ICON Research Needs Assessment January 9 2007, Bethesda, MD Assessing the risks of engineered nanomaterials Setting the Scene Andrew D. Maynard Chief Science Advisor
Defining Nanotechnology Richard Smalley Nanotechnology: The art and science of building stuff that does stuff at the nanometer scale (1943-2005) 2
What has risk got to do with nanotechnology?! New ways of doing things mean new risks to human health and the environment! The long-term success of nanotechnology will depend on identifying, assessing and managing potential risks! Defining nanotechnology risk research: The art and science of addressing how stuff that does stuff at the nanometer scale might harm our health and the environment 3
Nanotechnology Risk What does this mean? Giant Magneto- Resistance hard drive heads Risk? Nanotech insoles Risk? ipod oversight? Nano-membrane water purification Risk? Stain-resistant pants Risk? Nanotechnologybased food additives Risk? Nanotechnology Risk has relatively little meaning......unless we apply appropriate boundaries to the discussion 4
Setting Boundaries Engineered nanomaterials which potentially present new challenges! Criteria: Nanomaterials capable of entering or interacting with the body or environment Nanomaterials which potentially exhibit nanostructure-dependent biological activity Nanoparticles Simple, complex, smart. Aerosols, powders, suspensions, slurries Agglomerates or aggregates of nanoparticles www.osha.gov www.picturearts.comov Comminution Aerosols from grinding, cutting, machining nanomaterials Degredation/Failure Aerosols and suspensions resulting from degradation and failure of nanomaterials Aerosolized suspensions Including slurries and solutions of nanomaterials? Unintentional use Potential exposure from unanticipated/unintentional use 5
What makes nano different: The significance of structure ZnO: One chemistry, many shapes - Courtney of Prof. Z.L. Wang, Georgia Tech 6
Nanotechnology and potential risk A thought experiment in the significance of structure on potential impact Physical Structure Low High Size Unconventional Understanding Shape Nano-Materials & Devices Surface Area Surface Activity Nano-Structure Conventional Understanding Macro-Materials Mass Liquids Composition Gases & Vapors Low Compositional Structure High 7
Physicochemistry and the lungs Comparison of insoluble materials with different biological activities 10 Inflammatory Response (PMN cont x10 6 ) 8 6 4 2 0 Fine TiO (Tran) 2 Fine TiO (Oberdörster) 2 BaSO (Tran) 4 Ultrafine TiO (Oberdörster) 2 Crystalline SiO (Porter) 2 0 0.05 0.1 0.15 0.2 0.25 0.3 Particle Surface Area Dose (m 2 /lung) Maynard and Kuempel (2005). J. Nanoparticle Res. 8 8
Physicochemistry and the skin Dermal Penetration - Quantum dots 4.6 nm diameter quantum dots Stratum Corneum Different coatings Dermis Epidermis Confocal Microscopy / fluorescence analysis Scale bar: 50!m Ryman-Rasmussen, J. P., J. E. Riviere and N. A. Monteiro- Riviere (2006). Tox. Sci. ToxSci Advanced Access: Published January 27 2006 9
Physicochemistry and Translocation Translocation Following Inhalation - Lungs to Liver Fraction of inhaled insoluble 192 Ir translocating to liver in rats 0.006 15 nm particles 0.005 80 nm particles 192 Ir fraction retained in liver 0.004 0.003 0.002 0.001 0 0.25 1 3 7 Retention Days Kreyling, W. G., et al., J. Toxicol. Env. Health Pt A 65 (20), 1513-1530, 2002. 10
Nano is NOW Nano-Consumer Products www.nanotechproject.org/consumerproducts Nearly 400 manufacturer-identified nano consumer products are commercially available worldwide 11
Addressing Potential Impact Exposure Routes Exposure Characterization Dose Education Risk Control Reduced Impact Health Effects Knowledge Level Poor Good Toxicity 12
Responding to the challenge Sound Science Identifying critical questions, and finding applicable answers Specificity Focusing on how the technology is used, not the technology itself Simplification Identifying patterns and commonalities which will transform apparently intractable problems into a merely difficult ones 13
Simplification: An Example Handling single walled carbon nanotubes - used for illustration purposes only Measuring exposure to airborne nanostructured particles Many potentially significant attributes: Few measurement metrics 14
Classifying Engineered Nanoparticles Some thoughts Compact/Sphere Homogeneous Heterogeneous Core-surface High aspect ratio Homogeneous Heterogeneous Distributed Complex non-spherical Homogeneous Heterogeneous aggregates Many particle classes Active External stimuli Homogeneous agglomerates Single particle class Multifunctional Complex responses Note: size is treated separately 15
Identifying important attributes Some more thoughts Differentiated component release Core-surface Heterogeneity Response to environment Shape Charge Porosity Response to stimulus Surface Chemistry Surface Area Crystal Structure Composition Solubility Distributed Heterogeneity Propensity to change structure 16
Matching exposure metrics, attributes and particle class Shape Surface area Surface chemistry Composition Core-surface composition heterogeneity Distributed composition heterogeneity Solubility Charge (in lung fluid) Crystal structure Porosity Changes in particle size/structure following deposition Preferential release of constituent components following deposition Relevance High Medium Low None Stimulus-associated behavior Functional response to environment Exposure Metric 17
Surface Area Concentration Shape Surface area Surface chemistry Composition Core-surface composition heterogeneity Distributed composition heterogeneity Solubility Charge (in lung fluid) Crystal structure Porosity Changes in particle size/structure following deposition Preferential release of constituent components following deposition Relevance High Medium Low None Stimulus-associated behavior Functional response to environment Surface Area Concentration Aitken and Maynard (2007), Nanotoxicology. In Preparation 18
Number Concentration Shape Surface area Surface chemistry Composition Core-surface composition heterogeneity Distributed composition heterogeneity Solubility Charge (in lung fluid) Crystal structure Porosity Changes in particle size/structure following deposition Preferential release of constituent components following deposition Relevance High Medium Low None Stimulus-associated behavior Functional response to environment Number Concentration Aitken and Maynard (2007), Nanotoxicology. In Preparation 19
Mass Concentration Shape Surface area Surface chemistry Composition Core-surface composition heterogeneity Distributed composition heterogeneity Solubility Charge (in lung fluid) Crystal structure Porosity Changes in particle size/structure following deposition Preferential release of constituent components following deposition Relevance High Medium Low None Stimulus-associated behavior Functional response to environment Mass Concentration Aitken and Maynard (2007), Nanotoxicology. In Preparation 20
Assessing the risk of engineered nanomaterials The Challenge: Sound Science Identifying critical questions, and finding applicable answers Specificity Focus on how the technology is used, not the technology itself Simplification Identifying patterns and commonalities which will transform apparently intractable problems into a merely difficult ones 21
Further Reading Maynard, A. D. and E. D. Kuempel (2005). Airborne nanostructured particles and occupational health. Journal Of Nanoparticle Research 7(6): 587-614. Maynard, A. D. (2006). Nanotechnology: The next big thing, or much ado about nothing? Ann. Occup. Hyg. Available online: DOI: 10.1093/annhyg/mel071 Maynard, A. D. (2006) Nanotechnology: Managing the risks. Nano Today 1, 22-33. Available online. DOI:10.1016/S1748-0132(06)70045-7 Maynard, A. D. (2006). Nanotechnology: A research strategy for addressing risk. Washington DC. Woodrow Wilson International Center for Scholars, Project on Emerging Nanotechnologies. PEN 03. Download from www.nanotechproject.org/ file_download/77 Maynard, A. D., R. J. Aitken, T. Butz, V. Colvin, K. Donaldson, G. Oberdörster, M. A. Philbert, J. Ryan, A. Seaton, V. Stone, S. S. Tinkle, L. Tran, N. J. Walker and D. B. Warheit (2006). Safe handling of nanotechnology. Nature 444(16): 267-269. 22
Further Information Andrew D. Maynard PhD Chief Science Advisor Project on Emerging Nanotechnologies Woodrow Wilson International Center for Scholars Tel: +1 202 691 4311 Email: andrew.maynard@wilsoncenter,org Web: www.nanotechproject.org 23