CEFIC Stakeholder Dialogue:

Enabling responsible innovations

of nanotechnologies

Accelerated Innovation in Nanomanufacturing.

Research Strategies for addressing Ethical,
Environmental, Health, safety and responsibilities
Professor Terry Wilkins
Yorkshire Forward Professor of Nanomanufacturing Innovation
CEO, Nanomanufacturing Institute, University of Leeds, UK

Brussels, 24 June 2008

Topics

Why E, H & S considerations are important

Strategies for addressing E, H &S
Latest position on Carbon Nanotubes
Ethics debate and public engagement
Concluding remarks

Nanoparticles & Health

Nanoparticles

Brain

Nose
Lung

Skin

gut

blood

spleen

endothelium

liver

heart

atherogenic
plaques
Professor K Donaldson, U Edinburgh

Research funding in Europe

Substantial interdisciplinary research is needed
Member States have responded to the challenge Eg:
UK
CH
DK

46 Projects
24 Projects
12 Projects

(6 Env)
(2 Env)
(1 Env)

EC has developed a visionary strategic approach:

(Helped by Expert Advisory Group and Programme Committee)
Largest source of funds for collaborative research
Sought to develop and stimulate international collaborations

EU Investment in Nano E, H & S

Research
Millions

No projects

10

Env. Projects

A Strategy for Nanotoxicity for Research?

Interdisciplinary science research skills are needed for toxicology studies
of new nanomaterials:

Materials Characterisation (size, shape & chemical

properties)
Data mining & QSAR
Cell Membrane penetration
DNA damage (free radical & oxidative damage)
Intra-cell interactions (Inc Mutagenicity)
Whole organ effects
Whole organism effects
Clinical studies
Environmental impact
E, H & S Monitoring tools (Sensors & High-throughput systems)
Leeds research strategy

Leeds QSAR Nanotoxicity Research Capability

Integrated Data Mining Tool Box
Descriptor
calculation

Data Pre-processing
Scaling
Missing values
Outlier identification
Feature extraction

Data import
Excel
ASCII Files
Database
XML

Data Mining Toolbox

Regression
PCA and ICA
ART2 networks
Kohonen networks
K-nearest neighbours
Fuzzy c-means
Decision trees and
rules
Feedforward neural
networks (FFNN)
Summary statistics
Visualisation
Mixture QSAR models

Discovery
DiscoveryValidation
Validation
Statistical
Statisticalsignificance
significance
Results
for
Results fortraining
training
and
test
sets
and test sets

Results Presentation
Graphs
Tables
ASCII files
Professor Xue Wang, IPSE, Leeds

Lipid Bilayer Sensors

Nanoparticle passing
through lipid bilayer
changes electrical
properties detected
at electrodes

Dr Andrew Nelson, SOMS, Leeds

Examples of Comet Assay Results

Strategy
Assess DNA damage in:
Lung epithelial cells
Skin epithelial cells

Minimal

Mild

Gut CaCo2 cells

Study
Size
Shape
Structure

Moderate

Severe

(Bio)chemistry

Professor Alastair Hay, LIGHT, Leeds

supF Mutation Assay

(Secondary screen for germ cell mutation risk)
Human cells

supF
pSP189

Damaged DNA is replicated in human cells

and mutants are screened for in E.coli

mutant

Professor Alastair Hay, LIGHT, Leeds

New approaches for occupational

exposure monitoring
Leeds was the first trial site for UK
government Health and Safety
Executives new equipment for
monitoring nanoparticles in the
atmosphere
..biggest contribution to
nanoparticles in our laboratories
atmosphere was from traffic
exhausts from road outside!!!!!

The Challenge of Standardisation

Can pragmatic approaches of the past help us?
Rosalyn Yalows invention of radioimunnoassay stimulated
an explosion of new clinical assays for diseases based on
impure, degraded and poorly characterised proteins
.Yet we made useful diagnoses and later through
good normative research we iterated to:

Pure and fully characterised reference materials

Proper standards
International consensus on clinical ranges
Improved our diagnoses and patient management

Recent Nature Nanotechnology

Letter

Professor K Donaldson, U Edinburgh

The Asbestos Pathogenicity Paradigm

Asbestos is harmful
because the fibres it
releases into the air
are: thin,
long,
A key

do not
dissolve
in
parameter
in
the paradigm
the lungs

Professor K Donaldson, U Edinburgh

NT Morphology
Long
Mechanism
Straight

TangledLong
for the Short
Harmfulness
of
Tangled
Long Straight Fibres

Long straight

Short tangled Long tangled

Short

Short
straight

Incomplete or frustrated
phagocytosis
Complete phagocytosis

Long amosite
CNTlong2

BAD = pro-inflammatory

GOOD = cleared from

Conclusions of Poland et als St

Quantitative Structure activity relationships (QSAR) control particle

toxicity

The onus is on toxicologists to determine them and put them to use

in

models

to

predict

toxicity

without

recourse

to

animal

experimentation

The fibre QSAR is mature and predicts that any fibre longer than
about

15microns,

that

is

thin

(less

than

3-5

microns)

and

biopersistent (does not dissolve so the dose builds up) will be

pathogenic

All fibres so far studied have conformed to this paradigm asbestos,

glass fibres, ceramic fibres, para-aramid fibres, MWCNTs etc

Our

study

confirmed

the

length-dependent

pathogenicity

of

MWCNT , using a direct mesothelial exposure model.

Further research is needed to determine ifProfessor

inhaled
long MWCNT can
K Donaldson, U Edinburgh

Ethics & Nanotechnology?

I value democratic
procedures, but
only when they
give the right
result

The
Navigator
Problem
Or
?

Plato

George Bush

Research by Rob Naylor IDEA Applied Ethics Centre, Leeds

Ethics, E, H & S for Nanotechnology

Solving Platos problem?
The best:
Vision
Strategy
Technologies
People
& just do it!

The
Navigator
Problem

Plato

Henry
The Navigator

Conclusions
Europe has a distinguished track record, led by industry, in innovation of
Safety, Health and Environment standards & procedures (E.g. HAZOP,
COSHH etc).
.But the world moves on. There has been a healthy debate on the
societal issues since 2000 and both EU industry and the regulators
(REACH) are preparing:

We now need to get on with the science and deliver new knowledge
The science is complex and needs interdisciplinary research
Planned FP7 EU/US Joint Calls key for success
China (CAS) and India are keen to join in
Global collaboration makes sense
Work with industry to inform regulation (REACH & EPA)
Involve citizens every step of the way
Learn from the best practice of the past
to earn our License to Operate in the future

Stop Press

INTERIM ADVICE on Wastes containing

unbound Carbon Nanotubes - 19 May 2008

The hazard classification of CNTs should be similar to asbestos

Unbound CNT waste should be rendered safe by exposure to 850
deg C for at least 2 seconds

US NNI Reauthorisation Bill

Prioritize nanoscale characterization and metrology research as
the basis for understanding and addressing any risks or dangers
associated with nanoparticles and nanomaterials.
FDA does not have separate category yet for nano materials (Inc.
CNTs) but is keeping the situation under review