ENVIRONMENTAL DEFENSE Quantum Leaps: Knowledge gaps in nanotechnology health and safety John M. Balbus, MD, MPH Chief Health Scientist

ENVIRONMENTAL DEFENSE Nanotechnology Project Overview Introduction: growth of EH and S researchIntroduction: growth of EH and S research Early answers to early questionsEarly answers to early questions First data addressing hypothetical risksFirst data addressing hypothetical risks Managing uncertain risksManaging uncertain risks

ENVIRONMENTAL DEFENSE Nanotechnology Project Research is beginning to accumulate…

ENVIRONMENTAL DEFENSE Nanotechnology Project And the budget for research is growing… Total research funding ($M) EH&S research funding ($M) NNI 2008 Budget ( NNI 2007 Budget ( Sources: National Science Foundation, National Science and Technology Council; NNI 2008 Budget ( NNI 2007 Budget ( Fiscal Year

ENVIRONMENTAL DEFENSE Nanotechnology Project Why have special concerns with nanoparticles? Analogy to fine particle pollutionAnalogy to fine particle pollution –Ability to move around the body –Possible shared mechanisms of toxicity Size is uniquely suited to interact with biological machinerySize is uniquely suited to interact with biological machinery

ENVIRONMENTAL DEFENSE Nanotechnology Project What we need to assure safety Reliable ways to detect and measure nanoparticles in air, water, foodReliable ways to detect and measure nanoparticles in air, water, food Understanding of distribution and persistence of nanomaterials in the bodyUnderstanding of distribution and persistence of nanomaterials in the body Reliable testing methods for both acute and chronic toxicityReliable testing methods for both acute and chronic toxicity Test results for range of materials and endpointsTest results for range of materials and endpoints Assurance that protective technologies work for nanoparticlesAssurance that protective technologies work for nanoparticles

ENVIRONMENTAL DEFENSE Nanotechnology Project Early findings of a young science… What properties affect the transport and toxicity of a nanoparticle?What properties affect the transport and toxicity of a nanoparticle? Do nanoparticles accumulate in the body?Do nanoparticles accumulate in the body? How do nanoparticles behave in the natural environment?How do nanoparticles behave in the natural environment?

ENVIRONMENTAL DEFENSE Nanotechnology Project The superficial is profound…

ENVIRONMENTAL DEFENSE Nanotechnology Project

ENVIRONMENTAL DEFENSE Nanotechnology Project Differential Penetration of QDs with Different Surface Treatments PEG-CoatedNH2-CoatedCOOH-Coated Ryan-Rasmussen, 2006

ENVIRONMENTAL DEFENSE Nanotechnology Project Surface treatments of CNT’s determine where they go Liu et al., 2007

ENVIRONMENTAL DEFENSE Nanotechnology Project QD size determines excretion Choi et al., 2007

ENVIRONMENTAL DEFENSE Nanotechnology Project Early data on key questions What properties affect the transport and toxicity of a nanoparticle?What properties affect the transport and toxicity of a nanoparticle? –Surface treatment, size critical Do nanoparticles accumulate in the body?Do nanoparticles accumulate in the body? –Some do, some don’t; percent retained tends to be low, no long term studies

ENVIRONMENTAL DEFENSE Nanotechnology Project Agitation may be required to generate high air concentrations Maynard et al. 2004

ENVIRONMENTAL DEFENSE Nanotechnology Project Sanding processes release nanoparticles

ENVIRONMENTAL DEFENSE Nanotechnology Project Early surprises in carbon nanoparticle environmental fate Conventional wisdom:Conventional wisdom: –Carbon nanoparticles just stick to soil Studies show:Studies show: –Carbon nanotubes dissolve in Georgia river water –Buckyballs form soluble, toxic nano-crystals –Hyung et al. 2007

ENVIRONMENTAL DEFENSE Nanotechnology Project Past as prologue? Learning by analogy

ENVIRONMENTAL DEFENSE Nanotechnology Project Hypothetical: Nanoparticles scar lungs like asbestos Carbon nanotubes are fiber-likeCarbon nanotubes are fiber-like Early studies showed inflammation, activation of toxic oxygen (ROS)Early studies showed inflammation, activation of toxic oxygen (ROS)

ENVIRONMENTAL DEFENSE Nanotechnology Project What do early studies show? Nanoparticles poorly cleared by white blood cells (macrophages) in the lungNanoparticles poorly cleared by white blood cells (macrophages) in the lung Carbon nanotubes cause short-term inflammationCarbon nanotubes cause short-term inflammation –Iron contaminants lead to much greater inflammation Two CNT studies show surprising lung fibrosis or growthsTwo CNT studies show surprising lung fibrosis or growths –Appeared in the absence of ongoing inflammation No study has looked for effects longer than 90 daysNo study has looked for effects longer than 90 days

ENVIRONMENTAL DEFENSE Nanotechnology Project Hypothetical: nanoparticles harm the heart like fine particle air pollution Nanoparticles are small enough to go through the lungsNanoparticles are small enough to go through the lungs Early lab and mouse studies show similar types of damageEarly lab and mouse studies show similar types of damage

ENVIRONMENTAL DEFENSE Nanotechnology Project Carbon nanotubes caused aortic plaques in mice Instilled SWCNTs damaged lung, aorta, and heart tissueInstilled SWCNTs damaged lung, aorta, and heart tissue Mice developed aortic DNA damage at 7, 28, and 60 days after exposureMice 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 dietRepeated exposure to SWCNTs resulted in accelerated plaque formation in mice fed high fat diet Li et al. 2007

ENVIRONMENTAL DEFENSE Nanotechnology Project Hypothetical: Nanoparticles containing toxic metals convey risk

ENVIRONMENTAL DEFENSE Nanotechnology Project Quantum dots vary in toxicity Studies have shown cellular toxicity, DNA damage (Hardman, 2007,Green 2005 )Studies have shown cellular toxicity, DNA damage (Hardman, 2007,Green 2005 ) –Longer exposure times more likely to show toxicity Use of cadmium raises concernsUse of cadmium raises concerns –Long-term stability of caps not certain –Widespread applications may lead to environmental loading

ENVIRONMENTAL DEFENSE Nanotechnology Project Hypothetical: Nanoparticles disrupt proteins like prions Nanoparticles translocate to the brainNanoparticles translocate to the brain Uniform nature of nanoparticles may alter proteins within cellsUniform nature of nanoparticles may alter proteins within cells

ENVIRONMENTAL DEFENSE Nanotechnology Project Olfactory Nerve Translocation Pathway: Images used with permission Slide courtesy Dr. Eva Oberdorster

ENVIRONMENTAL DEFENSE Nanotechnology Project Early studies suggest importance of protein binding Serum protein binding facilitated uptake in the liver and spleenSerum protein binding facilitated uptake in the liver and spleen Two different types of nanoparticles sped up the creation of Alzheimer-like protein fibrillationTwo 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

ENVIRONMENTAL DEFENSE Nanotechnology Project More than quantum leaps Enormous gaps remainEnormous 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

ENVIRONMENTAL DEFENSE Nanotechnology Project Temporary bridges Using the best available information to make decisionsUsing the best available information to make decisions Increasing the budget and focus of governmental funded researchIncreasing the budget and focus of governmental funded research Protecting workers and the environment in the face of uncertaintyProtecting workers and the environment in the face of uncertainty

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

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

ENVIRONMENTAL DEFENSE Nanotechnology Project Conclusions Nanoparticles defy generalizationNanoparticles defy generalization Surface properties determine behavior and toxicitySurface properties determine behavior and toxicity Few nanoparticles show significant short-term toxicityFew nanoparticles show significant short-term toxicity Early studies suggest some novel and some known toxic mechanismsEarly studies suggest some novel and some known toxic mechanisms Very little known about long-term effectsVery little known about long-term effects Risk management guidance is availableRisk management guidance is available

ENVIRONMENTAL DEFENSE Nanotechnology Project