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1 CLEAN TECHNOLOGY, Vol. 17, No. 3, September 2011, pp. 273~279 산업생태학 서로다른물리화학적특성을갖는탄소나노튜브 (CNT) 의생물학적독성분석 김수남, 강민성, 한영아, 김재환, 노진규, 김영훈, 최상돈 *, 박은정 * 아주대학교분자과학기술학과 경기도수원시영통구원천동산 5 한국화학연구원부설안전성평가연구소 전라북도정읍시신정동 1051 광운대학교화학공학과 서울특별시노원구월계동 (2011 년 7 월 14 일접수 ; 2011 년 8 월 21 일 1 차수정본접수 ; 2011 년 9 월 16 일 2 차수정본접수 ; 2011 년 9 월 18 일채택 ) Toxicity Analysis of Carbon Nanotubes Based on Their Physicochemical Properties Soo Nam Kim, Min Sung Kang, Young-Ah Han, Jae Hwan Kim, Jinkyu Roh, Younghun Kim, Sangdun Choi*, and Eun-Jung Park* Department of Molecular Science and Technology, Ajou University, San 5, Woncheon-dong, Yeongtong-gu, Suwon , Korea Inhalation Toxicology Center, KIT Jeongeup Campus, 1051, Shinjeong-dong, Jeongeup , Korea Department of Chemical Engineering, Kwangwoon University, Wolgye-dong, Nowon-gu, Seoul , Korea (Received for review July 14, 2011; 1st Revision received August 21, 2011; 2st Revision received September 16, 2011; Accepted September 18, 2011) 요 약 제조나노물질은원료물질이동일하더라도제조방법에따라최종생산물의물리화학적특성은매우상이해질수있고더불어독성또한크게달라질수있을것으로추정되고있다. 본연구에서우리는 2 종의탄소나노튜브 ( 단층벽탄소나노튜브및다층벽탄소나노튜브 ) 를마우스에경구와경기관지로처리한후체중당상대무게및염증반응지표를조사함으로써길이와전기전도성에따른독성을동정하였다. 실험결과, 다층벽탄소나노튜브의경우체중감소는길이가짧은그룹에서더강하게관찰된반면, 염증반응은비교적길이가긴그룹에서더강하게유도되었다. 경기관지로처리된단층벽탄소나노튜브는뇌와신장의상대무게를의미있게감소시켰고, 기관지세척액과혈액내면역세포의의미있는변화는처리후 1 일과 7 일에서주로관찰되었다. 이결과를통해길이, 입경, 층벽의수와같은탄소나노튜브의물리화학적특성이물질에의한독성과염증반응에매우중요한인자로작용하고있음을확인할수있었다. 주제어 : 제조나노물질, 탄소나노튜브, 독성, 염증반응 Abstract : The physicochemical properties of manufactured nanomaterials can vary depending upon the methods of manufacture, although the utilized raw materials are same. Hence, the toxicity can also vary based on the methods of nanomaterials manufacture. In this study, we compared the toxicity effect of two types of CNTs (MWCNT, multi-walled carbon nanotube; SWCNT, single-walled carbon nanotube) that differ in length and wall number. In case of MWCNTs, inflammatory responses were more strongly induced in longer groups, whereas body weights more clearly decreased in shorter groups. SWCNT significantly decreased the relative weights of brain and kidney, and the inflow of immune cells and the hematological changes were observed significantly on day 1 and day 7 after exposure, respectively. Our results showed that the length and wall number of CNTs can serve as critical factors in the exhibited inflammation and toxicity. Keywords : Carbon nanotube, Inflammation, Manufactured nanomaterials, Toxicity 1. 서론 * To whom correspondence should be addressed. sangdunchoi@ajou.ac.kr, pejtoxic@daum.net 이논문은한국연구재단지정중점연구소, 아주대학교분자과학기술연구센터특집으로투고되었습니다. 과학기술의발전과더불어새로운물질에대한노출의기회가빈번해짐에따라그유해성에대한관심또한고조되고있다. 제조나노물질의경우도그러한예중하나이며, 21세기들어제조나노물질은높은전기전도성, 강도, 지속기간, 화학 273

2 274 청정기술, 제 17 권제 3 호, 2011 년 9 월 반응등독특한물리화학적특성으로인해전기 / 전자, 통신, 재료 / 제조, 의료 / 생명공학, 환경 / 에너지, 국방, 항공우주등그응용범위가급속도로증가하고있음에도불구하고독성에관한연구는매우더디게진행되고있다 [1-3]. 경제협력개발기구 (OECD, Organization for Economic Cooperation and Development) 에서는 2007년부터단층벽탄소나노튜브 (SWCNT, single-walled carbon nanotube), 다층벽탄소나노튜브 (MWCNT, multi-walled carbon nanotube), 플러렌, 티타늄, 철등을포함하는우선관리대상나노물질 14종을선정하고각물질별로 lead sponsor, co-sponsor, contributor등을지정하여독성자료의수집, 생산등을총괄하게하고있으며, 2008년부터본격적으로시행되고있는 GHS (Globally Harmonized System of Classification and Labeling of Chemicals) 에서는생산된제품의원료물질과더불어최종산물에함유된성분의독성자료도요구하고있다. 그러나, 제조나노물질의경우기존의일반화학물질과는달리원료물질이동일하더라도제조방법에따라최종생산된나노물질의물리화학적특성은매우상이해질수있으므로원료물질이동일하더라도최종산물의독성결과를동일하다고평가하는데는많은한계가있을것으로판단되어기존의독성분류방식을보완할방안을마련하고자많은노력을기울이고있다. 본연구에서는나노물질의응용분야의확대로인한노출경로의다양화를반영하기위하여서로다른길이와 wall number를갖는단층벽탄소나노튜브와다층벽탄소나노튜브를경구및경기관지로주입한후일어나는체중변화, 각조직의상대무게변화, 염증반응등을관찰함으로써탄소나노튜브의길이나 wall number가독성에미치는영향을조사해보고자하였다. 2. 실험 2.1. 시험물질서로다른길이 (240, 394, 3,088, 6,261 nm) 의다층벽탄소나노튜브는서울대학교화학생물공학부이종협교수실험실에서제공받았다. 도체와반도체성분으로이루어진단층벽탄소나노튜브로부터산을이용하여반도체성분만을분리하는작업은광운대학교화학공학과김영훈교수실험실에서수행하였으며복합성분과반도체성분의단층벽탄소나노튜브의평균길이는각각 760과 1,000 nm였다. 로실시하였다. 본시험에적용되는모든수순은동물실험윤리위원회 (Institutional Animal Care and Use Committee, IACUC) 에의해검토되어실시되었다 시험물질투여다층벽탄소나노튜브의길이에따른독성을비교하기위하여용매대조군및처리군 (240, 394, 3,088, 6,261 nm) 모두각각 5마리씩 15일간 5 mg/kg의농도로 1일 1회경구로투여하였으며, 성별에따른독성을비교하기위하여 3,088 nm의 1.25, 2.5, 5 mg/kg의다층벽탄소나노튜브를암 / 수각각 7마리씩 15일간 1일 1회경구투여하였다. 단층벽탄소나노튜브의처리는 GLP (Good Laboratory Practice) 시스템하에서안전성평가연구소의 SOP (Standard Operating Procedure) 에따라 100 µg/kg의단층벽탄소나노튜브를경기관지로단회투여되었으며, 처리후 1, 7, 14 및 28일에추후시험에필요한시료를회수하였다 체중및장기무게측정순화기간의경우1일 1회일반증상관찰을실시하였으며, 투여기간에는 1일 2회로, 투여전및후에관찰하였다. 체중은투여개시전에 1회, 투여기간에는주 1회씩및부검전에그룹별로측정하였다. 계획도살시까지생존한모든동물및빈사또는사망동물에대하여부검후간, 폐, 뇌, 흉선, 심장, 신장 ( 좌, 우 ), 비장, 자궁및고환 ( 좌, 우 ) 등의절대장기중량을측정하고, 부검전절식된체중에대한상대장기중량을산출하였다 혈액학적검사최종부검시에모든생존동물에대해서후대정맥에서채혈하여채혈된혈액약 0.5 ml을 EDTA-2K 함유채혈병에분주하여 White blood cell count (WBC), Red blood cell count (RBC), Hemoglobin concentration (HGB), Hematocrit (HCT), Mean corpuscular volume (MCV), Mean corpuscular hemoglobin (MCH), Mean corpuscular hemoglobin concentration (MCHC), Platelet (PLT), Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils, Large unstained cells, Reticulocyte에대해혈구자동계측장치 (ADVIA120 Hematology system, Bayer, USA) 를이용하여검사하였다 실험동물및사육환경 5주령 ICR마우스를 ( 주 ) 오리엔트바이오 ( 경기도성남 ) 로부터공급받아 2주일간순화후본실험에사용하였다. 실험동물의사육환경은온도 23 ± 3, 상대습도 55 ± 10%, 환기횟수 10~20회 /hr, 조명주기 12시간 (08:00~20:00), 조도 150~300 Lux 로조절되었으며, 순화, 검역, 투여및관찰기간동안스테인레스제망사육상자 (255 W 465 L 200 H mm) 에수용하여사육하였다. 실험에사용된모든동물은방사선조사된실험동물용고형사료 (P.M.I.) 와음수 ( 여과멸균정제수 ) 를자유급식하도록하였다. 또한, 동물의개체식별은 tail tattoo 표시법으 2.6. Broncho-alveolar lavage (BAL) fluid 채취멸균식염수 1 ml을기관지를통하여 1회왕복하여채취하는방법으로 2회채취한후동일한방법으로 2회더채취하였다. 처음 2회채취한시료를원심분리 (3,000 rpm, 10분 ) 하여얻어진상등액은사이토카인측정을위해보관하였으며, 세포는 2차로회수한분획과혼합하여 Cell Viability Analyzer (Vi-CELL TM, Beckman Coulter) 로총세포수를측정하였고, 가라앉은세포들을재부유시켜 Wright-Giemsa로염색한후 Shandon Cytospin 4 (Thermo) 를이용하여면역세포수를측정하였다.

3 서로다른물리화학적특성을갖는탄소나노튜브 (CNT) 의생물학적독성분석 혈액내사이토카인측정혈액내사이토카인농도는시판중인 ELISA kit (ebioscience, San Diego, CA, USA) 을이용하여제조회사의매뉴얼에따라실행하였다. 간략히기록하면, 96 well plate에 assay dilution으로희석한 capture antibody를 100 µl씩분주한후, 4 에서 overnight하였다. Well plate을세척하고 assay dilution으로 1시간동안실온에서 blocking한후대조군과나노입자처리군으로부터준비된혈청과 standard를각 well에넣고 2시간동안실온에서방치하였다. 다시세척후, biotin-conjugated detecting mouse antibody를넣고 1시간동안반응시킨후 avidin-hrp를넣고 30분동안실온에서방치하였다. TMB 용액을넣고 15분이경과한후, 1 M H 3PO 4 를넣어반응을종료시켰다. ELISA reader기 (Molecular Devices, Sunnyvale, CA, USA) 를이용하여 450 nm에서흡광도를측정하였으며, 사이토카인의양은표준곡선을적용하여계산되었다 [11,12] 통계처리모든실험결과의통계처리는각실험군의평균 ± 표준편차로나타내었으며, 각군의비교는 p< 0.05 및 0.01 수준에서 one-way ANOVA test를하였고, 군간의평균차이에대한유의성검정은 Dunnett's test를이용하여검증하였다. 3. 결과 3.1. 다층벽탄소나노튜브의길이에따른독성비교 체중변화비교길이가서로다른 4종의다층벽탄소나노튜브를 15일간경 구로투여한후각그룹의체중을측정한결과 (Figure 1), 길이가짧아질수록체중감소가더욱뚜렷하게관찰되었다. 즉, 용매대조군의경우부검일의체중은 38.97±1.83 g인데반해, 240, 394, 3,088, 6,261 nm로처리한그룹의체중은각각 ± 1.13 g, ± 2.02 g, ± 0.80 g, ± 2.01 g로측정되었다 체중당조직무게비교동일한그룹에대해체중에대한조직의무게비를비교한결과 (Figure 2), 240 nm로처리한그룹의흉선무게 ( ± g) 가용매대조군에비해의미있게증가되었고 ( ± g), 240과 6,091 nm로처리한그룹의신장무게가각각 ± g과 ± g으로용매대조군 ( ± g) 에비해감소되었으며, 3,088 nm로처리한그룹의고환무게 ( ± g) 가대조군 ( ± g) 에비해의미있게감소되었다 사이토카인분비량비교다층벽탄소나노튜브길이에따른염증반응정도를비교하기위하여그룹별로혈액내 IL-4, IL-5, IL-10, IL-12, TGFbeta 농도를측정한결과, Figure 3에서보이는바와같이측정한모든사이토카인의농도가모든처리군에서용매대조군에비해의미있게높게검출되었다. 그러나 IL-5, IL-10, TGF-beta의검출농도는모든그룹에서매우낮은수준이었으며, IL-12는길이가길어질수록분비량이증가한반면, IL-4는 3,088 nm로처리한그룹에서가장높게검출되었다 성별에따른다층벽탄소나노튜브의독성비교 Figure 1. A comparison of growth rates with the length of MWCNTs. Mice (5/group) were orally treated to a concentration of 5 mg/kg with MWCNTs of different lengths (240, 394, 3,088, 6,261 nm) for 15 days. Control was replaced by vehicle control. Error of weight between groups on experiment starting day was ±0.5 g. *; P<0.05, **; P<0.01. Figure 2. A comparison of relative organ weight with the length of MWCNTs. Relative weight of each tissue was computed from the formula (tissue weight/body weight). *; P<0.05.

4 276 청정기술, 제 17 권제 3 호, 2011 년 9 월 (a) Figure 3. A comparison of cytokine concentration in blood stream with the length of MWCNTs. Blood was harvested at 24 hours after final treatment and was pooled by group after centrifuge. The measured cytokines were significantly detected in all treated groups relative to vehicle control. **; P<0.01. (b) Figure 5. Change of relative organ weight after MWCNT exposure (female). Relative weight of each organ was computed from the formula (tissue weight/body weight). (a) Female, (b) Male, *; P<0.05. Figure 4. Comparison of body weight according to sex differences after MWCNT exposure. Mice (7/group) were orally treated to concentrations of 1.25, 2.5, 5 mg/kg with MWCNTs (3088 nm) for 15 days. Control was replaced to vehicle control. Error of weight between groups on experiment starting day was ±0.4g. *; P<0.05. g) 에서용매대조군 (37.98 ± 2.28 g) 에비해의미있는감소가관찰되었다. 더나아가, 암컷의경우는 3,088 nm의다층벽탄소나노튜브를 5 mg/kg으로처리한그룹의뇌 ( ± g : ± g), 간 (0.05 ± g : ± g), 폐 ( ± g : ± g), 심장 ( ± g : ± g), 자궁 ( ± g : ± g) 과 2.5 mg/kg으로처리한그룹의간 ( ± g), 심장 ( ± g) 에서용매대조군에비해의미있는상대조직무게비의감소가관찰된반면, 수컷의경우는 5 mg/kg으로처리한그룹의흉선 ( ± g : ± g) 과간 ( ± g : ± g) 에서만의미있는감소가관찰되었다 (Figure 5). 암컷과수컷각각에 3,088 nm의다층벽탄소나노튜브를 15 일간경구로투여한결과, Figure 4에서보는바와같이암컷의체중은용매대조군에비해의미있는변화가관찰되지않은반면, 수컷의경우는 5 mg/kg으로처리한그룹 (36.26 ± 단층벽탄소나노튜브의독성관찰 시간에따른체중변화복합성분 ( 반도체와도체 ) 으로이루어진단층벽탄소나노튜브를경기관지로처리한후 1, 7, 14, 28일에서의체중을

5 서로다른물리화학적특성을갖는탄소나노튜브 (CNT) 의생물학적독성분석 277 않았다. 처리후 28일에서의체중은용매대조군과처리군에서각각 37.8 ± 1.68과 40.1 ± 3.24 g이었다 (Figure 6) 혈액학적변화단층벽탄소나노튜브를처리한후 1, 7, 14, 28일에서의혈액내세포구성을관찰한결과 (Table 1), 처리후 7일에서용매대조군에비해 WBC와 MCV 수가의미있게감소된반면, MCHC 수가의미있게증가되었고, WBC내의호중구비의감소와림프구비의증가또한의미있게관찰되었다. Figure 6. Change of body weight after SWCNT exposure. Mice (15/group) were given a single intratracheal dose of 100 µg/kg. 측정한결과, 대조군에비해처리군에서비교적체중증가가뚜렷한경향을나타내었으나유의성있는변화는관찰되지 체중당조직무게단층벽탄소나노튜브를단회경기관지로처리한후 1, 7, 14, 28일에서의체중당조직무게를뇌, 폐, 흉선, 심장, 신장, 비장에서관찰한결과, 처리후 1일과 7일에서는뇌와폐의상대무게비가처리군에비해의미있게감소되었으나 14일이후로는회복되는경향을나타내었다. 그러나, 신장의무게는처리후 7일부터 28일까지의미있는변화를나타내었다 (Table 2) BAL fluid내총세포수및구성비율단층벽탄소나노튜브를처리한후 1일과 28일에서기관지내세포의총수및구성비를관찰한결과, Table 2에서보는바와같이처리후 1일의처리군에서대조군에비해총세포 Table 1. Hematological changes after SWCNT exposures WBC RBC HGB HCT MCV MCH MCHC PLT RET NEU LYM MON EOS BAS LUC X10 3 ul X10 6 ul g/dl % fl pg g/dl X10 3 ul % % % % % % % DAY Control 2.6± ± ± ± ± ± ± ± ± ± ± ± ± ± ±0.3 1 SWCNT 3.4± ± ± ± ± ± ± ± ± ± ± ± ± ± ±0.2 DAY Control 4.9± ± ± ± ± ± ± ±21 5.6± ± ± ± ± ± ±0.4 7 SWCNT 3.3± ± ± ± ±2.1* 15.6± ±0.7* 1468±83 4.4± ±3.6* 81.2±5.0* 2.0± ± ± ±0.1 DAY Control 4.51± ± ± ± ± ± ± ± ± ± ± ± ± ± ± SWCNT 6.61± ± ± ± ± ± ± ± ± ± ± ± ± ± ±0.3* DAY Control 4.3± ± ± ± ± ± ± ±30 3.1± ± ± ± ± ± ± SWCNT 3.0± ± ± ± ± ± ± ±45 3.4± ± ± ± ± ± ±0.4 *; P<0.05 Table 2. Relative organ weight changes after SWCNT exposures (Unit: g) Brain Lung Thymus Heart Kidney Spleen DAY 1 Control 1.371± ± ± ± ± ±0.044 SWCNT 1.288±0.014* 0.541±0.031* 0.136± ± ± ±0.057 DAY 7 Control 1.357± ± ± ± ± ±0.115 SWCNT 1.247±0.071* 0.580±0.051* 0.100± ± ±0.179* 0.443±0.281 DAY 14 Control 1.257± ± ± ± ± ±0.068 SWCNT 1.185± ± ± ±0.040* 1.484±0.162* 0.361±0.114 DAY 28 Control 1.282± ± ± ± ± ±0.058 SWCNT 1.247± ± ± ± ±0.073* 0.279±0.040 *; P<0.05

6 278 청정기술, 제 17 권제 3 호, 2011 년 9 월 Table 3. Changes in BAL cells after SWCNT exposures DAY 1 DAY 28 *; P<0.05, **; P<0.01 (Unit: X10 6 cells) Total cells (X10 6 ul) Macrophage (%) Neutrophils (%) Lymphocytes (%) Control 0.24± ±0.0 0±0.0 SWCNT 0.75±0.19** 84.7±1.8** 15.3±3.1** 0±0.0 Control 1.26± ±3.4 0±0.00 0±0.00 SWCNT 1.85±0.20** 99.0± ± ±0.2 수는 3.1배, 호중구의비는 15.3배증가되었다. 총세포수의증가는 28일에서뚜렷하게완화되었으나, 호중구와림프구비의증가가여전히관찰되었다. 4. 결론나노물질의독성은원료물질의화학적성분뿐만아니라제조과정에서생성된다양한물리적특성에의해좌우될것으로추정되고있다. 탄소나노튜브또한제조과정에따라표면화학, 길이, 조성, wall number에있어다양한특성을가지며, 길이, 금속함량, 금속의조성, aggregation 또는 agglomeration 정도, 표면화학등은탄소나노튜브의독성을좌우하는중요한요인이될것으로추정되고있다 [4-9]. 예를들면, 산업적으로생산된코팅되지않은다층벽탄소나노튜브 (NT1), acidbased polymer로코팅된다층벽탄소나노튜브 (NT2), polystyrene-based polymer로코팅된다층벽탄소나노튜브 (NT3) 를각각 RAW264.7 세포주와 Balb/c mice에처리한결과, 다층벽탄소나노튜브가유도한독성, 산화적스트레스, 염증은 acidbased polymer코팅에의해증가된반면, polystyrene-based polymer코팅에의해서는감소되었으며, 이때세시료의입경은유사한반면, 표면적은두코팅시료에서훨씬작았다 [10]. 또한, 서로다른크기의다층벽탄소나노튜브와단층벽탄소나노튜브를동일한농도로처리했을때, 단층벽탄소나노튜브는비교적낮은독성을나타낸반면, 길고두꺼운다층벽탄소나노튜브는가장강한 DNA손상을유도하였으며, 짧고두꺼운다층벽탄소나노튜브와는달리길고두꺼운다층벽탄소나노튜브의복강투여는복강액내의총세포수의증가와함께강한염증반응을유도하였다 [11]. 길이에따른독성반응및체내잔존정도를관찰하기위하여 15일동안경구로반복투여된다층벽탄소나노튜브는길이가짧을수록체중증가를감소시킨반면, 길이가길수록보다강한염증반응을유도하였다. 체중및체중당조직무게의변화가시험물질의독성유무를추정하는데중요한지표로활용되는점을감안할때길이가긴다층벽탄소나노튜브에의해염증반응이상대적으로강하게유도된것은길이가길수록엉킴이용이해져대식세포에의한탐식및제거가어려워지기때문일것으로추정된다 [12-14]. 또한, 암컷과수컷에경구로노출된다층벽탄소나노튜브는주로간과심장의무게에영향을주었으며, 이결과를바탕으로우리는간과심장이경구노출된다층벽탄소나노튜브의표적장기일가능성에대해추가연구가필요할것 으로생각된다. 또한, 경기관지로처리된단층벽탄소나노튜브는처리후 1일과 7일에서뇌와폐의의미있는상대무게비감소를유도하였고, 신장의무게는처리후 28일까지대조군과의미있는차이를나타내었다. 혈액내면역세포의변화는처리후 7일에서주로관찰되었으며, BAL fluid에서의변화는처리후 28 일까지지속되었다. 다층벽탄소나노튜브를경기관지로처리한이전의연구에서 [15], 우리는 5, 20, 50 mg/kg의다층벽탄소나노튜브를처리한후 1일에서총세포수가 2내지 3배증가하고, 호중구의비율이약 10 내지 19배증가한다고기록하였다. 또한, 지난실험에서사용된다층벽탄소나노튜브는내입경 (inner diameter) 이 5 nm 이하였고, 외입경 (outer diameter) 은 110~170 nm 이하였으며, 길이는 5~9 µm였던반면, 이연구에서이용된단층벽탄소나노튜브는입경이 1.2 nm이고, 평균길이가 0.76 µm였다 [16]. 추후입경과길이에따른독성반응의비교와함께기관지로유입된단층벽탄소나노튜브가뇌와신장기능에미치는영향에대한추가연구가필요할것으로판단되었다. 감사본연구는 2011년도식품의약품안전청용역연구개발과제의연구개발비지원 (10182 독성평 ) 및한국연구재단의기초연구사업 ( ) 과대학중점연구소지원사업 ( ) 으로수행된연구이며이에감사드립니다. 참고문헌 1. Ji, S. R., Liu, C., Zhang, B., Yang, F., Xu, J., Long, J., Jin, C., Fu, D. L., Ni, Q. X., and Yu, X. J., Carbon Nanotubes in Cancer Diagnosis and Therapy, Biochim. Biophys. Acta, 1806(1), (2010) _1_1_1_37465,00.html 3. Lam, C. W., James, J. T., McCluskey, R., Arepalli, S., and Hunter, R. L., A Review of Carbon Nanotube Toxicity and Assessment of Potential Occupational and Environmental Health Risks, Crit. Rev. Toxicol. Mar., 36(3), (2006). 4. Yoshioka, Y., Nanosafety Studies of Nanomaterials about Biodistribution and Immunotoxicity, Yakugaku Zasshi., 131(2), (2011).

7 서로다른물리화학적특성을갖는탄소나노튜브 (CNT) 의생물학적독성분석 van derzande, M., Junker, R., Walboomers, X. F., and Jansen, J. A., Carbon Nanotubes in Animal Models: A Systematic Review on Toxic Potential, Tissue Eng. Part B Rev., 17(1), (2011). 6. Kayat, j., Gajbhiye, V., Tekade, R. K., and Jain, N. K., Pulmonary Toxicity of Carbon Nanotubes: A Systematic Report, Nanomedicine, 7(1), (2011). 7. Mutlu, G. M., Budinger, G. R., Green, A. A., Urich, D., Soberanes, S., Chiarella, S. E., Alheid, G. F., McCrimmon, D. R., Szleifer, I., and Hersam, M. C., Biocompatible Nanoscale Dispersion of Single-walled Carbon Nanotubes Minimizes in Vivo Pulmonary Toxicity, Nano Lett., 10(5), (2010). 8. Johnston, H. J., Hutchison, G. R., Christensen, F. M., Peters, S., Hankin, S., Aschberger, K., and Stone, V., A Critical Review of the Biological Mechanisms Underlying the in Vivo and in Vitro Toxicity of Carbon Nanotubes: The Contribution of Physico-chemical Characteristics, Nanotoxicology, 4(2), (2010). 9. Kim, M., Choi, K., Kim, Y., and Yi, J., Risk Assessment for Health and Environmental Hazards of Nanomaterials, Clean Technology, 13(3), (2007). 10. Tabet, L., Bussy, C., Setyan, A., Simon-Deckers, A., Rossi, M. J., Boczkowski, J., and Lanone, S., Coating Carbon Nanotubes with a Polystyrene-based Polymer Protects Against Pulmonary Toxicity, Part Fibre Toxicol., 8, 3 (2011). 11. Yamashita, K., Yoshioka, Y., Higashisaka, K., Morishita, Y., Yoshida, T., Fujimura, M., Kayamuro, H., Nabeshi, H., Yamashita, T., Nagano, K., Abe, Y., Kamada, H., Kawai, Y., Mayumi, T., Yoshikawa, T., Itoh, N., Tsunoda, S., and Tsutsumi, Y., Carbon Nanotubes Elicit DNA Damage and Inflammatory Response Relative to Their Size and Shape, Inflammation, 33(4), (2010). 12. Donaldson, K., Murphy, F., Schinwald, A., Duffin, R., and Poland, C.A., Identifying the Pulmonary Hazard of High Aspect Ratio Nanoparticles to Enable Their Safety-by-design, Nanomedicine (Lond)., 6(1), (2011). 13. Donaldson, K., Murphy, F. A., Duffin, R., and Poland, C. A. Asbestos, Carbon Nanotubes and the Pleural Mesothelium: A Review of the Hypothesis Regarding the Role of Long Fibre Retention in the Parietal Pleura, Inflammation and Mesothelioma. Part Fibre Toxicol., 7, 5 (2010). 14. Pacurari, M., Castranova, V., and Vallyathan, V. Single- and Multi-wall Carbon Nanotubes Versus Asbestos: Are the Carbon Nanotubes a New Health Risk to Humans?, J. Toxicol. Environ. Health A, 73(5), (2010). 15. Park, E. J., Cho W. S., Jeong J, Yi, J., Choi, K., and Park, K., Pro-inflammatory and Potential Allergic Responses Resulting from B Cell Activation in Mice Treated with Multi-walled Carbon Nanotubes by Intratracheal Instillation, Toxicology, 259(3), (2009). 16. Park, E. J., Roh, J. Kim, S. N., Kim, Y., Hong, J. T., and Choi, K., A Single Intratracheal Instillation of Single-walled Carbon Nanotubes Induced Early Lung Fibrosis and Subchronic Tissue Damage in Mice, Arch. Toxicol., 85(9), (2011).

025~038-오공약침의

025~038-오공약침의 25 DOI : 10.3831/KPI.2008.11.4.025 A Study on Subchronic Toxicity Test and Method of Increasing Output of Scolopendrid Pharmacopuncture Kim Sung-chul *Dept. of Acupuncture & Moxibustion, Gwang-Ju Oriental