NanoRelease Task Group 1 : Material Characteristics Characteristics Relevant to Uptake and Bioavailability

1. NanoRelease Task Group 1: Material Characteristics Characteristics Relevant to Uptake and Bioavailability www.riskscience.org

2. TG1: Material CharacteristicsCHARGE • Provide overview of physical and chemical attributes of nanoparticles that may affect their uptake in the alimentary tract. • Provide overview of physical and chemical attributes of the food matrix that may affect nanoparticle uptake in the alimentary tract. www.riskscience.org

3. Task Group 1: Sub-Groups Task Group 1 Material Characteristics Sub-Group 1 - What is (may be) in the food chain Sub-Group 2 – Nanomaterial properties Matrix interactions relevant to uptake & bioaccessibility www.riskscience.org

4. TG1 Members Sub-Group 1: ‘Catalogue’ Sub-Group 2: ‘Particle Properties’ Additional involved members/advisors: Anil Patri (US NIH), Jun Jie Yin (US FDA), Kevin Powers (U. of Florida), LekhJuneja (Taiyo Kagaku Co, Japan), Sean Linder (US FDA), Il Je Yu (Hoseo University, S. Korea), Jonathan Powell (MRC Human Nutrition Research) www.riskscience.org

5. Sub-Group 1: Catalogue Purpose of the Nanomaterial Catalogue • Review of ENM that are purportedly in internationally marketed food products • Provide “real time” input to NanoRelease task groups to support identification • and development of analytical detection and characterization methods • on nanomaterials used in commerce. Collection methods • Resources: • FoodEssentialsLabelBase, Gladson Nutrition database, Mintel Global New • Products database • U. S. Patent and Trademark Office and European Patent Office databases • Project on Emerging Nanotechnologies consumer inventory • Published literature and business press • Threshold® professional literature/patent search firm • Regional sources www.riskscience.org

6. Sub-Group 1: Catalogue Results

7. Sub-Group 1: Catalogue Summary • Catalogue is just a snapshot of what may be on the international market. • Two nanomaterials, calcium and silver, predominate, although nano-calcium was found only in Asia. • Supplements (nutritional and dietary) dominate the product classes for the • incorporation of nanomaterials. Conclusions • Lack of labeling requirements in most countries make compilation of a comprehensive catalogue difficult. • Although this snapshot is focused primarily on North America and Asia, we feel that it may be representative of food-related nanoproducts found in other regions of the world. • Without analytical data for the identified nanoproducts, it is impossible to confirm that they contain nanomaterials. www.riskscience.org

8. Sub-Group 1: Catalogue NanoMaterials known to be present in the food chain www.riskscience.org

9. Sub-Group 2: Material Characteristics www.riskscience.org

10. Sub-Group 2: Material Characteristics Particles Metals and metalloids Polymeric encapsulates Emulsions, Dispersions and Powders Thereof www.riskscience.org

11. General properties of interest Chou, L. Y. T, K. Ming and W. C. W. Chan. Chem. Soc. Rev.  2011, 40, 233-245. www.riskscience.org

12. Sub-Group 2: Material Characteristics Vasculature & lymphatics Mucus Epithelium Local tissues Nano Form Materials Transcellular Physical Change Paracellular Digestive Processes & Food Interaction Persorption Disruption to molecular components Sequestration & elimination Cytosis & accumulation www.riskscience.org

13. Sub-Group 2: Material CharacteristicsMetals and Metalloids • Definition and Usage: • Metal and metalloid particles in food are used for a wide range of applications: nutrients, colour additives, flow agents, food contact materials. Their nano-size may be intentional (e.g., to improve functionality as in the absorption of nutrients) or unintentional (portion of a particle population above the nano range). • Requirements for Characterisation: • Concentration and chemical composition (core and surface) • Primary size (and surface are), shape, and aggregation/agglomeration/exfoliation state. • Surface charge • Uncertainties: • Most relevant concentration units • At which point NM should be characterized. Prior to inclusion in food matrix, in the food matrix, in contact with gastrointestinal fluids… www.riskscience.org

14. Sub-Group 2: Material CharacteristicsMetals and Metalloids • Analytical Gaps and Difficulties: • How to extract nanomaterials from food matrices without altering their properties, such as aggregation/agglomeration/exfoliation state. • Quantitative method for metal content exist (e.g., ICP-MS) but do not inform on the properties of the material (size, shape, surface coating). • Methods that allow the evaluation of size, shape, and aggregation state (e.g., TEM, RAMAN) are not quantitative, low throughput and expensive. • Matrix Interactions: • Food matrices may affect the properties (and ultimately uptake) of nanomaterials, by changing their aggregation/agglomeration/exfoliation state, by changing their surface properties (by coating them), and when considering relatively soluble nanomaterials by determining their dissolution rate into ions. • Nanomaterials can also change the food matrix by modifying the bioavailability of some nutrients or chemically modifying them. www.riskscience.org

15. Sub-Group 2: Material CharacteristicsPolymeric Encapsulates Definition and Usage Polymeric nanoparticles with a typical size range of 20-1000 nm formed by a polymeric core, with the active component entrapped in the polymeric matrix, usually surrounded by a surfactant layer that stabilizes the system. Requirements for Characterisation Size, zeta potential, morphology, hydrophobicity, solubility, stability, degradation Uncertainties GI fate, nanoparticle degradation, uptake through the gut, biodistribution, metabolism, excretion, toxicity Analytical Gaps and Difficulties Nanoparticle-food matrix interaction, nanoparticle tracing in the gut and in the body Matrix Interactions Largely unknown www.riskscience.org

16. Sub-Group 2: Material CharacteristicsEmulsions, Dispersions & Powders Thereof Definition and Usage Preparations of water-immiscible nutrients and additives, designed for stabilisation, ease of handling, delivery or organoleptic properties. Various preparation methods for emulsions and dispersions in water are available, powder production involves the use of soluble biopolymer and spray-drying or other similar method. • Requirements for Characterisation • Digestibility • Particle size distribution • Composition & Charge Uncertainties Whether there is direct absorption from the GI tract, thus circumventing normal physiological digestion. • Analytical Gaps and Difficulties • Sample preparation: what to model (as produced, as used, as prepared, GI environment) • Representative number-size distribution, lack of analytical methods suitable for emulsions Matrix Interactions Exacerbation of the above due to interference from complex matricies ‘Black box’ ….. www.riskscience.org

17. Summary www.riskscience.org

18. Conclusion • As far as can be ascertained current ‘nano-sized’ ingredients are minerals, silver and new nutrient/additive preparations. • Silver, ceramics and clays are used in contact materials. • List of required measurands is limited. • However, almost all measurands present difficulty: • what product stage should be considered? • matrix effects are mostly unknown. • what method(s) is suitable for sample preparation and analysis? www.riskscience.org

19. Conclusion As manufactured Ease of Analysis As formulated As prepared As eaten As passaged in GI Matrix Complexity Matrix Diversity www.riskscience.org