Intergovernmental Forum on Chemical Safety IFCS VI September

Intergovernmental Forum on Chemical Safety (IFCS) VI September. 15 -19, Dakar, Senegal Kyunghee CHOI (nierchoi@me. go. kr) NIER

Importance of study on manufactured nanomaterials Characteristic physicochemical properties of nanomaterials Undefined risk of manufactured nanomaterials Increased exposure-frequency of nanomaterials International issue NIER Difficult application of commercial analysis Complex risk-prediction due to manufacturing (e. g. surface modifications) Studies concentrated on “manufactured nanomaterials” have the highest priority

Nanomaterials : Emission & Exposure to Environment Exposure Sources Point : Manufacturing, Landfills, Wastewater effluent Non-Point : Wear/Attrition of tires, Sunscreen, Brake pads, etc; Storm water run-off; Wet deposition Accumulation Uptake Release Photolysis UV Air Surface Water Ground Water Aggregation Biotransformation NIER Transport and Transformation Inhalation Ambient air, Workplace exposure Ingestion Food, Drinking water, Incidental Dermal Sunscreen, Cosmetics Air filtration Coagulation and Sedimentation Sand filtration Removal

The Research for Nanotechnology in Ministries and Institutes Korea government is promoting the research of nanotechnology based on ‘Korea National Nanotechnology Development Plan’. At present, it is in ‘the 2 nd Korea National Nanotechnology Development Plan (2006~2010)’. In the 2 nd Korea National Nanotechnology Development Plan, 4. 8 mil. USD was invested from government and private corporations for the vision of ‘developing competitive power of nanotechnology for the technical big country. The many ministries have been participated in the research of nanotechnology. The Ministry of Education, Science and Technology (MEST) generalizes the research of nanotechnology at the governmental levels. By describing clearly as “After the head of the related ministries build the policy about nanotechnology in order to enhance the effectiveness of the policy promotion, it should be notified to the minister of the MEST (Nanotechnology Promotion Law, Clause 4, Art. 2)”, the national nanotechnology development policies have been promoted through the MEST to enhance effectiveness NIER

The Research Areas for Safety of Nanotechnology The 2 nd National Nanotechnology Development Plan Authorization of the risk assessment center for nanotechnology - Analysis of social and economic effects of nanotechnology - Research about health, safety, environment, and ecosystem of nanotechnology - Establishment of DB and information service - Mutual cooperation and connection to Ministry of Environment (NIER), Preparation of toxicity/environmental Korea Food & Drug Administration (KFDA), Korean Agency for test guideline Technology and Standards(KATS), and Korea Research Institute of Standards and Science (KRISS). Improvement of the related law and system - Survey on the existing laws relating to the effects such as health, safety, environment, and ecosystem of nanotechnology. The review about need for future legal and regulatory - Supporting the monitoring research for the environment surveillance system of nanomaterials release. - Research and preparing procedures for detecting the pollution source of nano-products and nanomaterials nd MEST et. al. (2005), 2006 -2015 The 2 NIER Korea National Nanotechnology Development Plan

The Research Investment for Potential risk of Nanotechnology in Ministries and Institutes • In the National Institute of Toxicological Research (NITR) under the KFDA, total 5. 5 mil. USD will be invested to ‘the fundamental project about the toxicity of nanomaterials’ from 2007 to 2011 (1 mil. USD in 2007). • In the Korea Institute of Environmental Science and Technology (KIEST) under the Ministry of Environment (MOE), total 1. 5 mil. USD will be invested to ‘Eco-technopia 21 Project’ from 2007 to 2010. • In the Korea Science and Engineering Foundation (KOSEF) under the MEST, the research expenses of total 5 mil. USD, 1. 5 mil. USD per year, will be invested to ‘three detail projects of creative research initiatives in the nanotechnology development project’ from 2008 to 2010. • The chemical management division under the MOE is drawing up the 5 -year roadmap for safe management of nanomaterials. The environmental health policy division is promoting the detail industrialization process of the large research field, ‘development of safe management for new environmental risky factors’ in the fusion environmental technology development project. NIER

Projects about Environmental, Health and Safety (EHS) of Nanomaterials Current EHS projects (completed/on-going) about nanomaterials Researcher Korea Research Foundation Subject title Environmental toxicity analysis and risk assessment of Si. O 2 and Ce 2 O 3 nanopowder Korea Occupational Safety & Nanomaterial hazardous assessment and prevention strategy Health Agency of occupational health effect Korea Institute of Assessment of environmental exposure and effects and Environmental Science and management technology of nanomaterials assessment and Technology management Sector Subsector Year Risk Safety assessment 2006 EHS system/educa tion/public relations 2007 Risk Safety assessment 2007 National Institute of Environmental Research Database inventory for risk assessment of nanomaterials and methodological research of risk assessment Risk Safety assessment 2007 Ministry of Environment Investigation of nanomaterials distribution (transfer and mitigation) and introduction strategy of survey system. Risk Management 2008 Korea Research Foundation Personal protection equipment for safety assessment of nanomaterials and penetration research on artificial skin Risk Safety assessment 2008 Creative research of basic science program about nanomaterials) – project no. 5, 6, & 7 (7/25) Risk Safety assessment 2008 Korea Science and Engineering Foundation NIER

Cooperation of Ministries and Institutes Ministry of Knowledge& Economy Ministry of Labor Ministry of Environment (Korean Agency for Technology and Standard) (National Institute of Environmental Research) Food & Drug Administration (National Institute of Toxicological Research) Ministry of Education, Science ad Technology (Korea Research Institute of Standard & Science)

3 -year Program (Mo. E) The present state of production, manufacturing study, toxicity experimental data of nanomaterials 1 st year (2007) Source examination Screening of nanomonitoring methods Selection of exposure pathway Suggestion of method for nano. LCA Selection / Development 2 nd year (2008) Report of state in Korea Drawing up roadmap Characterization of physico-chemical properties Toxicity evaluatio n Applicability test of LCA methods Applicability test Standardization Env. monitoring Source monitoring Exposure assessment by nano. LCA Survey on the perception of the nanotechnology hazard Selection of group of prior managing nanomaterials Determination of ‘metric’ for nanotoxicity test + Quantitative analysis for Adjustment nanotoxicity Exposure assessment 3 rd year (2009) environmental/huma n risk assessment Selection of prior managing nanomaterials Test guide line for evaluation of nanotoxicity Supporting international cooperation

Nano(materials) risk management system A close examination of sources of nanomaterials in environment Characterization of physico-chemical properties Development of monitoring methods in environment and sources Development of environmental/human risk assessment and OECD test guidelines Systemization of molecular biological analytic methods based on omics for investigation of nanomaterials' toxic mechanism NIER

Development/achievement of nanomaterials' LCA Development of monitoring methods in environment and sources A close examination of sources of nanomaterials Development of environmental/human risk assessment and OECD test guide lines Systemization of molecular biological analytic methods based on omics for investigation of nanomaterials' toxic mechanism Priority scoring of nanomaterials Characterization of physicochemical properties Establishment of nanotoxicity D/B Supporting decision making NIER Supporting international cooperation of ministry of environment Survey on the perception of the nanotechnology hazard Road-map

Exposure assessment for nanomaterials LCA methodology for Nanomaterials Nano-consumer Products in Korea Questionnaire Survey about Emission Source in Korea NIER Monitoring and Characterization Exposure Assessment Safety test of PPE to nanoparticles

Status of use of nano materials in Korea NIER

Example of Nano-consumer Products in Korea Frying pan (Zr. O 2 coating) Nano lab Refrigerator (Ag. NP) Samsung, LG Filter of water purifier (Ag. NP) Hankook bionano-tech Lexon: conductivity coating sol Nanochemical: Photocatalyst Carbon nonotec: CNT, Nanofilter ABC nanotec: Antibiotic Ag. NP Nanomirea: Carbon nanofiber 1. Consumer products large companies 2. Raw materials Venture, small companies NIER Toothpaste (Ag. NP) NPC

Environmental health hazard assessment for nanomaterials Effects on Daphnia Magna, Chironomus riparius, Caenorhabditis elegans • Acute toxicity • experiments for physiological effects – growth & reproduction • Gene expression related to DNA damage / stress Test methods for fish toxicity(Lethality of nanoparticle in Medaka embrio) • Coagulation/Granule-like precipitates /Developmental arrest, Curved spine • Non-inflated swim bladder, Swollen yolk • Cardiovascular system : Colorless Blood / Stasis of circulation Inhalation toxicity/ Test methods for genotoxicity Comet Assay • MN Assay Nanomaterials and oxidative stress NIER

Evaluation for toxicity mechanism based on the ‘Omics’ Test organisms DNA microarray Toxicity Classifications Modes of Toxic Actions - Real-Time RT-PCR - Superoxide dismutase and catalase Stress-specific recombinant bioluminescent bacteria - Protein damage strain - Oxidative damage strain - DNA damage strain Saccharomyces cerevisiae m. RNA extraction Test toxicants [1] Silver Nanoparticles / [2] Silver Nitrate [3] Gold Nanoparticles / [4] Silver Microparticle Japanese Medaka Control & exposur e concent rations Contro l& stock solutio ns Toxicogenomics - Bioinformatics tools - Public Web Database (NCBI, TIGR, Eco. Cyc, SGD ) - Literature survey NPs Analysis TEM NIER ELSS ICP-OES FTIR

International Cooperation on Nanosafety OECD Activities 1. Introduction 2. Organization 3. Progress Statue 4. Future Plan Reference NIER

International Activities OECD WPMN : 8 Steering group Exposure Measurements & Exposure Mitigation OECD Database on EHS Research Alternative methods in Nano Toxicology EHS Research Strategies on MN Safety Testing of a Representative of MN NIER OECD Cooperation on Risk Assessment Cooperation on Voluntary Schemes & regulatory MN & Test Guidelines Programs

Participation to OECD activities q WPMN (Working Party on Manufactured Nanomaterial) (3 rd Meeting, Nov. 2007) decided to organize SG 7 and SG 8. q Korea is working for SG 1, SG 3, SG 4, and SG 8 as a participant. SG 1: OECD Database on EHS Research (Australia) SG 5: Co-operation on Voluntary Schemes and Regulatory Programs (Canada) SG 2: EHS Research Strategies on Manufactured Nanomaterials (Germany) SG 3: Safety Testing of Representative Set of Manufactured Nanomaterials (USA), (EC) Section 1: NIER Physical Chemistry Properties Jeff Morris (US), Peter Hatto (ISO/TC 229) SG 4: Manufactured Nanomaterials and Test Guidelines (USA), (EC) SG 6: Co-operation on Risk Assessment (UK) Section 2: Section 3: Section 4: Effects on Biotic Systems Steve Diamond (US) Degradation & Accumulation Vacant Health Effects Robin Fielder (UK) SG 8: Exposure Measurements and Exposure Mitigation (USA) SG 7: Alternative Methods in Nano Toxicology (UK)

Progress Status - (SG 3) The list of manufactured nanomaterials; This list of manufactured nanomaterial should be consider as a “snapshot in time” of those nanomaterials in commerce or likely to enter into commerce in the near term. Fullerenes 1) Fullerene (C 60) Carbon nanotubes 2) Single-walled carbon nanotube (SWCNTs) 3) Multi-walled carbon nanotubes (MWCNTs) Nanoparticles of elements 4) Silver nanoparticles, 5) Iron nanoparticles, 6) carbon black Nanoparticles of metal oxides Polymers and other organics Dendrimers Nanoplates 7) Titanium dioxide 8) Aluminum oxide 9) Cerium oxide, 10) Zinc oxide 11) Silicon dioxide 12) polystyrene 13) dendrimers 14) Nanoclays q 5 types of fullerene (C 60), MWCNT, Silver nanoparticles, Ti. O 2, Si. O 2 since 2007 (Eco-Technopia-21 project, Ministry of Environment). NIER

Progress Status - (SG 4) Review of existing standards for physico-chemical test methods: SG 4 is considering the following set of physico-chemical characteristics to be a necessary prerequisite of such toxicological assessment. l l l l l Agglomeration/ aggregation Catalytic properties Composition Concentration Crystalline phase Dustiness Fat solubility/ oleophilicity Grain size Hydrodynamic size/particle size measurement/ distribution Length Purity Shape Specific surface area Surface charge Surface chemistry Water solubility/ hydrophilicity Zeta potential q Key metrics (bold letter) and researched nanotoxicity since 2007 (Eco-Technopia-21 project, Ministry of Environment) NIER

¡ Phase 1 (’ 08 -’ 10) - Data gathering - Research Project : “Exploratory” ¡ Interim Assessment : WPMN 8 (’ 11) ¡ Phase 2 - Based on the result of the phase 1 - Decide additional endpoints/material to investigate - develop data for decision support: “Regulatory” NIER

• How to share test materials • How to account for testing already done on sponsored materials and endpoints http: : //www. nature. com/nmat/journal NIER

Materials Lead Sponsor(s) Co-Sponsor(s) Contributor Fullerenes (C 60) Japan, USA China* SWCNTs Japan, USA Germany, Canada, EU, France, China* MWCNTs Japan, USA Korea, BIAC Germany, Canada, EU, France, China* Silver USA, Korea Germany, Canada, Australia* Australia, EU France, China* Iron China* Canada, USA Carbon black Titanium dioxide Germany Korea, Canada, BIAC, USA Aluminum oxide Germany, USA Cerium oxide UK/BIAC(NIA), USA Netherland Australia, Germany, EU Zinc oxide UK/BIAC(NIA) Australia*, BIAC(CEFIC) Australia, Canada Silicon dioxide EU* Korea, BIAC(CEFIC) EU, France Polystyrene Korea Spain USA Dendrimers Nanoclays NIER Germany, USA Spain, France, China*

• Cooperation & coodination with relevant stakeholders : OECD, ISO & national activities – Completed/On-going/Planned : Manufactured nanomaterials/technology, Environment and health safety ⇒ Report research status to OECD secretariat for information sharing - Testing for OECD test guideline application (Target : Molecular, Cellular, Cultural level of biota) • OECD Workshop on the Safety Testing of Manufactured Nanomaterials (19 -21 November 2008, Busan, Korea) DDP for Sponsorship Program : SG 3, SG 4, SG 7

Information sharing OECD Korea Workshop (Nov. 19 -21, 2008, Busan) Development of DDP for Sponsorship Program : SG 3, SG 4, SG 7 (alternatives) * Symposium on EHS of Nanomaterials (Nov. 18, 2008, Busan) Nurimaru APEC House NIER

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