ISIS Report 10/03/10
Nanotoxicity in Regulatory Vacuum
A vast and rapidly expanding array of
engineered nano-products floods the consumer market unregulated as evidence of
toxicities accumulate Dr. Mae-Wan Ho
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First cases of nanotoxicity occupational
Seven young women (aged 18–47yrs)
working in a paint factory and exposed to nanoparticles for
5–13months fell ill and were admitted to hospital. Two subsequently died.
Pathological examinations of the patients' lung tissue showed
nonspecific inflammation, fibrosis and foreign-body granulomas
(tumours resulting from inflammation) of the pleura (membrane around the
lungs). Transmission electron microscopy revealed nanoparticles of
polyacrylate lodged in the cytoplasm and the nucleus of cells and
in the chest fluid . The polyacrylate nanoparticles were confirmed in the
These first suspected cases of nanotoxicity from occupational exposure have
heightened concerns over the huge and rapidly expanding array of nanotechnology
products in the market that remains unregulated despite accumulating evidence
that many nano-ingredients, including those most common in commercial use, are
Common nano-ingredients are toxic
Nanotechnologies are technologies at the
scale of nanometres (10-9m), where new quantum effects can alter the
chemistry and physics of elements and compounds, offering exciting new
possibilities in industrial applications, and for exactly the same reasons,
posing unprecedented risks to health and the environment.
It was difficult
to separate hype from reality when it all began, and almost no one worried
about safety  (Nanotechnology,
a Hard Pill to Swallow, SiS 16). But evidence of health hazards soon
started to emerge [3-5] (Nanotox,
Metal Nanoshells, Cure or
Highly Toxic, SiS 21), and nanotoxicology became established as a
discipline in 2005  (Nanotoxicity:
A New Discipline, SiS 28). By then, many serious health impacts had
already been observed in laboratory experiments; and more appeared in
subsequent years. I describe a few recent examples below.
researchers at University of California Los Angeles Jonsson Cancer Center led
by Robert Schiest reported that  titanium dioxide nanoparticles (TiO2),
found in “everything from cosmetics and sunscreens to paint and vitamins” (see
Box), caused DNA damage when fed to mice. They induced breaks in DNA, damaged
chromosomes, and caused inflammation of tissues; “all of which increase the
risk of cancers.”
The mice were exposed to the nanoparticles in their drinking water, and genetic
damage started showing up on the fifth day , equivalent to occupational
exposure in humans of 1.6 years. Once taken into the body, the TiO2
nanoparticles accumulate in different organs because the body cannot eliminate
them, and they are so small that they can go everywhere.
These latest findings confirm the results of numerous other studies indicating
that nano-TiO2 increases cell death, DNA damage, and genome
instability in the short-term and the risk of cancer in the longer term. A team
of researchers at several institutes in Taiwan showed that exposing mammalian
cells to TiO2 nanoparticles at 10 ppm in the short-term (days)
resulted in enhancement of cell growth and survival, and increase in reactive
oxygen species (oxidative stress). In the long-term – after 12 weeks - a
dramatic increase in transformed (cancerous) cells was observed, resulting from
a disturbance of cell division and genome instability . Similar toxicities
have been found for other nanoparticles often used with TiO2, such
as ZnO2 and SiO2 [10, 11].
even more widely used than nano-TiO2, is toxic to beneficial bacteria
that break down wastes and recycle nutrients in the soil . It also killed
half of all zebrafish embryos in laboratory tests at concentrations of 25 to 50
ppm ; whereas a solution of ordinary silver ions (Ag+) was
Fullerenes, a new
form of carbon in the shape of a football (buckyball) discovered in the mid
1980s, rapidly found applications in electronics, electro-optics and much more
besides, including cosmetics. They are being considered for drug delivery and
cancer therapy. Fullerenes caused oxidative brain damage (through lipid
peroxidation) in juvenile largemouth bass after 48 hours of exposure at 0.5 ppm
, mostly likely through the ability of fullerenes to home in on lipid-rich
membrane. One main route to the brain is via the olfactory nerve. Fullerenes
were also highly toxic to zebrafish embryos at 0.2 ppm . Carbon nanotubes,
long thin structures derived from fullerenes and often compared to asbestos,
caused inflammation and granulomas when instilled into the lungs of mice. These
results have now been confirmed in a study in which the mice inhaled aerosols
of multiwall carbon nanotubes. Inflammation and granulomas were found in the
lungs even at the lowest concentration of 0.1 mg/m3 .
Quantum dots are
nanosized semi-conductors that generate electron-hole pairs confined in all
three dimensions (quantum confinement), and hence behave like giant molecules
rather than bulk semiconductors . They have numerous applications in light
emitting diodes, transistors, solar cells etc., and are also being developed
for drug delivery, cancer therapy and cell imaging. Unfortunately, most quantum
dots contain highly toxic metals such as cadmium, which tends to be released
when the quantum dots enter the cells or organisms. This was thought to be the
main reason why CdSe/ZnSe quantum dots at nanomolar (10-9mol)
concentrations were toxic to Daphnia magna, but much less toxic than the
equivalent concentration of cadmium ions . However, CdTe quantum dots
coated with hydrophilic sodium thioglycolate caused disruption in a cultured
monolayer of Caco-2 human intestinal cells and cell-death at 0.1 ppm, which was
thought to be caused by the quantum dots, rather than cadmium . In a third
study, CdSe/ZnS quantum dots injected intravenously into mice caused marked
vascular thrombosis in the lungs at 0.7 to 3.6 nanomol per mouse, especially
when the quantum dots had carboxylate surface groups . Three out of four
mice injected at the higher concentration died immediately. The injected quantum
dots were mainly found in the lungs, liver and blood; and the authors
hypothesized that the quantum dots activated the coagulation cascade through
contact. In fact, many kinds of nanoparticles enhance the formation of
insoluble fibrous protein aggregates (amyloids) , which are associated with
human diseases including Alzheimer’s, Parkinson’s and Creutzfeld-Jacob disease.
A burgeoning trillion dollar industry
with no safeguards in place
There are now more than 1 000
nanotechnology products on the market (see Box), ranging from microelectronics,
solar cells, medicine, to cosmetics, clothing, food, and agriculture .
Nanotechnology products already on the
A public inventory currently lists more
than 1 000 nanotechnology products on the market ; but this is likely to be
an underestimate, as both the number and variety are growing rapidly, and some
companies may be reluctant to disclose ingredients produced by nanotechnology.
numerous products contain nanosilver particles used as an
antibacterial in filters for air conditioners, coating for refrigerators, food
packaging, tableware, kitchenware, mobile phones, baby toys, pacifiers, cups
and mugs, toothpaste, pet products, clothing, bath and sporting towels, sprays,
and food supplement.
Also common are titanium
oxide and zinc oxide nanoparticles used in cosmetics and
sunscreens. Titanium oxide and silicon oxide nanocrystals are
combined with organic polymers in anti-dirt, anti-graffiti coatings [23, 24] on
windscreens and other surfaces.
nanotubes and nanofibres are incorporated in
sports goods such as tennis rackets, racing bicycle frames and golf club to
give strength at reduced weight . They are widely used as conductive
elements in computer microprocessors, flash memory, organic light emission
diodes, and light emission diodes for display screens, giving high performance
at reduced size and power consumption. Carbon nanotubes are in heavy-duty
anti-corrosion coatings for sea-going vessels .
dots have found applications in laser diodes, LEDs for a new kind of
display screen, as well as solar panels, and batteries.
The food and
cosmetic industry have taken nanotechnology to heart, in addition to the
nanosilver used in packaging and appliances. A new line of nutritional and
skincare supplements called NanoceuticalsTM includes cocoa nanoclusters
to enhance flavour . Nanosized liposomes are used for more
efficient nutrient delivery and other “nanostructured supplements”; nanosized
self-assembled structured liquids (e.g., Canola Active Oil) are sold as
anti-cholesterol. Nanostarch adhesive for McDonald’s burger
containers is saving cost and energy. Nanoclay mixed with plastic
in beer bottles makes them stronger and less permeable to gas. Nanoparticles/nanospheres-encapsulated
vitamins and oils are also on offer.
At the farm, fertilizers and pesticides are dispensed with nanoclay particles
and other materials for slow release and increased potency 
The UK government is about to announce a new strategy for
nanotechnologies , predicted by the US National Science Foundation to worth
more than $1 trillion by 2015 .
The European Union’s Scientific Committee on Emerging and Newly
Identified Health Risks (SCENIHR) report in 2006  admitted that existing
toxicological and ecotoxicological methods may not be sufficient to address the
risks of nanoparticles. Exposure
to nanoparticles having characteristics not previously encountered in evolution
(and in increasing concentrations and varieties) may well challenge the normal
defence mechanisms associated with the immune and inflammatory systems. In
particular, safety evaluation of nanoparticles and nanostructures cannot rely
on the toxicological and ecotoxicological profile of the bulk material that has
been historically determined.
A report released in 2009 by the
European Commission Joint Research Centre’s Institute for Health and Consumer
 called for “further development of thorough characterisation.”
The US Environment Protection
Agency (EPA) officials are planning to take enforcement action against
companies manufacturing or importing carbon nanotubes that have not submitted
premanufacture notices (PMNs) as required by its Toxic Substance Control Act
(TSCA) . EPA may issue additional test rules for carbon nanotubes.
Otherwise, EPA has been criticised for its “no-data, no risk” approach .
The European guidelines for nanotechnology fall under the
Registration, Evaluation, Authorisation and Restriction of Chemical Substances
(REACH), intended to take a “no data, no market” approach, requiring companies
to provide evidence of the safety of their chemicals before they can enter the
marketplace. In practice, however, REACH fails to apply a robust precautionary
principle . As it was designed to regulate chemicals produced in quantities
of one tonne or more, manufacturers and handlers of nanomaterials could simply
limit the scale of their operations to escape regulation. REACH is also weakened
by the exclusions from regulatory purview of some materials that were
previously shown to be safe in larger particle sizes, such as TiO2.
In 2008, the European Commission, removed carbon and graphite from
noting that at the nano-scale, these materials have not demonstrated themselves
to be risk-free. The European Food Safety Authority (EFSA) has questioned the
adequacy of established toxicological methodologies for testing nanomaterials.
But a high-ranking official at the European Commission’s Health and Consumer
Affairs Directorate General (DG SANCO), Robert Madelin, when asked whether
supermarket foods, possibly containing nanotechnology, were safe for consumers,
he answer emphatically that they were; and scolded consumer groups and
non-government organizations for attacking nanotechnology .
In early 2009, the European Commission adopted a proposal that would
allow the EU to regulate nano-foods under the Novel Foods Regulation. The
European Parliament has endorsed the proposal, further asking the Commission to
include mandatory nanomaterial labels in the list of ingredients. No further
action has yet been taken.
Nano-products have been foisted on unsuspecting consumers
essentially in a regulatory vacuum, while billions of taxpayer’s money are
being spent on research and development. To compound the risks, there is no
standard protocol for the manufacture of any product, let alone standards of
characterisation of the products. Some of these problems are only beginning to
be addressed by the Organisation for Economic Cooperation and Development .
The Royal Society and the Royal Academy of Engineering, two of the UK’s most prestigious scientific societies produced the first report in 2004 
highlighting both the risks and the opportunities of nanotechnologies. However,
there has been a distinct lack of progress in addressing the risks; UK still does not have a dedicated centre for risk research in nanomaterials .
Nanoparticles, natural, artificial, old
What’s new about nanoparticles, as far as
risk is concerned, is that many of them are chemically inert as
ordinary ions or as larger particles (and hence never had to go through
regulatory approval before the nanoparticles were used); but as soon as the particle
size reaches nanometre dimensions, they acquire novel physicochemical
properties, causing oxidative stress and breaking DNA, and they can get access
to every part of the body including the brain, via inhalation and the olfactory
review  by Cristina Buzea and colleagues at Queen’s University, Kingston,
Ontario, in Canada, pointed out that human beings have been exposed to natural
nanoparticles since the origin of our species, in the form of viruses, dusts
from terrestrial and extraterrestrial dust storms, volcanic eruptions, forest
fires, and sea salt aerosols (which are largely beneficial).
Nanoparticles have been created by human activities for thousands of years, by
burning wood in cooking, and more recently, chemical manufacturing, welding,
ore refining and smelting, burning of petrol in vehicles and airplane engines,
burning sewage sludge, coal and fuel oil for power generation, all of which are
already known to have health impacts. Automobile exhaust particular pollution
is linked to heart and lung diseases and childhood cancers.
Tobacco smoke is composed of nanoparticles with size ranging from
around 10 nm up to 700 nm, with a peak around 150 nm. It has a very complex
composition with more than 100 000 chemical components and compounds. First or
second hand cigarette smoke is associated with an increased risk of chronic
respiratory illness, lung cancer, nasal cancer, and cardiovascular disease, as
well as other malignant tumours, such as pancreatic cancer, and genetic
alterations. Children exposed to cigarette smoke show an increased risk of
sudden infant death syndrome, middle ear disease, lower respiratory tract
illnesses, and exacerbated asthma.
building demolition is an important source of particulate pollution. Older
buildings are likely to contain asbestos, fibres, lead, glass, wood, paper and
other toxic particles
Natural and artificial nanoparticles overlap. For example, C60 fullerenes have
been reported in 10 000-year-old ice core samples .
It is important
to distinguish nanoparticles from nano-structured materials that do not
exist as free particles during any part of the manufacturing process,
which therefore are not expected to present the same hazards.
are faced with an unprecedented and ever-growing volume and diversity of
nanoparticles as nanotechnologies take off in all directions.
Diseases associated with nanoparticles
Nanoparticles may be inhaled, ingested or taken
in through contact with the skin. The known possible adverse health impacts are
summarised in Figure 1 , which includes both natural and anthropogenic
nanoparticles. Obviously not all nanoparticles are harmful, but without
exhaustive tests especially in the case of the newly engineered nanoparticles,
it is impossible to tell.
Figure 1 Diseases linked to nanoparticles
from different pathways of exposure 
Diseases associated with inhaled
nanoparticles include asthma, bronchitis, emphysema, lung cancer, and
neurodegenerative diseases, such as Parkinson’s and Alzheimer’s diseases.
Nanoparticles in the gastrointestinal tract have been linked to Crohn’s disease
and colon cancer. Nanoparticles that enter the circulatory system are
in arteriosclerosis, blood clots, arrhythmia,
heart diseases, and ultimately death from heart disease. Nanoparticles entering
other organs, such as liver, spleen, etc., may lead to diseases of these
organs. Some nanoparticles are associated with autoimmune diseases, such as
systemic lupus erythematosus, scleroderma, and rheumatoid arthritis.
There is clearly an urgent need not only to
stem but also to reverse the unregulated tide of nanoparticles that are
released onto the market. In view of the existing evidence, the following
actions should be taken.
· Engineered nano-ingredients in food, cosmetics and baby products for
which toxicity data already exist (e.g., silver, titanium oxide, fullerenes,
etc.) should be withdrawn immediately
· A moratorium should be imposed on the commercialization of
nano-products until they are demonstrated safe
· All consumer products containing nanotechnology should be clearly
· The Health and Consumer Protection Directorate General (SANCO) of
the European Commission should require manufacturers of nano-products to
register their products in a database that is publicly available on the SANCO
· The voluntary code of conduct for nanotechnology research that the
European Commission adopted in 2008 should become mandatory :
Nanotechnology research activities must be made comprehensible to the public,
performed in a transparent manner, accountable, safe and sustainable, and not
pose a threat to the environment
· A robust regulatory programme on nanotechnology - including
characterisation and standardisation of manufacture - should be implemented as
soon as possible
· There should be earmarked funding for research into the hazards of
There are 5 comments on this article so far. Add your comment
|Mae-Wan Ho Comment left 11th March 2010 06:06:15|
Yes Dan,by all means send it on. You are right they know this and need to take the recommendations on board.
|Gene Sperling Comment left 19th November 2010 13:01:42|
I am a respiratory pharmacist that has been performing home audits for allergists and immunologists in So California for the past two years.
Recently, there has been a proliferation of chronic rhinitis with recurring infections. One common theme in homes and offices is the increased use of odor laden cleaning products heavy with surfactants. I would name Swiffer, Fabreeze, and Any fabric softener.---But the list is becoming endless.
I have suspected this family of chemicals for some time now in deteriorating respiratory health. I have also been troubled of late with the mix (sometimes masked by trade secrets) of pesticides with surfactants AND the introduction of nano-technology. This would appear to create a chemical with one listed concentration but effectively exhibiting affects that are multiples of times more.
Can you direct me to current science articles and research on this topic. I am having difficulty finding any.
When I present my thesis to physicians, they see it as plausible, but want to see research. The EPA is no help at all.
I would appreciate any help that you can give me to research further.
Cheers, Gene Sperling
|Don Reid Comment left 11th March 2010 05:05:12|
Much of this is already known, seemingly ignored. The reported deaths are very important to acknowledge. Australia is currently preparing draft regulations. May I send this on to the contact person (even though the submissions have closed)?
|Diana DEES Comment left 13th January 2011 09:09:13|
I am a school teacher with a degree in environmental studies from UCSB. Your research is excellent! Thank you for your efforts to protect the public. I have used Lancome facial products containing nano particles of titanium and other dyes and have developed Morgellons fiber disease on my face. Gene, I have had 4 colds in 4 months and will look into air/heat filters that are nanosilver free. Any suggestion on treating Morgellon or who makes silver free filters?
661 722 8174 firstname.lastname@example.org
|Ruth Lyons Comment left 21st February 2011 18:06:13|
i am grateful to the author of the above article
for taking such complex material, simplifying it
and showing me where the paths of diseases
associated with nanoparticles can be found.
it is unbelievable a moratorium has not been