Nanotechnology and Health: Is Nano Safe?

1. Nanotechnology and Health: Is Nano Safe? Seán Barry, Carleton University

2. The Scale of “Nanoscale” 1 – 100 nm 1x10-9 – 1x10-7 m across Canada → a centimetre

3. What Nanotechnology is Not • Modern nanotechnology is not the fabrication of tiny mechanical devices that can and will enter human systems to repair or damage cells.

4. History of Nanotechnology • As early as 500 AD, glass artisans weremaking stained glass windows withvibrant reds and yellows. • These colours were much moreluminous and durable than dyes couldproduce, and were the products of“coinage metal” nanoparticles imbeddedin the glass. • As these nanoparticles get smaller, the colours shift from red, through yellow and green, to blue.

5. Modern Nanotechnology - Investment Investments in nanotechnology are on the rise. These advances are in both basic university-basedresearch, as well as industry. Many of these advances use nanoparticles in some form or other.

6. Modern Nanotech - Hard Drive Read Heads Recording heads are miniature (about 1mm2) and read and write information to and from a hard-drive disk or another storage medium. They have a “supermagnetic” layer that is nanometres thick. (typically Ni80Fe20, Ni45Fe55 or “FeAlN”)

7. oxide Modern Nanotechnology - Microchips Intel is incorporating nanotechnology into its microchip. New chips are being made on the “sub 45 nm” node, which means that the feature size is 45 nm, or less. gate electode++++++++ drain source - - - - - - - - n-type silicon n-type silicon p-type silicon

8. Modern Nanotechnology - Shapes Adapted from J. Nanosci. Nanotechnol.2007, 7, 3048.

9. Nanoparticles in Medicine To use nanoparticles in vivo, one often selects polymers known to be non-toxic. Polyglycolic-lactic acid (PGLA) is a good example. Nanoparticles of this materialcan be dosed with specifictherapeutic agents and injectedinto biological systems. Drug release from a nanoparticle is slow and steady over time. PNAS 2006, 103(16), 6315.

10. Targeting a Tumour • The polymer nanoparticle can be modified with a bio-nanosensor to chemically recognise a cancer cell. • The surface of the particle is “decorated” with aptamers. • An aptamer is a small “piece of DNA” that is developed to specifically bind to a cancer cell. • With the aptamer in place, the nanoparticles adhere to the cancer cell, and release the drug at the site where it is required. PNAS 2006, 103(16), 6315.

11. Specific Uptake Specific uptake occurs when a nanoparticle has surface “chemistry” that binds to specific sites on the cell walls. Mostly, this is engineered. Nature Mater.2009, 8, 543.

12. Nonspecific Uptake Non-specific uptakeis due to the characteristics of thenanoparticle, but will be taken up by any cell wall. This is a general toxicity. Nature Mater.2009, 8, 543.

13. Nanotoxicity The toxicity, like many properties of nanomaterials, differ from their macroscale characteristics. J. Nanosci. Nanotechnol.2007, 7, 3048.

14. Specific Toxicity – Cell Apoptosis Superparamagnetic iron oxide (SPION) was shown to enhance medical magnetic imaging. However, normal SPION is toxic. When coated with a sugar derivative (Pullulan), it was found to be non-toxic. Biomaterials2005,26, 1565.

15. Modification and Study Healthy cells. Cells incubated with iron oxide nanoparticles. Cells incubated with pullulan-coated iron oxide nanoparticles. Biomaterials2005,26, 1565.

16. Carbon Nanotubes: An Asbestos Debate There is presently debate about whether they have health risks akin to asbestos: “Our data demonstrate that asbestos-like pathogenic behaviour associated with CNTs conforms to a structure–activity relationship based on length, to which asbestos and other pathogenic fibres conform.” Nature Nano. 2008,3, 423. “The recent findings are quite specific for this particular subclass of long, unfunctionalized MWNTs and it is difficult to extrapolate to other nanotube types.” Nature Nano. 2008,3, 378.

17. Landfills andIncinerators Industrial and municipaldischarge Nanomaterials in Biological Systems recycling worker exposure consumer exposure Production(raw) Production(consumer) Use Disposal(end of life) Human and ecological systems EPA Nanotechnology White Paper2007

18. Government Response Policy and Science interconnect on many planes, and nanoscience is becoming one of them. An excellent summary of the different responses of governments to nanoscience regulation has been compiled by Jennifer Pelley and Marc Saner. http://www.regulatorygovernance.ca/

19. United States of America: Policy Statement The U.S.A. is investing $1.5 billion in nanoscience in 2009. This includes the responsible development of nanoscience, but no Federal regulation yet exists. “Existing statutory authorities are adequate to address oversight of nanotechnology and its applications.” “Where possible, regulatory approaches should enable rather than hinder innovation…” “Benefits of regulation should justify their costs.” Joint memorandum by the Director of the Office of Science and Technology Policy and the Chairman of the Council on Environmental Quality

20. United States of America: Regulation The Environmental Protection Agency issued a White Paper, and has a voluntary “Nanoscale Materials Stewardship Program” The Food and Drug Administration have a task force, but feel that existing regulations can govern nanomaterials. California and Massachusetts both have State and Municipal regulations of nano health and safety.

21. European Union: Policy Statement The European Union is more inclined to precaution. “Where the full extent of a risk is unknown, but concerns are so high that risk management measures are considered necessary,…measures must be based on the Precautionary Principle” “The regulatory challenge is therefore to ensure that society can benefit from novel applications of nanotechnology, whilst a high level of protection of health, safety and the environment is maintained” The European Commission Regulatory Aspects of Nanomaterials.

22. European Union: Regulation The Registration, Evaluation, Authorisation and Restriction of Chemical Substances (REACH) regulation has no specific statement on nano materials, except to differentiate carbon nanotubes from bulk carbon. The “Cosmetics Directive” and “Novel Food Regulation” both mention specific assessment for nanomaterials, defining such as having one or more dimension on the scale of 1 to 100 nm.

23. Canada: Policy Statement Canada adopted a mediated outlook in 2007: “…strong science and effective regulation to protect human health and the environment while supporting Canadian competitiveness.” “…an effective, forward-looking, and responsive regulatory environment that promotes a competitive marketplace and protects the health and safety of Canadians and the environment.” Government of Canada, Comprehensive Science & Technology (S&T) Strategy: Mobilizing Science & Technology to Canada‟s Advantage

24. Canada: Regulation Canada is focused on international cooperation, but has made some regulatory changes: Canadian Environmental Protection Act 1999 governs “new” material and its regulation in Canada. Environment Canada issued an advisory note in 2007 stating that it considered a material new if it “possesses unique structures or molecular arrangements” and proposed an amendment to the Act. This covers nanomaterials, and was included specifically for nanotubes.

25. Summary • Nanotechnology is not very new. • but our ability to image it (and so, modify it) has increased. • Nanotechnology will modify existing technologies, and enable new ones. • “Free” nanomaterials are a real health concern. “Nanoparticles” and “nanotubes” are a strong focus of toxicity. • Governments range from trusting their existing regulations (U.S.A.) to defining and amending new regulations (E.U) • Canada is intermediate in its efforts, and is focusing its attention on international cooperation.

26. Reading List • EPA White Paper, 2007: • http://www.epa.gov/OSA/pdfs/nanotech/epa-nanotechnology-whitepaper-0207.pdf • Or Google “EPA nanotech white paper 2007” • Pelley and Saner summary on governance, 2009: • http://www.carleton.ca/regulation/publications/Nanotechnology_Regulation_Paper_April2009.pdf • Or Google “ Carleton nanotech regulatory” • Nature Materials review of the nano-bio interface, 2009: • http://www.nature.com/nmat/journal/v8/n7/full/nmat2442.html • Or Google “Nature Materials nano–bio interface” • This requires a subscription