0

20

40

60

80

100

0 10 50 100 150 200

% a

bn

orm

al

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 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