Transcript Slide 1

Paul E. Burrows PhD
Science and Technology Consultant
Reata Research, Kennewick, WA
Society for Nuclear Medicine Molecular Imaging Summit,
Albuquerque, NM, Jan 31- Feb 1, 2010

Why Bother?
◦ Nanoscale materials have unique and useful
properties not predictable from bulk
characteristics.
◦ Few standards or guidelines exist.
◦ NGO activity risks distorting public opinion
and chilling development.
◦ Nanotechnology offers the opportunity to get
it right from the beginning.


How to Define Nanotechnology.
Dealing With the Complex Life-Cycle.
◦ Life-cycle risk management frameworks.

Communication is Critical!

Unbounded Problem?
◦ “Nanoscale” represents an infinite class of
materials.

Poor Controls
◦ From personal experience, it can be a challenge to
buy the same sample of a nanoscale material twice.
◦ Nanoparticles are not monodisperse.

What is important?
◦ Dose by mass? By surface area?
◦ If a gold nanoparticle is tagged with an antibody (or
radionuclide) how relevant is the toxicity of gold
nanoparticles?
◦ What changes with time? (aggregation?)

How to prevent precautionary approaches
leading to paralysis in the context of
incomplete data sets?
www.nano.gov: 1 – 100nm
Worse: Anything less than 100nm
Even worse: Anything with one dimension less than 100nm
“If you can see
it with that, it’s
not nano!”
What is different about the nanoscale?
Confinement Effects  Photophysical Changes
Confinement Effects  Chemical Changes
Surface Effects  Chemical Changes
Campell, University of Washington
Proposal:
“The nanoscale is the size range where the basic physical or chemical
properties of a particle depend on its size or shape.”
influenza (200 nm)
hepatitis B (42 nm)
parvovirus (25 nm)
7
Scientific American, February 1965
100 nm
Electron micrograph of real T4 bacteriophages
Injects its DNA into a bacterium and
rearranges the bacterium’s own structure to
make > 100 copies in about 25 minutes
8
Washington Post, Thursday, April 6, 2006; p. A02
Government officials in Germany have reported what appears
to be the first health-related recall of a nanotechnology product,
raising a potential public perception problem for the rapidly
growing but still poorly understood field of science.
At least 77 people reported severe respiratory problems over a
one-week period at the end of March -- including six who were
hospitalized with pulmonary edema, or fluid in the lungs -- after
using a "Magic Nano" bathroom cleansing product, according to
the Federal Institute for Risk Assessment in Berlin.
•
•
•
There was nothing “nano” in the product
A chemical propellant caused the reactions
“Nano” was just used as a cool name
Just to be clear:
THERE WAS ABSOLUTELY NO NANOTECHNOLOGY IN “MAGIC NANO”
Poor definitions lead to perceived risk and poor regulation
http://www.ci.berkeley.ca.us/citycouncil/ordinances/2006/6960.pdf
 Confusion between natural, incidental and engineered nanoparticles
 Instituted because of perceived lack of regulation at U.C. Berkeley and
Lawrence Berkeley National Laboratory

Neither institution is actually regulated by the city
 No minimum threshold

Implies that 5 mg of nanoparticles are as dangerous as 500kg of lead or mercury
 Less than 100 nm in any one dimension includes… almost everything!

And excludes important examples
 “To the extent known” can be interpreted as “should be known”

No specification as to what database should be used or what search criteria are deemed
acceptable
 Surface modification unaddressed- can you regulate a nano-hole?
 Use of hazardous materials ordinance to regulate nanotechnology that
has no proven health risks encourages opportunistic litigation
 No indication of what (if anything) the city intends to do with the
information disclosed
John C. Monica Jr. et al. Nature Nanotechnology 2, 68 (2007)
The Behavior of Silver Nanotextiles during Washing
Environ. Sci. Technol., 2009, 43 (21), pp 8113–8118
L. Geranio, M. Heuberger‡ and
B. Nowack
•
•
Ag content of fabrics
varies by > 7000x
Up to 50% lost on
washing
NPs may agglomerate and partially denature proteins...
NPs may alter cellular structure in new and
interesting ways...
Nanoparticles can actively modulate the
phase structure of lipid membranes so that
the stiffness differs from spot-to-spot

Raw materials
◦ novel structures, material combinations, higher reactivity

Manufactured Products
◦ New potential exposures, applications, waste generation

Packaging and distribution
◦ Customer knowledge, communication, labeling

Product Usage
◦ Novel behavior in matrix, potential consumer exposure

End of Life
◦ Environmental dispersion; recycling/disposal impacts
First recognized in 2004, reiterated in 2007... Implemented yet?
It is rare that all this information will be available for a new material or process
Wingspread Conference Center, Racine, Wisconsin
23-25 January 1998
“Where an activity raises threats of harm
to the environment or human health,
precautionary measures should be taken
even if some cause and effect
relationships are not fully established
scientifically.”
Level of exposure /control
RAW
Process
MATERIALS
PRODUCT
Packaging
USE
REUSE/
RECYCLE
DISPOSAL
END OF
LIFE
Number of potential receptors
Courtesy Jo Ann Shatkin, CLF Ventures
Adaptive life cycle approaches in context of limited data:
•
Provide a framework for assessing biological and environmental
exposure for emerging substances
•
Effective resource allocation by using
exposure as a key determinant of risk:
No exposure = No risk.
•
Risk assessments inform data collection
and analysis.
•
Key uncertainties become priorities for
additional data gathering.
•
Reiterate risk assessment and revisit risk
management in light of new data.
–
Nano LCRA (Shatkin 2008.
Nanotechnology Health and
Environmental Risks CRC Press)
IDENTIFY AND
CHARACTERIZE
HAZARDS
RAW
MATERIALS
Process
ASSESS
EXPOSURE
PRODUCT Packaging
CHARACTERIZE RISK
USE
EVALUATE
TOXICITY
Reuse/
Recycle/
Disposal
END OF LIFE
RISK MANAGEMENT/
ASSESS
CONFIDENCE
ITERATE
Hazard x Exposure = Risk
Courtesy Jo Ann Shatkin, CLF Ventures
Does the message fit the risk?
Study Raises Concerns About Carbon
Nanotech buckyballs
kill fish
Particles
By Lucy Sherriff
Possible health risks are found
from exposure to carbon particles
By BARNABY J. FEDER (NYT) 744 words
Late Edition
- Final
, Section C , Page 5 , Column 4
Scientists today announced
research
suggesting
Buckyballs, a spherical form of carbon
buckyball molecules can trigger organ damage
- Environmental
toxicologist Dr
Eva Oberdorster
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Oberdorster cites need for more study, interview; rejects calls by
some critics for moratorium on development and sale of
nanoscale materials
23
Nanoparticles Toxic in Aquatic Habitat, Study Finds
The study, described at a scientific meeting yesterday, was small and has yet to be peer reviewed or published in a scientific
journal. And although some companies anticipate making tons of the particles within the next few years, current production
levels are relatively low, so the risk of exposure for humans and other animals is still quite small.
Nonetheless, the findings underscore the growing recognition that the hot new field of nanotechnology, which federal officials
have said will be at the heart of America's "next industrial revolution," may bring with it a number of old-fashioned trade-offs
in terms of potential environmental damage and health risks.
Other animal studies have suggested that a related class of nanoparticles causes lung injuries when inhaled, raising
concerns about worker safety in the small but growing number of nanoparticle factories.
Federal agencies including the Food and Drug Administration, the Environmental Protection Agency and the Occupational
Safety and Health Administration have acknowledged that current regulations may not adequately protect against
nanoparticles' unique toxicities, but those agencies have only recently begun considering how to respond.
"There are many potential benefits of nanotechnology, but its hazards and risks are poorly understood," said Eva
Oberdoerster, an environmental toxicologist at Southern Methodist University in Dallas, who led the new studies.
Nanotechnology is an emerging field of science that deals with engineered molecules a few billionths of a meter in size.
Because of the novel arrangements of the atoms in these molecules -- and because the laws of physics behave differently at
such scales -- nanoparticles display bizarre chemical properties. Those properties make them potentially useful in products
including stain-proof fabrics and computer components, but also make them potentially biologically disruptive.
The new research focused on C 60 fullerenes, also known as buckyballs, which resemble microscopic soccer balls.
Scientists hope to use them as drug delivery systems, components of fuel cells and as tools to clean up contaminated land.
But buckyballs can also steal electrons from surrounding molecules -- a process known as oxidation and a common
mechanism of tissue damage.
In her experiments, Oberdoerster kept young largemouth bass in 10-liter aquariums filled with fullerene-spiked water at
concentrations of 0.5 parts per million -- similar to that encountered with more common pollutants in U.S. ports. After 48
hours, the fish were removed and their brains studied for evidence of lipid peroxidation, a tissue-burning chemical reaction
that toxicologists use as a standard of biological damage.
The level of brain damage was "severe," Oberdoerster reported yesterday at the national meeting of the American Chemical
Society in Anaheim -- about 17 times higher than seen in fish kept in clean water for comparison.
"Given the rapid onset of brain damage, it is important to further test and assess the risks and benefits of this new
technology before use becomes even more widespread," she said in a statement.
In a telephone interview, Oberdoerster said some of the tissue damage may be caused directly by the buckyballs and some
may be inflicted by immune system cells responding to the exposure.
Oberdoerster also found that buckyballs caused die-offs of Daphnia, or water fleas -- crustaceans just a few millimeters long
that eat algae and serve as food for other aquatic animals. Because of their crucial role in the food chain, Daphnia is a
common test organism for aquatic toxicity.
At about the same concentration used for the fish, half the Daphnia were dead within 48 hours -- an effect Oberdoerster
characterized as "moderately toxic," more deadly than nickel but less so than copper.
The new findings are somewhat surprising because many scientists had predicted that buckyballs would not linger in water
but would quickly form clumps and sink, said John R. Bucher, deputy director of the environmental toxicology program at the
National Institute of Environmental Health Sciences in Research Triangle Park, N.C., a branch of the National Institutes of
Health.
"Everyone assumed they'd just become part of the muck, if you will," Bucher said. "This is telling us we need to pay attention
to this area."
Bucher is part of a multi-year federal effort, still largely in the planning stage, to test the toxicity of several kinds of
nanoparticles -- an effort made difficult, he noted, because companies have been reluctant to reveal the precise formulas
they are using to make their novel nano-products.
E. Clayton Teague, director of the National Nanotechnology Coordination Office, which advises the White House on
nanotechnology issues, said progress in designing those studies is "proceeding very nicely," though results are still several
years away.
"All of the relevant agencies are now very actively looking at existing regulations to examine the degree to which they do or
might not cover adequately these new nanoscale materials," he said. "I think that most people still believe that with some
modifications . . . the existing regulations will be effective in covering these new materials."
By Rick Weiss
Washington Post Staff Writer
Monday, March 29, 2004; Page A02
“… an effect Oberdoerster
characterized as ‘moderately
toxic,’ more deadly than nickel
but less so than copper.”
24
Relative Risk
Asbestos Fibers
Carbon Nanotube Bundles
What, exactly, is killing us?
Asbestos:
2,000 – 10,000 (depends how you count)
But asbestos is banned, right?
Not since the 5th circuit court of
appeals overturned it in 1991.
Corrosion Proof Fittings v. Environmental Protection Agency, (5th Circuit
1991), p.35.
13,100 metric tons used in the U.S. in 2001
http://www.epa.gov/asbestos/pubs/asbbans2.pdf
Asbestos products not banned –
asbestos-cement corrugated sheet, asbestos-cement flat sheet, asbestos
clothing, pipeline wrap, roofing felt, vinyl-asbestos floor tile, asbestos-cement
shingle, millboard, asbestos-cement pipe, automatic transmission components,
clutch facings, friction materials, disc brake pads, drum brake linings, brake
blocks, gaskets, non-roofing coatings, and roof coatings.
...because, properly managed throughout its lifecycle, the reward outweighs the risk!
Framing risk appropriately is critical!
Only some tubes are
“dangerous.”
 In the absence of specific information,
trends across materials can be useful for
setting conservative endpoints.

There is nothing magic about “nano”
◦ Nanostructure enables new properties via well-understood physics leading
to revolutionary applications.
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Complexity of the materials set necessitates research to draw risk
categories across classes of nanoscale materials
Both exposure and chemical properties may change during the lifecycle, dramatically affecting hazards.
Coupled, iterative risk assessment and life-cycle analysis allows us to
move forward in the absence of full data sets.
Communication!
Is there really anything here unique to
nanomaterals?
◦ Chemicals change in the environment
◦ Combinations of chemicals / drugs have unpredictable
effects
◦ Nanoscale materials could lead, and eventually fit
within, a comprehensive review of how we assess the
risks of chemicals in general.