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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 林宜長(Yi-Chang Lin),陳家揚(Chia-Yang Chan) | |
dc.contributor.author | Pao-Kuei Hsiao | en |
dc.contributor.author | 蕭寶桂 | zh_TW |
dc.date.accessioned | 2021-06-15T02:21:50Z | - |
dc.date.available | 2011-09-16 | |
dc.date.copyright | 2009-09-16 | |
dc.date.issued | 2009 | |
dc.date.submitted | 2009-08-19 | |
dc.identifier.citation | 1.NICNAS, para-Dichlorobenzene, N.I.C.N.A.S, Editor. 2000, The Australian Government regulator of industrial chemicals: Australian.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/43445 | - |
dc.description.abstract | 1,4-二氯苯(1,4-Dichlorobenzene, 1,4-DCB)又稱對二氯苯(p-Dichlorobenzene),其蒸氣壓高(1.28 mmHg)故易昇華。1,4-二氯苯除用在驅除蟲類、蛾類等病媒,也常被放置在廁所作為除臭劑。1,4-二氯苯主要是透過呼吸道,以吸入方式進入人體,其吸入的細微粉粒及晶體均可能造成健康危害。根據文獻顯示,高濃度的1,4-二氯苯暴露所造成的健康危害包括皮膚及黏膜的刺激、上呼吸道及眼睛的不適、影響肝腎功能、造成肺部的傷害以及呼吸系統的刺激等。因此本研究之目的在透過暴露評估,內在劑量評估及健康檢查結果瞭解人體暴露1,4-二氯苯後所造成的健康影響。
1,4-二氯苯的內在暴露劑量調查可經由分析尿液中的1,4-二氯苯原體,自由態2,5-二氯酚,及2,5-二氯酚共軛結合物(硫酸,葡萄糖苷酸)的濃度得知。為進行尿中代謝物的分析,本研究建立UPLC/MS/MS同步分析方法配合固相萃取方法分析尿液中2,5-二氯酚,2,5-二氯水合醌,及2,5-二氯酚共軛結合物(硫酸及葡萄糖苷酸)的濃度。由於2,5-二氯酚共軛結合物無市售標準品可供使用,因此本研究分別合成2,5-二氯酚葡萄糖苷酸與2,5-二氯酚硫酸共軛結合物,經鑑定後隨即建立尿液同步分析方法。經方法驗證及實際樣本分析後,確定本方法為一可靠且快速的分析方法,並將其實際應用於暴露調查之尿液分析。 本研究針對製造以1,4-DCB為主要成分的驅蟲劑工廠進行暴露調查,研究期間共完成三間工廠採樣, A、C廠在北台灣,B廠在南台灣,至於1,4-DCB的用量以C廠最大,B廠最小。勞工暴露調查項目包括個人空氣樣本採樣,尿液檢體收集,問卷調查以及血液常規檢測。經由尿液樣本的結果顯示,自由態2,5-二氯酚及2,5-二氯酚硫酸共軛化合物平均濃度較低(70 ~ 1050 ng/mL), 2,5-二氯酚葡萄糖苷酸共軛化合物平均濃度最高(20 ~ 350 mg/L),顯示暴露後的尿中代謝物以2,5-二氯酚葡萄糖苷酸共軛化合物為主。 空氣採樣的結果,本研究使用3M 3500被動式採樣器進行個人空氣採樣,採樣時間分別為工作8小時及非工作16小時,分析儀器為氣相層析儀搭配火焰離子偵測器。結果得知工作時的個人空氣時量濃度為C廠>A廠>B廠(最高9.15 ± 6.37 ppm,最低1.19 ± 0.84 ppm)。非工作時的個人空氣濃度也是C廠>A廠>B廠(最高0.84 ± 0.68 ppm,最低0.08 ± 0.04 ppm)。 將空氣濃度,尿中代謝物濃度與問卷資料及健檢資料進行統計分析,得知現場作業員工空氣濃度值顯著高於非現場作業員工;若以工作型態區分,原料操作者濃度顯著高於半成品收集、包裝者,而行政文書類者濃度最低(p < 0.05);暴露組非工作時空氣濃度顯著高於對照組(p < 0.05);家中使用含1,4-DCB類驅蟲劑之空氣濃度顯著高於未使用者(p < 0.05)。空氣濃度愈高者,尿中2,5-DCPG及2,5-DCP濃度愈高(p < 0.01)。在健檢方面,暴露空氣濃度及尿中代謝物濃度愈高者,白血球數量,血中尿素氮濃度及血中尿素氮濃度/肌苷酸比值有顯著較高的趨勢(p < 0.05)。 本研究成功建立UPLC/MS/MS同步分析尿中代謝物方法並將其實際應用於樣本分析中。空氣採樣結果顯示24小時全日採樣更接近實際暴露情形。暴露1,4-DCB的空氣濃度與尿中代謝物濃度與白血球數量、血中尿素氮濃度,血中尿素氮濃度/肌苷酸比值增加有顯著相關,但檢查數值仍在正常範圍內。本研究完成探討暴露1,4-DCB後空氣濃度,尿中代謝物濃度及健康效應間的相關探討。 | zh_TW |
dc.description.abstract | 1,4-Dichlorobenzene (1,4-DCB) is widely used as a deodorizer because of it’s volatility (vapor pressure is 1.08 mg/m3 at 25℃). It is also used as a moth repellent and toilet deodorizer. Many studies have showed that human exposed to 1,4-DCB mainly by inhalation. Human inhale high 1,4-DCB concentration may cause eye and upper respiratory tract irritation, abnormal liver/kidney function and lung disorders. In this study, we conduct an exposure assessment to clarify the relationship between 1,4-DCB exposure profile and the related health effects.
The human internal dose can be analyzed by the concentrations of 1,4-DCB, 2,5-dichlorophenol (2,5-DCP), 2,5-dichlorophenol glucuronide (2,5-DCPG), and 2,5-dichlorophenol sulphate (2,5-DCPS) in urine. However, chemical standards of 2,5-DCPG and 2,5-DCPS are not commercially available, therefore, 2,5-DCPG and 2,5-DCPS were synthesized in our study. In the present study, we developed a method to analyze urinary 2,5-dichlorophenol (2,5-DCP), 2,5-dichlorohydroquinone, 2,5-DCPS, and 2,5-DCPG simultaneously by ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC/MS/MS). Our method has been successfully used to detect urinary metabolites of 1,4-DCB with high throughput and represented a good sensitivity. After analysis method was established, we conducted an assessment of human 1,4-DCB exposure in three major moth repellent product plants, plant A and C are in northern Taiwan as well as plant B is in southern Taiwan. Plant C has the highest output of 1,4-DCB repellent product, and plant B has the smallest one. In our evaluated plants, samples of workers’ personal air and urine were simultaneously collected; in addition, we also collected workers’ questionnaire and biochemical test results. Our data has demonstrated the concentration of free form 2,5-DCP/2,5-DCPS in urine was generally lower (70 ~ 1050 ng/mL) than 2,5-DCPG (20 ~ 350 mg/L). Therefore, 2,5-DCPG was found to be the major metabolite after human exposed to 1,4-DCB. For air sampling, we used 3M 3500 passive sampler to evaluate repellent workers’ exposure profile. The sampling time included 8 hours daytime, and 16 hours overnight. After sampling, the air samples were analyzed by Gas Chromatography Flame Ionization Detector (GC-FID). Our results demonstrated that the highest air concentration (9.15 ± 6.37 ppm in daytime and 0.84 ± 0.68 ppm in over night) wad found in plant C, and plant B had the lowest concentration (1.19 ± 0.84 ppm in daytime and 0.08 ± 0.04 ppm in over night ). From the statistical results, the 1,4-DCB concentration in air was significantly higher in on-site workers than in non-on-site workers (p < 0.05). Moreover, the air concentration was also found to be higher in raw material operator than in semi-finished product collector (p < 0.05). The air concentration was higher in who has the habit of using mothball contained 1,4-DCB in home (p < 0.05). Once the worker has the higher air concentration of 1,4-DCB, their metabolite concentration in urine was also found to be higher (p < 0.05). In health effect, the biochemical indices such as white blood cell count (WBC), blood urea nitrogen (BUN) level and BUN/creatinine ratio are positively correlated with the air concentration and urinary metabolite concentration (p < 0.05). This study employed solid-phase extraction (SPE) to extract 1,4-DCB metabolites from urine and the metabolites were then subsequent to analysis by UPLC/MS/MS coupled with negative electrospray ionization. This method has successfully measured urinary metabolites of 1,4-DCB with high throughput and represented a good sensitivity. We found the major metabolite of 2,5-DCP in urine is 2,5-DCPG. From air sampling results, the 24 hours sampling data is much closer to the real exposure situation than 8 hours sampling. The concentration of 1,4-DCB in air and major metabolite in urine are positively correlated with WBC count, BUN concentration and BUN/creatinine ratio, but these indices is still in the normal range. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T02:21:50Z (GMT). No. of bitstreams: 1 ntu-98-F90844006-1.pdf: 1866114 bytes, checksum: 14aafc7707d399743a30913347f62149 (MD5) Previous issue date: 2009 | en |
dc.description.tableofcontents | 摘 要 i
Abstract iii 目錄 v 圖目錄 viii 表目錄 x 第一章 緒論 1 第一節 研究背景 1 第二節 研究目的 2 第二章 文獻探討 3 第一節 1,4-二氯苯理化特性、環境分佈及生物作用機制 3 第一項 1,4-二氯苯物理化學特性 3 第二項 1,4-二氯苯之用途及使用情形 4 第三項 1,4-二氯苯環境分佈 5 第四項 1,4-二氯苯的暴露情形及人類暴露資料 6 第五項 環境中1,4-二氯苯暴露容許濃度 7 第六項 1,4-二氯苯之毒物動力學 8 第七項 1,4-二氯苯的健康危害 15 第二節 空氣中1,4-二氯苯的採樣分析方法 20 第一項 主動式環境採樣 20 第二項 被動式採樣 22 第三節 尿中1,4-二氯苯及其代謝物濃度萃取分析方法 23 第一項 分析尿中1,4-二氯苯及自由態2,5-二氯酚 23 第二項 分析尿中自由態2,5-二氯酚及共軛態2,5-二氯酚 23 第四節 常見生物樣品前處理方法 24 第一項 固相微萃取與頂空固相微萃取 24 第二項 固相萃取法 29 第五節 液相層析質譜質譜儀作用機制 30 第一項 高效液相層析儀與極緻液相層析儀 30 第二項 質譜/質譜儀—電灑游離法 31 第三章 研究架構與材料方法 34 第一節 研究架構 34 第一項 主研究架構 34 第二項 暴露調查 34 第三項 健康效應評估 36 第二節 材料與方法 41 第一項 合成2,5-二氯酚硫酸共軛化合物及葡萄糖苷酸共軛化合物標準品 41 第二項 建立同步分析尿中1,4-二氯苯代謝物分析方法 43 第三項 尿中1,4-二氯苯及自由態2,5-二氯酚頂空固相微萃取分析方法 46 第四項 空氣採樣及分析之材料與方法 48 第五項 暴露調查 51 第六項 設計問卷收集相關資料 52 第七項 健康檢查 53 第八項 研究對象設定 56 第九項 環境、生物偵測,問卷調查,健康危害相關性探討 56 第四章 結果與討論 58 第一節 2,5-二氯酚葡萄糖苷酸共軛化合物及2,5-二氯酚硫酸共軛化合物標準品合成 58 第一項 2,5-二氯酚葡萄糖苷酸共軛化合物(2,5-DCP glucuronide)合成 58 第二項 2,5-二氯酚硫酸共軛化合物(2,5-DCP sulphate)標準品合成 71 第二節 尿中1,4-二氯苯代謝物同步分析方法建立 77 第一項 前軀試驗 77 第二項 高效液相層析質譜/質譜儀(HPLC/MS/MS)分析條件建立 84 第三項 極致液相層析質譜/質譜儀(UPLC/MS/MS)分析方法建立 96 第三節 樟腦丸作業勞工1,4-DCB暴露評估 115 第一項 作業環境測定 115 第二項 個人空氣樣本分析結果 118 第三項 尿中1,4-二氯苯及其代謝物濃度分析 122 第四項 頂空固相微萃取法分析結果 134 第五項 暴露劑量與尿中代謝物濃度相關性 138 第六項 暴露與血液常規測值關係 140 第四節 92 ~ 94年問卷調查結果 142 第一項 基本資料 142 第二項 工作及衛生習慣情形 144 第三項 自覺症狀 146 第五節 92 ~ 94年受訪對象肝腎功能檢查及血液常規檢測結果 147 第一項 肝臟功能 148 第二項 腎臟功能 149 第三項 血液常規 150 第五章 結論與建議 153 參考文獻 157 附錄一 驅蟲劑製造工廠勞工健康研究問卷調查 164 附錄二 驗尿濾紙說明 176 | |
dc.language.iso | zh-TW | |
dc.title | 1,4-二氯苯暴露及健康危害評估研究 | zh_TW |
dc.title | Exposure and health assessment of 1,4-dichlorobenzene | en |
dc.type | Thesis | |
dc.date.schoolyear | 97-2 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 劉紹興(Saou-Hsing Liou),林嘉明(Jia-Ming Lin),毛義方(I-Fang Mao),張靜文(Ching-Wen Chang) | |
dc.subject.keyword | 1,4-二氯苯,化學合成,暴露評估,健康效應, | zh_TW |
dc.subject.keyword | 1,4-dichlorobenzene,synthesis,exposure assessment,health effect, | en |
dc.relation.page | 176 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2009-08-19 | |
dc.contributor.author-college | 公共衛生學院 | zh_TW |
dc.contributor.author-dept | 環境衛生研究所 | zh_TW |
顯示於系所單位: | 環境衛生研究所 |
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