Safe handling of nanotechnology

Andrew D. Maynard1, Robert J. Aitken, Tilman Butz, Vicki Colvin, Ken Donaldson,
Gnter Oberdrster, Martin A. Philbert, John Ryan, Anthony Seaton, Vicki Stone,
Sally S. Tinkle, Lang Tran, Nigel J. Walker & David B. Warheit
1.

Andrew D. Maynard is at the Woodrow Wilson International Center for Scholars

Email: Andrew.Maynard@wilsoncenter.org

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Abstract
The pursuit of responsible nanotechnologies can be tackled through a
series of grand challenges, argue Andrew D. Maynard and his co-authors.
When the physicist and Nobel laureate Richard Feynman challenged the science
community to think small in his 1959 lecture 'There's Plenty of Room at the
Bottom', he planted the seeds of a new era in science and technology.
Nanotechnology, which is about controlling matter at near-atomic scales to produce
unique or enhanced materials, products and devices, is now maturing rapidly with
more than 300 claimed nanotechnology products already on the market 1. Yet
concerns have been raised that the very properties of nanostructured materials that
make them so attractive could potentially lead to unforeseen health or
environmental hazards2.
The spectre of possible harm whether real or imagined is threatening to slow
the development of nanotechnology unless sound, independent and authoritative
information is developed on what the risks are, and how to avoid them 3. In what
may be unprecedented pre-emptive action in the face of a new technology,
governments, industries and research organizations around the world are beginning
to address how the benefits of emerging nanotechnologies can be realized while
minimizing potential risks4. Yet despite a clear commitment to support risk-focused
research, opportunities to establish collaborative, integrated and targeted research
programmes are being missed5. In September, Sherwood Boehlert, chair of the US
House Science Committee, commented in a hearing that "we're on the right path to
dealing with the problem, but we're sauntering down it when a sense of urgency is
required". And in October, Britain's Royal Society raised concerns that the UK
government had not made enough progress on reducing the uncertainties
surrounding the health and environmental impacts of nanomaterials 6.
The risks

D. RAMSEY
Potential health risks from exposure to engineered nanomaterials must be understood and minimized.

As research leaders in our respective fields, we recognize that systematic risk

research is needed if emerging nano-industries are to thrive. We cannot set the
international research agenda on our own, but we can inspire the scientific
community including government, industry, academia and other stakeholders
to move in the right direction. So we propose five grand challenges to stimulate
research that is imaginative, innovative and above all relevant to the safety of
nanotechnology.

2006 D. HAWXHURST/WILSON CENTER

Nanotechnology is rapidly advancing, with more than 300 nanoproducts already on the market.

Fears over the possible dangers of some nanotechnologies may be exaggerated, but
they are not necessarily unfounded. Recent studies examining the toxicity of
engineered nanomaterials in cell cultures and animals have shown that size, surface
area, surface chemistry, solubility and possibly shape all play a role in determining
the potential for engineered nanomaterials to cause harm 7. This is not surprising:
we have known for many years that inhaled dusts cause disease, and that their
harmfulness depends on both what they are made of and their physical nature. For
instance, small particles of inhaled quartz lead to lung damage and the potential
development of progressive lung disease, yet the same particles with a thin coating
of clay are less harmful8. Asbestos presents a far more dramatic example: thin,
long fibres of the material can lead to lung disease if inhaled, but grind the fibres
down to shorter particles with the same chemical make-up and the harmfulness is
significantly reduced9.
It is generally accepted that, in principle, some nanomaterials may have the
potential to cause harm to people and the environment. But the way science is
done is often ill-equipped to address novel risks associated with emerging
technologies. Research into understanding and preventing risk often has a low
priority in the competitive worlds of intellectual property, research funding and
technology development. And yet there is much at stake in how potential nanospecific risks are understood and managed. Without strategic and targeted risk
research, people producing and using nanomaterials could develop unanticipated
illness arising from their exposure; public confidence in nanotechnologies could be
reduced through real or perceived dangers; and fears of litigation may make
nanotechnologies less attractive to investors and the insurance industry.

Understanding and preventing risk often has a low priority in the

competitive world of research funding.
The science community needs to act now if strategic research is to support
sustainable nanotechnologies, in which risks are minimized and benefits maximized.
Our five grand challenges are chosen to stimulate such research, as well as bring
focus to a range of complex multidisciplinary issues. The challenges span the next
15 years, and their successful achievement will depend on coordination,
collaboration, resources and ingenuity. They are not comprehensive there is
essential research that is not covered here but they do form a framework on
which others can build.
The challenges

IMAGES SUPPLIED BY A. D. MAYNARD

Develop instruments to assess exposure to engineered nanomaterials in air

and water, within the next 310 years. Because nanotechnologies are diverse
and exposures to nanomaterials will vary widely, assessing exposure and potential
impacts on health or the environment will require multiple sensor types operating
under different conditions. Three issues stand out as fertile ground for innovative
research: monitors for airborne exposure, detectors for waterborne nanomaterials,
and smart sensors that can measure both exposure and potential hazards.
We don't yet know which aspects of airborne nanomaterials should be measured
number, surface area or mass concentration, a combination of these, or something
else entirely. But people working with nanomaterials urgently need inexpensive
personal aerosol samplers that are capable of measuring exposure in the workplace
and environment. This universal aerosol sampler would log exposure against
aerosol number, surface area and mass concentration simultaneously, and provide a
historic record that can be interpreted in the light of new knowledge and new
exposure monitoring paradigms. It would be portable, sufficiently inexpensive to
ensure widespread use, and available commercially within the next 3 years.

Without strategic risk research, public confidence in nanotechnologies

could be reduced through real or perceived dangers.
Effluent from nanomanufacturing processes, use of nanoparticle-containing
substances such as sunscreens, and disposal of nanomaterial-containing products,
will inevitably lead to increasing quantities of engineered nanomaterials in water
systems. If we cannot track these materials, it will be almost impossible to
determine how benign or harmful their presence is. The second challenge therefore
is to develop instruments that can track the release, concentration and
transformation of engineered nanomaterials in water systems (including liquidbased nanotechnology consumer products), within the next 5 years.
Advances in information technology and sensor design are leading to the
development of smart sensors that combine information on various aspects of
exposure and hazard in a way that is useful for decision-making. The concept is
embodied in radiation monitors and biomonitoring, but has not yet been extended
to engineered nanomaterials. The final part of this challenge therefore is to develop

smart sensors that indicate potential harm to human health. An example would be
sensors that simultaneously detect airborne nanoparticles and determine their
potential to generate reactive oxygen species possibly providing early indications
of harm. Such sensors should be available within the next 10 years.
Develop and validate methods to evaluate the toxicity of engineered
nanomaterials, within the next 515 years. There are many aspects to
evaluating nanomaterial toxicity. But there are three that we consider crucial for
stimulating high-quality research and preventing the unnecessary use of hazardous
nanomaterials: validated screening tests, developing viable alternatives to in
vivo tests, and determining the toxicity of fibre-shaped nanoparticles.
The enormous diversity of engineered nanomaterials with different sizes, shapes,
compositions and coatings matches, and possibly exceeds, that of conventional
chemicals. High-throughput protocols that are benchmarked and validated are
urgently needed to screen for potential hazards. The first part of this challenge is to
reach international agreement on a battery of in vitroscreening tests for human and
environmental toxicity within the next 2 years, and to validate these tests within
the next 5 years. Essential to this challenge will be the widespread and global
availability of standard nanoparticle samples to allow comparison and refinement of
methods across government, industry and academic laboratories.
Although testing in vivo will continue to provide the most relevant information on
human (and other organism) hazards, there is an economic and ethical impetus to
minimize the burden of animal testing. Emerging technologies including
nanotechnology are providing new possibilities for simulating and predicting
nanomaterial behaviour in living organisms. We propose that relevant and validated
alternatives to in vivo toxicity testing of engineered nanomaterials be developed
over the next 15 years.
Fibre-shaped nanomaterials possibly represent a unique inhalation hazard, and
their pulmonary toxicity should be evaluated as a matter of urgency. Inhalation of a
sufficient dose of asbestos fibres can lead to the malignant disease mesothelioma,
the causation of which is related to the length, width and chemistry of the fibres, as
well as their ability to persist in the lungs.
Although it is not clear whether fibre-shaped nanoscale particles formed from
carbon and other materials will behave like asbestos or not, some materials are
sufficiently similar to cause concern: any failure to pick up asbestos-like behaviour
as early as possible would be potentially devastating to the health of exposed
people and to the future of the nanotechnology industry. We propose that the
potential health impact of high-aspect-ratio, biopersistent engineered nanotubes,
nanowires and nanofibres is systematically investigated within the next 5 years.
Develop models for predicting the potential impact of engineered
nanomaterials on the environment and human health, within the next 10
years. To assess the safety of complex multicomponent and multifunctional
nanomaterials, scientists will need systems capable of predicting the potential

impact of new nanomaterials, devices and products. Once again our challenge here
has three parts. First, to develop validated models capable of predicting the release,
transport, transformation, accumulation and uptake of engineered nanomaterials in
the environment. In parallel, validated models must be developed that are capable
of predicting the behaviour of engineered nanomaterials in the body, including dose,
transport, clearance, accumulation, transformation and response. These models
should: relate the physical and chemical characteristics of nanomaterials to their
behaviour; allow an integrated approach to predicting potential impact of
engineered nanomaterials and nanoproducts; and estimate impact within
susceptible populations.
Third, to use predictive models for engineering nanomaterials that are safe by
design. This might include engineering the nanomaterials in ways that enhance
desired properties while suppressing hazardous ones, or creating fail-safe
mechanisms that ensure a transition to benign materials upon disposal.
Develop robust systems for evaluating the health and environmental
impact of engineered nanomaterials over their entire life, within the next 5
years. Thinking in terms of life cycles leads to a holistic approach to managing
risks and benefits. Developing robust ways of evaluating the potential impact
good or bad of a nanoproduct from its initial manufacture, through its use, to its
ultimate disposal will stretch both scientific and policy communities, but will lead to
new methodologies that are widely applicable.
Develop strategic programmes that enable relevant risk-focused research,
within the next 12 months. Ultimately, systematic and organized risk research
will empower industry, consumers and policy-makers to make the best decisions
about the development and application of emerging nanotechnologies. As end-users
of the scientific data, these communities must play a central role in shaping what is
done and how. Government research strategies that systematically reduce
uncertainty surrounding the potential impact of nanotechnologies and support
science-based oversight are essential to the safe development of nanotechnology.
But these must be complemented by, and integrated with, industry-led research.
We highlight three areas that we believe are critical to the success of such risk
research: collaboration, communication and coordination.
The first challenge is identifying mechanisms that enable collaborative research
programmes whether interdisciplinary, between government and industry, or
between different stakeholders. Virtual interdisciplinary research centres and
networks are one way of stimulating collaboration, as long as they are accompanied
by adequate resources. We would also encourage joint governmentindustry
partnerships that underpin good product stewardship and oversight, while being
transparent and credible.

If the global research community can rise to the challenges we have

set, then we can surely look forward to the advent of safe
nanotechnologies.

Communicating research on nanotechnology risks and benefits outside the scientific

community is challenging, but is essential for a risk dialogue based on sound
science. This means developing communication activities that enable technical
information to be summarized, critiqued and ultimately synthesized for various
interested parties, including decision-makers and consumers. The advent of the
Internet provides an ideal venue for such activities and we encourage its use in
communicating with the end-users of risk-based science.
Finally, a global understanding of nanotechnology-specific risks is essential if large
and small industries are to operate on a level playing field, and developing
economies are not to be denied essential information on designing safe
nanotechnologies. We propose that mechanisms, networks and meetings are
established that enable international information-sharing and coordination between
the public and private sectors.
Nanotechnology comes at an opportune time in the history of risk research. We
have cautionary examples from genetically modified organisms and asbestos
industries that motivate a real interest, from all stakeholders, to prevent, manage
and reduce risk proactively. We have a global research infrastructure that supports
international collaboration. We also have revolutions in biotechnology, sensing and
computation that are transforming how health-focused research is performed. If the
global research community can take advantage of these circumstances and rise to
the challenges we have set, then we can surely look forward to the advent of safe
nanotechnologies.
Disclaimer: The opinions in this paper reflect those of the authors and do not
necessarily represent the official views or policies of their affiliations.
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References
1. The Nanotechnology Consumer Products Inventory (Woodrow Wilson
International Center for Scholars, Washington DC, 2006). Published online
at http://www.nanotechproject.org/consumerproducts.
2. Nanoscience and Nanotechnologies: Opportunities and Uncertainties (The
Royal Society and The Royal Academy of Engineering, London, 2004).
3. Taking Action on Nanotech Environmental, Health and Safety Risks (Lux
Research, New York, 2006).
4. Report of the OECD Workshop on the Safety of Manufactured Nanomaterials:
Building Co-operation, Co-ordination and Communication(Organization for
Economic Co-operation and Development, Paris, 2006).
5. Maynard, A. D. Nanotechnology: A Research Strategy for Addressing
Risk(Woodrow Wilson International Center for Scholars, Washington
DC,2006).

6. Two-Year Review of Progress on Government Actions: Joint Academies'

Response to the Council for Science and Technology's Call for Evidence(The
Royal Society and The Royal Academy of Engineering, London,2006).
7. Oberdrster, G., Oberdrster, E. & Oberdrster, J. Environ. Health
Perspect. 13, 823840 (2005).
8. Donaldson, K. & Borm, P. J. A. Ann. Occup.Hyg. 42, 287294
(1998). | Article | ChemPort |
9. Davis, J. G. et al. Br. J. Exp. Pathol. 67, 415430
(1986). | PubMed | ChemPort |

Abstract
Nano-this and nano-that. These days it seems you need the prefix "nano" for products
or applications if you want to be either very trendy or incredibly scary. This "nanotrend" has assumed "mega" proportions. Vague promises of a better life are met by
equally vague, generalized fears about a worse future. These debates have some
aspects in common: the subject is complex and not easy to explain; there is no
consensus on risks and benefits. - A particular problem with nanotechnology lies in
the huge gap between the public perception of what the hype promises and the
scientific and commercial reality of what the technology actually delivers today and in
the near future. There is nanoscience, which is the study of phenomena and
manipulation of material at the nanoscale, in essence an extension of existing sciences
into the nanoscale. Then there is nanotechnology, which is the design,
characterization, production and application of structures, devices and systems by
controlling shape and size at the nanoscale. Nanotechnology should really be called
nanotechnologies: There is no single field of nanotechnology. The term broadly refers
to such fields as biology, physics or chemistry, any scientific field really, or a
combination thereof, that deals with the deliberate and controlled manufacturing of
nanostructures. In addressing the health and environmental impact of nanotechnology
we need to differentiate two types of nanostructures: (1) Nanocomposites,
nanostructured surfaces and nanocomponents (electronic, optical, sensors etc.), where
nanoscale particles are incorporated into a substance, material or device ("fixed"
nanoparticles); and (2) "free" nanoparticles, where at some stage in production or use
individual nanoparticles of a substance are present. There are four entry routes for
nanoparticles into the body: they can be inhaled, swallowed, absorbed through skin or

be deliberately injected during medical procedures. Once within the body they are
highly mobile and in some instances can even cross the blood-brain barrier. How these
nanoparticles behave inside the organism is one of the big issues that need to be
resolved. Not enough data exists to know for sure if nanoparticles could have
undesirable effects on the environment. Two areas are relevant here: (1) In a free form
nanoparticles can be released in the air or water during production (or production
accidents) or as waste byproduct of production, and ultimately accumulate in the soil,
water or plant life. (2) In a fixed form, where they are part of a manufactured
substance or product, they will ultimately have to be recycled or disposed of as waste.
To properly assess the health hazards of engineered nanoparticles the whole life cycle
of these particles needs to be evaluated, including their fabrication, storage and
distribution, application and potential abuse, and disposal. The impact on humans or
the environment may vary at different stages of the life cycle. Regulatory bodies in the
U.S. as well as in the EU have concluded that nanoparticles form the potential for an
entirely new risk and that it is necessary to carry out an extensive analysis of the risk.
It is imperative that national and international regulatory bodies cooperate closely not
only with each other, but also with academia and industry; based on that,
nanomaterials and nanotechnology can be developed responsibly. With that in place
we can look forward to optimizing the benefits of nanotechnology while minimizing
and controlling the risks.

Abstract:
The field of nanotechnology has recently emerged as the most commercially
viable technology of this century because of its wide-ranging applications in our
daily lives. Man-made nanostructured materials such as fullerenes, nanoparticles,
nanopowders, nanotubes, nanowires, nanorods, nano-fibers, quantum dots,
dendrimers, nanoclusters, nanocrystals, and nanocomposites are globally produced
in large quantities due to their wide potential applications, e.g., in skincare and
consumer products, healthcare, electronics, photonics, biotechnology, engineering
products, pharmaceuticals, drug delivery, and agriculture. Human exposure to these
nanostructured materials is inevitable, as they can enter the body through the lungs
or other organs via food, drink, and medicine and affect different organs and tissues
such as the brain, liver, kidney, heart, colon, spleen, bone, blood, etc., and may
cause cytotoxic effects, e.g., deformation and inhibition of cell growth leading to
various diseases in humans and animals. Since a very wide variety of
nanostructured materials exits, their interactions with biological systems and
toxicity largely depend upon their properties, such as size, concentration, solubility,

chemical and biological properties, and stability. The toxicity of nanostructured

materials could be reduced by chemical approaches such by surface treatment,
functionalization, and composite formation. This review summarizes the sources of
various nanostructured materials and their human exposure, biocompatibility in
relation to potential toxicological effects, risk assessment, and safety evaluation on
human and animal health as well as on the environment.

Regulating Nanomedicine
NEW NANO TOOLS OFFER GREAT PROMISE FOR
THE FUTURE - IF REGULATORS CAN SOLVE THE
DIFFICULTIES THAT HOLD DEVELOPMENT BACK
Shannon Fischer

| March 13, 2014 |

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In 1979, a Hebrew University biochemist named Yechezkel Barenholz teamed with Alberto Gabizon, a newly minted Ph.D.
from the Weizmann Institute of Science, to find a better way to give
chemotherapeutic doxorubicin to patients with cancer.
Sixteen years later, the result of that collaborationDoxilwon
approval from the U.S. Food and Drug Administration (FDA). It
was a reformulation of doxorubicin into tiny, drug-loaded membrane
spheresliposomesfewer than 100-nm across. They were so
small they could course through the bloodstream until they leaked
right through the particularly porous vasculature that marked a
cancer site. And though the particles didnt necessarily fight the
cancer better, they did fight it with fewer side effects. As it happens,
they were also the first formal nanodrug in history.
Since its arrival to market, Doxil has made more than US$600
million in annual sales battling Kaposis sarcoma, multiple
myeloma, and ovarian and breast cancer. It has been joined by
dozens of nano bedfellows, most of them also anticancer drugs,
many also liposomes, although there are also dextran-coated iron

oxide nanoparticles for in vivo organ imaging, hydroxyapatite

nanocrystals that act as bone substitutes, and even gold
nanoparticles that work outside the body to diagnose infections.
But theres a catch: none of these nanomedicines were approved
under any specific nano guidelines. Even Doxil passed with a mere
expedited review as a reformulation of doxorubicin. But
nanomedicines dont always act like their larger counterparts, and
when they differ, its not always predictable. The fact is, despite all
the successes and the billions of dollars invested, nanomedicine
remains a regulatory minefield rife with exotic toxicology and
uncertain policies, badly in need of a few clear answers.

WHATS THE PROBLEM?

The problem is that something at the nanoscale is not just the
miniaturized equivalent to its larger self. For one thing, its shrunken
size results in an enormously increased ratio of surface area to
volume ratio. That translates in vivo as exponentially more surfaces
that can interact with the biological environment. That may be a
good thinga nanosized drug can be more bioavailable, more
stable, or more easily decorated with interactive add-ons that help
target organs of interestbut, in some cases, especially with certain
nanomaterials, like metal oxides, it also magnifies toxicities that
might have been absent or unnoticeable at a larger size.
Then, too, is the fact that when particle sizes drop to under 100
nm or so, all sorts of physicochemical properties can begin to shift
in ways that scientists still have not fully mapped. Thermal, optical,
and magnetic properties might be different; particles may become
more reactive, have faster ion transport or different structural
integrity. And, maddeningly, everything from the particles size and

shape to its surface area, solubility, crystallinity, charge, and even

aspect ratio affects exactly how those properties manifest.
Because of these variations, the end result of any given nanoscaled
particle may be a unique behavior markedly different from one
variation to the next. That, again, is part of the technologys
desirabilityharness these qualities correctly and the result is a
potential drug or device that arrives at a given disease site with
maximal efficiency and potency. But it can just as easily add
unexpected twists. In rats, for example, positively charged
nanovesicles caused swelling at the bloodbrain barrier, but neutral
ones, and small amounts of negatively charged ones, did not. In
another study, 10- and 60-nm-sized gold particles resulted in liver
damage in mice, but 5- and 30-nm sized particles did not.
Unfortunately, that pattern doesnt necessarily apply to other
particles, or other sizes, or even the same particles with altered
parameters; scientists are still trying to develop the measures they
need to predict how such particles will behave because they just
dont know yet.
For bulk size materials, youre basically talking about the chemical
composition, dose, and exposure route when studying toxicity
thats a few parameters, says Huan Meng, who studies
nanomedicines and nanotoxicology at the Jonsson Comprehensive
Cancer Center and the Center for Environmental Implications of
Nanotechnology (CEIN) at the University of California, Los
Angeles (UCLA). But with nanomaterials, you have multiple
directions that you can play with, Meng says. Youre talking about
a really dynamic, complicated system that traditional toxicology
cannot fully address.

CAUTION IS ADVISED

So far, the regulation of nanomedicines and devices has erred on the

side of caution. The FDA, for example, hasnt adopted any formal
guidelines for nanotechnology, although it has released guidelines
describing how it defines a nanoscale productspecifically, as
having at least one dimension between 1 and 100 nm, or as being
fewer than a micron in size and demonstrating size-dependent
behaviors. With that, however, the FDA reviews nanomedicines and
devices on a case-by-case, component-by-component basis under
existing drug and device guidelines, with additional questions and
tests as desiredalthough in a 2012 comment in Science, FDA
Commissioner Margaret Hamburg indicated that it may yet fold in
product-specific regulation in the future.
Russell Mumper, vice dean of the University of North Carolinas
Eshelman School of Pharmacy, calls it a rational, thoughtful
approach given how little is known and how stringent the review
process is. Its really no different than a non-nanotechnology
approach, he says, theyre going to want to see, on a
nanomedicine by nanomedicine basis, a comprehensive data set of
not only the physicochemical characterization of the manufactured
nanomedicine, but batch-to-batch reproducibility. They want to see
this comprehensive data set and manufacturing information, before
theyll ever let you dose even the first patient.
Other countries take a similar approach, including Canada, Japan,
and some in the European Union (EU), which, like the United
States, also rely largely on the scrutiny of their pre-existing
processes to evaluate nanomedicines (which they define similarly to
the United States, although there is still no formal internationally
agreed definition). Indeed, according to a 2013 Organization for
Economic Cooperation and Development survey of a dozen
different nations, including Australia and Poland, as well as the EU

and the United States, folding nanoproducts into existing regulatory

and legislative processes is by far the most common strategy to date.
And to an extent, its worked. After all, nanobased medical products
have been on the global markets for nearly 20 years, and no major
incidents have occurred. Yet, many are not entirely satisfied with
current measures, and the situation remains in flux.

WHAT WE DONT KNOW CAN HURT US

Critics accuse the measures of being both too risky and too cautious.
Cautious because such hesitancy toward definite regulation, along
with the absence of established testing protocols or manufacturing
guidelines, leaves the powerhouses of the industry reluctant to join
the fray. Big pharma has dabbled in nanomedicine, but it has yet to
throw its muscle into the field largely because of the potentially
multiplied expense and time that such an amorphous regulatory
landscape will likely entail, especially for novel nanomedicines that
propose to use new ingredients.
And its also a risky stance because of how many unknowns remain
in the science, says Raj Bawa, adjunct professor at Rensselaer
Polytechnic Institute and patent agent at Bawa Biotech LLC.
Nanoparticles are so unpredictable in vivo, he explains, in ways that
hinge on so many different elements and properties that it is entirely
possible current toxicology tests simply cannot ask the right
questions. Maybe they do, but it is hard to even know that for sure.
Were dealing with a very dynamic system in the human body, and
really, we dont understand fully the interaction of nanoparticles and
the biosurface at that nanoscale, he says. Youre having reactions
at the molecular and atomic level that arent fully studied.

But regulators are first to acknowledge their failings, and many are
at work to address these shortcomings. The FDA has invested
heavily in new in-house nanotechnology regulatory science
programs, aimed at ramping up new methods to profile and test
nanomaterials in vitro and vivo. The National Cancer Institutes
Nanotechnology Characterization Laboratory (NCL) has examined
nanomaterials and their complexities since 2004. Every year, it
accepts a dozen or so potential nanotherapeutics developed from
labs nationwide and runs a battery of tests that serve to both assess
those drugs and add to its growing body of assay protocols and
troublesome manufacturing pitfalls such as sterility and batch-tobatch variabilityall of which it shares with the science community
and FDA. In the past ten years, it has characterized nearly 300
different nanomaterials and sent six on to clinical trials. Meanwhile,
the information and standards that it has gathered have begun to
unofficially reshape not only the FDAs own review practices but
strategies internationally.
As the field is developing very quickly, a benefit is that people are
looking to establish protocols and normssimilar to best practices
and the NCL has helped to establish that, Mumper says. His lab,
he explains, has submitted investigational new drug applications to
the FDA for nanomaterials and was referred to protocols established
by the NCL. The position the FDA takes, he says, is: These are
the accepted best practices in terms of standard operations, and this
is generally what the community has adopted. You may not have to
do all the protocols, but you have to justify why youre not doing
them.
Internationally, the European Commission is collaborating with the
NCL to develop a European nanotechnology characterization lab
network of its own, which it hopes to launch this year in existing
labs. Recently, the European Medicines Agency (EMA)partially

in collaboration with Japans Pharmaceutials and Medical Devices

Agencyhas published a series of reflection papers highlighting
specific considerations for novel so-called next-generation
nanomedicines and known classes of nanomedical products, such as
liposomes and copolymer micelles. In addition, in 2009, the
EMA, with the United States, Japan, and Canada, launched an
international dialogue on the technology through the International
Regulators Subgroup on Nanomedicines. This exchange was also
aimed at identifying global knowledge gaps and upcoming
regulatory needs.
Work like thisidentifying gaps, building the sciencehas become
a global effort, taking place in government and academic labs alike.
At UCLA, Andre Nel, the director of CEIN, and chief of the
Nanomedicine Division, are developing a robotic system to perform
high-throughput and high-content screenings to assess the safety of
and even discover new nanomedicines. One of the goals is to link
the material properties to the biological outcome and establish the
predictive biology, says Meng, who works with Nel. Between
them, labs like his and the funding agencies are gaining a lot of
new knowledge and expertise, he says. We are learning. And we
are practicing.

FUTURE TENSE
Laying this foundation will be essential to the future. Across the
world, hundreds of nanomedicines and devices are wending their
way through the clinical testing pipeline. If the pace continues as is,
market forecasters predict that the global nanomedicine market will
hit US$130.9 billion by 2016.
Many of these compounds will still be relatively known quantities
liposomes, nanocrystalsbut as time goes on, more novel creations

will emerge and begin to blur the lines between physical devices and
chemical drugs, and that may be a problem. The FDA has an Office
of Combination Products to determine whether multifunction
products should be assessed as the drug, biologic, or device,
depending on its primary mode of action. Multipurpose
theranostic agents that can diagnose, treat, and track diseases may
not always be easily categorized and some researchers worry that
that could lead to inconsistent evaluations. Critics such as Bawa are
concerned that this process is too impreciseparticularly because,
he says, at the time of an investigational application, its not always
clear which mode of action provides the most important therapeutic
action and some products can even have two different, equally
critical modes of action.
Furthermore, not all regulatory bodies have defined combination
product offices, eitherthe EU assesses medical products and
devices separately and differently. Currently, advanced and
biotechnological drugs like nanomedicines are evaluated under the
centralized body of the EMA, but devices are regulated under the
various authorities of the individual member states. If a medicine
with a device component arrives for review at the EMA, the EMA
evaluates it in consultation with medical device authorities, and vice
versa.
With respect to the evaluation of the device component,
Logistically, its more difficult, says Falk Ehmann, the Innovation
Task Force coordinator in the EMAs Specialised Scientific
Disciplines Department. A worst-case scenario where one state rules
one way and its neighbor rules differently can happen, he says.
There are robust procedures in place to prevent that occurrence, and
collaboration is the norm, but still the potential is there, he says.
And with the theranostics, its getting more and more
complicated.

Rogrio Gaspar, vice rector at the University of Lisbon and head of

its Pharmaceutical Technology Department in Portugal, worries that
current device regulations in particular are poorly constructed to
handle the type of nanobased therapeutic-diagnostic devices that
might be delivered by routes traditionally used for drug products.
They will fall into the gap between medical devices and medical
products, he says, and that might bring us a number of products
that are not consistently regulated.
In time, yet thornier quandaries will emerge. As Mauro Ferrari,
president and chief executive officer of the Houston Methodist
Research Institute and the Alliance for NanoHealth in Houston,
Texas, points out, nanotechnologys improvements on drug delivery
and kinetics could be readily weaponized for mass destruction. For
instance, he argued in a 2012 discussion of nanomedical ethics,
nanoparticles could be used to change the modality of infection of
certain viruses, from blood contact-only to nanopathogens that are
effective through inhalation or oral ingestion. Regulatory hurdles
will not slow that concern, he points out. Terrorists, after all, are
hardly beholden to the FDA.
Less alarming but more complicated will be the fact that
nanotechnology will almost certainly enable truly personalized
medicine. Microtechnology opened the way to genomics, Ferrari
tells me. Nanotechnology opens proteomics and metabolomics, and
all the other omics where you need to be a lot smaller to process a
lot more information. When that area hits its stride, he worries, it
will open a more potent Pandoras box of privacy and consent issues
than even genetics has done. Genomic information tells who you
are and tells you your risk profile. When you unlock the proteomic
and metabolomic world, it not only tells you risk, it tells you where
you are, where youve been, what youre doing, how youre
feeling, he says. On one hand, the benefits to health care are huge.

On the other hand, it means a brave new world where the definition
of privacy is concerned.
These are more difficult issues that regulations cannot handle on
their own. Discussions among researchers and ethicists are
underway, but the critical group that needs to participate will be the
public, and that has yet to happen at a broad level. But the greatest
fear, as far as Ferrari can see, is that regulatory fears and ethical
quandaries be allowed to grow so large that nanomedicines future is
stifled. Its easy to build scary scenarios, he says. But I live in a
world where every patient who comes to me is facing death.
Nanomedicines abilities, in the end, will be key to saving lives like
theirs from cancer and other diseases, and not to take advantage of it
would be the greatest risk of all.

Nanotechnology In Medicine: Huge

Potential, But What Are The Risks?
Written by Catharine Paddock PhD
Published: Friday 4 May 2012
email
4.5519SHARE6

Nanotechnology, the manipulation of matter at the atomic and molecular scale to

create materials with remarkably varied and new properties, is a rapidly expanding
area of research with huge potential in many sectors, ranging from healthcare to
construction and electronics. In medicine, it promises to revolutionize drug delivery,
gene therapy, diagnostics, and many areas of research, development and clinical

application.
This article does not attempt to cover the whole field, but offers, by means of some
examples, a few insights into how nanotechnology has the potential to change
medicine, both in the research lab and clinically, while touching on some of the
challenges and concerns that it raises.

What is Nanotechnology?
The prefix "nano" stems from the ancient Greek for "dwarf". In science it means one
billionth (10 to the minus 9) of something, thus a nanometer (nm) is is one billionth of
a meter, or 0.000000001 meters. A nanometer is about three to five atoms wide, or
some 40,000 times smaller than the thickness of human hair. A virus is typically 100
nm in size.
The ability to manipulate structures and properties at the nanoscale in medicine is
like having a sub-microscopic lab bench on which you can handle cell components,
viruses or pieces of DNA, using a range of tiny tools, robots and tubes.

Manipulating DNA
Therapies that involve the manipulation of individual genes, or the molecular
pathways that influence their expression, are increasingly being investigated as an
option for treating diseases. One highly sought goal in this field is the ability to tailor
treatments according to the genetic make-up of individual patients.
This creates a need for tools that help scientists experiment and develop such
treatments.
Imagine, for example, being able to stretch out a section of DNA like a strand of
spaghetti, so you can examine or operate on it, or building nanorobots that can
"walk" and carry out repairs inside cell components. Nanotechnology is bringing that
scientific dream closer to reality.
For instance, scientists at the Australian National University have managed to attach
coated latex beads to the ends of modified DNA, and then using an "optical trap"
comprising a focused beam of light to hold the beads in place, they have stretched
out the DNA strand in order to study the interactions of specific binding proteins.

Nanobots and Nanostars

Meanwhile chemists at New York University (NYU) have created a nanoscale robot
from DNA fragments that walks on two legs just 10 nm long. In a 2004 paper
published in the journal Nano Letters, they describe how their "nanowalker", with the
help of psoralen molecules attached to the ends of its feet, takes its first baby steps:
two forward and two back.
One of the researchers, Ned Seeman, said he envisages it will be possible to create
a molecule-scale production line, where you move a molecule along till the right
location is reached, and a nanobot does a bit chemisty on it, rather like "spotwelding" on a car assembly line. Seeman's lab at NYU is also looking to use DNA

nanotechnology to make a biochip computer, and to find out how biological

molecules crystallize, an area that is currently fraught with challenges.
The work that Seeman and colleagues are doing is a good example of
"biomimetics", where with nanotechnology they can imitate some of the biological
processes in nature, such as the behavior of DNA, to engineer new methods and
perhaps even improve them.
DNA-based nanobots are also being created to target cancer cells. For instance,
researchers at Harvard Medical School in the US reported recently in Science how
they made an "origami nanorobot" out of DNA to transport a molecular payload.
The barrel-shaped nanobot can carry molecules containing instructions that make
cells behave in a particular way. In their study, the team successfully demonstrates
how it delivered molecules that trigger cell suicide in leukemiaand lymphoma cells.
Nanobots made from other materials are also in development. For instance, gold is
the material scientists at Northwestern University use to make "nanostars", simple,
specialized, star-shaped nanoparticles that can deliver drugs directly to the nuclei
of cancer cells. In a recent paper in the journal ACS Nano, they describe how drugloaded nanostars behave like tiny hitchhikers, that after being attracted to an overexpressed protein on the surface of human cervical and ovarian cancer cells,
deposit their payload right into the nuclei of those cells.
The researchers found giving their nanobot the shape of a star helped to overcome
one of the challenges of using nanoparticles to deliver drugs: how to release the
drugs precisely. They say the shape helps to concentrate the light pulses used to
release the drugs precisely at the points of the star.

Nanofactories that Make Drugs In Situ

Scientists are discovering that protein-based drugs are very useful because they can
be programmed to deliver specific signals to cells. But the problem with conventional

delivery of such drugs is that the body breaks most of them down before they reach
their destination.
But what if it were possible to produce such drugs in situ, right at the target site?
Well, in a recent issue of Nano Letters, researchers at Massachusetts Institute of
Technology (MIT) in the US show how it may be possible to do just that. In their
proof of principle study, they demonstrate the feasibility of self-assembling
"nanofactories" that make protein compounds, on demand, at target sites. So far
they have tested the idea in mice, by creating nanoparticles programmed to produce
either green fluorescent protein (GFP) or luciferase exposed to UV light.
The MIT team came up with the idea while trying to find a way to attack metastatic
tumors, those that grow from cancer cells that have migrated from the original site to
other parts of the body. Over 90% of cancer deaths are due to metastatic cancer.
They are now working on nanoparticles that can synthesize potential cancer drugs,
and also on other ways to switch them on.

Nanofibers

Nanofibers are fibers with diameters of less than 1,000 nm. Medical applications
include special materials for wound dressings and surgical textiles, materials used in
implants, tissue engineering and artificial organ components.
Nanofibers made of carbon also hold promise for medical imaging and precise
scientific measurement tools. But there are huge challenges to overcome, one of the
main ones being how to make them consistently of the correct size. Historically, this
has been costly and time-consuming.
But last year, researchers from North Carolina State University, revealed how they
had developed a new method for making carbon nanofibers of specific sizes. Writing
in ACS Applied Materials & Interfaces in March 2011, they describe how they
managed to grow carbon nanofibers uniform in diameter, by using nickel
nanoparticles coated with a shell made of ligands, small organic molecules with
functional parts that bond directly to metals.
Nickel nanoparticles are particularly interesting because at high temperatures they
help grow carbon nanofibers. The researchers also found there was another benefit
in using these nanoparticles, they could define where the nanofibers grew and by
correct placement of the nanoparticles they could grow the nanofibers in a desired
specific pattern: an important feature for useful nanoscale materials.
Lead is another substance that is finding use as a nanofiber, so much so that
neurosurgeon-to-be Matthew MacEwan, who is studying at Washington University
School of Medicine in St. Louis, started his own nanomedicine company aimed at
revolutionizing the surgical mesh that is used in operating theatres worldwide.
The lead product is a synthetic polymer comprising individual strands of nanofibers,
and was developed to repair brain and spinal cord injuries, but MacEwan thinks it
could also be used to mend hernias, fistulas and other injuries.
Currently, the surgical meshes used to repair the protective membrane that covers

the brain and spinal cord are made of thick and stiff material, which is difficult to
work with. The lead nanofiber mesh is thinner, more flexible and more likely to
integrate with the body's own tissues, says MacEwan. Every thread of the nanofiber
mesh is thousands of times smaller than the diameter of a single cell. The idea is to
use the nanofiber material not only to make operations easier for surgeons to carry
out, but also so there are fewer post-op complications for patients, because it breaks
down naturally over time.
Researchers at the Polytechnic Institute of New York University (NYU-Poly) have
recently demonstrated a new way to make nanofibers out of proteins. Writing
recently in the journalAdvanced Functional Materials, the researchers say they came
across their finding almost by chance: they were studying certain cylinder-shaped
proteins derived from cartilage, when they noticed that in high concentrations, some
of the proteins spontaneously came together and self-assembled into nanofibers.
They carried out further experiments, such as adding metal-recognizing amino acids
and different metals, and found they could control fiber formation, alter its shape,
and how it bound to small molecules. For instance, adding nickel transformed the
fibers into clumped mats, which could be used to trigger the release of an attached
drug molecule.
The researchers hope this new method will greatly improve the delivery of drugs to
treat cancer, heart disorders and Alzheimer's disease. They can also see
applications in regeneration of human tissue, bone and cartilage, and even as a way
to develop tinier and more powerful microprocessors for use in computers and
consumer electronics.

A schematic illustration showing how nanoparticles or other cancer drugs might be used to treat cancer.
This illustration was made for theOpensource Handbook of Nanoscience and Nanotechnology

What of the Future and Concerns Surrounding

Nanomaterials?
Recent years have seen an explosion in the number of studies showing the variety
of medical applications of nanotechnology and nanomaterials. In this article we have
glimpsed just a small cross-section of this vast field. However, across the range,
there exist considerable challenges, the greatest of which appear to be how to scale
up production of materials and tools, and how to bring down costs and timescales.
But another challenge is how to quickly secure public confidence that this rapidly
expanding technology is safe. And so far, it is not clear whether that is being done.
There are those who suggest concerns about nanotechnology may be overexaggerated. They point to the fact that just because a material is nanosized, it does
not mean it is dangerous, indeed nanoparticles have been around since the Earth
was born, occurring naturally in volcanic ash and sea-spray, for example. As

byproducts of human activity, they have been present since the Stone Age, in smoke
and soot.
Of attempts to investigate the safety of nanomaterials, the National Cancer Institute
in the US says there are so many nanoparticles naturally present in the environment
that they are "often at order-of-magnitude higher levels than the engineered particles
being evaluated". In many respects, they point out, "most engineered nanoparticles
are far less toxic than household cleaning products, insecticides used on family pets,
and over-the-counter dandruff remedies," and that for instance, in their use as
carriers of chemotherapeutics in cancer treatment, they are much less toxic than the
drugs they carry.

It is perhaps more in the food sector that we have seen some of the greatest
expansion of nanomaterials on a commercial level. Although the number of foods
that contain nanomaterials is still small, it appears set to change over the next few
years as the technology develops. Nanomaterials are already used to lower levels of
fat and sugar without altering taste, or to improve packaging to keep food fresher for
longer, or to tell consumers if the food is spoiled. They are also being used to
increase the bioavailablity of nutrients (for instance in food supplements).
But, there are also concerned parties, who highlight that while the pace of research
quickens, and the market for nanomaterials expands, it appears not enough is being
done to discover their toxicological consequences.
This was the view of a science and technology committee of the House of Lords of
the British Parliament, who in a recent report on nanotechnology and food, raise
several concerns about nanomaterials and human health, particularly the risk posed
by ingested nanomaterials.
For instance, one area that concerns the committee is the size and exceptional

mobility of nanoparticles: they are small enough, if ingested, to penetrate cell

membranes of the lining of the gut, with the potential to access the brain and other
parts of the body, and even inside the nuclei of cells.
Another is the solubility and persistence of nanomaterials. What happens, for
instance, to insoluble nanoparticles? If they can't be broken down and digested or
degraded, is there a danger they will accumulate and damage organs?
Nanomaterials comprising inorganic metal oxides and metals are thought to be the
ones most likely to pose a risk in this area.
Also, because of their high surface area to mass ratio, nanoparticles are highly
reactive, and may for instance, trigger as yet unknown chemical reactions, or by
bonding with toxins, allow them to enter cells that they would otherwise have no
access to.
For instance, with their large surface area, reactivity and electrical charge,
nanomaterials create the conditions for what is described as "particle aggregation"
due to physical forces and "particle agglomoration" due to chemical forces, so that
individual nanoparticles come together to form larger ones. This may lead not only to
dramatically larger particles, for instance in the gut and inside cells, but could also
result in disaggregation of clumps of nanoparticles, which could radically alter their
physicochemical properties and chemical reactivity.
"Such reversible phenomena add to the difficulty in understanding the behaviour and
toxicology of nanomaterials," says the committee, whose overall conclusion is that
neither Government nor the Research Councils are giving enough priority to
researching the safety of nanotechnology, especially "considering the timescale
within which products containing nanomaterials may be developed".
They recommend much more research is needed to "ensure that regulatory
agencies can effectively assess the safety of products before they are allowed onto
the market".

It would appear, therefore, whether actual or perceived, the potential risk that
nanotechnology poses to human health must be investigated, and be seen to be
investigated. Most nanomaterials, as the NCI suggests, will likely prove to be
harmless.
But when a technology advances rapidly, knowledge and communication about its
safety needs to keep pace in order for it to benefit, especially if it is also to secure
public confidence. We only have to look at what happened, and to some extent is
still happening, with genetically modified food to see how that can go badly wrong.
Written by

Catharine Paddock PhD

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References

Additional information

Citations

Key sources: "Nanotechnology in the EU - Bioanalytical and Biodiagnostic

Techniques", Christof Ruch, 2004, nanoforum.org; "Nanotechnologies and Food HL 22I, First Report of Session 2009-10 -- Volume I: Report", House of Lords - Science and
Technology Committee; published by TSO (The Stationery Office) 8 Jan 2010; ISBN
9780108459221;"Novel materials in the environment: the case of
nanotechnology" PDF, 27th Report of The Royal Commission on Environmental Pollution,
12 November 2008; Nanotechnology Now; Nanooze.org; Polymers and Soft Condensed
Matter, 2002 Annual Report, Edith Sevick, 2002, Australian National University; "A
Precisely Controlled DNA Biped Walking Device", William B. Sherman and Nadrian C.
Seeman, 2004, Nano Letters; "A Logic-Gated Nanorobot for Targeted Transport of
Molecular Payloads", Shawn M. Douglas, Ido Bachelet, and George M. Church, 17
February 2012, Science; "Smallest Robot", Karen Lurie, July 2004,
sciencentral.com; North Carolina State University news archive (2011);Polytechnic Institute
of New York University press release, Feb 2012; "Biomimetic Nanotechnology", Eric J.
Lerner, 2004, American Institute of Physics

Opinions on:
Nanotechnology In Medicine: Huge Potential, But What Are The Risks?
There are 6 opinions. Read now.

Nanotechnology Risks

Ready or not, here it comes. In the next 20 years, nanotechnology will touch the life of
nearly every person on the planet. The potential benefits are mind boggling and brain
enhancing. But like many of the great advancements in earth's history, it is not without risk
Here are some of the risks posed to society by nanotechnology.

Real Risk: Nanopollutants

When: Now
Nanopollutants are nanoparticles small enough to enter your lungs or be absorbed by your
skin. Nanopollutants can be natural or man-made. Nanoparticles are used in some of the
products found on shelves today, like anti-aging cosmetics and sunscreen. The highest risk
is to the workers in nano-technology research and manufacturing processes.

Potential Risk: Privacy Invasion

When: 5 to 15 years
Virtually undetectable surveillance devices could dramatically increase spying on
governments, corporations and private citizens.

Potential Risk: Economic Upheaval

When: 10 to 20 years
Molecular manufacturing is the assembly of products one molecule at a time. It could make
the same products you see today, but far more precisely and at a very low cost. It is unclear
whether this would bring boom or bust to the global economy.

Potential Risk: Nanotech weapons

When: 10 to 20 years
Untraceable weapons made with nanotechnology could be smaller than an insect with the
intelligence of a supercomputer. Possible nano and bio technology arms race.

Far-Fetched Risk: Gray Goo

When: 30+ years
Free range, self-replicating robots that consume all living matter. However unlikely, experts
say this scenario is theoretically possible, but not for some time.
We have just scratched the surface.
There are many areas of nanotechnology science that hold potential dangers to society.
Bio-engineering and artificial intelligence for example, have their own set of risks.

As we enter an era of unprecedented understanding, it is important that society takes a

proactive role in the responsible development of nanotechnology.
Allotropes
Diamonds, the hardest known natural mineral, and the flaky graphite used in pencils are
both made of carbon. How is it that they are so different?
Pure carbon occurs as many different allotropes (structures which differ only in the way the
atoms are arranged.) Allotropes generally differ in physical properties such as color and
hardness.
Diamond and graphite are two allotropes of the element carbon. Buckyballs and nanotubes
are two more. This diagram shows how the atoms are arranged for each allotrope.
The discovery in 1985 of buckminsterfullerene (buckyball), opened a new era for the
chemistry of carbon and for novel materials. The Japanese Sumi Ijima discovered
nanotubes in 1991. The nanotubes synthesized in the laboratory showed remarkable
mechanic properties as well as thermal conductivity and resistance to flame.

NANOTOXICOLOGY

Nanotoxicology is the study of the toxicity of nanomaterials. Because of quantum size

effects and large surface area to volume ratio, nanomaterials have unique properties
compared with their larger counterparts. Nanotoxicology is a branch of bionanoscience
which deals with the study and application of toxicity of nanomaterials. Nanomaterials, even
when made of inert elements like gold, become highly active at nanometer dimensions.
Nanotoxicological studies are intended to determine whether and to what extent these
properties may pose a threat to the environment and to human beings. For instance, Diesel
nanoparticles have been found to damage the cardiovascular system in a mouse model.
Source: Wikipedia

THE FUTURE CODE

I found a hidden message inside an article reporting on a new method of preventing

nanoparticle induced lung damage in mice.
Here are some actual quotes from the article:
"Nanomaterials are now used in a variety of products, including sporting goods, cosmetics
and electronics."
"Nanotechnology... is an important emerging industry with a projected annual market of
around one trillion US dollars by
2015."
"The US Food and Drug Administration has approved some first generation nanodrugs."
"Although nanoparticles have been linked to lung damage, it has not been clear how they
cause it."
"...the findings could also provide important insight into how nanoparticles cause other toxic
effects."
The message I decoded from this article is--"Industry" is using materials in consumer
products, that are believed to be unsafe.
My biggest concern is not the nanotubes on your face. It is the long-standing business
practice of putting profit before people--and what will happen in the future, when technology
really gets scary.
The greatest dangers that technology can pose to humanity, will come from its rush to
market.
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Nanotechnology - a new hazard

Nanotechnology is the generic name given to the production or use of very
small, or 'nano' particles. These are particles that are less than one hundred
nanometres or about one thousandth the width of a human hair. A nanometre
is one billionth of a metre.

 Introduction
Possible dangers of Nanotechnology
Australian News - Carbon nanotubes
The importance of prevention
Government Initiatives - Australia
In Europe
More information
Introduction

Nanotechnology is likely to be extremely important in the future as it allows

materials to be built up atom by atom. This can lead to the development of
new materials that are better suited for their purpose. There are several
branches of nanotechnology, but most of them are in an early stage.
It is an area for which there is no regulation in Australia. Companies are
under no obligation to even notify any government authority if they import, use
or manufacture nanomaterials.
The potential effects of nanomaterials on worker health and that of the general
community, as well as on the environment, are largely unknown.
The only nanotechnologies that are commercially available at present are ultra
fine powders and coatings, although this is changing all the time. These are
used in a variety of products including sunscreens, self-cleaning glass, and
textiles - but the list of materials being developed commercially using
nanotechnology is growing at a very fast rate. For example, there have been

recent media reports of research into the use of nanoparticles to treat dental
cavities. The Project on Emerging Technologies (based at the Woodrow
Wilson International Center for Scholars) keeps a list of commercially
available products containing nano materials. Recently updated (October
2013), the Nanotechnology Consumer Products Inventory now contains 1,628
consumer products that have been introduced to the market since 2005,
representing a 24 percent increase since the last update in 2010. The list is
updated regularly, and can be browsed, or searched by product or country.
Other forms of nanotechnology being developed include tiny sensors called
nano-units, of which some simple types are readily available; 'smart materials'
that change in response to light or heat; 'nano-bots' - tiny mobile robots that
have yet to be developed but are theoretically possible; and self-assembling
nano-materials that can be assembled into larger equipment. These are being
actively developed. Australia's own CSIRO, for example, has developed a
building material that with nanotechnology, is able to repair itself multiple
times.
Nanotechnology is already a huge industry with billions of dollars being spent
on research and development worldwide. There is still a great deal to learn
about both the potential benefits and risks of the technology.
Nevertheless, most experts agree that the use of nanotechnology in
electronics, the pharmaceutical industry and in areas such as medical imaging
is outstripping our understanding of the OHS risks.
Nanotechnology could lead to significant developments in medicine,
manufacturing and computing. However it may also bring significant new
health hazards.
Back to top

What are the possible dangers of nanotechnology?

Although most of the press coverage has been on the dangers of 'nano-goo'
such as self-replicating particles that get out of control, or 'nano-robots', the
real risks are much more simple, and real. The miniature size of
nanomaterials and the way their surfaces are modified to increase the ease
with which they can interact with biological systems - the very characteristics
that make them attractive for applications in medicine and industry - makes
nanomaterials potentially damaging for humans and the environment.
Nanoparticles are likely to be dangerous for three main reasons:
1. Nanoparticles may damage the lungs. We know that 'ultra fine' particles
from diesel machines, power plants and incinerators can cause
considerable damage to human lungs. This is both because of their size
(as they can get deep into the lungs) and also because they carry other
chemicals including metals and hydrocarbons in with them.
2. Nanoparticles can get into the body through the skin, lungs and
digestive system. This may help create 'free radicals' which can cause
cell damage and damage to the DNA. There is also concern that once
nanoparticles are in the bloodstream they will be able to cross the
blood-brain barrier.
3. The human body has developed a tolerance to most naturally occurring
elements and molecules that it has contact with. It has no natural
immunity to new substances and is more likely to find them toxic.
The danger of contact with nanoparticles is not just speculation. As more
research is undertaken, concerns increase. Here are some of the recent
findings:

 some nanoparticles cause lung damage in rats. Several studies have

shown that carbon nanotubes, which are similar in shape to asbestos
fibres, cause mesothelioma in the lungs of rats (see below)
other nanoparticles have been shown to lead to brain damage in fish
and dogs
a German study found clear evidence that if discrete nanometer
diameter particles were deposited in the nasal region (in rodents in this
case), they completely circumvented the blood/brain barrier, and
travelled up the olfactory nerves straight into the brain
inhaled carbon nanotubes can suppress the immune system by
affecting the function of T cells, a type of white blood cell that organises
the immune system to fight infections.
According to the USA's Woodrow Wilson International Centre for
Scholars chief science advisor (speaking at a conference organised by the
Australian Institute of Occupational Hygienists - AIOH), Dr Andrew Maynard,
'Whether [the research] is relevant to humans we're not sure yet. But it does
indicate nanometer-size particles and nano-structured materials behave in
different ways to what we're used to.' One of the big problems is that it's
impossible to know whether a product or substance contains nanoparticles, as
current legislation does not require these to be labelled.
The US government safety research body NIOSH has produced a guide (see
below) which states nanomaterials may interact with the human body in
different ways than more conventional materials, due to their extremely small
size. For example, studies have established that the comparatively large
surface area of inhaled nanoparticles can increase their toxicity. Such small

particles can penetrate deep into the lungs and may move to other parts of the
body, including the liver and brain.
NIOSH's Nanotechnology Research Centre (NTRC), has also released an
interim report Progress Towards Safe Nanotechnology in the Workplace[pdf]
(Feb 2007). The NTRC was established to coordinate and facilitate research
in nanotechnology and develop guidance on the safe handling of
nanomaterials in the workplace. The report identifies 10 critical OHS areas
and reports on the advancements to date. The areas include toxicity and
internal dose -determined heart and lung responses to nanoparticles; risk
assessment; epidemiology and surveillance - developing guidance for
nanotechnology employers and workers on how to implement OHS
surveillance programs in the workplace; engineering controls and PPE; and
measurement methods.
Back to top
As hazardous as asbestos?

A major study published in Nature Nanotechnology in May 2008 suggested

some forms of carbon nanotubes could be as harmful as asbestos if inhaled in
sufficient quantities. The study used established methods to see if specific
types of nanotubes have the potential to cause mesothelioma. The results
show that long, thin multi-walled carbon nanotubes that look like asbestos
fibres, behave like asbestos fibres. The study shows there is strong evidence
that if carbon nanotubes get into the wrong place, they can cause
mesothelioma. Still unanswered questions are whether exposure to the
material will actually occur, whether people can breathe it in, and if they do,
whether these fibres can work their way to the outer edge of the lung and then
cause an effect.

For more information on the study, go to the website of the International

Council on Nanotechnology. Friends of the Earth has produced commenton
the studies, and also interesting is a June 2009 article in the online
magazine newmatilda.
Australian news

Safe Work Australia has done quite a bit of work on carbon nanotubes.
In June 2011: a research report, Durability of carbon nanotubes and their
potential to cause inflammation. The report considered the durability of carbon
nanotubes and the tendency to cause lung inflammation if inhaled, two
indicators of potential asbestos-like behaviour. Carbon nano-tubes are
already being used in a number of different applications.
Key findings in the report include:
Some types of carbon nanotubes can be durable, but others may also
break down in simulated lung fluid.
Carbon nanotubes of certain length and aspect ratio can induce
asbestos-like responses in mice, confirming previous findings. However,
this response may be reduced if the nanotubes are less durable.
tightly agglomerated particle-like bundles of carbon nanotubes did not
cause an inflammatory response in mice.
In October 2012, a further report: Human Health Hazard Assessment and
Classification of Carbon Nanotubes which it commissioned NICNAS to do. In
addition, an information sheet Classification of Carbon Nanotubes as
Hazardous Chemicals has also been published.

The report recommends classification of carbon nanotubes as hazardous for

repeated or prolonged inhalation exposure and for carcinogenicity. With
respect to the carcinogenicity of carbon nanotubes, the Information sheet
summarises it as follows: 'Based on the limited data available on
mesothelioma formation in animal studies and difficulty in conclusively
determining whether a specific multi-walled carbon nanotube (MWCNT) can
present as a fibre of pathogenic dimensions, the report recommends that all
MWCNTs should be considered as hazardous and classified for
carcinogenicity as follows in accordance with:
Approved Criteria Classification: Carcinogen Category 3, Harmful
(Xn). Risk Phrase: R40 Limited evidence of a carcinogenic effect
GHS Classification: Carcinogen Category 2. Hazard Statement:
Suspected of causing cancer
The report notes that there are no studies demonstrating that single-walled
carbon nanotubes (SWCNTs) cause mesothelioma.
This work has had international implications, with the US's NIOSH
recommending a new level of exposure for carbon nanomaterials (see Update
- April 2013). The recommendations include reducing worker exposures to
airborne concentrations of those materials to no more than 1 microgram per
cubic meter of air as a recommended exposure limit. This is the lowest
airborne concentration that can be accurately measured. The recommended
exposure limit is intended to minimize potential risk for adverse lung effects in
workers who might be exposed at this concentration over a working lifetime.
Back to top
The importance of prevention

At the moment no one knows for certain how dangerous the many different
types of nanoparticles are likely to be to humans. However it is important that
we do not allow workers to be exposed to an unknown danger where effects
may not be known for years, even decades.
These risks were highlighted in a report from the UK's Royal Society which
said 'nanotechnology offers many potential benefits, but its development must
be guided by appropriate safety assessments and regulation to minimise any
possible risks to people and the environment.' It also called for a tightening up
of regulations.

The UK Royal Commission on Environmental Pollution released a report in

November 2008: Novel Materials in the Environment: The case of
nanotechnology, stating that nanomaterials are likely to kill people in the
future just as asbestos did unless extensive safety checks are put in place.
The team of experts assessing the likely impacts of the emerging technology
expressed concerns that when nanomaterials escape into the environment
they will damage people and wildlife - but that it will be years before the
effects are seen. Past generations have brought into general usage materials
such as asbestos, leaded petrol, CFCs and cigarettes without adequately
considering the potential damage and the commission fears nanomaterials will
prove similarly dangerous.
The international insurance company, Swiss Re issued warnings at least
fifteen years ago that the uncertainty about the risks that nanotechnology and
nano-pollution pose means that they currently will not offer insurance to the
industry.
There has been very little attention paid to nanotechnology in
Australia. Unions made a number of submissions to a Senate inquiry

intoWorkplace Exposure to Toxic Dusts that raised the emerging issue of

nanotechnology in Australia. The VTHC, together with the ACTU and our
union affiliates is calling on government to use its existing capabilities and
authorities, or develop new ones as needed, to ensure that the risks of
nanomaterials are identified before they are incorporated into products for
commercial production.
Employers should take a precautionary approach and ensure that workers are
not exposed to nanoparticles. This is the advice given by the UK government,
which adds that 'as the risks arising from exposure to many types of
nanoparticles are not yet completely understood, control strategies should be
based on a principle of reducing exposure as much as possible.'
For unions that means seeking to ensure that the production and use of
nanoparticles is done within a contained process so that employees are not
exposed to any potential unknown risk. Nanomaterials should be treated just
like any other serious health risk.
It is important that unions act now to ensure that we do not have a re-run of
the asbestos tragedy where hundreds of thousands of people were exposed
to a killer dust that even today kills many thousands of people a year. On
September 19, 2007, the ACTU and its affiiates signed up to the
international Declaration on the Principles for the Oversight of
Nanotechnologies and Nanomaterials. The declaration identifies eight
fundamental principles for the effective oversight and assessment of
nanotechnology, including mandatory government regulation. It can be
downloaded at the top right hand side of this page.
In June of 2008, the European Trade Union Confederation (ETUC) adopted its
first resolution on nanotechnology and nanomaterials: that the precautionary
principle must apply. The resolution states: 'nanometre forms of chemicals

should not be allowed on the market unless sufficient data are supplied to
show no harmful effect for human health and the environment.' It adds that
risk reduction measures must be used and employers must involve workers
and their representatives in the assessment and reduction of nanomaterialrelated risks. Other measures called for by ETUC include training and health
surveillance for workers exposed to nanomaterials, at least 15 per cent of
public research budgets on nanotech to be dedicated to health and
environmental aspects and for workplace health and safety to be included in
all research programmes.Statement and Resolution.
The ACTU Occupational Health and Safety, Rehabilitation and Compensation
Policy (2012) now has a specific section on Nanotechnology. Download the
Policy here.
Back to top
Government initiatives

The Federal Government established a National Nanotechnology Strategy

Taskforce under the auspices of the then Department of Industry, Tourism and
Resources (DITR). The taskforce did work in the following areas:
details of research and other activities - recently undertaken, current
and planned;
a critical review of substantial work done. This will include input from
nanotechnology scientific expertise to ensure the scope of the review is
relevant and covers current technologies;
a synthesis of the current state of knowledge in the area relevant to
OH&S, and relevant to the workplaces in Australian industries; and

 identification of key gaps in knowledge and areas where further

research may be targeted.
The Department of Industry, Innovation, Science, Research and Tertiary
Education now 'houses' the Enabling Technologies area, and has
awebsite with information on government initiatives on nanotechnology.
In August 2006 the ASCC (now Safe Work Australia) released its
report: Review of the Potential Occupational Health and Safety Implications of
Nanotechnology. The report stated: 'The distinctive and oftentimes unique
properties which are observed with nanoparticles have been proposed to
revolutionise manufacturing and consuming in the future - much as the
industrial revolution did in the late 18th and early 19thcenturies' and 'At this early
stage the potential applications of nanoparticles seem to be limited only by the
imagination'.
It concludes that '[t]he occupational health and safety effects of engineered
nanoscale particles are mostly unknown,' while acknowledging however, that
'findings from animal and in vitro test systems have provided some valuable
information and these results indicate that human and environmental health
consequences are possible from nanoparticle use and exposure.'
The report recommended addressing the 'greatest gaps in our current
knowledge' as a matter of priority, namely:
developing cost-effective and robust ambient air monitoring systems to
provide accurate information on worker exposures
setting priorities to acquire the necessary information for the
determination of meaningful workplace exposure standards and
adequate worker protection.

 undertaking chronic exposure studies in order to generate information

on the long-term health effects
A 2007 publication from NSW WorkCover, Nanotechnology: OHS overview,
summed up some of the concerns. It called for a more proactive approach to
regulating public and worker safety when it comes to nanotech. The paper
pointed out that the pace of the industry's development meant OHS
researchers and regulators already lagged behind. There is still no specific
nano regulation. Some of the points in the paper:
Existing regulations do not sufficiently cover nanotechnology.
Current OHS risk management processes do not readily apply because
of the different structures and behaviours of nanoparticles
So, there is no guarantee that existing safe work practices will transfer
to nanotech.
There is a crucial gap because OHS regulations focus on the chemical
composition rather than the size or surface area, such as is the case
with nanoparticles.
However an effective gap analysis of how existing legislation applies to
nanotech will not be possible until further knowledge of measurement
procedures and exposure levels is gained.
Back to top
2008
In July, Senator the Hon Kim Carr, the then Minister for Innovation, Industry,
Science and Research released two documents:

1. The Australian Government Approach to the Responsible Management

of Nanotechnology [pdf]: identified objectives to guide government
agencies, including regulators and policy makers in their decision
making process and policy development for nanotechnology.
2. The independent report, A review of possible impacts of
nanotechnology on Australia's regulatory framework [pdf]:
commissioned by the Australian Office of Nanotechnology to assess the
adequacy of nanotechnology regulation and produced by the Centre for
Regulatory Studies at Monash University. It concluded that there were a
number of regulatory 'triggers' (that is 'gaps') that needed to be
addressed. NOTE: in 2013, many of these gaps had not yet been fixed.
2013
In April 2010, a large group of Non-government organisations, including
unions and Not for Profit organisations, raised concerns with government
regarding the information being produced by various departments on
nanotechnology. The groups believed that much of the information was biased
- understating the potential problems with the legislation, and overstating the
potential benefits. After much discussion and delay, an independent review of
the material (and a number of events) was undertaken. While the review was
completed in 2012, the findings of of the review were not released by
government until the end of 2013. The review concluded: 'Australian
government public information on nanotechnology has had a bias in favour of
promoting the technology.'
The reviewers, Toss Gascoigne from the Australian Science Communicators,
and Dr Karen Cronin from the Asia-Pacific Science and Technology Studies
Network, said, 'Some of the items make only brief reference to scientific

research and public concerns about potential health and environment risks.
There is little in the materials about ethical, cultural or privacy issues.'
Below are the documents, now on the Department of Industry website:

Nanotechnology and the environment - Hazard potentials and

risks
(Nanowerk Spotlight) Some products and applications involving nanomaterials
promise advantages in the environmental and climate protection sectors (see
our Nanowerk Spotlight yesterday: "Nanotechnology and the environment - Potential
benefits and sustainability effects"). Nonetheless, determining the hazard potentials
and possible risks posed by the special physical and chemical properties of
engineered nanoparticles (ENPs) requires more detailed study. On one hand, there is
currently no evidence that ENPs pose a significant threat to the environment; on the
other hand, many gaps in our knowledge remain with regard to ENP ecotoxicity. The
lack of evidence should by no means be interpreted to imply that environmental
damage cannot occur.
At present, ecotoxicological research focuses primarily on controlled laboratory
studies involving cell cultures or model organisms. One of the major critiques here is
the use of unrealistically high dosages1. Such overdoses are often necessary to
trigger any kind of effect at all. In lab studies, however, they can lead to analytical
artifacts. This is because some ENPs form large aggregates that can alter the
bioavailability and thus the toxicity of a material. The concentrations used often lie
far above realistic exposure scenarios. Risk assessments for nanosilver, for
example, show that maximum concentrations in waters are currently probably
about 0.1 g/liter. Despite this, most ecotoxicological studies use nanosilver in
concentrations in the mg/liter range1.
Laboratory studies follow text protocols originally developed for conventional
chemicals such as pesticides and do not consider the specific properties of
nanomaterials. Moreover, natural ecosystems are considerably more complex than
a petri dish, limiting the interpretability of lab results. Fortunately, no accidents
involving major releases of ENPs into the environment have been documented to
date; this also means that there have been no opportunities to directly study the
impact of such an event under natural conditions 1.
The present dossier illustrates the problems in the field of environmental analytics,
presents the current state of knowledge on the fate and behavior of ENPs in various

environmental compartments and provides an overview of the preliminary results

from ecotoxicological research and from model calculations of exposure
assessments.
Environmental analytics
A number of methods are available to determine, measure or characterize
nanoparticles in simple media. These include microscopy, chromatography,
spectroscopy, centrifugation, filtration and related techniques 2.
The choice of a particular approach depends on the type of sample and the
nanomaterial, the desired information, the time constraints and the available funds.
Some methods can only confirm the presence of nanoparticles, others provide
information on the amounts, the size distribution or the surface area size 3. A
combination of several methods is often required to fully investigate a specific
issue.
Suitable analytical methods remain to be developed to determine nanoparticle
concentrations and properties in complex environmental media such as water, soil,
sediment or sewage sludge, as well as in organisms.
The difficulties facing environmental analyses are manifold and start with the
sampling procedure and treatment, which can produce artifacts. Distinguishing
between natural and artificial nanoparticles is also difficult. Finally, sample
preservation and storage can create problems because chemical changes can
occur4.
To date, no scientific publications are available on methods to quantify carbon
nanotubes (CNTs) in the environment5. Unpublished results from a study at Duke
University show that the presence of Single-Walled Carbon Nanotubes (SWCNTs)
can be demonstrated using special spectroscopic methods, although the isolation of
the nanomaterial from the sample matrix is problematic 6. Moreover, no publications
exist on quantitative or qualitative measurements of synthetic nanomaterials in the
air, with the exception of measurements at workplaces 7.
Only few studies have been able to demonstrate the presence of ENPs that have
entered the environment through a specific application: one study, for example,
showed that 20-300-nm-sized TiO2 particles were washed out from facade paints by
rain and entered natural waters8. Another study reported small amounts of 4-30nm-sized TiO2 nanoparticles that had been released into the environment from the
run-off of wastewater treatment facilities9.
Fate and behavior of nanomaterials in the environment
Ecological research on the behavior of ENPs can rely on numerous studies from the
geosciences that have examined the behavior of naturally occurring nanoparticles
in the environment. Nonetheless, ENPs differ in certain respects from those

occurring naturally.
While natural nanoparticles are randomly structured and diffusely distributed in the
environment, industrially produced suspensions or powders contain pure
nanomaterials of very uniform size, shape and structure. Such nanomaterials have
unique properties such as the high tensile strength of CNTs or the photocatalytic
activity of nano-TiO2, which make them interesting for novel products and
applications. Precisely these special features make it so difficult to predict the fate
and behavior of ENPs in the environment1.
In the environment, nanomaterials can undergo a range of chemical processes (see
info box) that depend on many factors (e.g. pH value, salinity, concentration
differences, the presence of organic or inorganic material).
The characteristics and properties of a nanomaterial also play a major role.
Bioavailability is decisive in determining potential toxicity. This depends strongly on
whether nanoparticles remain stable in an environmental medium or are removed
from the respective medium through agglomeration and deposition, or are
transformed into a form that organisms cannot take up.
The current lack of data prevents a comprehensive picture of the fate and behavior
of nanomaterials in the environment. Moreover, the available studies are poorly
comparable because different nanomaterials with different properties (for example
surface functionalization see below) are used, and because both the methodology
and the duration of the studies also often differ considerably.
The research results on the potential impacts of ENPs on the environment and
human health were recently compiled in the framework of an EU project 7.
The following account briefly summarizes our current state of knowledge on the fate
and behavior of ENPs in the environmental compartments air, water, soil and
sediment based on that report.
Air
When nanoparticles enter the atmosphere, they move from zones of higher
concentration to zones of lower concentration (diffusion). Air currents distribute the
particles rapidly; these can migrate great distances from their original source.
Nonetheless, nanoparticles tend to aggregate into larger structures
(agglomeration). Detecting nanoparticles in the air is very difficult because simple
measurements of size distributions can hardly distinguish such agglomerates from
natural particulates. The speed with which particles in the air are deposited on the
ground, in the water or onto plants (deposition) depends on particle diameter.
Nanoparticles from the air are deposited much slower than larger particles due to
their smaller diameters.
Water

The general rule is that nanoparticles distributed in the water behave much like
colloids, which are well described in the chemical literature. Colloids are droplets or
particles that are finely distributed in a medium; they are relatively unstable
because they rapidly adhere to one another due to electrostatic attractive forces
and then sink as a result of gravity. Natural water bodies typically contain dissolved
or distributed materials, including natural nanomaterials. As expected, synthetic
nanomaterials that enter a natural water body bind themselves to such natural
materials. The fate and behavior of nanomaterials in the water, however, are also
influenced by factors such as pH, salinity (ionic strength) and the presence of
organic material.
Naturally present organic material (NOM) can lead to the decomposition of
C60 fullerenes or of their aggregates and thus alter particle size and shape. A NOM
such as humic acid can stabilize certain carbon nanotubes (MWCNT) in the water
and thus prevent their settlement. Some CNTs are also deliberately produced
through special surface changes so that they do not aggregate. The type of such
functionalization helps determine whether CNTs can be removed from a natural
water body through sedimentation.
As CNTs are very polymorphic, it is usually impossible to provide generally valid
statements about their fate and behavior in the environment. A strong influence of
the surrounding environment on behavior, in particular the presence of NOM, has
also been determined for other nanomaterials such as metals or metal oxides 10.
Soil and sediment
Unfortunately, the data for this environmental compartment are insufficient to draw
general conclusions. Considerably fewer studies are available for this sector than for
water or air. There is, however, comprehensive literature on the mobility of natural
colloids in the soil and groundwater, which helps draw conclusions about
nanomaterial behavior.
Accordingly, nanomaterials in the soil and in sediments are assumed to bind
themselves to solids. The generally very low concentrations of particles in the
groundwater support this notion. The bioavailability and therefore the potential
toxicity of a nanomaterial for soil organisms apparently depend strongly on
whether it binds to NOM. The bioavailability of nanosilver in complex media such as
soil is considerably lower than in water because the reactive silver ions can bind to
components in the soil (e.g. NOM)11.
The co-transport of pollutants in the soil with ENPs has only been poorly studied, but
is probably not relevant for most pollutants and ENPs due to the extremely low ENP
concentrations in soils12.
Potential environmental processes that can influence the behavior and the
properties of nanomaterials (after 7)

Dissolution: A solid nanomaterial dissolves in a solvent, yielding a chemical solution.

Precipitation/Sedimentation: Nanomaterials are separated from a suspension or
solution.
Speciation: Formation of chemical variants (species) of a nanomaterial that are in a
reaction equilibrium with one another.
Binding to biotic or abiotic particles: Nanomaterialien interact with other living or
non-living materials in the environment, for example in the form of adhesion or
sorption.
Transformation: A nanomaterial undergoes a biological or chemical transformation.
Agglomeration/Disagglomeration: Nanomaterials combine into larger units or are
separated again.
Mineralization: Transformation of a carbon-containing nanomaterial into an inorganic
state through biotic and abiotic decomposition.
Diffusion: Transport of a nanomaterial from a zone of high concentration into one
with a lower concentration through random (Brownian) molecular movement.
Deposition: Deposition of a nanomaterial, for example from the air into the water.
Resuspension: Renewed distribution of an insoluble nanomaterial in a liquid or a gas
(for example from a surface into gas or from sediment into water) after it was
previously separated through precipitation.
Environmental toxicity
Nanoparticles have been naturally present in the environment since the origin of
earth, for example as the result of combustion processes (forest fires), in volcanic
ash, in most natural waters, or as dust in the air due to weathering and erosion.
Organisms produce various substances in nanoform (for example proteins, DNA) in
their cells or are themselves only several nanometers large, such as viruses. During
their evolution, all living organism have adapted to an environment that contains
nanoparticles, some of which can also be toxic (e.g. volcanic ash). This adaptation is
a function of exposure, dose and the speed with which habitats change 13.
These natural nanoparticles in the environment are now accompanied by those that
have been released unintentionally due to human activities such as household
heating, industry, slash-and-burn clearance, transport and, most recently, through
the industrial application of various, extremely polymorphic synthetic nanoparticles
in unknown amounts. This additional burden on humans and the environment has
taken place over a very short period (from an evolutionary standpoint). To what
degree can organisms deal with such artificial nanoparticles without suffering
damage?
Most data on acute toxicity as well as on sublethal effects are available for

freshwater organisms (e.g. water fleas, fishes). More studies on marine and
terrestrial invertebrates are also necessary to determine potential toxicities, as are
further studies on amphibians, reptiles, birds or plants, bacteria and in particular
microorganisms. To date, no ecotoxicological studies are available that could explain
in detail the mechanisms of uptake, distribution, metabolization and excretion of
nanoparticles13.
In an overview of the relevant scientific literature compiled in 2010, only 12 studies
were identified that can actually be classified as ecological studies (i.e. that more or
less consider the complexity of natural ecosystem). These few studies on the effects
of ENPs on ecological communities failed to detect significant increases in mortality
rates or changes in their compositions1.
The following paragraphs briefly summarize the results of ecotoxicological studies
on selected nanomaterials (for a comprehensive review see 7).
Carbon nanotubes (CNTs)
The ecotoxicity of CNTs has been treated in only a few studies, and in some cases
the results are highly contradictory. While some studies were unable to determine
any negative effects on test organisms, others clearly did, for example in the case
of fishes and amphibian larvae. The reason for this is the great variability of CNTs:
they differ considerably in length, structure, surface charge, surface chemistry,
agglomeration behavior and purity (see also14; 15). Moreover, investigating the
toxicity of CNTs for aquatic organisms is very difficult because CNTs are very poorly
soluble in water, have different sizes and diameters, and form complex
aggregates5.
CNTs are often surface functionalized so that their fine distribution in water remains
very stable and they do not sediment to the bottom. Such surface changes,
however, promote the tendency of CNTs to accumulate heavy metals, which can
influence their transport in water bodies or even in biological systems 16.
Nano-TiO2
Titanium dioxide nanoparticles are among the most frequently investigated
nanomaterials. A range of standardized tests are already available for fishes,
crustaceans and algae. Nano-TiO2 has a photocatalytic effect, i.e. under UV
radiation, reactive oxygen species (ROS) develop that can damage the cell
membrane of microorganisms.
Studies have been conducted to simulate the conditions in natural running waters
at the laboratory scale (so-called aquatic microcosms). They show that
TiO2 nanoparticles and low concentrations of larger, naturally developed
agglomerates can both significantly damage the cell membranes of
microorganisms.
Microorganisms are very sensitive to nano-TiO2 the precise effect on ecosystem

function, however, remains unknown17. Preliminary results show that aquatic

organisms such as small crustaceans (which play an important role as zooplankton
in aquatic food chains) are not damaged by the photocatalytic effect of nano-TiO 2.
Nonetheless, the nanoparticles can attach themselves to the chitinous exoskeleton
of the animals and hinder molting, which is necessary for growth in juveniles. This
can kill such animals. This effect was determined atconcentrations of 0.24 mg/liter
of water; nano-TiO2 proved to be twice as toxic as the larger form 18.
Nanosilver
Silver ions from silver compounds or those that develop from nanosilver particles
through contact with water are highly toxic to microorganisms such as bacteria,
fungi and algae (see also 19). Soil microorganisms can be affected when, for
example, sewage sludge contaminated with nanosilver is spread on fields.
Nanosilver particles show negative effects on fishes and crustaceans already at low
concentrations; in mammals, this material is toxic only at very high concentrations.
Few studies on plants are available, but a more recent paper shows an impact of
nanosilver particles on the growth of grass seedlings due to cell damage 20. A
plausible primary entry pathway of nanosilver is via water because nanosilver can
be washed out of special textiles (see also 21) or is an ingredient in cosmetics and
cleaning agents. Nanosilver in waste water has therefore been identified by an
international group of researchers from different scientific disciplines as one of 15
areas of concern that can threaten biological diversity 22.
Exposure
Whether ENPs pose a risk to the environment depends not only on the toxicity of the
respective material but also on exposure, i.e. on the amount released into the
environment.
Unfortunately, no quantitative data are available for even a single nanomaterial.
This is because there is no obligatory registration of nanomaterials, and companies
are very reticent about divulging production volumes 23. Only very few studies have
dealt with the environmental exposure to nanomaterials. These are based on rough
estimates of production volumes and releases as well as on model calculations,
which do not allow comprehensive risk assessments.
Thus, a recently published study23 estimates the annual production volume of nanoTiO2 in the USA at 7800 to 38,000 t, followed by CNTs at 55 to 1101 t and nanoceroxide at 35 to 700 t. The production volume of nanosilver is estimated to be 2.8
to 20 t per year. Knowledge about production volumes alone is insufficient to
estimate potential environmental risk: the actually released amounts must be
known.
To date, the assumption has been that nanomaterials that are tightly embedded in a
matrix pose no or only minimal environmental risk. This holds true for example for

CNTs that are incorporated into plastics or for nano-TiO 2 in permanent

photocatalytic coatings.
Nonetheless, only very few studies have examined the release of ENPs from
consumer products. Nanosilver, both in the form of particles as well as ions, can be
released when such treated textiles are washed; the release rate depends strongly
on the type of production process 24. TiO2-particles can also be washed out of
facade paints and enter the environment8.
For Europe, the USA and Switzerland, the concentrations of five nanomaterials
expected in the environment (Predicted Environmental Concentrations, PEC) were
estimated based on model calculations. The highest concentration in all
environmental compartments was found for nano-TiO 2, followed by nano-zinc oxide.
These values were compared with concentrations of the studied nanomaterials for
which no negative environmental effects are expected (Predicted No-EffectsConcentration, PNEC).
The results revealed a potential risk for aquatic organisms through nano-TiO 2,
nanosilver and nano-zinc oxide in wastewater of sewage treatment plants. The PEC
of CNTs and fullerenes was classified as so low that no environmental risk is
currently to be expected25.
The most likely entry pathways of nanomaterials into the environment are sewage
water and wastes. Wastes that contain nanomaterials can arise either during the
production of the raw materials, the manufacture of products with nanomaterials, as
well as at the end of the products lifecycles. The current legal framework contains
no specific regulations for treating wastes containing nanomaterials 26. A release of
ENPs into the environment from wastes is possible, although virtually no studies
have been conducted on this aspect. The assumption is that ENPs are efficiently
removed by filters during waste incineration 27.
LEDs contain nano-scale coatings of the semiconductor materials arsenic, gallium,
phosphorus and their compounds. They therefore belong to the waste category
requiring special treatment or monitoring. In particular the semiconductor material
gallium arsenide is problematic because, in the absence of atmospheric oxygen and
water, a very thin layer can develop on the surface of the material. This is highly
toxic and could create environmental damage in a normal landfill 28.
Nanosilver can enter wastewater via various pathways, for example when washing
special textiles, through cosmetics or cleaning agents. About 90% of the nanosilver
is apparently removed from waste water in sewage treatment plants and is then
contained in the sewage sludge29. If this is spread on fields as fertilizer, this
nanomaterial enters the environment, whereby damage to soil microorganisms
cannot be excluded (see also 19).
An additional open question is the recyclability of products that contain
nanomaterials. Plastic bottles made of polyethylene terephthalate (PET) can be

recycled as long as they do not contain coloring agents or additives. Coatings of

nanocomposite materials, which reduce gas permeability or provide light protection,
create recycling problems30.
Conclusions
Little is known about the fate and behavior of synthetic nanomaterials in the
environment, and suitable methods to detect them in complex environmental media
are only in the development stage. Model calculations on exposure alone are
insufficient for comprehensive risk assessments. This calls for developing methods
to monitor nanomaterials in the environment.
Ecotoxicological investigations show a certain hazard potential of some
nanomaterials. Even though scientific uncertainties still exist, the precautionary
principle should be applied in the sense of preventive risk minimization.
Environmental inputs should be avoided to the extent possible. Ecotoxicological
research should increasingly focus on the environmental relevance of the materials
and consider the complexity of natural systems.
Longterm studies would be necessary to determine delayed impacts of
environmental exposure to ENPs and to help determine potential adaptive
mechanisms. More studies on bioaccumulation in the food chain are also necessary,
as are studies on the interaction of ENPs with other pollutants in the environment.
Under certain conditions, ENPs might change the transport and effects of such
pollutants.
Notes and References
1 Bernhardt, Emily, et al., 2010, An Ecological Perspective on Nanomaterial Impacts
in the Environment (pdf), Journal of Environmental Quality 39, 1954-1965.
2 Tiede, Karen, et al., 2008, Detection and characterization of engineered
nanoparticles in food and the environment, Food Additives and Contaminants 25(7),
795-821.
3 University of Essex, o.J., Measurement Techniques for Nanoparticles (pdf),
commissioned by: Nanocap.
4 Von der Kammer, Frank, et al., 2011, Analysis of Engineered Nanomaterials in
Complex Matrices (Environment and Biota): General Considerations and Conceptual
Case Studies, Environmental Toxicology and Chemistry 31(12), 1-18.
5 Hassellv, Martin, et al., 2008, Nanoparticle analysis and characterization
methodologies in environmental risk assessment of engineered
nanoparticles, Ecotoxicology 17, 344-361.
6 Aitken, Robert J., et al., 2008, Engineered Nanoparticles: Review of Health and
Environmental Safety (ENRHES) (pdf). Final Report.

7 Aitken, Robert J., et al., 2008, Engineered Nanoparticles: Review of Health and
Environmental Safety (ENRHES) (pdf). Final Report.
8 Kaegi, R., et al., 2008, Synthetic TiO 2 nanoparticle emission from exterior facades
into the aquatic environment, Environmental Pollution 2008(156), 233-239.
9 Westerhoff, Paul, et al., 2011, Occurrence and removal of titanium at full scale
wastewater treatment plants: implications for TiO 2 nanomaterials, Journal of
Environmental Monitoring 13(5), 1195-1203.
10 Ottofuelling, Stephanie, et al., 2011, Commercial Titanium Dioxide Nanoparticles
in Both Natural and Synthetic Water: Comprehensive Multidimensional Testing and
Prediction of Aggregation Behavior,Environmental Science & Technology 45 (23), pp
10045-10052.
11 Lapied, Emmanuel, et al., 2010, Silver nanoparticles exposure causes apoptotic
response in the earthworm Lumbricus terrestris (Oligochaeta), Nanomedicine 5(6),
975-984.
12 Hofmann, Thilo/Von der Kammer, Frank, 2009, Estimating the relevance of
engineered carbonaceous nanoparticle facilitated transport of hydrophobic
contaminants in porous media, Environmental Pollution157, 1117-1126.
13 Handy, Richard D., et al., 2008, The ecotoxicology of nanoparticles and
nanomaterials: current status, knowledge gaps, challenges, and future
needs, Ecotoxicology 17, 315-325.
14 NanoTrust-Dossier 022en (pdf).
15 NanoTrust-Dossier 024en (pdf).
16 Schierz, A./Znker, H., 2009, Aqueous suspensions of carbon nanotubes: Surface
oxidation, colloidal stability and uranium sorption, Environmental Pollution 157,
1088-1094
17 Battin, Tom J., et al., 2009, Nanostructured TiO 2: Transport Behavior and Effects
on Aquatic Microbial Communities under Environmental Conditions, Environmental
Science & Technology 43(21), 8098-8104
18 Dabrunz, Andr, et al., 2011, Biological Surface Coating and Molting Inhibition as
Mechanisms of TiO2 Nanoparticle Toxicity in Daphnia magna, PLoS ONE 6(5), 1-7.
19 NanoTrust-Dossier 010en (pdf).
20 Yin, Liyan, et al., 2011, More than the Ions: The Effects of Silver Nanoparticles on
Lolium multiflorum, Environmental Science & Technology 45, 2360-2367.
21 NanoTrust-Dossier 015en (pdf).
22 Sutherland, William J., et al., 2009, A horizon scan of global conservation issues

for 2010, Trends in Ecology and Evolution 25(1), 1-7.

23 Hendren, Christine O., et al., 2011, Estimating Production Data for Five
Engineered Nanomaterials As a Basis for Exposure Assessment, Environmental
Science & Technology 45, 2562-2569.
24 Benn, Troy M./Westerhoff, Paul, 2008, Nanoparticle Silver Released into Water
from Commercially Available Sock Fabrics, Ibid.42(11), 4133-4139.
25 Gottschalk, Fadri, et al., 2009, Modeled Environmental Concentrations of
Engineered Nanomaterials (TiO2, ZnO, Ag, CNT, Fullerenes) for Different Regions,
Ibid. 43(24), 9216-9222.
26 Verband der Chemischen Industrie e.V., 2009, Guidance for the Safe Recovery
and Disposal of Wastes containing Nanomaterials (pdf), Frankfurt: Verband der
Chemischen Industrie e.V.
27 Mueller, Nicole C./Nowack, Bernd, 2008, Exposure modeling of engineered
nanoparticles in the environment, Environmental Science & Technology 42(12),
4447-4453.
28 Steinfeldt, Michael, et al., 2004, Nachhaltigkeitseffekte durch Herstellung und
Anwendung nanotechnologischer Produkte (pdf), commissioned by BMBF.
29 Nowack, Bernd, 2010, Nanosilver Revisited Downstream, Science 330 no. 6007
pp. 1054-1055.
30 Van Dongen, Cees/Dvorak, Robert, 2011, Design Guide for PET Bottle
Recyclability, March 2011: Union of European Beverages Associations (UNESDA);
European Federation of Bottled Waters (EFBW).
By NanoTrust, Austrian Academy of Sciences. NanoTrust Dossiers are published
irregularly and contain the research results of the Institute of Technology
Assessment in the framework of its research project NanoTrust. The Dossiers are
made available to the public exclusively on epub.oeaw.ac.at/ita/nanotrust-dossiers.

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Read more: Nanotechnology and the environment - Hazard potentials and risks

A summary of what is currently understood about the

toxicological properties of nanomaterials
The scientific community still does not have a good understanding of all of the health effects
likely to arise from exposure to different types of engineered nanomaterials. Knowledge gaps
exist in key areas that are essential for predicting health risks such as routes of exposure, the
way nanomaterials are taken up into the body, the way nanomaterials are transported once
inside the body and the ways in which nanomaterials interact with the body's biological systems.
Although work is underway that will help to fill these knowledge gaps, the range of
nanomaterials for which comprehensive hazard data are available and will be available in the
foreseeable future is very narrow. Given the wide diversity of nanomaterials and observations
that different nanoforms with the same chemical composition can have different toxicological
properties, it likely that new approaches that do not rely on conventional toxicity testing
approaches will need to be found to assess the hazards of nanomaterials.
In vitro methods and in silico approaches are potential alternative sources of hazard information.
At present, it is not clear how findings from in vitro studies relate to potential effects in humans.
Often the doses that are used in these studies far exceed the doses that would be obtained
from workplace exposure. Also, an in vitro test may not replicate the changes a nanomaterial
will undergo during its passage from the point of entry into the body to the target site. It is
therefore difficult to draw general conclusions from in vitro data. It is also not clear if the
structure activity relationships that are used by computer models to predict toxicological
behaviour are applicable to nanomaterials. Further work is required in this area.

Routes of nanomaterial exposure

Inhalation
For inhaled engineered nanomaterials, the target site most likely to be affected is the lungs.
There is evidence that inhaled nanomaterials have the potential to initiate inflammatory
responses. However, the factors that determine the severity of the response are not fully
understood. Also the longer term health consequences for repeated exposure are in many
cases unknown. Epidemiological studies looking at the health effects of exposure to ambient air
pollution have suggested that in addition to effects in the lungs, people inhaling air that contains
high levels of particles with sizes in the ultrafine range (this includes particles that fall within the
Commission definition of a nanoparticle) are more likely to suffer from diseases of the
cardiovascular system. However, the relevance of this finding to workers exposed to
nanomaterials at work is unclear.

Dermal
In addition to inhalation, there is the potential for nanomaterials to contact the skin and
gastrointestinal tract as a result of workplace exposure. With the exception of nanomaterials that
are used in cosmetic products there have been few investigations into the effects of
nanomaterials on the skin. Any effects that do arise as a result of skin contact are expected to
be site of contact effects. Research looking at the skin absorption potential for nanomaterials
has suggested that if there is any absorption across the skin the amounts that are absorbed will
be low.

Injection

There is no information that will enable general conclusions to be drawn about the fate of
nanomaterials that enter the gastrointestinal tract as a result of workplace exposure.

Characterise nanomaterials
It is important to understand the physical characteristics and the chemical composition of a
nanomaterial before you begin to work with it since this information will be a key element of your
risk assessment. If you have good information on the physical and chemical characteristics of
the nanomaterials that you are using, this will help you to determine how similar or different it is
to other nanomaterials.
When trying to assess the hazards of nanomaterials, it may be tempting to refer to information
that is available for apparently similar materials. All comparisons of biological/toxicological data
between nanomaterials need to be supported by a detailed physical characterisation of both
materials demonstrating the similarities and differences between the materials. In the absence
of an adequate assessment of the physical characteristics, general conclusions drawn on
nanoparticles which may have similar chemical compositions but, in fact, have different sizes,
shapes, crystal structures, surface coatings, and surface reactivity characteristics may be
misleading. In general, we do not recommend that you rely on hazard information for similar
nanomaterials in your risk assessment unless you have good data to confirm that this approach
is appropriate.
Characterisation information for engineered nanomaterials should be available from
manufacturers or suppliers along with a safety data sheet. If this information is not available you
could ask the manufacturers or suppliers to provide this information.

Physicochemical determinants of toxicity

The following physical and chemical properties are likely to be important in determining the
hazardous potential of engineered nanomaterials. This list is not exhaustive. Future research
may identify other physical or chemical properties that are important.

Size
There is no clear evidence for a step change in hazardous properties relating to the specific
dimensions of a particle. However, it has been reported that particles with dimensions below 20
- 30 nm are less thermodynamically stable and undergo dramatic changes in their crystalline

structure compared to larger particles with the same chemical composition . These changes will
influence the way these very small particles interact with their environment and biological media.
Consequently it is harder to predict their toxicological behaviour based on information obtained
for larger sized particles, including those at the nano scale, even where the chemical
composition is the same.
The size cut-off of 100 nm that has been used within the Commission definition has been
chosen because many of the specified effects of nanomaterials occur with particles with
dimensions in the range 1 100 nm. Also this ensures consistency with definitions that are used
elsewhere. It should not be assumed that a particle that has no dimensions below 100 nm is
free from hazard and it should not be assumed that a particle that has at least one dimension
that is below 100 nm is highly hazardous. There will be a wide variation in the hazard potential
of nano-sized particles just as there is a wide variation in the hazard potential of other
substances.

Aggregation/agglomeration state
When nanomaterials are released, in nearly all situations they will rapidly form aggregates and
agglomerates so that exposure in practice is to a much larger secondary particle than a nanosized primary particle. The size of aggregates/ agglomerates will influence the residence time of
the material in workroom air and may reduce the potential for a nanomaterial to be inhaled. The
aggregation/agglomeration behaviour of nanomaterials is heavily influenced by the external
environment i.e. workroom air, dispersion media, etc. It is therefore useful to understand the
aggregation/agglomeration behaviour in the environment for which the risk assessment is being
conducted.

Aggregates/agglomerates
Aggregates/agglomerates of nanoparticles are not necessarily stable and when the external
environment changes e.g. the transition from workroom air to inhaled air, the
aggregation/agglomeration state may change. So although a nanomaterial may be present in
comparatively large aggregates/ agglomerates in the workroom air, there is the potential for
disaggregation and disagglomeration to occur within the respiratory tract allowing smaller
primary particles to penetrate to the deep lung. For this reason, although the
aggregation/agglomeration state may reduce the potential to inhale a nanomaterial, it should not
be assumed that nanomaterials that are exclusively present in workroom air as large

aggregates/agglomerates will retain this state once inhaled. A precautionary assumption is that
any nanomaterial that is inhaled has the potential to penetrate to the deep lung.

Surface area
Many, but not all, of the toxic effects of particulate materials are mediated by events that take
place at the particle surface. As the size of a particle decreases, the surface area to mass ratio
increases. Therefore, any effects that are caused as a result of interactions at the particle
surface are likely to be enhanced for nanomaterials compared to larger particles. This is one
reason why nano-sized particles appear to be more potent than larger sized particles with the
same chemical composition when doses are compared on the basis of mass. When doses are
compared on the basis of total surface area, the apparent difference in toxicological potency is
often not seen. This has led the scientific community to recommend that exposures and doses
in toxicity studies for nanomaterials should be expressed in terms of surface area as well as
mass.
There is very little experience with the use of surface area to express exposures and doses. The
majority of the hazard data that is currently available will have been obtained from studies using
mass to express dose. In this situation, a dose-response relationship for a larger particle that is
expressed in terms of mass may underestimate the dose-response relationship for a
nanomaterial, even though the chemical composition may be the same. For this reason, it is not
appropriate to extrapolate dose-response relationships and no-effect levels that have been
obtained from studies with larger particle sizes to nanomaterials unless there is scientific
evidence to demonstrate that the extrapolation is valid.

Shape
There is evidence that the shape of a nanomaterial can influence its toxicity. This has been
demonstrated most coherently for certain high aspect ratio nanomaterials (HARN). High aspect
ratio means that one or two of the three dimensions of a particle are much smaller than the
other dimension(s). Fibres are a classic example of high aspect ratio materials. The World
Health Organisation (WHO) defines a respirable fibre as an object with length greater than 5m,
a width less than 3m and a length to width ratio (aspect ratio) greater than 3:1 . Where any of
these dimensions is in the nanoscale, a particle that has an aspect ratio greater than 3:1 would
be considered a HARN. Platelet like structures where only one dimension falls within the nano
size range are also considered to be HARN.

Carbon nanotubes (CNTs)Carbon nanotubes (CNTs)

There is evidence that HARNs with the following characteristics:

are thinner than 3 m,

are longer than 10-20 m,

are biopersistent,

do not dissolve/break into shorter fibres

May be retained within the narrow space surrounding the lungs - the pleural cavity - for long
periods of time.
It is known that long fibres that are retained in the pleural cavity can cause persistent
inflammation, which may lead to diseases such as lung cancer, HSEs advice is to take a
precautionary risk management approach when there is the potential for workers to inhale
nanomaterials with these characteristics.
If you are uncertain about the hazardous properties of the nanomaterials
that you are using, precautionary control measures aimed at preventing
exposure should be followed.
There is an increasing body of evidence that HARN with the characteristics identified in box 1
have the potential to cause serious adverse effects . Carbon nanotubes (CNTs) are an example
of a diverse group of HARN. Some CNTs exist as long, straight fibres and in the absence of
evidence to the contrary, it should be assumed that these types of CNTs have the properties
identified in box 1. Other types of CNTs have a more tangled structure and exist as low density
fluffy bundles of nanotubes. For these CNTs, no evidence has so far emerged to indicate that
they represent a hazard for the pleural cavity. However, they may still have the potential to
cause inflammation in the lungs. It is currently not possible to make statements about the
potential long term health consequences of repeated exposure to tangled CNTs.
The situation is similar for other structures that may be considered as HARN such as thin platelike particles. Their aerodynamic behaviour is likely to result in penetration to the deep lung.
There is no information to indicate how easily plate-like particles will be cleared from the lungs,
but it is possible that their shape and size may prevent effective clearance. In this situation there
is the potential for inflammatory reactions to occur in the deep lung. The long term health

consequences of exposure to plate-like particles are not known. Much more research is needed
into these particle types to understand the level of hazard that they represent.
There is no information to indicate how the shape of nanomaterials that are not HARN may
influence their toxicological properties, but it will be useful to obtain information on particle
shape to inform future scientific investigations into the importance of this parameter for nonHARN nanomaterials.

Surface charge
The surface charge of a particle can influence the adsorption of ions, contaminants, the
interaction of the particle with biomolecules, uptake into cells and the way the cells react when
exposed to the particle. The zeta potential of a particle is a measure of its surface charge.
Recent research has identified that certain metal and metal oxide nanoparticles that are known
to be inflammogenic also have a high positive zeta potential . This suggests that this parameter
may be a useful predictor of certain types of toxicological effects. Further research is required to
fully understand the relationship between zeta potential and toxicological effect, but it may be
useful to obtain information on this property so that you can use it in future to inform your risk
assessment.

Surface chemistry/surface modification

This is a broad and non-specific term. It includes elements of solubility equilibrium, catalytic
properties, surface charge, surface adsorption and desorption of molecules in solution. These
properties are functions of the atomic or molecular composition and the physical surface
structure. Chemical purity, functionalisation and surface coating are also important aspects that
could affect surface chemistry.
Surface modification has been found to enhance or reduce the toxicity of CNTs depending on
the modification that is employed . This has also been observed with titanium dioxide (TiO2).
Based on the information currently available, it is very difficult to predict the effect that a specific
surface modification may have on hazard. However, functionalisation and surface modification
are important issues to consider when deciding if the hazard information that is available is
relevant to your material.

Chemical composition

Some elements have been identified as carcinogens, mutagens, reproductive toxicants

(collectively referred to as CMRs) or have the potential to cause asthma. It is reasonable to
assume that a nanoparticle containing an element(s) that has these hazardous properties also
has the potential to exhibit these hazards.
The presence of reactive metals is thought to be responsible for the toxicity of complex
particulate mixtures such as welding fume. A nanomaterial that contained a significant
proportion of such metals (e.g. large amounts of catalyst residues in CNTs) could pose a greater
hazard to health than a similar material with no or low amounts of reactive metals.

Solubility
Some of the adverse effects that may arise following exposure to nanomaterials arise as a
result of solubilisation of the material. It has been found that the solubility of a nanomaterial may
be different to that of larger particles of the same substance. For example, nano sized silver
particles have a greater tendency to release silver ions into solution compared to larger silver
particles. If dissolution leads to the release of reactive or cytotoxic components, and these are
released more readily from a nano form compared to larger particles, the dose-response
relationship for the larger particle may underestimate the dose-response relationship for the
nano form.
In some cases, where reactive or cytotoxic components are not released, enhanced dissolution
will speed up the rate at which nano sized particles are cleared from e.g. the lungs. This could
result in a nano form presenting a lower level of hazard compared to a larger particle depending
on the type of effects that are seen with the larger particle.
It may be useful to consider information on the toxicological properties of ionic forms of
elements that are present in nanomaterials to help understand which sites in the body could be
affected following exposure. It is not appropriate to extrapolate dose response relationships and
no-effect levels that have been obtained from studies with larger particle sizes or ionic forms to
nanomaterials unless there is scientific evidence to demonstrate that the extrapolation is valid.

Other potentially relevant properties

It has been suggested that nanomaterials that have photocatalytic activity may have a greater
potential to cause inflammation because the particle becomes more reactive when exposed to
light.

It has also been suggested that nanomaterials that are highly acidic or alkaline could produce
localised irritation at the site of contact (e.g. lungs, skin or gastrointestinal tract).

Assessing the hazards of nanomaterial

In order to conduct a risk assessment it is important to understand the hazardous properties of
the material that you are using. Given the current limited availability of hazard data for most
nanomaterials it will be challenging to establish the toxicological behaviour of specific
nanomaterials with any degree of certainty. In most cases it will be necessary to refer to
information that has been obtained for similar materials. In this case it is important to establish
that the information you find is relevant for the material that you are using.
Many of the most commonly used nanomaterials have similar or the same chemical composition
as larger scale particulates (often referred to as bulk materials). However, it is not clear which
properties from a bulk material can be assumed to apply to a nano sized particulate. Also, given
the diversity of nanomaterials that may be produced which share the same or similar chemical
composition but have different physical characteristics, it is often not clear which properties of a
nano sized particulate can be assumed to apply to other nano sized particulates. It is therefore
important to consider sameness when you are using information from one material to establish
the hazardous properties of another material.

Establishing sameness
In order to determine the similarities and differences between the material that you are working
with and the material for which hazard data is available, it is important to obtain as much
information as possible on the physical and chemical characteristics of both materials. The
previous section identifies some physical and chemical characteristics that may be particularly
relevant; future research may identify other relevant characteristics. For this reason, sameness
should be assessed on the basis of all available information. It is suggested that as a minimum
the following characteristics could be used to establish sameness (other characteristics may be
added to this list as our understanding of the relationships between physical characteristics and
hazard improves):

Chemical composition and purity

Primary particle size distribution with an indication of the number fraction of

primary particles smaller than 100 nm

Other particle size distributions representing possible

agglomerated/aggregated forms during the uses of the nanoform

Surface functionalisation/treatment

Shape

Surface area
The greater the differences between the physical and chemical characteristics of your material
and the physical and chemical characteristics of another material, even though they may have
the same chemical composition, the greater the uncertainty in extrapolating hazard data
between the two materials. It is therefore important to have information on the physical and
chemical characteristics of the material that you are using to ensure that you identify hazard
data for materials with similar physical and chemical characteristics. If you find hazard data, but
cannot properly establish the identity and characteristics of the material that has been tested, it
is unwise to assume that the results are applicable to your material.
In the absence of adequate information about the physical characteristics (size, shape, crystal
structure, surface coating, surface reactivity, etc), of the particular nanomaterial you are going to
work with, it is unwise to make general conclusions about its potential hazards based on other
nanoparticles which may have a similar chemical composition, unless you have good data to
confirm that this approach is appropriate. Where nanomaterials have an uncertain or not clearly
defined toxicology and unless, or until, sound evidence is available on the hazards from
inhalation, ingestion, or absorption a precautionary approach should be taken to the risk
management.