(3.238.186.43) 您好!臺灣時間:2021/02/28 12:34
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:何采築
研究生(外文):Tsai-Chu Ho
論文名稱:以超高效液相層析搭配飛行時間串聯式質譜儀篩查人體血清中之環境汙染物
論文名稱(外文):Suspect Screening of Environmental Pollutants in Human Serum Using UHPLC-QTOF MS
指導教授:陳家揚陳家揚引用關係
指導教授(外文):Chia-Yang Chen
口試委員:呂廷璋郭錦樺陳保中
口試日期:2019-07-30
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:環境衛生研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:2019
畢業學年度:107
語文別:中文
論文頁數:131
中文關鍵詞:化學品高解析質譜儀生物偵測血清篩查圖譜資料庫優先化
DOI:10.6342/NTU201903040
相關次數:
  • 被引用被引用:0
  • 點閱點閱:61
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
隨著工業的發展及為了因應日常生活所需,近年來我們所使用的化學品種類日益增加,人體可能會藉由不同途徑暴露到這些化學品,進而產生不良的健康效應。然而,以常規的定量監測能獲取的資料數量相當有限,對於未在管制內的化學品更是無從得知其暴露情形。透過生物偵測的方式檢測人體檢體,可以釐清我們常見的暴露,藉此可作為未來化學品檢測及健康風險評估的優先項目。本研究利用超高效液相層析搭配飛行時間串聯式質譜儀(UHPLC-QTOF MS)分析新竹地區446個自2016年開始到2018年期間進行社區檢查之成人及孩童血清 (IRB編號:104-025-E及104-007-F),後端比對資料庫鑑定化學品種類,並連結問卷蒐集的樣本資訊進行統計分析,以找出常見的化學品暴露及了解是否暴露情形與特定族群、生活或飲食習慣相關聯,最後針對篩查出之化學品,以樣本中的篩查頻率、暴露情形及生物可利用性等資訊做為排序的條件依據,建置優先化學品清單。
資料庫的比對中,共計篩查出326種化合物。其中有60%為醫療用藥,而多數的化合物其在樣本中的陽性篩查頻率(detection frequency)皆低於10%,僅有3個化合物其陽性篩查頻率大於90%,分別為人體必需胺基酸 (Phenylalanine)、治療癲癇藥物(Ethotoin)及食品添加物 (Piperine)。近年來高度關注的鄰苯二甲酸酯類(DEHP 和DBP)及全氟烷基化合物(PFOA和PFOS)其陽性篩查頻率僅接近30%。在統計分析的結果中,我們發現篩查到的化學品數量在成人及青少年、居住地(新竹縣和新竹市)和家庭年收入高低之間呈現顯著差異。另外,成人男性相較於女性有較高的風險暴露到DBP、PFOS和PFOA,而隨著攝取高油脂食物及貝類的頻率增高亦會增加DBP和PFOS的暴露風險。在優先化的排序結果中,排名前五分別為4-tert-Octylphenol、Caffeine、Piperine、trans-Calcifediol和Phenylalanine。透過敏感度分析,呈現出排序的結果以篩查頻率為主要貢獻因子(60%),儘管篩查頻率可以真實反映出常見的暴露,但也因此稀釋了其他因子對於排序結果的重要性。
綜合以上,我們以高解析質譜儀來進行生物偵測,找出人體常見的暴露化學品,並結合問卷分析以釐清暴露特徵及相關的風險因子,最後進行化學品的優先化排序。此排序結果能提供台灣未來進行定量方法開發、制定常規檢測項目及健康風險評估的參考清單。
The number of emerging contaminants is increasing annually, and humans may be constantly exposed to these chemicals through diet, using consumer products, or contacting with environmental matrices. However, only the exposure information on a few chemicals are available from common targeted analysis. It is important to clarify highly exposed chemicals through biomonitoring.
In this study, ultra-high performance liquid chromatography coupled with quadrupole-TOF MS (UHPLC-QTOF MS) was used to analyze 446 human serum samples from Hsinchu area and acquired data at All Ions MS/MS mode (AIM) with both positive and negative ESI modes. We used libraries of tandem MS spectra to achieve chemicals identification. The identified chemicals were also compared with demographic data to explore the differences and associations among variables. Finally, we prioritized chemicals through the chemical detection frequencies, peak abundance, bioactivity data, and exposure information and provided a prioritized chemicals list in Taiwan.
A total of 326 chemicals were found and most of them were in low detection frequency (DF). The common detected ones (DF > 90%) were Phenylalanine (amino acid), Ethotoin (an anticonvulsant drug), and Piperine (food additives). In addition, the detection frequencies of PAEs (DBP and DEHP) and PFASs (PFOA and PFOS), which were highly concerned in recent years, were near to 30%. We also found that the number of detected chemicals was significantly different among groups (adults and adolescents), living area (city and county), and annual household income. Comparing with females, males had a higher risk of exposure to DBP, PFOA, and PFOS. The risk of exposure to DBP and PFOS was associated with high fatty food and shellfish consumption frequencies. Finally, the priorities in our identified chemicals were 4-tert-Octylphenol, caffeine, piperine, trans-Calcifediol, and Phenylalanine. Sensitivity analysis showed that the detection frequency was the major contribution (60%) to the ranking results. It might diminish the influences of other parameters (e.g., bioactivity and exposure information), although detection frequency was a good indicator to reflect the common exposure.
Overall, we used high-resolution mass spectrometry (HRMS) to conduct biomonitoring for identifying which were the mostly exposure to, and also connected to the demographic information to demonstrate the risk factor of exposure. This study provided a list of prioritized chemicals for further quantitative analysis and exposure assessment in Taiwan.
口試委員會審定書 #
誌謝 i
中文摘要 iii
ABSTRACT v
CONTENTS i
LIST OF FIGURES iv
LIST OF TABLES v
Chapter 1 Introduction 1
1.1 Introduction 1
1.2 High-resolution mass spectrometry (HRMS) and non-targeted analysis 1
1.3 Biomonitoring 3
1.4 Chemicals prioritization 5
1.5 Objectives 7
Chapter 2 Material and Methods 9
2.1 Reagents and materials 9
2.2 Sample collection 9
2.3 Sample preparation 10
2.4 UHPLC-QTOF MS Instrumental analysis 11
2.4.1 Chromatographic conditions 11
2.4.2 Mass spectrometry 12
2.4.3 Suspect screening data processing 13
2.5 Statistical analysis 15
2.5.1 Questionnaire variables transformation 15
2.5.2 Statistical analysis method 16
2.6 Chemical prioritization criteria 17
2.6.1 ToxPi framework 17
2.6.2 Prioritization criteria 17
2.6.3 Bioactivity and exposure information 18
2.6.4 Peak abundance calibration and transformation 19
2.7 Quality assurance and quality control (QA/QC) 20
2.7.1 Quality assurance 20
2.7.2 Quality control 20
Chapter 3 Results and Discussion 23
3.1 Quality assurance and quality control 23
3.2 General characteristics of participants 24
3.3 Detection frequencies of suspect chemicals 24
3.4 Statistical analysis and the participant''s characteristics 26
3.4.1 General characteristics and habits of the participants according to detected chemicals number 26
3.4.2 Associations between the participants'' characteristics and specific detected chemicals 28
3.5 Prioritization 29
3.5.1 Overview of prioritized results 30
3.5.2 Prioritizations in other studies 31
3.5.3 The prioritized chemicals in this study 33
3.6 Limitation 39
Chapter 4 Conclusions 41
References 43
Figures 52
Tables 62
Attachment(Ⅰ): The Questionnaire for Adults 86
Attachment(Ⅱ): The Questionnaire for Adolescents 102
1.Petrovic, M., Farré, Marinella, de Alda, Miren Lopez, Perez, Sandra, Postigo, Cristina, Köck, Marianne, Radjenovic, Jelena, Gros, Merixell, Barcelo, Damia, Recent trends in the liquid chromatography–mass spectrometry analysis of organic contaminants in environmental samples. Journal of Chromatography A, 2010. 1217(25): p. 4004-4017.
2.Andra, S.S.A., C. Patel, D. Dolios, G. Awawda, M. Arora, M., Trends in the application of high-resolution mass spectrometry for human biomonitoring: An analytical primer to studying the environmental chemical space of the human exposome. Environment International, 2017. 100: p. 32-61.
3.Acena, J.S., S. Perez, S. Barcelo, D., Advances in liquid chromatography-high-resolution mass spectrometry for quantitative and qualitative environmental analysis. Analytical and Bioanalytical Chemistry, 2015. 407(21): p. 6289-6299.
4.Hernández, F., Ibáñez, M., Bade, R., Bijlsma, L., Sancho, J. V., Investigation of pharmaceuticals and illicit drugs in waters by liquid chromatography-high-resolution mass spectrometry. Trends in Analytical Chemistry, 2014. 63: p. 140-157.
5.Plumb, R., Castro-Perez, Jose, Granger, Jennifer, Beattie, Iain, Joncour, Karine, Wright, Andrew, Ultra-performance liquid chromatography coupled to quadrupole-orthogonal time-of-flight mass spectrometry. Rapid Communications in Mass Spectrometry, 2004. 18(19): p. 2331-2337.
6.Denoroy, L., Zimmer, Luc, Renaud, Bernard, Parrot, Sandrine, Ultra high performance liquid chromatography as a tool for the discovery and the analysis of biomarkers of diseases: A review. Journal of Chromatography B, 2013. 927: p. 37-53.
7.Krauss, M., Singer, Heinz, Hollender, Juliane, LC–high resolution MS in environmental analysis: from target screening to the identification of unknowns. Analytical and Bioanalytical Chemistry, 2010. 397(3): p. 943-951.
8.Phillips, K.A., Yau, A., Favela, K. A., Isaacs, K. K., McEachran, A., Grulke, C., Richard, A. M., Williams, A. J., Sobus, J. R., Thomas, R. S., Wambaugh, J. F., Suspect Screening Analysis of Chemicals in Consumer Products. Environmental Science & Technology, 2018. 52(5): p. 3125-3135.
9.Colby, J.M.T., K. L. Lynch, K. L., Suspect Screening Using LC-QqTOF Is a Useful Tool for Detecting Drugs in Biological Samples. Journal of Analytical Toxicology, 2018. 42(4): p. 207-213.
10.Leendert, V.V.L., Herman Demeestere, Kristof, Trends in liquid chromatography coupled to high-resolution mass spectrometry for multi-residue analysis of organic micropollutants in aquatic environments. Trends in Analytical Chemistry, 2015. 67: p. 192-208.
11.Bade, R., Rousis, Nikolaos I., Bijlsma, Lubertus, Gracia-Lor, Emma, Castiglioni, Sara, Sancho, Juan V., Hernandez, Felix, Screening of pharmaceuticals and illicit drugs in wastewater and surface waters of Spain and Italy by high resolution mass spectrometry using UHPLC-QTOF MS and LC-LTQ-Orbitrap MS. Analytical and Bioanalytical Chemistry, 2015. 407(30): p. 8979-8988.
12.Xiao, J.F., Zhou, Bin, Ressom, Habtom W., Metabolite identification and quantitation in LC-MS/MS-based metabolomics. Trends in Analytical Chemistry, 2012. 32: p. 1-14.
13.Rappaport, S.M., Implications of the exposome for exposure science. Journal Of Exposure Science And Environmental Epidemiology, 2010. 21: p. 5.
14.Miller, G.W., Jones, Dean P., The Nature of Nurture: Refining the Definition of the Exposome. Toxicological Sciences, 2013. 137(1): p. 1-2.
15.Kristine K. Dennis, E.M., David M. Balshaw, Yuxia Cui, Michael A. Lynes, Gary J. Patti, Stephen M. Rappaport, Daniel T. Shaughnessy, Martine Vrijheid, Dana Boyd Barr, Biomonitoring in the Era of the Exposome. Environmental Health Perspectives, 2017. 125(4): p. 502-510.
16.Dennis, K.K., Marder, Elizabeth, Balshaw, David M., Cui, Yuxia, Lynes, Michael A., Patti, Gary J., Rappaport, Stephen M., Shaughnessy, Daniel T., Vrijheid, Martine, Barr, Dana Boyd, Biomonitoring in the Era of the Exposome. Environmental health perspectives, 2017. 125(4): p. 502-510.
17.Centers for Disease Control and Prevention (CDC)., Overview National Health and Nutrition Examination Survey. 2017.
18.Bundesmt, U. German Environmental Survey. 2014-2017; Available from: https://www.umweltbundesamt.de/en/topics/health/assessing-environmentally-related-health-risks/german-environmental-survey-geres.
19.Ministry of the Environment Government of Japan. Japan Environment and Children''s Study (JECS). 2011; Available from: http://www.env.go.jp/chemi/ceh/en/.
20.Government of Canada. The Canadian Health Measures Survey. 2017; Available from: https://www.canada.ca/en/health-canada/services/environmental-workplace-health/environmental-contaminants/human-biomonitoring-environmental-chemicals/canadian-health-measures-survey.html.
21.Ha, M., Kwon, H. J., Leem, J. H., Kim, H. C., Lee, K. J., Park, I., Lim, Y. W., Lee, J. H., Kim, Y., Seo, J. H., Hong, S. J., Choi, Y. H., Yu, J., Kim, J.Yu, S. D., Lee, B. E., Korean Environmental Health Survey in Children and Adolescents (KorEHS-C): survey design and pilot study results on selected exposure biomarkers. International Journal of Hygiene and Environmental Health, 2014. 217(2-3): p. 260-270.
22.Flemish Center of Expertise on Environment and Health. 2019; Available from: http://www.milieu-en-gezondheid.be/en/about-the-center-0.
23.Thomsen, M., Knudsen, Lisbeth E., Vorkamp, Katrin, Frederiksen, Marie, Bach, Hanne, Bonefeld-Jorgensen, Eva Cecilie, Rastogi, Suresch, Fauser, Patrik, Krongaard, Teddy, Sorensen, Peter Borgen, Conceptual framework for a Danish human biomonitoring program. Environmental health : a global access science source, 2008. 7 Suppl 1(Suppl 1): p. S3-S3.
24.Deeb, A.A.S., S. Schmitz, O. J. Schmidt, T. C., Suspect screening of micropollutants and their transformation products in advanced wastewater treatment. Science of the Total Environment, 2017. 601-602: p. 1247-1253.
25.Gago-Ferrero, P., Krettek, A., Fischer, S., Wiberg, K., Ahrens, L., Suspect Screening and Regulatory Databases: A Powerful Combination To Identify Emerging Micropollutants. Environmental Science and Technology, 2018. 52(12): p. 6881-6894.
26.Wang, A., Gerona, R. R., Schwartz, J. M., Lin, T., Sirota, M., Morello-Frosch, R., Woodruff, T. J., A Suspect Screening Method for Characterizing Multiple Chemical Exposures among a Demographically Diverse Population of Pregnant Women in San Francisco. Environmental Health Perspectives, 2018. 126(7): p. 077009.
27.Gerona, R.R.S., J. M. Pan, J. Friesen, M. M. Lin, T. Woodruff, T. J., Suspect screening of maternal serum to identify new environmental chemical biomonitoring targets using liquid chromatography-quadrupole time-of-flight mass spectrometry. Journal of Exposure Science and Environmental Epidemology, 2018. 28(2): p. 101-108.
28.Government of Canada. The identification of risk assessment priorities. 2017; Available from: https://www.canada.ca/en/health-canada/services/chemical-substances/fact-sheets/identification-risk-assessment-priorities.html.
29.Government of Canada. Chemicals Management Plan. 2016; Available from: https://www.canada.ca/en/health-canada/services/chemical-substances/chemicals-management-plan.html.
30.Van Asselt, E.D., Noordam, M. Y., Pikkemaat, M. G., Dorgelo, F. O., Risk-based monitoring of chemical substances in food: Prioritization by decision trees. Food Control, 2018. 93: p. 112-120.
31.European Commission and European Environmental Agency. About HBM4EU project. 2017; Available from: https://www.hbm4eu.eu/about-hbm4eu/.
32.European Commission. REACH. 2019; Available from: https://ec.europa.eu/growth/sectors/chemicals/reach_en.
33.Chou, W.-C., Tsai, Wei-Ren, Chang, Hsiu-Hui, Lu, Shui-Yuan, Lin, King-Fu, Lin, Pinpin, Prioritization of pesticides in crops with a semi-quantitative risk ranking method for Taiwan postmarket monitoring program. Journal of Food and Drug Analysis, 2019. 27(1): p. 347-354.
34.Birgit Geueke, P.A.I., Maricel Maffini, Thomas Backhaus, Bethani Carney-Almroth, Ksenia J. Groh, Jane Muncke, Prioritization approaches for hazardous chemicals associated with plastic packaging 2018: Zenodo. http://doi.org/10.5281/zenodo.1436442.
35.Liu, Y.-C., Determination of Perfluoroalkyl Substances, Feminizing Compounds and Mycotoxins in Serum Using Ultra-performance Liquid Chromatography/tandem Mass Spectrometry, in Institute of Environmental Health College of Public Health. 2016, National Taiwan University. p. 1-77.
36.Liu, S.-H., Determination of phthalate metabolites, bisphenol A glucuronide, 1-hydroxypyrene glucuronide, perfluorinated chemicals and leukotriene E4 in urine, in Institute of Environmental Health College of Public Health. 2012, National Taiwan University. p. 1-62.
37.European Chemicals Agency (ECHA)., Candidate List of Substances of Very High Concern for Authorisation. 2015.
38.European Chemicals Agency (ECHA)., Substances restricted under REACH. 2015.
39.U.S. EPA., Endocrine Disruptor Screening Program Tier 1 Assessments. 2015.
40.Ministry of the Environment Government of Japan. Endocrine Disrupting Effects of Substances. 2010; Available from: http://www.env.go.jp/en/chemi/ed.html.
41.行政院環境保護署. 公告毒性化學物質及其管制濃度與大量運作基準一覽表. 2014; Available from: https://flora2.epa.gov.tw/ToxicC/Query/database.aspx.
42.行政院農業委員會動植物防疫檢疫局, 限用農藥. 2015. Bureau of Animal and Health Plant Health Inspection and Quarantine, Council of Agriculture, The restricted agro-pesticides
43.行政院農業委員會動植物防疫檢疫局, 禁用農藥. 2015. Bureau of Animal and Health Plant Health Inspection and Quarantine, Council of Agriculture, The prohibited agro-pesticides
44.農業藥物毒物試驗所, 劇毒性成品農藥名稱. 2013. Bureau of Animal and Health Plant Health Inspection and Quarantine, Council of Agriculture, The prohibited agro-pesticides The highly toxic formulated agro-pesticides
45.Centers for Disease Control and Prevention (CDC). Adult Overweight and Obesity. 2017; Available from: https://www.cdc.gov/obesity/adult/defining.html.
46.World Health Organization (WHO). Body mass index (BMI). Available from: http://www.euro.who.int/en/health-topics/disease-prevention/nutrition/a-healthy-lifestyle/body-mass-index-bmi.
47.衛生福利部國民健康署,每日飲食指南手冊.2018 Health Promotion Administration, Ministry of Health and Welfare, Daily food guide. 2018.
48.衛生福利部國民健康署, 食物代換表. 2019. Health Promotion Administration, Ministry of Health and Welfare, Meal exchange list. 2019
49.Reif, D.M., Martin, M. T., Tan, S. W., Houck, K. A., Judson, R. S., Richard, A. M., Knudsen, T. B., Dix, D. J., Kavlock, R. J., Endocrine profiling and prioritization of environmental chemicals using ToxCast data. Environmental Health Perspectives, 2010. 118(12): p. 1714-1720.
50.Marvel, S.W., To, K., Grimm, F. A., Wright, F. A., Rusyn, I., Reif, D. M., ToxPi Graphical User Interface 2.0: Dynamic exploration, visualization, and sharing of integrated data models. BMC Bioinformatics, 2018. 19(1): p. 80.
51.Reif, D.M., Sypa, M., Lock, E. F., Wright, F. A., Wilson, A., Cathey, T., Judson, R. R., Rusyn, I., ToxPi GUI: an interactive visualization tool for transparent integration of data from diverse sources of evidence. Bioinformatics, 2013. 29(3): p. 402-403.
52.Newton, S.R., McMahen, R. L., Sobus, J. R., Mansouri, K., Williams, A. J., McEachran, A. D., Strynar, M. J., Suspect screening and non-targeted analysis of drinking water using point-of-use filters. Environment Pollutant, 2018. 234: p. 297-306.
53.Rager, J.E., Strynar, M. J., Liang, S., McMahen, R. L. ,. Richard, A. M., Grulke, C. M., Wambaugh, J. F., Isaacs, K. K., Judson, R., Williams, A. J., Sobus, J. R., Linking high resolution mass spectrometry data with exposure and toxicity forecasts to advance high-throughput environmental monitoring. Environmental international, 2016. 88: p. 269-280.
54.McEachran, A.D., Sobus, J. R.,Williams, A. J., Identifying known unknowns using the US EPA''s CompTox Chemistry Dashboard. Analytical and Bioanalytical Chemistry, 2017. 409(7): p. 1729-1735.
55.U.S. EPA. The CompTox Chemistry Dashboard. 2018; Available from: https://comptox.epa.gov/dashboard.
56.Williams, A.J., Grulke, Christopher M., Edwards, Jeff, McEachran, Andrew D., Mansouri, Kamel, Baker, Nancy C., Patlewicz, Grace, Shah, Imran, Wambaugh, John F., Judson, Richard S., Richard, Ann M., The CompTox Chemistry Dashboard: a community data resource for environmental chemistry. Journal of Cheminformatics, 2017. 9(1): p. 61.
57.Rappaport, S.M., Smith, Martyn T., Environment and Disease Risks. Science, 2010. 330(6003): p. 460-461.
58.U.S. EPA. ToxCast & Tox21 Summary Files from invitrodb_v3. 2018; Available from: https://epa.figshare.com/articles/ToxCast_Database_invitroDB_/6062623/2.
59.Wambaugh, J.F., Setzer, R. Woodrow, Reif, David M., Gangwal, Sumit, Mitchell-Blackwood, Jade, Arnot, Jon A., Joliet, Olivier, Frame, Alicia, Rabinowitz, James, Knudsen, Thomas B., Judson, Richard S., Egeghy, Peter, Vallero, Daniel, Cohen Hubal, Elaine A., High-Throughput Models for Exposure-Based Chemical Prioritization in the ExpoCast Project. Environmental Science & Technology, 2013. 47(15): p. 8479-8488.
60.Wambaugh, J.F., Wang, Anran, Dionisio, Kathie L, Frame, Alicia, Egeghy, Peter, Judson, Richard, Setzer, R. Woodrow, High Throughput Heuristics for Prioritizing Human Exposure to Environmental Chemicals. Environmental Science & Technology, 2014. 48(21): p. 12760-12767.
61.U.S. Food and Drug Adminstration., FDA Proffessional Drug information: Allopurinol. 2019.
62.International Labour Organization., Encyclopedia of Occupational Health and Safety. 2011.
63.Joanna Burger, M.G., Conceptual Environmental Justice Model for Evaluating Chemical Pathways of Exposure in Low-Income, Minority, Native American, and Other Unique Exposure Populations. American Journal of Public Health, 2011. 101(S1): p. S64-S73.
64.Ruiz, D., Becerra, Marisol, Jagai, Jyotsna S., Ard, Kerry, Sargis, Robert M., Disparities in Environmental Exposures to Endocrine-Disrupting Chemicals and Diabetes Risk in Vulnerable Populations. Diabetes Care, 2017: p. dc162765.
65.Arbuckle, T.E., Davis, Karelyn, Marro, Leonora, Fisher, Mandy, Legrand, Melissa, LeBlanc, Alain, Gaudreau, Eric, Foster, Warren G., Choeurng, Voleak, Fraser, William D., Phthalate and bisphenol A exposure among pregnant women in Canada — Results from the MIREC study. Environment International, 2014. 68: p. 55-65.
66.Hsu, J.-Y., Hsu, Jing-Fang, Ho, Hsin-Hui, Chiang, Chow-Feng, Liao, Pao-Chi, Background levels of Persistent Organic Pollutants in humans from Taiwan: Perfluorooctane sulfonate and perfluorooctanoic acid. Chemosphere, 2013. 93(3): p. 532-537.
67.Vu, C.T., Lin, Chitsan, Liao, Chien Sen, Chen, Jenq-Renn, Occurrence of phthalate esters around the major plastic industrial area in southern Taiwan. Environmental Earth Sciences, 2018. 77(12): p. 457.
68.Chen, W.-L., Bai, Fang-Yu, Chang, Ying-Chia, Chen, Pau-Chung, Chen, Chia-Yang, Concentrations of perfluoroalkyl substances in foods and the dietary exposure among Taiwan general population and pregnant women. Journal of Food and Drug Analysis, 2018. 26(3): p. 994-1004.
69.Serrano, S.E., Braun, Joseph, Trasande, Leonardo, Dills, Russell, Sathyanarayana, Sheela, Phthalates and diet: a review of the food monitoring and epidemiology data. Environmental health : a global access science source, 2014. 13(1): p. 43-43.
70.Gronen, S., Denslow, N., Manning, S., Barnes, S., Barnes, D., Brouwer, M., Serum vitellogenin levels and reproductive impairment of male Japanese Medaka (Oryzias latipes) exposed to 4-tert-octylphenol. Environment Health Perspectives, 1999. 107(5): p. 385-390.
71.Gronen, S., Denslow, N., Manning, S., Barnes, S., Barnes, D., Brouwer, M., Serum vitellogenin levels and reproductive impairment of male Japanese Medaka (Oryzias latipes) exposed to 4-tert-octylphenol. Environmental Health Perspectives, 1999. 107(5): p. 385-390.
72.Nimrod, A.C., Benson, William H., Environmental Estrogenic Effects of Alkylphenol Ethoxylates. Critical Reviews in Toxicology, 1996. 26(3): p. 335-364.
73.Government of Canada., Substance list: National Pollutant Release Inventory. 2018.
74.Government of Canada., List of substances in the third phase of CMP. 2018.
75.U.S. EPA. TSCA Chemical Substance Inventory. 2019; Available from: https://www.epa.gov/tsca-inventory/about-tsca-chemical-substance-inventory#whatdoesitmean.
76.Lu, Y.-Y., Chen, Mei-Lien, Sung, Fung-Chang, Paulus Shyi-Gang, Wang, Mao, I. Fang, Daily intake of 4-nonylphenol in Taiwanese. Environment International, 2007. 33(7): p. 903-910.
77.Li, C.-T., Cheng, Chin-Yuan, Ding, Wang-Hsien, Determination of alkylphenol residues in baby-food purees by steam distillation extraction and gas chromatography–mass spectrometry. Food and Chemical Toxicology, 2008. 46(2): p. 803-807.
78.Lin, W.-C., Wang, Shu-Li, Cheng, Chin-Yuan, Ding, Wang-Hsien, Determination of alkylphenol residues in breast and commercial milk by solid-phase extraction and gas chromatography–mass spectrometry. Food Chemistry, 2009. 114(2): p. 753-757.
79.Dong, C.-D., Chen, Chiu-Wen, Chen, Chih-Feng, Seasonal and spatial distribution of 4-nonylphenol and 4-tert-octylphenol in the sediment of Kaohsiung Harbor, Taiwan. Chemosphere, 2015. 134: p. 588-597.
80.衛生署福利部食品藥物管理署, 食品法規飲料類衛生標準. 2013. Food and Drug Administration, Ministry of Health and Welfare, Sanitation Standard for Beverage.2013
81.U.S. Food and Drug Adminstration. Multiple purpose gras food substance-Caffeine. 2018; Available from: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=182.1180&SearchTerm=caffeine.
82.European Union., Caffeine risk assessment, E.F.S. Authority, Editor. 2015.
83.Nogara, L., Naber, Nariman, Pate, Edward, Canton, Marcella, Reggiani, Carlo, Cooke, Roger, Piperine’s mitigation of obesity and diabetes can be explained by its up-regulation of the metabolic rate of resting muscle. Proceedings of the National Academy of Sciences, 2016. 113(46): p. 13009-13014.
84.Rather, R.A., Bhagat, Madhulika, Cancer Chemoprevention and Piperine: Molecular Mechanisms and Therapeutic Opportunities. Frontiers in cell and developmental biology, 2018. 6: p. 10-10.
85.Chopra, B., Dhingra, Ashwani Kumar, Kapoor, Ram Prakash, Prasad, Deo Nandan, Piperine and Its Various Physicochemical and Biological Aspects: A Review. Open Chemistry Journal, 2016. 3(1): p. 75-96.
86.European Food Safety Authority (EFSA)., Peer review of the pesticide risk assessment of the active substance 8‐hydroxyquinoline. EFSA Journal, 2016. 14(6).
87.U.S. National Library of Medicine., Hazardous Substances Data Bank-8-Hydroxyquinoline. 2019; Available from: https://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+hsdb:@term+@rn+@rel+148-24-3.
88.Pippi, B., Lopes, William, Reginatto, Paula, Silva, Fernanda Émili Klein, Joaquim, Angélica Rocha, Alves, Ricardo José, Silveira, Gustavo Pozza, Vainstein, Marilene Henning, Andrade, Saulo Fernandes, Fuentefria, Alexandre Meneghello, New insights into the mechanism of antifungal action of 8-hydroxyquinolines. Saudi Pharmaceutical Journal, 2019. 27(1): p. 41-48.
89.United States Department of Agriculture. 2019; Available from: https://ndb.nal.usda.gov/ndb/nutrients/report/nutrientsfrm?max=25&offset=0&totCount=0&nutrient1=508&nutrient2=%E2%8A%82=0&sort=c&measureby=g.
90.Kapalka, G.M., Chapter 6 - Depression, in Nutritional and Herbal Therapies for Children and Adolescents, G.M. Kapalka, Editor. 2010, Academic Press: San Diego. p. 141-187.
91.BM, M. Tyrosine and Stress: Human and Animal Studies. Food Components to Enhance Performance: An Evaluation of Potential Performance-Enhancing Food Components for Operational Rations 1994; Available from: https://www.ncbi.nlm.nih.gov/books/NBK209061/.
92.Matthews, D.E., An overview of phenylalanine and tyrosine kinetics in humans. The Journal of nutrition, 2007. 137(6 Suppl 1): p. 1549S-1575S.
93.Windey, K., De Preter, Vicky, Verbeke, Kristin, Relevance of protein fermentation to gut health. Molecular Nutrition and Food Research, 2012. 56(1): p. 184-196.
94.Andriamihaja, M., Lan, A., Beaumont, M., Audebert, M., Wong, X., Yamada, K., Yin, Y., Tome, D., Carrasco-Pozo, C., Gotteland, M., Kong, X., Blachier, F., The deleterious metabolic and genotoxic effects of the bacterial metabolite p-cresol on colonic epithelial cells. Free Radical Biology and Medicine, 2015. 85: p. 219-227.
95.World Health Organization (WHO)., Fifty-fifth report of the Joint FAO/WHO Expert Committee on Food Additives. 2001.
96.Takaç, S., Akay, Bülent, Özdamar, Tunçer H., Bioconversion of trans-cinnamic acid to l-phenylalanine by l-phenylalanine ammonia-lyase of Rhodotorula glutinis: Parameters and kinetics. Enzyme and Microbial Technology, 1995. 17(5): p. 445-452.
97.Yamada, S., Nabe, K., Izuo, N., Nakamichi, K., Chibata, I., Production of l-Phenylalanine from trans-Cinnamic Acid with Rhodotorula glutinis Containing l-Phenylalanine Ammonia-Lyase Activity. Applied and environmental microbiology, 1981. 42(5): p. 773-778.
98.Huang, P.-C., Tsai, Chih-Hsin, Liang, Wei-Yen, Li, Sih-Syuan, Pan, Wen-Harn, Chiang, Hung-Che, Age and Gender Differences in Urinary Levels of Eleven Phthalate Metabolites in General Taiwanese Population after a DEHP Episode. Public Library of Science A peer-reviewed, open access journal, 2015. 10(7): p. e0133782.
99.World Health Organization (WHO)., Di(2-ethylhexyl)adipate in Drinking-water 2004.
100.U.S. EPA. Di(2-ethylhexyl) adipate. 1998; Available from: https://iaspub.epa.gov/sor_internet/registry/substreg/searchandretrieve/advancedsearch/externalSearch.do?p_type=CASNO&p_value=103-23-1#.
101.衛生署福利部食品藥物管理署. 食品器具容器包裝衛生標準. 2013, Food and Drug Administration, Ministry of Health and Welfare, Sanitation Standard for Food Utensils, Containers and Packages.2013; Available from: https://consumer.fda.gov.tw/Law/Detail.aspx?nodeID=518&lawid=107&k=%u98DF%u54C1%u5668%u5177%u5BB9%u56.
102.Bach, C.C., Bech, Bodil Hammer, Brix, Nis, Nohr, Ellen Aagaard, Bonde, Jens Peter Ellekilde, Henriksen, Tine Brink, Perfluoroalkyl and polyfluoroalkyl substances and human fetal growth: A systematic review. Critical Reviews in Toxicology, 2015. 45(1): p. 53-67.
103.Tsuda, S., Differential toxicity between perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). The Journal of Toxicological Sciences, 2016. 41(Special): p. SP27-SP36.
104.Buekers, J., Colles, Ann, Cornelis, Christa, Morrens, Bert, Govarts, Eva, Schoeters, Greet, Socio-Economic Status and Health: Evaluation of Human Biomonitored Chemical Exposure to Per- and Polyfluorinated Substances across Status. International Journal of Environmental Research and Public Health, 2018. 15(12): p. 2818.
105.Lin, A.Y.-C., Panchangam, Sri Chandana, Lo, Chao-Chun, The impact of semiconductor, electronics and optoelectronic industries on downstream perfluorinated chemical contamination in Taiwanese rivers. Environmental Pollution, 2009. 157(4): p. 1365-1372.
106.Toms, L.M.L., Thompson, J., Rotander, A., Hobson, P., Calafat, A. M., Kato, K., Ye, X., Broomhall, S., Harden, F., Mueller, J. F., Decline in perfluorooctane sulfonate and perfluorooctanoate serum concentrations in an Australian population from 2002 to 2011. Environment international, 2014. 71: p. 74-80.
107.Olsen, G.W., Mair, David C., Church, Timothy R., Ellefson, Mark E., Reagen, William K., Boyd, Theresa M., Herron, Ross M., Medhdizadehkashi, Zahra, Nobiletti, John B., Rios, Jorge A., Butenhoff, John L., Zobel, Larry R., Decline in Perfluorooctanesulfonate and Other Polyfluoroalkyl Chemicals in American Red Cross Adult Blood Donors, 2000−2006. Environmental Science & Technology, 2008. 42(13): p. 4989-4995.
108.The U.S. National Institutes of Health. Propylparaben. 2019; Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Propylparaben#section=FIFRA-Requirements.
109.U.S. Food and Drug Administration. Regulations of the National Archives and Records Administration (NARA). 2016; Available from: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=184.1670.
110.衛生署福利部食品藥物管理署. 化粧品防腐劑成分名稱及使用限制表. 2018; Food and Drug Administration, Ministry of Health and Welfare, List of Ingredients Prohibited in Cosmetic Products. Available from: https://www.fda.gov.tw/TC/siteListContent.aspx?sid=1152&id=8568.
111.Agilent Technologies., All Ions MS/MS: Targeted Screening and Quantitation Using Agilent TOF and Q-TOF LC/MS Systems. 2013.
112.Wang, L., Rishishwar, Lavanya, Mariño-Ramírez, Leonardo, Jordan, I. King, Human population-specific gene expression and transcriptional network modification with polymorphic transposable elements. Nucleic acids research, 2017. 45(5): p. 2318-2328.
113.Tuğrul, M., Paixão, Tiago, Barton, Nicholas H., Tkačik, Gašper, Dynamics of Transcription Factor Binding Site Evolution. Public Library Of Science Genetics, 2015. 11(11): p. e1005639.
114.Schymanski, E.L., Jeon, Junho, Gulde, Rebekka, Fenner, Kathrin, Ruff, Matthias, Singer, Heinz P., Hollender, Juliane, Identifying Small Molecules via High Resolution Mass Spectrometry: Communicating Confidence. Environmental Science & Technology, 2014. 48(4): p. 2097-2098.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
系統版面圖檔 系統版面圖檔