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Balbus10-11-07.ppt
- 1. ENVIRONMENTAL DEFENSE Quantum Leaps: Knowledge gaps in nanotechnology health and safety John M. Balbus, MD, MPH Chief Health Scientist
- 2. ENVIRONMENTAL DEFENSE Nanotechnology Project Overview ⢠Introduction: growth of EH and S research ⢠Early answers to early questions ⢠First data addressing hypothetical risks ⢠Managing uncertain risks
- 3. ENVIRONMENTAL DEFENSE Nanotechnology Project Research is beginning to accumulate⌠Scientific Journal Articles on Nanotechnology and Toxicity, 1982-2007 0 50 100 150 200 250 300 1 9 8 2 - 1 9 9 5 1 9 9 6 1 9 9 7 1 9 9 8 1 9 9 9 2 0 0 0 2 0 0 1 2 0 0 2 2 0 0 3 2 0 0 4 2 0 0 5 2 0 0 6 2 0 0 7 * Year of Publication Number of Articles
- 4. ENVIRONMENTAL DEFENSE Nanotechnology Project And the budget for research is growing⌠0 250 500 750 1000 1250 1500 '00 '01 '02 '03 '04 '05 '06 07E 08P 0 25 50 75 100 125 NIOSH OTHER EPA USDA NASA NIST NIH DOE DOD NSF EH&S Total research funding ($M) EH&S research funding ($M) Sources: National Science Foundation, National Science and Technology Council; NNI 2008 Budget (http://www.nano.gov/NNI_08Budget.pdf); NNI 2007 Budget (http://www.nano.gov/NNI_07Budget.pdf) Fiscal Year
- 5. ENVIRONMENTAL DEFENSE Nanotechnology Project Why have special concerns with nanoparticles? ⢠Analogy to fine particle pollution â Ability to move around the body â Possible shared mechanisms of toxicity ⢠Size is uniquely suited to interact with biological machinery www.nanowerk.com/spotlight/spotid=2019.php http://www.transportation.anl.gov/research/engine/diesel_structure.html
- 6. ENVIRONMENTAL DEFENSE Nanotechnology Project What we need to assure safety ⢠Reliable ways to detect and measure nanoparticles in air, water, food ⢠Understanding of distribution and persistence of nanomaterials in the body ⢠Reliable testing methods for both acute and chronic toxicity ⢠Test results for range of materials and endpoints ⢠Assurance that protective technologies work for nanoparticles
- 7. ENVIRONMENTAL DEFENSE Nanotechnology Project Early findings of a young science⌠⢠What properties affect the transport and toxicity of a nanoparticle? ⢠Do nanoparticles accumulate in the body? ⢠How do nanoparticles behave in the natural environment?
- 8. ENVIRONMENTAL DEFENSE Nanotechnology Project The superficial is profoundâŚ
- 10. ENVIRONMENTAL DEFENSE Nanotechnology Project Differential Penetration of QDs with Different Surface Treatments PEG-Coated NH2-Coated COOH-Coated Ryan-Rasmussen, 2006
- 11. ENVIRONMENTAL DEFENSE Nanotechnology Project Surface treatments of CNTâs determine where they go Liu et al., 2007
- 12. ENVIRONMENTAL DEFENSE Nanotechnology Project QD size determines excretion Choi et al., 2007
- 13. ENVIRONMENTAL DEFENSE Nanotechnology Project Early data on key questions ⢠What properties affect the transport and toxicity of a nanoparticle? â Surface treatment, size critical ⢠Do nanoparticles accumulate in the body? â Some do, some donât; percent retained tends to be low, no long term studies
- 14. ENVIRONMENTAL DEFENSE Nanotechnology Project Agitation may be required to generate high air concentrations Maynard et al. 2004
- 15. ENVIRONMENTAL DEFENSE Nanotechnology Project Sanding processes release nanoparticles http://www.pnl.gov/nanotoxicology/capability.asp?id=20
- 16. ENVIRONMENTAL DEFENSE Nanotechnology Project Early surprises in carbon nanoparticle environmental fate ⢠Conventional wisdom: â Carbon nanoparticles just stick to soil ⢠Studies show: â Carbon nanotubes dissolve in Georgia river water â Buckyballs form soluble, toxic nano-crystals âHyung et al. 2007
- 17. ENVIRONMENTAL DEFENSE Nanotechnology Project Past as prologue? Learning by analogy
- 18. ENVIRONMENTAL DEFENSE Nanotechnology Project Hypothetical: Nanoparticles scar lungs like asbestos ⢠Carbon nanotubes are fiber-like ⢠Early studies showed inflammation, activation of toxic oxygen (ROS)
- 19. ENVIRONMENTAL DEFENSE Nanotechnology Project What do early studies show? ⢠Nanoparticles poorly cleared by white blood cells (macrophages) in the lung ⢠Carbon nanotubes cause short-term inflammation â Iron contaminants lead to much greater inflammation ⢠Two CNT studies show surprising lung fibrosis or growths â Appeared in the absence of ongoing inflammation ⢠No study has looked for effects longer than 90 days
- 20. ENVIRONMENTAL DEFENSE Nanotechnology Project Hypothetical: nanoparticles harm the heart like fine particle air pollution ⢠Nanoparticles are small enough to go through the lungs ⢠Early lab and mouse studies show similar types of damage
- 21. ENVIRONMENTAL DEFENSE Nanotechnology Project Carbon nanotubes caused aortic plaques in mice ⢠Instilled SWCNTs damaged lung, aorta, and heart tissue ⢠Mice developed aortic DNA damage at 7, 28, and 60 days after exposure ⢠Repeated exposure to SWCNTs resulted in accelerated plaque formation in mice fed high fat diet Li et al. 2007
- 22. ENVIRONMENTAL DEFENSE Nanotechnology Project Hypothetical: Nanoparticles containing toxic metals convey risk http://www.orau.org/ptp/collection/shoefittingfluor/shoe.htm
- 23. ENVIRONMENTAL DEFENSE Nanotechnology Project Quantum dots vary in toxicity ⢠Studies have shown cellular toxicity, DNA damage (Hardman, 2007,Green 2005 ) â Longer exposure times more likely to show toxicity ⢠Use of cadmium raises concerns â Long-term stability of caps not certain â Widespread applications may lead to environmental loading
- 24. ENVIRONMENTAL DEFENSE Nanotechnology Project Hypothetical: Nanoparticles disrupt proteins like prions ⢠Nanoparticles translocate to the brain ⢠Uniform nature of nanoparticles may alter proteins within cells
- 25. ENVIRONMENTAL DEFENSE Nanotechnology Project Olfactory Nerve Translocation Pathway: Images used with permission Slide courtesy Dr. Eva Oberdorster
- 26. ENVIRONMENTAL DEFENSE Nanotechnology Project Early studies suggest importance of protein binding ⢠Serum protein binding facilitated uptake in the liver and spleen ⢠Two different types of nanoparticles sped up the creation of Alzheimer-like protein fibrillation â Study used extreme conditions- needs to be replicated in more life-like conditions Linse et al., 2007
- 27. ENVIRONMENTAL DEFENSE Nanotechnology Project More than quantum leaps ⢠Enormous gaps remain â Chronic toxicity-virtually no long-term test results available â Effects on development, nervous system, immune system, etc., largely untested â Very few data on environmental fate and transport, ecotoxicity
- 28. ENVIRONMENTAL DEFENSE Nanotechnology Project Temporary bridges ⢠Using the best available information to make decisions ⢠Increasing the budget and focus of governmental funded research ⢠Protecting workers and the environment in the face of uncertainty
- 29. ENVIRONMENTAL DEFENSE Nanotechnology Project Four Keys to Getting Nano Right I. Significant increase in government risk- research investment II. Close nano-loopholes in regulations III. Voluntary interim standards IV. Meaningful stakeholder engagement
- 30. ENVIRONMENTAL DEFENSE Nanotechnology Project Evaluate Risks Profile Lifecycle(s) Exposure Hazards Properties Assess Risk Mgmt Decide, Document & Act Describe Material & Application Review & Adapt Iterate Assess, prioritize & generate data ED-DD Nano Risk Framework
- 31. ENVIRONMENTAL DEFENSE Nanotechnology Project Conclusions ⢠Nanoparticles defy generalization ⢠Surface properties determine behavior and toxicity ⢠Few nanoparticles show significant short-term toxicity ⢠Early studies suggest some novel and some known toxic mechanisms ⢠Very little known about long-term effects ⢠Risk management guidance is available