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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 exposure

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 [1]. The polyacrylate nanoparticles were confirmed in the workplace.

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 indeed toxic.

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 [2] (Nanotechnology, a Hard Pill to Swallow, SiS 16). But evidence of health hazards soon started to emerge [3-5] (Nanotox, Metal Nanoshells, Cure or Curse?, Nanotubes Highly Toxic, SiS 21), and nanotoxicology became established as a discipline in 2005 [6] (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.

In 2009, researchers at University of California Los Angeles Jonsson Cancer Center led by Robert Schiest reported that [7] 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 [8], 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 [9]. Similar toxicities have been found for other nanoparticles often used with TiO2, such as ZnO2 and SiO2 [10, 11].     

Nano-silver, even more widely used than nano-TiO2, is toxic to beneficial bacteria that break down wastes and recycle nutrients in the soil [12]. It also killed half of all zebrafish embryos in laboratory tests at concentrations of 25 to 50 ppm [13]; whereas a solution of ordinary silver ions (Ag+) was non-toxic.

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 [14], 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 [15]. 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 [16].

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 [17]. 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 [18]. 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 [19]. 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 [20]. 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) [21], 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 [22].

Nanotechnology products already on the market

A public inventory currently lists more than 1 000 nanotechnology products on the market [22]; 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.

The most 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.

Carbon nanotubes and nanofibres are incorporated in sports goods such as tennis rackets, racing bicycle frames and golf club to give strength at reduced weight [22]. 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 [25].

Semi-conducting quantum 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 [22]. 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 [12]

The UK government is about to announce a new strategy for nanotechnologies [26], predicted by the US National Science Foundation to worth more than $1 trillion by 2015 [27].

The European Union’s Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) report in 2006 [28] 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 [29] 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) [30]. EPA may issue additional test rules for carbon nanotubes. Otherwise, EPA has been criticised for its “no-data, no risk” approach [12].

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 [12]. 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 its exclusion

 list, 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 [12].

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 [31].

The Royal Society and the Royal Academy of Engineering, two of the UK’s most prestigious scientific societies produced the first report in 2004 [32] 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 [33].

Nanoparticles, natural, artificial, old and new

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 nerve.

A comprehensive review [34] 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.

Dust from 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 [35].

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.

Nevertheless we 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 [34], 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 [34]

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 implicated

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 labelled

· 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 website [12]

· The voluntary code of conduct for nanotechnology research that the European Commission adopted in 2008 should become mandatory [12]: 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 nanotechnology.


1. Song Y, Li X and Du X. Exposure to nanoparticles is related to pleural effusion, pulmonary fibrosis and granuloma. Eur Respir  J 2009, 34, 559-67.

2. Ho MW. Nanotechnology a hard pill to swallow. Science in Society 16 42-43, 2002.

3. Howard V. Nanotox. Science in Society 21, 34-35, 2004.

4. Ho MW. Metal nanoshells cure or curse? Science in Society 21, 35, 2004.

5. Ho MW. Nanotubes highly toxic. Science in Society 21, 36-37, 2004.

6. Ho MW. Nanotoxicity: a new discipline. Science in Society 28, 8, 2005.

7.  “Nanoparticles used in common household items cause genetic damage in mice”, Kim Irwin, UCLA Newsroom,18 November 2009,

8. Trouiller B, Reliene R, Westbrook A, Solaimani P and Schiestl RH. Titanium dioxide nanoparticles induce DNA damage and genetic instability in vivo in mice. Cancer research 69, 8784-9, 2009.

9. Huang S, chueh PJ, Lin Y-W, Shih T-S, Chuang S-M. Disturbed mitotic progression and genome segregation are involved in transformation mediated by nano-TiO2 long-term exposure. Toxciology and applied Pharmacology 2009, 241, 182-94.B

10. Han B, Wei C, Yang D, Hu C, Yu X and Yang X. Acute toxicity of suspension of nanosized silicon dioxide particles to Daphnia magna. Bioinformatics and Biomedical engineering 2009, DOI 10.1109/ICBBE 2009.5162276

11. Deng X, Luan Z, Chen W, Wang Y, Wuy M, Zhang H and Jiao Z. Nanosize zinc oxide particles induce nural stem cell apoptosis. Nanotechnology 2009, 20, 115101.

12. Unseen Hazards: from Nanotechnology to Nanotoxicity, Food and Water Europe, 21 December 2009,

13. Asharant PV, Wu YL, Gong Z and Vallyavettil S. Toxicity of silver nanoparticles in zebrafish models. Nanotechnology 2008, 19, 255102.

14. Oberdorster E. Manufactured nanomaterial (Fullerenes, C60) induce oxidative stress in the brain of juvenile largemouth bass. Environmental Health Perspectives 2004, 112, 1058-62.

15. Usenko CY, Harper SL and Tanguay RL. In vivo evaluation of carbon fullerene toxicity using embryonic zebrafish. Carbon 2007, 45, 1891-8.

16. Ma-Hock L, Treumann S, Strauss V, Brill S, Luizi F, Mertler M, Wiench K, Gamer AO, van Ravenzwaay B and Lansiedel R. Toxicity of multiwall carbon nanotubes in rats exposed for 3 months. Toxicological Sciences 2009, 112, 468-81.

17. Quantum dot, Wikipedia, 7 February 2010,

18. Lee J, Ji K, Kim J, Park C, Lim KH, Yoon TH and Choi K. Acute toxicity of two CdSe/ZnSe quantum dots with different surface coating in Daphnia magna under various light conditions. Environmental Toxicology DOI 10.1002/tox

19. Koeneman BA, Zhang Y, Hristoski K, Westerhoff P, Chen Y, Crittenden JC and Capco DG. Experimental approach for an in vitro toxicity assay with non-aggregated quantum dots. Toxicology in Vitro 2009, 23, 955-62.

20. Geys J, Nemmar A, Verbeken E, Smolders E, Ratoi M, Hoylaerts MF,  Nemery B and Hoet PHM. Acute toxicity and prothrombotic effects of quantum dots: impact of surface charge. Environ Health Perspect 2008, 116, 1607-13.

21. Linse S, Cabaleiro-Lago C,. Xue WF, Lynch I, Lindman S, Thulin E, Radford SE and Dawson KA.  Nucleation of protein fibrillation by nanoparticles. Proc. Natl. Acad. Sci. U. S. A. 2007, 104,  8691-6.

22. Consumer Products, An Inventory of nanotechnology-based consumer products currently on the market. The project on emerging nanotechnologies,

23. “Mimicking nature creates self-cleaning coatings”,, 24 October 2006,

24. “New anti-graffiti coating able to protect cultural heritage ancient materials has been developed to prevent damage caused by graffiti attacks”, Science Daily, 22 February 2009,

25. “Baytubes carbon nanotubes in marine coatings help reduce frictional resistance”,, 24 November 2009,

26. Nanotechnologies: influence and inform the UK strategy. Department for Business Innovations and Skills, accessed 11 February 2009,

27. Editorial. Recommended reading. Nature Nanotechnology 2009, 4, 533.

28. The Appropriateness of Existing methodologies to Assess the Potential Risks Assoicated with Engineered and Adventitious Products of Nanotechnologies, Brussels, Belgium, Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR).

29. “Unknown toxicity of nanotubes sparking EPA interest”, Asbestos News, 26 January 2010,

30. Stone V. Engineered Nanoparticles: Review of Health and Environmental Safety, Edinburgh Napier University, Institute of Occupational Medicine, Denmark Technical University, European Commission Joint Research Centre, Institute of Nanotechnology, Seventh Framework Programme, 2009, European Commission Joint Research Centre

31. Nanotechnologies: influence and inform the UK strategy. Summary of evidence January 2010,

32. OECD Working Party on Nanotechnology,,3343,en_21571361_41212117_41226376_1_1_1_1,00.html

33. Nanoscience and Nanotechnologies: Opportunities and Uncertainties (The Royal Society and The Royal Academy of Engineering, 2004); available at

34. Buzea C, Pacheco II and Robble K. Nanomaterial and nanoparticles: Sources and toxicity. Biointerphases 2007, 2 (4), December.

35. Murr LE, Esquivel EV, Bang JJ, de la Rosa G, and Gardea-Torresdey JL. Chemistry and nanoparticulate compositions of a 10,000 year-old ice core melt water. Water Res. 2004, 38, 4282–96.

There are 6 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. thanks
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 Environmental Pharmacist 800-400-2118
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? Diana Dees 661 722 8174
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 called!
Lienke Katz Comment left 8th July 2014 17:05:08
I have a question about the use of colloidal silver used to treat resistant bacterial and viral infections. Are the particles in this presentation "nano size" , or are they larger? What is the safety record of this medication as it is used regularly by naturopath and other integrative doctors. I would appreciate it very much if someone can enlighten me. Thanks! Lienke

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