Development of test methods and database for the risk assessment of manufactured nanomaterials (I) 2007
Development of test methods and database for the risk assessment of manufactured nanomaterials (I) K.H.Choi, J.H.Yoon, S.H.Lee, C.W.Lee, S.J.Kim, J.S.Ryu, E.R.Park, H.Y.Ro, J.H ong, H.J.Kim Environmental Exposure Assessment Division Chemicals Assessment Department National Institute of Environmental Research 2007
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Abstract Nanotechnology has been emerging as one of the promising ares for the leading growth of national revenue, resulting in that human and environment have a greater exposure probability to nanomaterials. However, the information on the hazardous properties of manufactured nanomaterials is not enough. The concerns has been raised since it has been reported that smaller particles have larger surface areas suggesting possible higher bio-reactivity. OECD also recognised this concern and organized the working party for manufactured nanomaterials (OECD, WPMN) under the chemical committee in 2006. Republic of Korea is actively participating the WPMN activities. NIER (National Institute of Environmental Research) initiated researches on the sound management of nanotoxicity, including (a) development of the database providing information on the research activities on physicochemical properties and the environment, safety, and health effects of manufactured nanomaterials (b) collection of the information on target materials, test methods internationally agreed, (c) toxicity test of nanomaterials as a preliminary study. The lists of nanomaterials and end points, required to be investigated, are endorsed by the third OECD WPMN meeting in 2007. In addition, the aquatic toxicity and acute inhalation toxicity to fishes and rats of silver nanoparticles were respectively investigated as a preliminary study resulting from the consideration of those lists. The results suggested that 48-hr exposure to sliver nanoparticles could induce the changes in the glutathione (GSH) level in fish and the GSH level could be a good indicator to study the toxicity of nanomaterials. The 4-hr exposure via inhalation route did not cause death or severe
changes in rats. Therefore, further study would be required to clarify the effects of silver nanoparticles. Moreover, the investigation on GSH level in the organs of rats would be a valuable approach to find the effects of nanomaterials.
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(Abbreviation Lists) CNT : Carbon Nano Tubes ( ) DEP : Diesel Exhausted Particles( ) DTNB : 5,5-Dithiobis (2-nitrobenzoic acid) EPA NNI : Environmental Protection Agency National Nanotechnology Initiative ( ) ER : Estrogen Receptor ( ) GSH : Glutathione ( ) HEK : Human keratinocytes ( ) ILSI : International Life Sciences Institute ( ) ISO : International Organization for Standardization ( ) KISTI : Korea Institute of Science and Technology Information ( ) LC 50 : 50% Lethal Concentration ( ) LDH : Lactate dehydrogenase ( ) MWCNT : Multi-Walled Carbon Nanotube( ) NHBE : Normal Human Bronchial Epithelial ( ) OECD : Organization for Economic Cooperation and Development ( ) RNA : Ribonucleic acid ( ) SETAC : The Society of Environmental Toxicology and Chemistry ( )
SPF : Specific Pathogen-Free ( ) SSA : 5-sulfosalicylic acid (5- ) SWCNT : Single-Walled Carbon Nanotube( )
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45±20% L/min, 8±20% L/min, 7±20% L/min AC 95±10% V. 22, 45%. differential mobility analyzer (nano-dma, 4220, HCT Co., Ltd. Korea) ultra-condensation particle counter (UCPC, 4312, HCT Co., Ltd. Korea). 1. 1. Group G1 (Control) G2 (Low) G3 (Medium) G4 (High) Target dose (particles/cm 3 ) Surface area (nm 2 /cm 2 ) Mass (μg/m 3 ) 0 0 0 0.6 10 6 ±20% 1.0 10 9 ±20% 50.0±20% 1.4 10 6 ±20% 2.5 10 9 ±20% 200.0±20% 3.0 10 6 ±20% 5.0 10 9 ±20% 700.0±20% Gender N M 5 F 5 M 5 F 5 M 5 F 5 M 5 F 5 4) 2,.
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. 2),,,,,,.,,. 2007 11 28 (SETAC) (CeO 2 ) C60 fullerene Daphnia magna Moina macrocopa (SETAC 2007). Hyallela azteca C60 fullerene, (ceriodaphnia). (nanocopper) (silver nano), (nano-tio 2 ) Zebra fish (sub-lethal concentration) 24, 48 (SETAC 2007).
5. (Oberdorster G., et al, 2005) 3),.,.,, (deformability), (stability)..,
(transcriptomics) (proteonmics)., (high-throughput screening).,,,, DNA., (end-points).,,. DNA (MWCNT, 1-20 /L) (nanosilver) (0.1-5 /L) Zebra fish in vivo., (SWCNT, Single-Walled Carbon Nanotube) in vitro (Mary Jane Cunningham et al., 2007). HEK (human keratinocytes) NHBE (normal human bronchial epithelial cell) SWCNT SiO 2 CI (carbonyl iron) 24, RNA 2.
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Project DB Information 1. Title free text 2. Start year Dropdown list 3. End year Dropdown list 4. Total funding ($US) 5. Funding source (organization (s)) 6. 'Status' of the project range and absolute values in local currency free text Dropdown list (planned, current, complete) 7. Project Summary/expected free text outcomes 8. Project web link free text (official website) 9. Web link to the relevant free text website 1. Main categories of the select any relevant research themes research themes from the (from SG2 s list of list or select Others if not Research themes) find relevant theme 2. Subcategories within the select any relevant research themes research themes from the (from SG2 s list of list. or select Others if Research themes) not find relevant theme Categorisation select any relevant 3. Chemical nanomaterials from the characterisation list provided by SG3 or (chemical name)s enter text for other nanomaterials select relevant test methods from the list of 4. Test method OECD TGs or enter text for 'other' test methods Overall Outcomes + Outputs free text, web link, and attachment
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Group End point Known catalytic activity Method of production (e.g., precipitation, gas phase) Agglomeration/aggregation Water solubility Crystalline phase Dustiness Crystallite size Representative TEM picture(s) Physical-Chemic al Properties and Material Characterization Particle size distribution Specific surface area Zeta potential (surface charge) Surface chemistry (where appropriate) Photocatalytic activity Pour density Porosity Octanol-water partition coefficient, where relevant Redox potential Radical formation potential Other relevant information (where available) Dispersion stability in water Biotic degradability Ready biodegradability Environmental Fate Simulation testing on ultimate degradation in surface water Soil simulation testing Sediment simulation testing Sewage treatment simulation testing Identification of degradation product(s)
Group End point Further testing of degradation product(s) as required Abiotic degradability and fate Hydrolysis, for surface modified nanomaterials Adsorption- desorption Adsorption to soil or sediment Bioaccumulation potential Other relevant information (when available) Effects on pelagic species (short term/long term) Effects on sediment species (short term/long term) Environmental Toxicology Effects on soil species (short term/long term) Effects on terrestrial species Effects on microorganisms Other relevant information (when available) Pharmacokinetics (ADME) Acute toxicity Repeated dose toxicity Mammalian Toxicology If available: Chronic toxicity Reproductive toxicity Developmental toxicity Genetic toxicity Experience with human exposure Other relevant test data Where available: Material Safety Flammability Explosivity Incompatibility
3.. Glutathione(GSH),. GSH GSH. 48,, GSH, 9 GSH., GSH,.. GSH (Eva, 2004)., GSH. GSH GSH., GSH.
1.6 1.2 대조군 Ag(0.5 ppm) Ag(1 ppm) 0.8 0.4 0 아가미 간 뇌 9. 48 Glutathione (GSH). 6. 22, 43%.
6. G1 (Control) G2 (Low) G3 (Medium) G4 (High) ( ) 22.96±0.37 22.32±0.37 21.72±0.44 22.48±0.51 (%) 43.00±0.00 45.60±0.25 43.20±0.20 43.46±0.25 (mmh 2 O) -5.00±1.00-4.00±1.00-4.00±1.00-3.40±0.60 (m/sec) 4.00±1.00 4.00±1.00 4.00±1.00 4.00±1.00 (nm, GM(GSD)) - 18.66(0.35) 17.90(0.35) 20.35(0.69) 0.94x10 6 6 6 1.64x10 3.08x10 - (particles/cm 3 ) ±0.09x10 5 ±0.15x10 5 ±0.64x10 5 1.49x10 9 9 9 2.55x10 8.69x10 - (nm 2 /cm 3 ) ±0.44x10 8 ±0.75x10 8 ±0.26x10 9 (μg/m 3 ) - 75.84±3.25 134.62±5.99 750.00±35.62 0.94x10 6 ±0.09x10 5, 1.64x10 6 ±0.15x10 5, 3.08x10 6 ±0.64x10 5 particles/cm 3, 10. 75.84±3.25, 134.62±5.99, 750.00±35.62 μg/m 3.
10. 1,,, 14.,, 1, 3, 7, 14. 1, 3, 7, 14,,,,,,.,,., LC 50 750 μg/m 3.
28 (Ji JH et al, 2007)., (ACGIH) 100 μg/m 3.. 4. OECD OECD (WPMN), (SG),,,,, ( 07.4 ). ( 07.4, ).. OECD (ISO). 2007 3 (SG3) 2 OECD
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IV. 1.,. 2. DB OECD, DB OECD MS ACCESS 3. OECD 14 46 4.,. 5. GSH. 6..
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