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ENVIRONMENTAL DEFENSE
Quantum Leaps:
Knowledge gaps in nanotechnology
health and safety
John M. Balbus, MD, MPH
Chief Health Scientist
ENVIRONMENTAL DEFENSE
Nanotechnology Project
Overview
• Introduction: growth of EH and S
research
• Early answers to early questions
• First data addressing hypothetical risks
• Managing uncertain risks
ENVIRONMENTAL DEFENSE
Nanotechnology Project
Research is beginning to
accumulate…
Scientific Journal Articles on Nanotechnology and Toxicity,
1982-2007
0
50
100
150
200
250
300
1
9
8
2
-
1
9
9
5
1
9
9
6
1
9
9
7
1
9
9
8
1
9
9
9
2
0
0
0
2
0
0
1
2
0
0
2
2
0
0
3
2
0
0
4
2
0
0
5
2
0
0
6
2
0
0
7
*
Year of Publication
Number
of
Articles
ENVIRONMENTAL DEFENSE
Nanotechnology Project
And the budget for research is
growing…
0
250
500
750
1000
1250
1500
'00 '01 '02 '03 '04 '05 '06 07E 08P
0
25
50
75
100
125
NIOSH
OTHER
EPA
USDA
NASA
NIST
NIH
DOE
DOD
NSF
EH&S
Total
research
funding
($M)
EH&S
research
funding
($M)
Sources: National Science Foundation, National Science and Technology Council; NNI 2008 Budget (http://www.nano.gov/NNI_08Budget.pdf); NNI
2007 Budget (http://www.nano.gov/NNI_07Budget.pdf)
Fiscal Year
ENVIRONMENTAL DEFENSE
Nanotechnology Project
Why have special concerns with
nanoparticles?
• Analogy to fine particle
pollution
– Ability to move around the
body
– Possible shared mechanisms
of toxicity
• Size is uniquely suited to
interact with biological
machinery
www.nanowerk.com/spotlight/spotid=2019.php
http://www.transportation.anl.gov/research/engine/diesel_structure.html
ENVIRONMENTAL DEFENSE
Nanotechnology Project
What we need to assure safety
• Reliable ways to detect and measure
nanoparticles in air, water, food
• Understanding of distribution and persistence of
nanomaterials in the body
• Reliable testing methods for both acute and
chronic toxicity
• Test results for range of materials and endpoints
• Assurance that protective technologies work for
nanoparticles
ENVIRONMENTAL DEFENSE
Nanotechnology Project
Early findings of a young
science…
• What properties affect
the transport and
toxicity of a
nanoparticle?
• Do nanoparticles
accumulate in the
body?
• How do nanoparticles
behave in the natural
environment?
ENVIRONMENTAL DEFENSE
Nanotechnology Project
The superficial is
profound…
ENVIRONMENTAL DEFENSE
Nanotechnology Project
ENVIRONMENTAL DEFENSE
Nanotechnology Project
Differential Penetration of QDs with
Different Surface Treatments
PEG-Coated NH2-Coated COOH-Coated
Ryan-Rasmussen, 2006
ENVIRONMENTAL DEFENSE
Nanotechnology Project
Surface treatments of CNT’s
determine where they go
Liu
et
al.,
2007
ENVIRONMENTAL DEFENSE
Nanotechnology Project
QD size determines excretion
Choi et al., 2007
ENVIRONMENTAL DEFENSE
Nanotechnology Project
Early data on key questions
• What properties affect the transport and
toxicity of a nanoparticle?
– Surface treatment, size critical
• Do nanoparticles accumulate in the
body?
– Some do, some don’t; percent retained
tends to be low, no long term studies
ENVIRONMENTAL DEFENSE
Nanotechnology Project
Agitation may be required to
generate high air concentrations
Maynard et al. 2004
ENVIRONMENTAL DEFENSE
Nanotechnology Project
Sanding processes release nanoparticles
http://www.pnl.gov/nanotoxicology/capability.asp?id=20
ENVIRONMENTAL DEFENSE
Nanotechnology Project
Early surprises in carbon
nanoparticle environmental fate
• Conventional wisdom:
– Carbon nanoparticles just stick to soil
• Studies show:
– Carbon nanotubes dissolve in Georgia river water
– Buckyballs form soluble, toxic nano-crystals
–Hyung et al. 2007
ENVIRONMENTAL DEFENSE
Nanotechnology Project
Past as prologue? Learning by
analogy
ENVIRONMENTAL DEFENSE
Nanotechnology Project
Hypothetical: Nanoparticles scar
lungs like asbestos
• Carbon nanotubes
are fiber-like
• Early studies showed
inflammation,
activation of toxic
oxygen (ROS)
ENVIRONMENTAL DEFENSE
Nanotechnology Project
What do early studies show?
• Nanoparticles poorly cleared by white blood cells
(macrophages) in the lung
• Carbon nanotubes cause short-term inflammation
– Iron contaminants lead to much greater inflammation
• Two CNT studies show surprising lung fibrosis or
growths
– Appeared in the absence of ongoing inflammation
• No study has looked for effects longer than 90 days
ENVIRONMENTAL DEFENSE
Nanotechnology Project
Hypothetical: nanoparticles harm the
heart like fine particle air pollution
• Nanoparticles are
small enough to
go through the
lungs
• Early lab and
mouse studies
show similar
types of damage
ENVIRONMENTAL DEFENSE
Nanotechnology Project
Carbon nanotubes caused aortic
plaques in mice
• Instilled SWCNTs damaged
lung, aorta, and heart tissue
• Mice developed aortic DNA
damage at 7, 28, and 60
days after exposure
• Repeated exposure to
SWCNTs resulted in
accelerated plaque
formation in mice fed high
fat diet
Li et al. 2007
ENVIRONMENTAL DEFENSE
Nanotechnology Project
Hypothetical: Nanoparticles containing
toxic metals convey risk
http://www.orau.org/ptp/collection/shoefittingfluor/shoe.htm
ENVIRONMENTAL DEFENSE
Nanotechnology Project
Quantum dots vary in toxicity
• Studies have shown cellular
toxicity, DNA damage
(Hardman, 2007,Green 2005 )
– Longer exposure times
more likely to show toxicity
• Use of cadmium raises
concerns
– Long-term stability of caps
not certain
– Widespread applications
may lead to environmental
loading
ENVIRONMENTAL DEFENSE
Nanotechnology Project
Hypothetical: Nanoparticles
disrupt proteins like prions
• Nanoparticles
translocate to the
brain
• Uniform nature of
nanoparticles may
alter proteins
within cells
ENVIRONMENTAL DEFENSE
Nanotechnology Project
Olfactory Nerve Translocation Pathway:
Images used with permission
Slide courtesy Dr. Eva Oberdorster
ENVIRONMENTAL DEFENSE
Nanotechnology Project
Early studies suggest importance
of protein binding
• Serum protein binding
facilitated uptake in the
liver and spleen
• Two different types of
nanoparticles sped up the
creation of Alzheimer-like
protein fibrillation
– Study used extreme
conditions- needs to be
replicated in more life-like
conditions
Linse et al., 2007
ENVIRONMENTAL DEFENSE
Nanotechnology Project
More than quantum leaps
• Enormous gaps remain
– Chronic toxicity-virtually no long-term test
results available
– Effects on development, nervous system,
immune system, etc., largely untested
– Very few data on environmental fate and
transport, ecotoxicity
ENVIRONMENTAL DEFENSE
Nanotechnology Project
Temporary bridges
• Using the best available information to
make decisions
• Increasing the budget and focus of
governmental funded research
• Protecting workers and the environment
in the face of uncertainty
ENVIRONMENTAL DEFENSE
Nanotechnology Project
Four Keys to Getting Nano Right
I. Significant increase in
government risk-
research investment
II. Close nano-loopholes in
regulations
III. Voluntary interim
standards
IV. Meaningful stakeholder
engagement
ENVIRONMENTAL DEFENSE
Nanotechnology Project
Evaluate
Risks
Profile
Lifecycle(s)
Exposure
Hazards
Properties
Assess
Risk Mgmt
Decide,
Document
&
Act
Describe
Material
&
Application
Review
&
Adapt
Iterate
Assess, prioritize & generate data
ED-DD Nano Risk Framework
ENVIRONMENTAL DEFENSE
Nanotechnology Project
Conclusions
• Nanoparticles defy generalization
• Surface properties determine behavior and
toxicity
• Few nanoparticles show significant short-term
toxicity
• Early studies suggest some novel and some
known toxic mechanisms
• Very little known about long-term effects
• Risk management guidance is available
ENVIRONMENTAL DEFENSE
Nanotechnology Project
www.nanoriskframework.com
www.environmentaldefense.comgonano

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Balbus10-11-07.ppt