Quantum Leaps: Knowledge gaps in nanotechnology health and safety

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

2. Overview • Introduction: growth of EH and S research • Early answers to early questions • First data addressing hypothetical risks • Managing uncertain risks

3. Research is beginning to accumulate…

4. 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)

5. 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

6. 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. 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. The superficial is profound…

10. Differential Penetration of QDs with Different Surface Treatments PEG-Coated NH2-Coated COOH-Coated Ryan-Rasmussen, 2006

11. Surface treatments of CNT’s determine where they go Liu et al., 2007

12. QD size determines excretion Choi et al., 2007

13. 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

14. Agitation may be required to generate high air concentrations Maynard et al. 2004

15. Sanding processes release nanoparticles http://www.pnl.gov/nanotoxicology/capability.asp?id=20

16. 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

17. Past as prologue? Learning by analogy

18. Hypothetical: Nanoparticles scar lungs like asbestos • Carbon nanotubes are fiber-like • Early studies showed inflammation, activation of toxic oxygen (ROS)

19. 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

20. 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. 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. Hypothetical: Nanoparticles containing toxic metals convey risk http://www.orau.org/ptp/collection/shoefittingfluor/shoe.htm

23. 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

24. Hypothetical: Nanoparticles disrupt proteins like prions • Nanoparticles translocate to the brain • Uniform nature of nanoparticles may alter proteins within cells

25. Olfactory Nerve Translocation Pathway: Slide courtesy Dr. Eva Oberdorster Images used with permission

26. 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

27. 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

28. 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. Four Keys to Getting Nano Right • Significant increase in government risk-research investment • Close nano-loopholes in regulations • Voluntary interim standards • Meaningful stakeholder engagement

30. 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

31. 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

32. Thank you! www.nanoriskframework.com www.environmentaldefense.com\go\nano