM-4, Lutz Mädler, Suman Pokhrel
1%, 2%, 4%, 6%, 8%, 10% Fe doping reduced
the TiO2 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
Cubed=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 (TiO2, ZnO, CeO2, CuO…)
Doped metal oxides: 3 (Fe-ZnO, Fe-TiO2, 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
Hyd
roth
erm
al
Themes 2 and 6: Zebrafish HTS to Perform
Hazard Ranking of Metals and Metal Oxides
Theme 3: TiO2 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 TiO2)
and lowest for TiO2 dots
• Highest risk for mobile (bioavailable) and
photoactive NPs
ZnO NPs were
biotransformed
Photo: G. de la Rosa
CeO2 XAS results
CeO2 remained Unchanged and
taken up in roots??
Zn(OH)2?
Zn2+ ?
ZnO
ZnO XAS results
Theme 4: Differential Processing of ZnO and CeO2 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
TiO2
CuO
neg
0 1
0
20
30
40
50
No
rma
lize
d f
luo
res
ce
nce
inte
ns
ity (
A.U
.)
NiO
ZnO
CuO
NiO
ZnO
CuO
Co3O4
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