卷烟烟气小动物口鼻暴露方法的建立及评价
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摘要
【背景和目的】国际经济合作与发展组织(OECD)测试导则(TG)对化学物质暴露环境参数和浓度稳定性有明确要求,本文的目的是建立符合其要求的卷烟烟气小动物口鼻暴露方法。【方法】在小动物口鼻暴露系统中测定4种卷烟烟气在不同稀释倍数下颗粒物数量浓度和挥发性有机物浓度,以确定符合OECD要求的卷烟烟气稀释倍数等参数。在该参数条件下,对40小鼠口鼻暴露连续2周,用酶联免疫吸附方法(ELISA)检测小鼠肺灌洗液白细胞介素-10(IL-10)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平变化,以进一步评估方法的稳定性。【结果】(1)4种卷烟主流烟气颗粒物浓度和总挥发性有机物(TVOC)在大于100倍稀释时,时间和空间变异系数均小于10%,符合OECD的要求,低于100倍则变异较大。(2)IL-10变异系数在6.9%～8.6%之间,TNF-α变异系数在13.4%～17.6%;IL-6变异系数在16.8%～23.2%之间。【结论】所建立的卷烟烟气口鼻暴露方法符合OECD导则要求,生物学效应指标检测结果可靠稳定。
A novel cigarette smoke nose-only exposure method for small animal was established and evaluated. Particle number concentration, particle size distribution and total volatile organic compound concentration of four mainstream cigarette smoke aerosols under different dilution ratios were measured in nose-only exposure system. Forty mice were exposed for 14 consecutive days under such parameters condition. Bronchoalveolar lavage ?uid(BALF) were collected to determine levels of in?ammatory markers, such as IL-10,IL-6 and TNF-α. Results show that temporal and spatial coef?cient of variation for particle number concentration and total volatile organic compounds for mainstream cigarette smoke aerosol diluted more than 100 times were less than 10%. The coef?cient of variation for IL-10 in BALF were in the range of 6.9-8.6%, 13.4-17.6% for TNF-αand 16.8-23.3% for IL-6. These experimental results demonstrated that the proposed nose-only cigarette smoke exposure method met well with the OECD test guidelines, and may provide reliable and stable results for experiment.
A novel cigarette smoke nose-only exposure method for small animal was established and evaluated. Particle number concentration, particle size distribution and total volatile organic compound concentration of four mainstream cigarette smoke aerosols under different dilution ratios were measured in nose-only exposure system. Forty mice were exposed for 14 consecutive days under such parameters condition. Bronchoalveolar lavage ?uid(BALF) were collected to determine levels of in?ammatory markers, such as IL-10,IL-6 and TNF-α. Results show that temporal and spatial coef?cient of variation for particle number concentration and total volatile organic compounds for mainstream cigarette smoke aerosol diluted more than 100 times were less than 10%. The coef?cient of variation for IL-10 in BALF were in the range of 6.9-8.6%, 13.4-17.6% for TNF-αand 16.8-23.3% for IL-6. These experimental results demonstrated that the proposed nose-only cigarette smoke exposure method met well with the OECD test guidelines, and may provide reliable and stable results for experiment.
引文
[1]OECD,2009,Guidance Document on Acute Inhalation Toxicity Testing.Environmental Health and Safety Monograph Series on Testing and Assessment No.39,OECD,Paris.
[2]Harris A C,Mattson C,Lesage M G,et al.Comparison of the behavioral effects of cigarette smoke and pure nicotine in rats[J].Pharmacology Biochemistry and Behavior,2010,96(2):217-227.
[3]Phelps D W,Veal J T,Filipy R E,et al.Tobacco Smoke Inhalation Studies:A Dosimetric Comparison of Different Cigarette Types[J].Archives of Environmental Health:An International Journal,1984,39(5):359-363.
[4]US EPA National Center for Environmental Assessment.Methods for Derivation of Inhalation Reference Concentrations and Application of Inhalation Dosimetry[R].1994.
[5]Roger O McClellan,Rogene F Henderson.Concepts in Inhalation Toxicology[M].Second Edition.Baca Raton,CRC Press,1995.
[6]OECD,2017,Test No.412:Subacute Inhalation Toxicity:28-Day Study,OECD Guidelines for the Testing of Chemicals.
[7]OECD,2017,Test No.413:Subchronic Inhalation Toxicity:90-Day Study,OECD Guidelines for the Testing of Chemical[R].
[8]LI Xiang,KONG Haohui,ZHANG Xinying.Characterization of particle size distribution of mainstream cigarette smoke generated by smoking machine with an electrical low pressure impactor[J].Journal of Environmental Science,2014,26:827-833.
[9]Aldermana SL,Ingebrethsen BJ.Characterization of mainstream cigarette smoke particle size distributions from commercial cigarettes using a DMS500 fast particulate spectrometer and smoking cycle simulator[J].Aerosol Sci Technol,2011,45:1409-1421.
[10]段沅杏,赵伟,杨继.传统卷烟和电子烟烟气气溶胶粒径分布研究[J].中国烟草学报,2015,21(1):1-5.DUAN Yuanxing,ZHAO Wei,YANG Ji,et al.Research on particle size distribution in traditional cigarette and electronic cigarette smoke aerosols[J].Acta Tabacaria Sinica,2015.21(1):1-5.
[11]Dijk W D V,Gopal S,Scheepers P T J.Nanoparticles in cigarette smoke;Real-time undiluted measurements by a scanning mobility particle sizer[J].Analytical and Bioanalytical Chemistry,2011,399(10):3573-3578.
[12]Ingebrethsen B J,Cole S K,Alderman S L.Electronic cigarette aerosol particle size distribution measurements[J].Inhalation Toxicology,2012,24(14):976-984.
[13]Parmod Kulkarni,Paul A Baron.Aerosol Measurement:Principle,Technique,and Applications[M].Third Edition.New Jersey,Wiley,2011,Chapter 1:3-10.
[14]Ryan J Potts,Daniel R Meckley,W Keith Shreve.Comparative13-Week Inhalation Study of Cigarette Smoke from Cigarettes Containing Cast Sheet Tobacco[J].Inhalation Toxicology,2007,19:701-724.
[15]Pauluhn J.Validation of an Improved Nose-only Exposure System for Rodents[J].Journal of Applied Toxicology,1994,14:55-62.
[16]周宗灿.毒理学教程[M].北京:北京大学医学出版社,2006:778-779.
[17]Omar F Khabour,Karenm H Alzoubi,Mohammed Bani-Ahmad,et al.Acute exposure to waterpipe tobacco smoke induces changes in the oxidative and inflammatory markers in mouse lung[J].Inhal Toxicol,2012,24(10):667-675.
[18]Churg A,Dai J,Tai H.Tumor necrosis factor-αis central to acute cigarette smokeinduced inflammation and connective tissue breakdown[J].Am J Respir Crit Care Med,2002,166:849-854.
[19]Churg A,Wang RD,Tai H.Macrophage metalloelastase mediates acute cigarette smoke-induced inflammation via tumor necrosis factor-αrelease[J].Am J Respir Crit Care Med,2003,167:1083-1089.
[20]Sato A,Hoshino Y,Hara T.Thioredoxin-1 ameliorates cigarette smoke-induced lung inflammation and emphysema in mice[J].JPharmacol Exp Ther,2008,325:380-388.
[21]赵俊伟,杨陟华,李翔,等.基于两种细胞的卷烟烟气体外免疫毒性评价[J].烟草科技,2016,49(8):51-56.ZHAO Junwei,YANG Zhihua,LI Xiang,et al.Evaluation of in vitro immunotoxicity of mainstream cigarette smoke by using two kinds of cells[J].Tobacco Science&Technology,2016,49(8):51-56.
[22]Klein L,Khazaie K,von Boechmer H.In vivo dynamics of antigenspecific regulatory T cell not predicted from behavior in vitro[J].Pro Natl Acad Sci USA,2003,100(15):8886-91.Sun L,Louie M C,Vannella K M,et al.New concepts IL-10induced lung fibrosis:firbrocyte recruitment and M2 activation in a CCL2/CCR2 axis[J].Am J Physiol Lung Cell Mol Physiol,2011,300(3):L341-53.
[2]Harris A C,Mattson C,Lesage M G,et al.Comparison of the behavioral effects of cigarette smoke and pure nicotine in rats[J].Pharmacology Biochemistry and Behavior,2010,96(2):217-227.
[3]Phelps D W,Veal J T,Filipy R E,et al.Tobacco Smoke Inhalation Studies:A Dosimetric Comparison of Different Cigarette Types[J].Archives of Environmental Health:An International Journal,1984,39(5):359-363.
[4]US EPA National Center for Environmental Assessment.Methods for Derivation of Inhalation Reference Concentrations and Application of Inhalation Dosimetry[R].1994.
[5]Roger O McClellan,Rogene F Henderson.Concepts in Inhalation Toxicology[M].Second Edition.Baca Raton,CRC Press,1995.
[6]OECD,2017,Test No.412:Subacute Inhalation Toxicity:28-Day Study,OECD Guidelines for the Testing of Chemicals.
[7]OECD,2017,Test No.413:Subchronic Inhalation Toxicity:90-Day Study,OECD Guidelines for the Testing of Chemical[R].
[8]LI Xiang,KONG Haohui,ZHANG Xinying.Characterization of particle size distribution of mainstream cigarette smoke generated by smoking machine with an electrical low pressure impactor[J].Journal of Environmental Science,2014,26:827-833.
[9]Aldermana SL,Ingebrethsen BJ.Characterization of mainstream cigarette smoke particle size distributions from commercial cigarettes using a DMS500 fast particulate spectrometer and smoking cycle simulator[J].Aerosol Sci Technol,2011,45:1409-1421.
[10]段沅杏,赵伟,杨继.传统卷烟和电子烟烟气气溶胶粒径分布研究[J].中国烟草学报,2015,21(1):1-5.DUAN Yuanxing,ZHAO Wei,YANG Ji,et al.Research on particle size distribution in traditional cigarette and electronic cigarette smoke aerosols[J].Acta Tabacaria Sinica,2015.21(1):1-5.
[11]Dijk W D V,Gopal S,Scheepers P T J.Nanoparticles in cigarette smoke;Real-time undiluted measurements by a scanning mobility particle sizer[J].Analytical and Bioanalytical Chemistry,2011,399(10):3573-3578.
[12]Ingebrethsen B J,Cole S K,Alderman S L.Electronic cigarette aerosol particle size distribution measurements[J].Inhalation Toxicology,2012,24(14):976-984.
[13]Parmod Kulkarni,Paul A Baron.Aerosol Measurement:Principle,Technique,and Applications[M].Third Edition.New Jersey,Wiley,2011,Chapter 1:3-10.
[14]Ryan J Potts,Daniel R Meckley,W Keith Shreve.Comparative13-Week Inhalation Study of Cigarette Smoke from Cigarettes Containing Cast Sheet Tobacco[J].Inhalation Toxicology,2007,19:701-724.
[15]Pauluhn J.Validation of an Improved Nose-only Exposure System for Rodents[J].Journal of Applied Toxicology,1994,14:55-62.
[16]周宗灿.毒理学教程[M].北京:北京大学医学出版社,2006:778-779.
[17]Omar F Khabour,Karenm H Alzoubi,Mohammed Bani-Ahmad,et al.Acute exposure to waterpipe tobacco smoke induces changes in the oxidative and inflammatory markers in mouse lung[J].Inhal Toxicol,2012,24(10):667-675.
[18]Churg A,Dai J,Tai H.Tumor necrosis factor-αis central to acute cigarette smokeinduced inflammation and connective tissue breakdown[J].Am J Respir Crit Care Med,2002,166:849-854.
[19]Churg A,Wang RD,Tai H.Macrophage metalloelastase mediates acute cigarette smoke-induced inflammation via tumor necrosis factor-αrelease[J].Am J Respir Crit Care Med,2003,167:1083-1089.
[20]Sato A,Hoshino Y,Hara T.Thioredoxin-1 ameliorates cigarette smoke-induced lung inflammation and emphysema in mice[J].JPharmacol Exp Ther,2008,325:380-388.
[21]赵俊伟,杨陟华,李翔,等.基于两种细胞的卷烟烟气体外免疫毒性评价[J].烟草科技,2016,49(8):51-56.ZHAO Junwei,YANG Zhihua,LI Xiang,et al.Evaluation of in vitro immunotoxicity of mainstream cigarette smoke by using two kinds of cells[J].Tobacco Science&Technology,2016,49(8):51-56.
[22]Klein L,Khazaie K,von Boechmer H.In vivo dynamics of antigenspecific regulatory T cell not predicted from behavior in vitro[J].Pro Natl Acad Sci USA,2003,100(15):8886-91.Sun L,Louie M C,Vannella K M,et al.New concepts IL-10induced lung fibrosis:firbrocyte recruitment and M2 activation in a CCL2/CCR2 axis[J].Am J Physiol Lung Cell Mol Physiol,2011,300(3):L341-53.
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