UC CEIN: Predictive Toxicology Assessment and
Safe Implementation of Nanotechnology in the
Environment
Principal Investigators:
A. Nel1,2,3,4,Y. Cohen2,3,5, H. Godwin1,2,3, A. Keller2,6, R. Nisbet2,7
Mission and Objectives
UC CEIN Interdisciplinary Research Groups (IRGs)
The mission of the UC CEIN is to ensure that nanotechnology is introduced in
a responsible and environmentally compatible manner to allow the US and
international communities to leverage the benefits of nanotechnology for
global, economic, and social benefit.
The UC CEIN seeks to:
•Develop a library of reference nanomaterials (NMs);
•Develop a predictive model of toxicology & the environmental impacts of NMs;
•Understand the impacts of NMs on organisms and ecological systems, and
•Develop guidelines and decision tools for the safe design and use of NMs.
High Throughput Screening and Data Mining based on
property-activity relationships that can be used to rank NM for
risk and priority in vivo testing
IRG 3
Education/Outreach
Organism, population,
community & ecosystem
toxicology
10,000’s/day
Computerized expert
system, multimedia
modeling, risk ranking
Cellular/tissue/system
Molecular, cellular, &
organ injury pathways
Prioritize in vivo testing
at increasing trophic levels
Data collection
in progress
IRG 4
Comparative Risk
Case Analysis
EST 2009
publication
• Cost is prohibitive to assess all NMs
• Published ES&T Feb 2009
US Public Environmental
RP Survey
Fate &
Transport
Aug 2008 ASA
presentation
• Nuclear energy vs. Nanotechnology
• Regulatory caution evident in NM case
Modeling Regulatory
Challenges in NM
Lifecycle
High Throughput Bacterial,
Cellular or Molecular Screening
• 2010 national survey in development
• CNS-UCSB 2008 public survey as baseline—Enviro Nature Nano 2009;
RP, weighting relative concerns about NMs in soil, air, ChemE 2009 (in
H2 0
press)
IRG Leader – Barbara Herr Harthorn, UCSB
•Seminars & Workshops for all UC CEIN members:
•Two half-day workshops on effective journalistscience communications
•Five seminars (2 at UCLA; 3 at UCSB)
IRG1: Standard Reference and
Combinatorial Libraries
•Training Modules:
• Two modules on safe handling developed/being transferred to interactive online
format and two modules on development & validation of standard protocols
IRG2: Interactions at Molecular, Cellular,
Organ & Systemic Levels
Trophic Transfer & Biomagnification of CdSe Quantum Dots
Combinatorial library designed to
provide the same material in
different sizes, shapes, roughness,
aspect ratios, states of dispersal,
chemical composition, etc.
Regulatory Policy
•Worked with legislators/policymakers to ensure
future legislation is based on sound science, such as
mark-ups for Nano EHS bill, HR 5940 (2008)
•A Working Conference on Nanotech Regulatory Policy
was co-organized and co-sponsored by UC CEIN and
the UCLA Law School on April 17, 2009, and the papers
presented will be published in an upcoming issue of the
UCLA Law Review.
NPs
X
Y
Z
IRG3: Effects of Nanomaterials on Marine Ecosystems
Phase 1: Rapid
Toxicity Bioassays
Phytoplankton
Phase 2: Toxic effects
predicted by IRG2
(ROS, lysosomal
stability, apoptosis)
Investigator
driven
Surface charge
Hydrophilicity/phobicity
Biomolecules
Drug molecules
780-fold QD
Biomagnificatio
5.6-fold QD
n
Bioaccumulatio
n
Automated Nanocrystal
Synthesis
Synergistic Activities
•Student/Postdoc Advisory Committee (SPAC) Activities:
• July 2009 retreat at UCSB – introduce research to
all Center trainees
• Leadership workshop – in conjunction with ICEIN
2009 – 30 researchers from both CEINs engaged
in leadership activities and interactive learning experiences
•Standard Protocols Project: An Interdisciplinary Protocols Working Group has been
established, a standard template for protocols has been developed,
and individuals across IRGs are working on transferring
protocols to this template.
R. Werlin, J.H. Priester, R.E. Mielke, S.
Jackson, G.D. Stucky, G. Cherr, E. Orias, P.A.
Holden
Phase 3: Mesocosm
experiments for
species interactions,
bioaccumulation and
biomagnification
Phase 1
Screen 20 NP’s identified
via High-Throughput
system (HTS) at UCLA
Phase 2
5-10 NP’s
identified in
phase 1
Mussels
Phase 3
2-3
NP’s
from
phase
2
Spiny lobster
Coastal Marine Food Web
IRG Leader – Jeffrey Zink, UCLA
IRG Leader – Patricia Holden, UCSB
IRG4: Nanoparticle Fate and Transport
IRG Leader – Hunter Lenihan, UCSB
IRG5: High Throughput Screening to Develop Predictive
Toxicological Paradigms based on Material Properties
IRG6: Develop Decision Tool to Assess the
Environmental Impact of Nanomaterials
Challenges: Screening the effects of new nanomaterials (NM) requires the
development of models for the environmental distribution of NM and their toxicity.
K-12 Outreach
•For K-12 outreach activities, the UC CEIN lead handson activities at local schools, and H. Godwin gave a
lecture and lead an interactive activity for the 2009
SciArt summer program, Nanotechnology, Health, and
the Environment.
Department of Environmental Health Science, UCLA School of Public Health, 16-035 CHS,
BOX 951772, Los Angeles, CA 90095.
2 UC Center for the Environmental Implications of Nanotechnology (UC CEIN), University of
California Los Angeles, 6522 CNSI, 570 Westwood Plaza, Los Angeles, CA 90095-7277.
3 California NanoSystems Institute, University of California Los Angeles, 570 Westwood Plaza,
Building 114, Los Angeles, CA 90095.
4 Division of NanoMedicine, Department of Medicine, University of California, Los Angeles,
California 90095.
5 Department of Chemical and Biomolecular Engineering, 5531 Boelter Hall, University of
California Los Angeles, Los Angeles, California, USA
6 School of Environmental Science and Management, University of California, Santa Barbara
7 Department of Ecology, Evolution & Marine Biology University of California Santa Barbara
High Throughput
Screening
•2009 N. Am, Europe, Asia, ~100
businesses
•Safe handling, product stewardship,
perceived risks of NMs
IRG 2
Risk perception
Courses, Seminars & Training Modules in Year 1
(All available via web)
•Formal coursework made available to CEIN Members:
• Nanotoxicology
• Fundamentals of Toxicology
• Nanotechnology & The Environment
1
IRGs 5, 6, 7
IRG #3
100’s/year
100,000’s/day
Acknowledgements
NM libraries &
characterization
Industry Risk Perception
Survey
1000’s/year
Goals:
• Similarity criteria for NM and data-driving QSPRs and
QSARs models for NM physicochemical properties
and toxic effects
• Environmental intermedia transport relations for NM
and multimedia NM transport
NP
input
• Decision tools for the safe use and design of NM
TiO2, CeO2, ZnO, and
NH2PS
1.00
1.00
0.90
0.90
0.80
0.80
0.70
0.70
0.60
0.60
C/C o
C/C o
Ongoing & Future Initiatives
•In a partnership with California Teach at the UCLA
Campus, UC CEIN will recruit and train undergraduates for volunteering to lead science
activities in K-12 schools and at the CA Science Center.
•Predictive models developed in the UC CEIN will inform the development of oversight and
regulation approaches for nanomaterial production.
IRG7: Environmental Risk Perception
IRG 1
0.50
0.40
25 mL NP suspension at 50,
25, 12.5, 6.25 and 3.125
mg/mL
25 mL of dye
combinations
0.50
0.40
ZnO 10
0.30
ZnO 50
0.20
ZnO 100
0.10
ZnO 200
0.00
0
100
ZnO 10
0.30
ZnO 50
0.20
200
Time (min)
300
400
IRG4 research focuses on understanding the
mobility and bioavailability of NPs in different
environmental conditions. Our work with metal oxide
NPs has shown that they can be easily stabilized
under freshwater conditions, which is a major
pathway from the sources (e.g. wastewater
treatment plant discharge, stormwater, other runoff)
into other environmental compartments, such as
estuaries and oceans, where the particles sediment
rapidly. This has important implications for aquatic
organisms that are exposed to particles either in the
water column or sediments.
ZnO 100
0.10
ZnO 200
0.00
0
100
200
300
Cell viability
Mitochondria
Nucleus
Intracellular Ca++
Atmospheric NP
Microlayer
Aggregation
Water Body
Advection
Disaggregation
Resuspension
Sedimentation
Sediment
400
Time (min)
IRG Leader – Arturo Keller, UCSB
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), 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).
Epifluorescence
microscopy
IRG Leader – Kenneth Bradley, UCLA
Solutions: Develop and apply machine learning techniques for NM classification and
property predictions; Apply multimedia transport and fate models to evaluate the
dynamic mass distribution of NM, and Apply decision tools incorporating quantitative
and qualitative information for decision making
IRG Leader – Yoram Cohen, UCLA
This material is based upon work supported by the National Science Foundation
and the Environmental Protection Agency under Cooperative Agreement Number
EF 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.