UC CEIN: Predictive Toxicology Assessment and UC CEIN: Predictive Toxicology Assessment and Safe Implementation of Nanotechnology in the Safe Implementation of Nanotechnology in the

EnvironmentEnvironmentPrincipal Investigators:

A. Nel1,2,3,4,Y. Cohen2,3,5, H. Godwin1,2,3, A. Keller2,6, R. Nisbet2,7

Mission and ObjectivesMission and Objectives

Education/OutreachEducation/OutreachCourses, Seminars & Training Modules in Year 1(All available via web)•Formal coursework made available to CEIN Members:

• Nanotoxicology• Fundamentals of Toxicology• Nanotechnology & The Environment

• Seminars & Workshops for all UC CEIN members:•Two half-day workshops on effective journalist-science communications•Five seminars (2 at UCLA; 3 at UCSB)

•Training Modules:• Two modules on safe handling developed/being transferred to interactive online

format and two modules on development & validation of standard protocols

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.

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.

K-12 Outreach•For K-12 outreach activities, the UC CEIN lead hands-on 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.

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.

UC CEIN Interdisciplinary Research Groups (IRGs)

AcknowledgementsAcknowledgements1 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, USA6 School of Environmental Science and Management, University of California, Santa Barbara7 Department of Ecology, Evolution & Marine Biology University of California Santa Barbara

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.

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).

IRG5: High Throughput Screening to Develop Predictive Toxicological Paradigms based on Material Properties

TiO2, CeO2, ZnO, and NH2PS

25 mL NP suspension at 50, 25, 12.5, 6.25 and 3.125 mg/mL

25 mL of dye combinations

Epifluorescence microscopy

Cell viabilityMitochondriaNucleusIntracellular Ca++

Spiny lobster

Mussels

Phytoplankton

Phase 1Screen 20 NP’s identified

via High-Throughput system (HTS) at UCLA

Phase 25-10 NP’s

identified in phase 1

Phase 32-3

NP’s from

phase 2

Phase 1: Rapid Toxicity Bioassays

Phase 2: Toxic effects predicted by IRG2 (ROS, lysosomal stability, apoptosis)

Phase 3: Mesocosm experiments for species interactions, bioaccumulation and biomagnification

IRG3: Effects of Nanomaterials on Marine Ecosystems

Coastal Marine Food Web

IRG6: Develop Decision Tool to Assess the Environmental Impact of Nanomaterials

• Nuclear energy vs. Nanotechnology• Regulatory caution evident in NM case

Comparative Risk Case Analysis

IRG7: Environmental Risk Perception

Modeling Regulatory Challenges in NM

Lifecycle

• Cost is prohibitive to assess all NMs• Published ES&T Feb 2009

US Public Environmental RP

Survey

• 2010 national survey in development• CNS-UCSB 2008 public survey as baseline—Enviro

RP, weighting relative concerns about NMs in soil, air, H20

Data collection in progress

Aug 2008 ASA presentation

EST 2009 publication

Nature Nano 2009; ChemE 2009 (in press)

Combinatorial library designed to provide the same material in different sizes, shapes, roughness, aspect ratios, states of dispersal, chemical composition, etc.

NPs Y Z

Surface chargeHydrophilicity/phobicityBiomoleculesDrug molecules

XNPs Y Z

Surface chargeHydrophilicity/phobicityBiomoleculesDrug molecules

X

IRG1: Standard Reference and Combinatorial Libraries

Automated Nanocrystal Synthesis

Investigator driven

5.6-fold QD Bioaccumulatio

n

780-fold QD Biomagnificatio

n

IRG2: Interactions at Molecular, Cellular, Organ & Systemic Levels

Trophic Transfer & Biomagnification of CdSe Quantum Dots

IRG4: Nanoparticle Fate and Transport

Cellular/tissue/system

NM libraries & characterization

IRG 2IRG #3 High Throughput

Screening

Computerized expert system, multimedia

modeling, risk ranking

Risk perception

Fate & Transport

Molecular, cellular, & organ injury pathways

Organism, population, community & ecosystem

toxicology

IRG 1

IRG 4

IRG 3IRGs 5, 6, 7

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.

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

High Throughput Bacterial, Cellular or Molecular Screening

Prioritize in vivo testingat increasing trophic levels

100’s/year

1000’s/year10,000’s/day

100,000’s/day

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ZnO 10

ZnO 50

ZnO 100

ZnO 2000.00

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ZnO 200 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.

R. Werlin, J.H. Priester, R.E. Mielke, S. Jackson, G.D. Stucky, G. Cherr, E. Orias, P.A. Holden

IRG Leader – Jeffrey Zink, UCLA IRG Leader – Patricia Holden, UCSB IRG Leader – Hunter Lenihan, UCSB

IRG Leader – Barbara Herr Harthorn, UCSB

IRG Leader – Yoram Cohen, UCLAIRG Leader – Kenneth Bradley, UCLAIRG Leader – Arturo Keller, UCSB

Challenges: Screening the effects of new nanomaterials (NM) requires the development of models for the environmental distribution of NM and their toxicity.

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• Decision tools for the safe use and design of NM

NPinput

Microlayer

Atmospheric NP

Resuspension

Sedimentation

AdvectionAggregation

Sediment

DisaggregationWater Body

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