Presentation Transcript

1. Effective Risk Assessment Over the Nanotechnology Life Cycle

   Paul E. Burrows PhD Science and Technology Consultant Reata Research, Kennewick, WA Society for Nuclear Medicine Molecular Imaging Summit, Albuquerque, NM, Jan 31- Feb 1, 2010
2. What are the Risks of Nanotechnology? Why Bother? Nanoscale materials have unique and useful properties not predictable from bulk characteristics. Few standards or guidelines exist. NGO activity risks distorting public opinion and chilling development. Nanotechnology offers the opportunity to get it right from the beginning. How to Define Nanotechnology. Dealing With the Complex Life-Cycle. Life-cycle risk management frameworks. Communication is Critical!
3. What are the Peculiar Challenges? Unbounded Problem? “Nanoscale” represents an infinite class of materials. Poor Controls From personal experience, it can be a challenge to buy the same sample of a nanoscale material twice. Nanoparticles are not monodisperse. What is important? Dose by mass? By surface area? If a gold nanoparticle is tagged with an antibody (or radionuclide) how relevant is the toxicity of gold nanoparticles? What changes with time? (aggregation?) How to prevent precautionary approaches leading to paralysis in the context of incomplete data sets?
4. Is it possible to create a meaningful definition of nanoscale? www.nano.gov: 1 – 100nm Worse: Anything less than 100nm Even worse: Anything with one dimension less than 100nm “If you can see it with that, it’s not nano!”
5. Confinement Effects  Photophysical Changes What is different about the nanoscale? Confinement Effects  Chemical Changes Surface Effects  Chemical Changes Campell, University of Washington
6. ...but size is not a good indicator of “nanoscale” effects Proposal: “The nanoscale is the size range where the basic physical or chemical properties of a particle depend on its size or shape.”
7. influenza (200 nm) hepatitis B (42 nm) parvovirus (25 nm) Nanoparticles or molecules? Nanoparticles or proteins? 7
8. Nanorobots or... biology? Scientific American, February 1965 Electron micrograph of real T4 bacteriophages Injects its DNA into a bacterium and rearranges the bacterium’s own structure to make > 100 copies in about 25 minutes 100 nm 8
9. Why Do Definitions Matter?Scare: The First Nano Product Recall Has Happened. Washington Post, Thursday, April 6, 2006; p. A02 Government officials in Germany have reported what appears to be the first health-related recall of a nanotechnology product, raising a potential public perception problem for the rapidly growing but still poorly understood field of science. At least 77 people reported severe respiratory problems over a one-week period at the end of March -- including six who were hospitalized with pulmonary edema, or fluid in the lungs -- after using a "Magic Nano" bathroom cleansing product, according to the Federal Institute for Risk Assessment in Berlin. There was nothing “nano” in the product A chemical propellant caused the reactions “Nano” was just used as a cool name Just to be clear: THERE WAS ABSOLUTELY NO NANOTECHNOLOGY IN “MAGIC NANO”
10. Poor definitions lead to perceived risk and poor regulation Berkeley Ordinance 6,960-N.S. http://www.ci.berkeley.ca.us/citycouncil/ordinances/2006/6960.pdf
11. Berkeley Ordinance 6,960-N.S. Confusion between natural, incidental and engineered nanoparticles Instituted because of perceived lack of regulation at U.C. Berkeley and Lawrence Berkeley National Laboratory Neither institution is actually regulated by the city No minimum threshold Implies that 5 mg of nanoparticles are as dangerous as 500kg of lead or mercury Less than 100 nm in any one dimension includes… almost everything! And excludes important examples “To the extent known” can be interpreted as “should be known” No specification as to what database should be used or what search criteria are deemed acceptable Surface modification unaddressed- can you regulate a nano-hole? Use of hazardous materials ordinance to regulate nanotechnology that has no proven health risks encourages opportunistic litigation No indication of what (if anything) the city intends to do with the information disclosed John C. Monica Jr. et al. Nature Nanotechnology 2, 68 (2007)
12. Silver NPs Already Undergoing Life-Cycle... The Behavior of Silver Nanotextiles during Washing Environ. Sci. Technol., 2009, 43 (21), pp 8113–8118 L. Geranio, M. Heuberger‡ and B. Nowack Ag content of fabrics varies by > 7000x Up to 50% lost on washing
13. What happens to NPs in the body? NPs may agglomerate and partially denature proteins... NPs may alter cellular structure in new and interesting ways... Nanoparticles can actively modulate the phase structure of lipid membranes so that the stiffness differs from spot-to-spot
14. Screening for Potential NANO Risks is necessary across the entire product life cycle Raw materials novel structures, material combinations, higher reactivity Manufactured Products New potential exposures, applications, waste generation Packaging and distribution Customer knowledge, communication, labeling Product Usage Novel behavior in matrix, potential consumer exposure End of Life Environmental dispersion; recycling/disposal impacts
15. Recognize that Risk May Change During Product Life Cycle First recognized in 2004, reiterated in 2007... Implemented yet?
16. A Great Deal of Information may be Needed It is rare that all this information will be available for a new material or process
17. The Paralysis Principle The Precautionary Principle Wingspread Conference Center, Racine, Wisconsin 23-25 January 1998 “Where an activity raises threats of harm to the environment or human health, precautionary measures should be taken even if some cause and effect relationships are not fully established scientifically.”
18. In the product life cycle, environmental exposures are less easily assessed and managed Level of exposure /control Packaging REUSE/ RECYCLE DISPOSAL Process RAW MATERIALS PRODUCT USE END OF LIFE Number of potential receptors Courtesy Jo Ann Shatkin, CLF Ventures
19. Adaptive life cycle approaches in context of limited data: Provide a framework for assessing biological and environmental exposure for emerging substances Effective resource allocation by using exposure as a key determinant of risk: No exposure = No risk. Risk assessments inform data collection and analysis. Key uncertainties become priorities for additional data gathering. Reiterate risk assessment and revisit risk management in light of new data. Nano LCRA (Shatkin 2008. Nanotechnology Health and Environmental Risks CRC Press)
20. NANO SLCRAAdaptive Streamlined Life Cycle/ Risk Assessment Framework for Nano Materials (Shatkin 2008) ASSESS EXPOSURE IDENTIFY AND CHARACTERIZE HAZARDS EVALUATE TOXICITY Process Packaging Reuse/ Recycle/ Disposal RAW MATERIALS PRODUCT USE END OF LIFE CHARACTERIZE RISK RISK MANAGEMENT/ ASSESS CONFIDENCE ITERATE Hazard x Exposure = Risk Courtesy Jo Ann Shatkin, CLF Ventures
21. Communication is Critical Does the message fit the risk?
22. Study Raises Concerns About Carbon Particles By BARNABY J. FEDER (NYT) 744 words Late Edition - Final , Section C , Page 5 , Column 4 - Environmental toxicologist Dr Eva Oberdorster says tells American Chemical Society meeting, Anaheim, Calif, that her study found buckyballs, spherical form of carbon used in nanotechnology, can cause extensive brain damage in fish and alter behavior of genes in liver cells of bass she studied; report is latest of several that raise questions about potential health and environmental effects of synthetic nanoscale materials; Oberdorster cites need for more study, interview; rejects calls by some critics for moratorium on development and sale of nanoscale materials Report with contexte.g. Oberdorster C60 toxicity resultAmerican Chemical Society March Meeting,2004. Nanotech buckyballs kill fish By Lucy Sherriff Scientists today announced research suggesting buckyball molecules can trigger organ damage in fish, raising fears over the safety of the technology. When added to aquarium water, the particles also devastated the population of Daphnia, the tiny water-fleas near the bottom of the food chain. Possible health risks are found from exposure to carbon particles Buckyballs, a spherical form of carbon discovered in 1985 and an important material in the new field of nanotechnology, can cause extensive brain damage in fish, according to research presented at a national meeting of the American Chemical Society in Anaheim, California. 23
23. _____Biotech Headlines_____• NIH Clears Most Researchers In Conflict-of-Interest Probe (The Washington Post, Feb 23, 2005) • Genetics Expert Charged With Molestation in Md. (The Washington Post, Feb 18, 2005) • Drugs Raise Risk of Suicide (The Washington Post, Feb 18, 2005) • More Biotech News _____Related Coverage_____• If It's Nano, It's BIG (The Washington Post, Feb 22, 2004) • For Science, Nanotech Poses Big Unknowns (The Washington Post, Feb 1, 2004) Nanoparticles Toxic in Aquatic Habitat, Study Finds By Rick Weiss Washington Post Staff WriterMonday, March 29, 2004; Page A02 The study, described at a scientific meeting yesterday, was small and has yet to be peer reviewed or published in a scientific journal. And although some companies anticipate making tons of the particles within the next few years, current production levels are relatively low, so the risk of exposure for humans and other animals is still quite small. Nonetheless, the findings underscore the growing recognition that the hot new field of nanotechnology, which federal officials have said will be at the heart of America's "next industrial revolution," may bring with it a number of old-fashioned trade-offs in terms of potential environmental damage and health risks. Other animal studies have suggested that a related class of nanoparticles causes lung injuries when inhaled, raising concerns about worker safety in the small but growing number of nanoparticle factories. Federal agencies including the Food and Drug Administration, the Environmental Protection Agency and the Occupational Safety and Health Administration have acknowledged that current regulations may not adequately protect against nanoparticles' unique toxicities, but those agencies have only recently begun considering how to respond. "There are many potential benefits of nanotechnology, but its hazards and risks are poorly understood," said Eva Oberdoerster, an environmental toxicologist at Southern Methodist University in Dallas, who led the new studies. Nanotechnology is an emerging field of science that deals with engineered molecules a few billionths of a meter in size. Because of the novel arrangements of the atoms in these molecules -- and because the laws of physics behave differently at such scales -- nanoparticles display bizarre chemical properties. Those properties make them potentially useful in products including stain-proof fabrics and computer components, but also make them potentially biologically disruptive. The new research focused on C 60 fullerenes, also known as buckyballs, which resemble microscopic soccer balls. Scientists hope to use them as drug delivery systems, components of fuel cells and as tools to clean up contaminated land. But buckyballs can also steal electrons from surrounding molecules -- a process known as oxidation and a common mechanism of tissue damage. In her experiments, Oberdoerster kept young largemouth bass in 10-liter aquariums filled with fullerene-spiked water at concentrations of 0.5 parts per million -- similar to that encountered with more common pollutants in U.S. ports. After 48 hours, the fish were removed and their brains studied for evidence of lipid peroxidation, a tissue-burning chemical reaction that toxicologists use as a standard of biological damage. The level of brain damage was "severe," Oberdoerster reported yesterday at the national meeting of the American Chemical Society in Anaheim -- about 17 times higher than seen in fish kept in clean water for comparison. "Given the rapid onset of brain damage, it is important to further test and assess the risks and benefits of this new technology before use becomes even more widespread," she said in a statement. In a telephone interview, Oberdoerster said some of the tissue damage may be caused directly by the buckyballs and some may be inflicted by immune system cells responding to the exposure. Oberdoerster also found that buckyballs caused die-offs of Daphnia, or water fleas -- crustaceans just a few millimeters long that eat algae and serve as food for other aquatic animals. Because of their crucial role in the food chain, Daphnia is a common test organism for aquatic toxicity. At about the same concentration used for the fish, half the Daphnia were dead within 48 hours -- an effect Oberdoerster characterized as "moderately toxic," more deadly than nickel but less so than copper. The new findings are somewhat surprising because many scientists had predicted that buckyballs would not linger in water but would quickly form clumps and sink, said John R. Bucher, deputy director of the environmental toxicology program at the National Institute of Environmental Health Sciences in Research Triangle Park, N.C., a branch of the National Institutes of Health. "Everyone assumed they'd just become part of the muck, if you will," Bucher said. "This is telling us we need to pay attention to this area." Bucher is part of a multi-year federal effort, still largely in the planning stage, to test the toxicity of several kinds of nanoparticles -- an effort made difficult, he noted, because companies have been reluctant to reveal the precise formulas they are using to make their novel nano-products. E. Clayton Teague, director of the National Nanotechnology Coordination Office, which advises the White House on nanotechnology issues, said progress in designing those studies is "proceeding very nicely," though results are still several years away. "All of the relevant agencies are now very actively looking at existing regulations to examine the degree to which they do or might not cover adequately these new nanoscale materials," he said. "I think that most people still believe that with some modifications . . . the existing regulations will be effective in covering these new materials." “… an effect Oberdoerster characterized as ‘moderately toxic,’ more deadly than nickel but less so than copper.” 24
24. The risk of not doing something may outweigh the risk of doing it. Or vice versa. This sounds obvious but is rarely explained to the general public.
25. Relative Risk Asbestos Fibers Carbon Nanotube Bundles
26. What, exactly, is killing us? Asbestos: 2,000 – 10,000 (depends how you count)
27. But asbestos is banned, right? Not since the 5th circuit court of appeals overturned it in 1991. Corrosion Proof Fittings v. Environmental Protection Agency, (5th Circuit 1991), p.35. 13,100 metric tons used in the U.S. in 2001 http://www.epa.gov/asbestos/pubs/asbbans2.pdf Asbestos products not banned – asbestos-cement corrugated sheet, asbestos-cement flat sheet, asbestos clothing, pipeline wrap, roofing felt, vinyl-asbestos floor tile, asbestos-cement shingle, millboard, asbestos-cement pipe, automatic transmission components, clutch facings, friction materials, disc brake pads, drum brake linings, brake blocks, gaskets, non-roofing coatings, and roof coatings. ...because, properly managed throughout its lifecycle, the reward outweighs the risk! Framing risk appropriately is critical!
28. What is Missed in “The Asbestos Result?” Only some tubes are “dangerous.”  In the absence of specific information, trends across materials can be useful for setting conservative endpoints.
29. The important points: There is nothing magic about “nano” Nanostructure enables new properties via well-understood physics leading to revolutionary applications. Complexity of the materials set necessitates research to draw risk categories across classes of nanoscale materials Both exposure and chemical properties may change during the life-cycle, dramatically affecting hazards. Coupled, iterative risk assessment and life-cycle analysis allows us to move forward in the absence of full data sets. Communication! Is there really anything here unique to nanomaterals? Chemicals change in the environment Combinations of chemicals / drugs have unpredictable effects Nanoscale materials could lead, and eventually fit within, a comprehensive review of how we assess the risks of chemicals in general.