Do Food Nanomaterials Pose a Safety Concern?

1. Do Food Nanomaterials Pose a Safety Concern? • Issues for Safety Evaluation/Risk Assessment • Presentation by Nga Tran • Food Products Association’s Workshop on Nanomaterials • September 18, 2006 • Washington, DC

2. Royal Society 2004 Nanoscience and Nanotechnologies • Nanoscience The study of phenomena and manipulation of materials at atomic, molecular and macromolecular scales, where properties differ significantly from those at a larger scale • Nanotechnologies The design, characterization, production and application of structures, devices and systems by controlling shape and size at nanometer scale.

3. More definitions • Nanoscale: having one or more dimensions of the order of 100 nm or less • Nanomaterial: material with one or more external dimensions, or an internal structure, which could exhibit novel characteristics compared to the same material without nanoscale features. • Nanoparticle: particle with one or more dimensions at the nanoscale. • Nanocomposite: composite in which at least one of the phases has at least one dimension on the nanoscale. • Nanostructured: having a structure at the nanoscale (EU, SCENIHR/002/05)

4. Nanotechnology in our Lives Over 200 manufacturer-identified “nano” consumer products are commercially available worldwide

5. NANOTECHNOLOGY AND FOODS • What are we dealing with? • Marketing and advertisement confusion and hype • To understand the potential safety issues, we need to define what types of nano applications are of interest • What’s REALLY likely to be commercialized earliest in the mainstream food industry???

6. Agricultural Application • Nano-formulation of pesticides • increase water solubility, enhance application, increase stability, optimize efficacy • “microemulsion concentrate” (enhance solubility) • “encapsulation” (release controls)

7. A Query of Nanotechnology Food Products -- Courtesy of the Woodrow Wilson Center

9. “NanoClusters™ a nanosize powder that combines with nutritional supplements. When consumed, it reduces the surface tension of foods and supplements to increase wetness and absorption of nutrients.” “1-5 nanometers in diameter, made from a silica-mineral hydride complex -- on exposure to moisture it releases H- ions, and becomes an antioxidant dietary supplement”

10. Familiar nanostructures in foods • Many food proteins are globular structures between 10's of nm to 100s nm in size - true nanoparticles • The majority of polysaccharides and lipids are linear polymers • less than 2 nms in thickness • one dimensional (1D) nanostructures • Preparing and stabilizing foams and emulsions • creating 2D layered nanostructures • one molecule thick, at the air-water or oil-water interface • Setting a gel, or adding polymers to delay the sedimentation of dispersions or the creaming of emulsions • creating 3D nanostructures, by causing food biopolymers to assemble into fibrous networks • Boiling starch to make custard -- melting small 3D crystalline 10s nm in thickness

11. Potential future manipulation at the nanoscale • Designing more complex multilayer structures using nanofabrication • Adding an extra layer to consolidate the weaknesses in the protein network -- stabilize against surfactant or lipid attack • Designing the properties of the interfacial layers by carefully choosing the molecular components • Enhancing or inhibiting coalescence of droplets • Regulating the porosity of the interface to optimize encapsulation and release • Designing new surface coatings or barriers

12. Alteration of intrinsic properties of foods on the nano-scale • Nanoparticles may be used in foods to alter other properties. For example, margarine, ice cream, butter and mayonnaise all belong to a class of foods known as colloids, where small particles are dispersed in some other medium – liquid, gas or solid • Ongoing research and patent on new ways to make colloids using nanoparticles that will extend shelf-life, prolong flavor sensation in the mouth, alter texture and improve stability

13. Nano-delivery system for conventional nutrients • Certainly nanoparticles may seem attractive as delivery vehicles … designed to target release of nutrients • One way to preserve an active component is by putting it in a protective ‘envelope.’ • The envelope can be engineered to dissolve or the active ingredient can be made to diffuse through the envelope triggered by the right stimulus

14. Nano-scale Food additives - $64M questions(1) are these really novel?(2) is anybody using them? BASF’s synthetic lycopene is formulated at the nanoscale …more easily absorbed …increases shelflife (on market) Edible products with inorganic coatings … coatings as barriers to prevent oxygen or moisture from reaching the product …increasing shelf life. …SiO2 and TiO2 are specifically mentioned (microencapsulation, distribution of micro-particle sizes likely contained nano-size, approved use, Not novel?) An antibacterial nanometer powder …nanometer zirconium phosphate particles as carrier of an active antibacterial component …broad spectrum (Patent data collected by ETC: Qingtian New Material Research & Development Co. (China) Food Additive CN1409966A 2003-04-16)

15. Food contact materials • Anti-microbial agents directly on the surface of the coated film • Increase or decrease gas permeability as required for different products • Improve the mechanical and heat-resistance properties and lower the oxygen transmission rate

16. POTENTIAL ISSUES GIVEN ASSUMED TYPES OF NANO-FOOD PRODUCTS (THERE MAY BE OTHERS) RUDIMENTS OF A RISK ANALYSIS/PRIORITIZATION FRAMEWORK

17. Manipulation of conventional food process on the nanoscale • Potential issue: alteration of food composition or nutritional profile • Available of detailed understanding of the nanostructures present in raw materials or processed food • use rational approaches to select new materials, or to enhance quality through food processing

18. Enhanced delivery systems • Potential issue: alterations in bioavailability - absorption, distribution, metabolism or excretion characteristics • Enhanced delivery of nutrients • Unintended consequence of getting too much of a good thing? The U-shape curve effect? • Neutraceuticals -- blurring of the distinction between functional foods and pharmaceuticals? • Additives (e.g. dyes/flavors) • Enhanced absorption from GI? • Unintended consequences? • Contaminants -- Increase bioavailability of not very bioavailable contaminants in foods?

19. Nanoscale ingredients that are natural at macroscale • In the case of additives that also occur naturally in foods, it is not clear what the nano-specific safety issues are • Ultimately, the digestive enzymes bring the natural macro particles back down to nano-scale.... conventional food is nano-scale by the time it reaches the bloodstream

20. Nanoscale additives not naturally occurring in the food • How relevant is the safety data at macro-level? • How do nanoscaled additive particles behave in food matrix? Do they stay agglomerated and bounded until digested in the gut? • What are the relevant chemical and physical characteristics of these particles in a food matrix? • What are their characteristics once in the gut? Rate of translocation to other target tissue?

21. Food contact materials (e.g.,packaging, surfaces) • Is nanomaterial bound? Or designed to migrate into the food? • Migration potential/measurement? • Erosion of surfaces during use? • Fate in the food matrix?

22. LESSONS LEARNED FROM NON-FOODS NANOTECHNOLOGY • Much of the research focuses on • Engineered nanomaterials important for electronics and pharmaceuticals • e.g., Novel carbon structures: single-walled carbon nanotubes (SWNT), buckeyballs • e.g., Drug delivery systems with specific tissue affinities • Inhalation or dermal exposures, some e-fate and ecotox • Comparison to effects of naturally-occurring nanoparticulate air pollutants on lung tissue • In vitro cytotoxicity assays

23. What safety considerations can be gleamed from nanos in electronics, pharmaceuticals and cosmetics? • Some substances show increased/altered toxicity in the nanoscale as compared to their effects when larger sized • Sometimes effects seen are different from those observed when dosing with the same material at micro- or macroscale • Local inflammation, immune responses • Different target organs • Safety considerations in production – worker risks • Safety considerations in product use – interaction with biological structures (human, animal and ecological targets)

24. Nanoparticles Simple, complex, “smart”. Aerosols, powders, suspensions, slurries Agglomerates or aggregates of nanoparticles Aerosolized suspensions Including slurries and solutions of nanomaterials How relevant is current safety assessment framework that is born out of particles and fibers to nanofoods? • Particle properties • Measurement and Exposure Assessment • Toxicology

25. What is different about engineered nanomaterials?The significance of structure The many shapes of ZnO - Courtney of Prof. Z.L. Wang, Georgia Tech

26. High Size Shape Surface Area Surface Activity Physical Structure Nano-Structure Mass Composition Low High Low Compositional Structure An experiment in the significance of structure on health impact Nano-Materials & Devices Macro-Materials Liquids Gases & Vapors

27. Exposure Exposure routes Characterization Dose Risk Control Reduced risk/impact Health Effects Toxicity Risk Characterization Context

29. Data on ingestion exposures • Very scarce • Jani at el 1990: 34% (50nm) and 26% (100 nm) polystyrene particles were absorbed, respectively. • >300 nm were absent from the blood • No particles were detected in heart or lung tissue. • Hillery et al, 1994: 10% of 60nm polystyrene particles recovered from GI tissues…most in lymphoid tissues (Peyer’s patches and lymphoid aggregates in the large intestines) • Szenkuti (1997): the smaller latex particle diameter the faster they could permeate the mucus to reach the colonic enterocytes: • 14 nm diameter permeated within 2 min, 415 nm (30 min) • 1000 nm particles unable to cross barrier

30. Algorithm of toxicodynamics on nanoparticles (based on inhaled particles) (SCENIHR/002/05)

31. Safety Decision Analysis framework Overview of influence diagram for assessing the safety of nanoparticles (Morgan, 2005)

32. Morgan’s (2005) Expert Elicitation • Aerosol physicist • Bioengineering and medicine • Biomaterials engineering • Chemistry/toxicology of ultrafines • Chemistry of nanomaterials • Exposure assessment and risk management • Mechanical engineer • Risk assessment • Toxicology

33. Particle-related characteristics module (Morgan, 2005)

34. Hypothetical Uptake Capacity Module(Morgan 2005)

35. Hypothetical and Simplified Safety Influence Diagram for Nanomaterials in Foods Exposure Presence of nano-materials Types of nano-foods Human Health Risks GI Uptake capacity Transport/Fate Food relevant nano particle-related characteristics Toxic Effects Toxicity

36. CONCLUSIONS Potential • Generally revolutionary technology, with many societal and environmental benefits anticipated • In foods, it will greatly depends on what technology we are talking about Risk • There may be unanticipated roadblocks, including unexpected risk to human health and the environment, and • Lack of public acceptance

37. Need for interaction between multiple disciplines • Food technologist/scientist • Engineers • Chemists • Toxicologists • Nutritionists • Exposure assessor • Risk assessor • “Strawmen”/case studies to develop the risk framework

38. Getting it right first time! • Societal Acceptance • Minimizing risk • Maximizing benefits