(35.175.212.130) 您好!臺灣時間:2021/05/17 19:54
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:張豊杰
研究生(外文):Li-Jie Chang
論文名稱:暴露變異對生物偵測指標測定結果的影響探討
論文名稱(外文):Exploration of Influence of Exposure Variability on the Measurements of Biological Monitoring
指導教授:陳友剛陳友剛引用關係
學位類別:碩士
校院名稱:長榮大學
系所名稱:職業安全與衛生研究所
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:2008
畢業學年度:96
語文別:中文
論文頁數:74
中文關鍵詞:暴露評估暴露變異空氣暴露連續監測生物偵測
外文關鍵詞:exposure assessmentexposure variabilitycontinuous monitoringbiological monitoring
相關次數:
  • 被引用被引用:2
  • 點閱點閱:165
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
使用短代謝半衰期的生物偵測指標物作為有害物暴露測定時,檢體採集時段前是否有高濃度的暴露,可能對生物偵測指標物測定結果產生影響。但有關短時間高濃度暴露或暴露濃度變異程度,對生物暴露指標物測定結果的影響則缺乏研究。本研究針對一位DMF暴露勞工進行20個連續工作天的暴露測定,其中空氣DMF暴露以直讀式Figaro氣體偵測器,搭配 HOBO Data Logger 進行連續監測;尿液和唾液生物偵測檢體在每天進行多次收集,並針對DMF本體和其生物暴露指標物 NMF 在檢體中含量,分別以不同型式的氣相層析儀進行測定。研究中評估空氣暴露和生物偵測指標物的關聯性,並探討尖峰暴露或暴露濃度變異對生物偵測指標物測定結果的影響;空氣暴露濃度測定值代入一個一階暴露模式中,推估唾液中DMF濃度或尿液中NMF濃度,推估與實際測定值被比較。結果顯示:(1)以空氣暴露濃度超過恕限值一倍、二倍或三倍的尖峰暴露發生百分比,皆無法顯著反應生物偵測指標物的濃度;(2)當空氣暴露變異大時,難以利用空氣暴露平均濃度值估計暴露後尿液NMF濃度;(3)超過恕限值的尖峰暴露發生百分比增加且空氣暴露濃度GSD大時,尿液NMF濃度大於或等於 7.5 mg/L (1/2 BEI) 的機會增加,顯示尖峰暴露與暴露變異二項因子對於生物偵測指標物的含量具有相當重要的影響。本研究確認對於使用短半衰期生物偵測指標物測定執行有害物暴露評估,需注意評估尖峰暴露和暴露變異。如何在暴露評估過程中,收集這二項因子的資料,作為生物偵測指標物測定的參考資訊,為未來重要的研究課題。
When a short half-life biomarker is used as the surrogate of exposure to a hazardous agent, the measured values of the biomarker can be influenced by the events of high concentration exposure occurring near the collection time of specimens. However, there is a lack of studies on the influence of short-term high concentration exposure and magnitude of exposure variability on the quantification of biomarkers. In this study, a worker with DMF exposure was recruited for exposure measurements on 20 consecutive workdays. Airborne DMF exposure was continuously monitored by a direct-reading instrument, Figaro sensor with a HOBO data logger. Urine and saliva samples of the worker were collected multiple times in each workday. DMF and its metabolite, NMF, in the samples were quantified by using different types of gas chromatography. The association between exposure measurements of airborne DMF and masses of the biomarkers of DMF was evaluated. The influence of peak exposure and magnitude of exposure variability on the quantification of biomarkers was explored. The measurements of airborne DMF exposure were input into a first-order exposure model to estimate the concentrations of DMF in the salivary samples and of NMF in the urine samples. A comparison was made between the estimates and the actual measured values. The results showed that: (1) The occurrence percentage of airborne DMF exposure exceeding one, two or three times of TLV could not significantly reflect the concentrations of biomarkers; (2) When the variability of airborne DMF exposure became large, the average of airborne DMF exposure could not estimate the concentration of NMF in urine well; (3) the increase of the occurrence percentage of peak exposure exceeding the TLV and the larger of the geometric standard deviation of airborne DMF exposure, the higher of the probability of urinary NMF concentration equal or greater than 7.5 mg/L (1/2 BEI). This indicated that peak exposure and exposure variability were two crucial factors in determining the amount of biomarkers in the specimens. The results of this study confirmed that these two factors should be characterized when the measurements of biomarkers with short half-lives were used to conduct exposure assessment for hazardous agents. How to collect the information of peak exposure and exposure variability as reference data in the process of exposure assessment is an important research topic for future studies of biomarkers.
目錄
致謝 i
摘要 ii
Abstract iii
目錄 v
圖目錄 vii
表目錄 viii
第一章 前言 1
1.1研究背景 1
1.2研究目的 2
第二章 文獻探討 3
2.1 二甲基甲醯胺 3
2.1.1二甲基甲醯胺物化特性 3
2.1.2二甲基甲醯胺代謝 3
2.1.3二甲基甲醯胺生物偵測 4
2.1.4二甲基甲醯胺健康效應 6
2.2 暴露變異 6
第三章 研究方法 9
3.1 研究設計 9
3.2 空氣暴露連續監測 10
3.2.1 儀器設備與校正 10
3.2.2 零值測試 13
3.2.3精確度測試 13
3.2.4 採樣策略 13
3.2.5 測定資料處理 14
3.3 唾液與尿液暴露樣本 14
3.3.1採樣策略 14
3.4 暴露模式方程式 15
3.4.1 暴露模式建立 15
3.4.2 數值方法 16
3.5 資料分析 19
第四章 結果與討論 20
4.1 空氣暴露連續監測結果 20
4.1.1 檢量線結果 20
4.1.2 零值測試結果 21
4.1.3 精確度測試結果 22
4.1.4 採樣測定結果 22
4.1.5 考量平均濃度對生物指標物之影響結果 27
4.1.5 考量尖峰暴露對生物指標物之影響結果 29
4.1.5 考量暴露變異對生物指標物之影響結果 35
4.1.5 考量多變數對生物指標物之影響結果 36
4.2 暴露模式方程式模擬結果 44
第五章  結論與建議 49
參考文獻 51
附錄一 暴露模式方程式唾液 DMF 濃度推估圖 56
附錄二 暴露模式方程式尿液 NMF 濃度推估圖 59
附錄三 暴露模式方程式推估唾液濃度與推估誤差資料 62
附錄四 暴露模式方程式唾液推估值與分析值分日比較圖 67
附錄五 暴露模式方程式唾液推估值與分析值分組比較圖 74

圖目錄
圖一 DMF 在人體的代謝途徑【Kafferlein et al., 1999】 4
圖二 研究流程圖 10
圖三 儀器校正配置圖 12
圖四 暴露模式方程式一階模式暴露與濃度變化 15
圖五 HOBO低濃度(0 ppm ~ 166.1 ppm)檢量線 20
圖六 HOBO高濃度(193.8 ppm ~ 415.3 ppm)檢量線 21
圖七 HOBO、唾液與尿液二十天濃度分布 24
圖八 二十天不同區段勞工暴露平均濃度變化趨勢 26
圖九 空氣暴露連續測定趨勢相異不同區段暴露平均濃度趨勢 27
圖十 二十天 HOBO、唾液與尿液濃度 28
圖十一 超過一倍TLV百分比與唾液濃度線性迴歸圖 33
圖十二 超過一倍TLV百分比與尿液濃度線性迴歸圖 33
圖十三 超過二倍TLV百分比與唾液濃度線性迴歸圖 34
圖十四 超過二倍TLV百分比與尿液濃度線性迴歸圖 34
圖十五 超過三倍TLV百分比與唾液濃度線性迴歸圖 34
圖十六 超過三倍TLV百分比與尿液濃度線性迴歸圖 34
圖十七 超過TLV百分比與空氣暴露平均值標記尿液濃度分組 37
圖十八 超過2×TLV百分比與空氣暴露濃度平均值標記尿液濃度分組 37
圖十九 超過3×TLV百分比與空氣暴露平均值標記尿液濃度分組 37
圖二十 超過TLV百分比與空氣暴露標準差標記尿液濃度分組 38
圖二十一 超過2×TLV百分比與空氣暴露標準差標記尿液濃度分組 38
圖二十二 超過3×TLV百分比與空氣暴露標準差標記尿液濃度分組 38
圖二十三 超過TLV百分比與空氣暴露幾何平均值標記尿液濃度分組 39
圖二十四 超過2×TLV百分比與空氣暴露幾何平均值標記尿液濃度分組 39
圖二十五 超過3×TLV百分比與空氣暴露幾何平均值標記尿液濃度分組 39
圖二十六 超過TLV百分比與空氣暴露幾何標準差標記尿液濃度分組 40
圖二十七 超過2×TLV百分比與空氣暴露幾何標準差標記尿液濃度分組 40
圖二十八 超過3×TLV百分比與空氣暴露幾何標準差標記尿液濃度分組 40
圖二十九 超過TLV百分比與空氣暴露GSD標記依BEI分組尿液濃度 42
圖三十 超過2×TLV百分比與空氣暴露GSD標記依BEI分組尿液濃度 42
圖三十一 超過3×TLV百分比與空氣暴露GSD標記依BEI分組尿液濃度 42
圖三十二 空氣暴露連續監測平均值對幾何標準差標記尿液濃度分組圖 43
圖三十三 尿液 NMF 濃度推估值與分析值線性迴歸圖 46
圖三十四 GSD對暴露模式方程式推估誤差線性迴歸圖 46
圖三十五 GSD對暴露模式方程式標準化推估誤差線性迴歸圖 47

表目錄
表一 系統零值測試結果 21
表二 精確度測試結果 22
表三 每日空氣暴露連續監測、唾液與尿液暴露統計分析資料 23
表四 暴露 DMF 勞工每日上、下工各區段空氣暴露連續監測統計分析資料 25
表五 暴露 DMF 勞工每日暴露超過恕限值次數與百分比 29
表六 空氣暴露、唾液與尿液濃度依超過一倍 TLV 百分比分組 30
表七 空氣暴露、唾液與尿液濃度依超過二倍 TLV 百分比分組 31
表八 空氣暴露、唾液與尿液濃度依超過三倍 TLV 百分比分組 32
表九 空氣暴露、唾液與尿液濃度依空氣暴露平均值分組表 35
表十 暴露模式方程式推估尿液濃度與推估誤差資料 45
American Conference of Governmental Industrial Hygienists: Threshold Limit Values(TLVs) for Chemical Substances and Physical Agents & Biological Exposure Indices (BEIs). ACGIH, Cincinnati, Ohio, 2004, 2006.
Angerer J., Goen T., Kramer A. and Kafferlein H.U.: N-methylcarbamoyl Adducts at The N-terminal Valine of Globin in Workers Exposed to N,N-dimethylformamide. Arch Toxicol, 1998, 72, 309-313.
Calvert G.M., Fajen J.M., Hills B.W. and Halperin W.E.: Testicular Cancer, Dimethylformamide, and Leather Tanneries. Lancet, 1990, 336, 1253-4.
Chang H.Y., Shih T.S., Cheng C.C., Tsai C.Y., Lai J.S. and Wang V.S.: The Effects of Co-Exposure to Methyl ethyl ketene on the Biological Monitoring of Occupational Exposure to N,N-dimethylformamide. Int Arch Occup Environ Health, 2003, 76(2), 121-128.
Chang H.Y., Shih T.S., Guo Y.L., Tsai C.Y. and Hsu P.C.: Sperm Function in Workers Exposed to N,N-dimethylformamide in The Synthetic Leather Industry. Fertility and Sterility, 2004b, 81(6), 1589-1594.
Chang H.Y., Tsai C.Y., Lin Y.Q., Shih T.S. and Lin Y.C.: Urinary Biomarkers of Occupational N,N-dimethylformamide(DMF) Exposure Attributed to Dermal Exposure. J Expo Anal Environ Epidemiol, 2004a, 14, 214-221.
Checkoway H., Pearce N. and Crawford-Brown D.J.: Characterizing the Workplace Environment. In: Research Methods in Occupational Epidemiology. New York, NY: Oxford University Press, 1989.
Ducatman A.M., Conwill D.E. and Crawl J.: Germ-cell Tumors of The Testicle Among Aircraft Repairman. J Urol, 1986, 136, 834-836.
Fisher J., Lumpkin M., Boyd J., Mahle D., Bruckner J.V. and El-Masri H.A.: PBPK Modeling of The Metabolic Interactions of Carbon Tetrachloride and Tetrachloroethylene in B6C3F1 Mice. Environ Toxicol Pharmacol, 2004, 16, 93-105.
Hansen E. and Meyer O.: Embryotoxicity and Teratogenicity Study in Rats Dosed Epicutaneously with Dimethylformamide(DMF). J Appl Toxicol, 1990, 10, 333-8.
Kafferlein H.U., Goen T., Muller J., Wrbitzky R. and Angerer J.: Simultaneous Determination of Two Human Urinary Metabolites of N,N-dimethylformamide Using Gas Chromatography-Thermionic Sensitive Detection with Mass Spectrometric Confirmation. J Chromatogr B, 1999, 734, 285-298.
Kennedy G.L. Jr.: Biological Effects of Acetamide, Formamide and Their Monomethyl and Dimethyl Derivatives. CRC Crit Rev Toxicol, 1986, 17, 129-182.
Kromhout H. and Heederik D.: Occupational Epidemiology in The Rubber Industry: Implications of Exposure Variability. Am J Ind Med, 1955, 27, 171-185.
Kromhout H., Swuste P. and Boleij J.S.M.: Empirical Modeling of Chemical Exposure in The Rubber Manufacturing Industry. Ann Occup Hyg, 1994, 38, 3-22.
Kumagai S.: Within-Day Variability of Short-Term Exposure to Organic Solvent in Indoor Workplaces. Am Ind Hyg Assoc J, 1999, 60(1), 16-21.
Lareo C. and Perbellini L.: Biological Monitoring of Workers Exposed to N,N-dimethylformamide. Dimethylformamide and Its Metabolisms in Urine of Exposed Workers. Int Arch Occup Environ Health, 1995, 67, 47-52.
Leung H.W.: Use of Physiologically Based Pharmacokinetic Models to Establish Biological Exposure Indexes. Am Ind Hyg Assoc J, 1992, 53(6), 369-374.
Levin S.M., Baker D.B., Landrigan P.J., Monaghan S.V., Frumin E., Braithwaite M. and Towne W.: Testicular Cancer in Leather Tanners Exposed to Dimethylformamide. Lancet, 1987, 2(8568), 1153.
Lyle W.H., Spence T.W., Mckinneley W.M.: Dimethylformamide and Alcohol Intolerance. Br J Ind Med, 1979, 36, 63-66.
Mage D.T.: Exposure Variability in The Workplace: Its Implications for The Assessment of Compliance. Am Ind Hyg Assoc J, 1995, 56(8), 840.
Maxfield M., Barnes J.R., Azar A.: Urinary Excretion of Metabolite Following Experimental Human Exposures to DMF or to DMAC. J Occup Med, 1975, 17, 506-511.
Mráz J., Jheeta P., Gescher A., Hyland R., Thummel K., Threadgill M.D.: Metabolism of N,N-dimethylformamide: Key to The Understanding of Its Toxicity. Chem Res Toxicol, 1993, 6, 245-251.
Mráz J., Nohova H.: Percutaneous Absorption of N,N-dimethylformamide in Humans. Int Arch Occup Environ Health, 1992, 64, 79-83.
Mráz J.: A New Approach to The Biological Monitoring of Expose to N,N-dimethylformamide. Proceedings from The VIII International Symposium on Occupational Health in The Production of Artificial Organic Fibers Nancy France October, 1989, 270-274.
Nomiyama T., Haufroid V., Buchet J.P. and et al.: Insertion Polymorphism of CYP2E1 and Urinary N-Methylformamide after N,N-Dimethylformamide Exposure in Japanses Workers. Int Arch Occup Environ Health, 2001, 74, 519-522.
Nomiyama T., Nakashima H., Chen L.L., Tanaka S., Miyauchi H., Yamauchi T., Sakurai H. and Omae K.: N,N-dimethylformamide: Significance of Dermal Absorption and Adjustment Method for Urinary N-methylformamide Concentration as a Biological Exposure Item. Int Arch Occup Environ Health, 2001, 74(3), 224-8.
Occupational Safety & Health Administration. TABLE Z-1 Limits for Air Contaminants.-1910.1000 TABLE Z-1, http://www.osha.gov/pls/oshaweb /owadisp.show _document?p_table=STANDARDS&p_id=9992.
Perbellini L., Mozzo P., Olivato D. and Brugnone F.: “Dynamic” Biological Exposure Indexes for n-Hexane and 2, 5-Hexanedione, Suggested by a Physiologically Based Pharmacokinetic Model. Am Ind Hyg Assoc J, 1990, 51(7), 356-362.
Rappaport S.M., Kromhout H. and Symanski E.: Variation of Exposure Between Workers in Homogeneous Exposure Groups. Am Ind Hyg Assoc J, 1993, 54, 654-662.
Roure M.B., Lambert A.M., Cour C., Bonnet P. and Saillenfait A.M.: Hepatotoxicity of N,N-dimethylformamide in Rats Following Intraperitoneal or Inhalation Routes of Administration. J Appl Toxicol, 1996, 16(3), 265-7.
Symanski E.: Heterogeneity in Sources of Exposure Variability Among Groups of Workers Exposure to Inorganic Mercury. Ann Occup Hyg, 2001, 45(8), 677-687.
Tardif R., Tardif C.G., Brodeur J. and Kannan K.: Physiologically Based Pharmacokinetic Modeling of a Ternary Mixture of Alkyl Benzenes in Rats and Humans. Toxicol Appl Pharmacol, 1997, 144, 120-134.
Wang S.M., Shih T.S., Huang Y.S., Chueh M.R., Chou J.S. and Chang H.Y.: Evaluation of The Effectiveness of Personal Protective Equipment Against Occupational Exposure to N,N-dimethylformamide. J Hazard Mater, 2006, 138(3), 518-25.
有機溶劑中毒預防規則, 行政院勞工委員會, 92 年 12 月 31 日修訂.
林育群, 建立唾液中二甲基甲醯胺職業暴露之生物指標分析方法, 成功大學環境醫學研究所碩士論文, 2003.
物質安全資料表-二甲基甲醯胺, 行政院勞工委員會勞工安全衛生研究所, 2000.
郭育良, 許昺奇, 蔡朋枝, 蘇德勝, 張火炎, 蘇慧貞, 黃筑筠, 吳佩芝, 李俊彰與蕭淑銖: 職業病概論, 華杏叢書, 華杏出版股份有限公司, 2001, 初版.
勞工作業環境空氣中有害物容許濃度標準, 行政院勞工委員會, 92 年 12 月 31 日修訂.
塗佳霖: 暴露濃度之變異特性對職業暴露評估影響性之研究, 國立高雄第一科技大學環境與安全衛生工程系研究所碩士論文, 2006.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊