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This article explores the gaps in our understanding of nanotechnology health and safety, including the transport, toxicity, and accumulation of nanoparticles in the body, as well as the potential risks they pose to human health. It also highlights the need for reliable detection methods and testing for both acute and chronic toxicity. The article concludes with the importance of using the best available information to make informed decisions about nanotechnology safety.
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Quantum Leaps: Knowledge gaps in nanotechnology health and safety John M. Balbus, MD, MPH Chief Health Scientist
Overview • Introduction: growth of EH and S research • Early answers to early questions • First data addressing hypothetical risks • Managing uncertain risks
And the budget for research is growing… EH&S research funding ($M) Total research funding ($M) Fiscal Year 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)
Why have special concerns with nanoparticles? • Analogy to fine particle pollution • Ability to move around the body • Possible shared mechanisms of toxicity • Size is uniquely suited to interact with biological machinery http://www.transportation.anl.gov/research/engine/diesel_structure.html www.nanowerk.com/spotlight/spotid=2019.php
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
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?
Differential Penetration of QDs with Different Surface Treatments PEG-Coated NH2-Coated COOH-Coated Ryan-Rasmussen, 2006
Surface treatments of CNT’s determine where they go Liu et al., 2007
QD size determines excretion Choi et al., 2007
Early data on key questions • What properties affect the transport and toxicity of a nanoparticle? • Surface treatment, size critical • Do nanoparticles accumulate in the body? • Some do, some don’t; percent retained tends to be low, no long term studies
Agitation may be required to generate high air concentrations Maynard et al. 2004
Sanding processes release nanoparticles http://www.pnl.gov/nanotoxicology/capability.asp?id=20
Early surprises in carbon nanoparticle environmental fate • Conventional wisdom: • Carbon nanoparticles just stick to soil • Studies show: • Carbon nanotubes dissolve in Georgia river water • Buckyballs form soluble, toxic nano-crystals • Hyung et al. 2007
Hypothetical: Nanoparticles scar lungs like asbestos • Carbon nanotubes are fiber-like • Early studies showed inflammation, activation of toxic oxygen (ROS)
What do early studies show? • Nanoparticles poorly cleared by white blood cells (macrophages) in the lung • Carbon nanotubes cause short-term inflammation • Iron contaminants lead to much greater inflammation • Two CNT studies show surprising lung fibrosis or growths • Appeared in the absence of ongoing inflammation • No study has looked for effects longer than 90 days
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
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
Hypothetical: Nanoparticles containing toxic metals convey risk http://www.orau.org/ptp/collection/shoefittingfluor/shoe.htm
Quantum dots vary in toxicity • Studies have shown cellular toxicity, DNA damage (Hardman, 2007,Green 2005 ) • Longer exposure times more likely to show toxicity • Use of cadmium raises concerns • Long-term stability of caps not certain • Widespread applications may lead to environmental loading
Hypothetical: Nanoparticles disrupt proteins like prions • Nanoparticles translocate to the brain • Uniform nature of nanoparticles may alter proteins within cells
Olfactory Nerve Translocation Pathway: Slide courtesy Dr. Eva Oberdorster Images used with permission
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 • Study used extreme conditions- needs to be replicated in more life-like conditions Linse et al., 2007
More than quantum leaps • Enormous gaps remain • Chronic toxicity-virtually no long-term test results available • Effects on development, nervous system, immune system, etc., largely untested • Very few data on environmental fate and transport, ecotoxicity
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
Four Keys to Getting Nano Right • Significant increase in government risk-research investment • Close nano-loopholes in regulations • Voluntary interim standards • Meaningful stakeholder engagement
Iterate Properties Review & Adapt Hazards Exposure Assess, prioritize & generate data ED-DD Nano Risk Framework Profile Lifecycle(s) Describe Material & Application Evaluate Risks Assess Risk Mgmt Decide, Document & Act
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
Thank you! www.nanoriskframework.com www.environmentaldefense.com\go\nano