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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 吳焜裕 | |
| dc.contributor.author | Ming-Yen Chien | en |
| dc.contributor.author | 簡銘延 | zh_TW |
| dc.date.accessioned | 2021-05-14T17:50:22Z | - |
| dc.date.available | 2015-09-14 | |
| dc.date.available | 2021-05-14T17:50:22Z | - |
| dc.date.copyright | 2015-09-14 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-08-20 | |
| dc.identifier.citation | Alexander BH, Olsen GW, Burris JM, Mandel JH and Mandel JS (2003) Mortality of
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/4912 | - |
| dc.description.abstract | 全氟碳化物的種類繁多，而大部分文獻聚焦在PFOS(C8)或PFOA(C8)等環境中濃度較高的全氟碳化物，為了建立更多種類的全氟碳化物之生理型藥物動力學 (Physiologically based pharmacokinetic, PBPK) 模式，其中，化合物在生物體內各臟器之分配係數(Partition coefficient, PC) 可以說是重要的參數之一。本研究對雄性SD 大鼠(N=40)經單一胃管灌食的方式，暴露個別劑量為500μg/kg之PFBA、PFBS、PFPeA、PFHxA、PFHxS、PFHpA等六種全氟碳化物，在為期10天的動物實驗其間於不同犧牲點(2、4、8、12、24、48、96、144、196、240小時)，每個時間點包含暴露組(N=3)、控制組(N=4)，收集SD大鼠的血清、肝臟、腎臟、小腸、副睪旁之脂肪等五種臟器，經由前處理後以液相層析串聯質譜儀(LC-MS/MS)方法分析全氟碳化物之濃度，用於後續分配係數之運算。並根據選擇碳數不同(4~7C)以及官能基不同(-COOH與-SO3)之全氟碳化物，探討碳數與官能基對於SD 大鼠全氟碳化物分配係數之影響。實驗結果發現除PFHxS以外，大部分的全氟碳化物在暴露後的48小時內，便經由小腸快速吸收至血液中進行循環並分配到不同的臟器，隨後經由腎臟排出體外；而PFHxS則是在收樣時間結束(240小時)後，仍持續存在於SD大鼠各臟器之中。在分配係數的部分，帶有羧基(R-COOH)之全氟碳化物(PFBA、PFPeA、PFHxA、PFHpA)其分配係數由大到小依序為腎臟>肝臟>小腸>脂肪，碳鏈長度的增加對於任何臟器/血清分配係數並無顯著影響；而帶有硫酸基(-SO3)之全氟碳化物(PFBS、PFHxS)其分配係數由大到小依序為肝臟>腎臟>小腸>脂肪。這樣的差異歸因於帶有硫酸基(-SO3)之全氟碳化物易與肝細胞脂肪酸結合蛋白(Hepatic fatty acid-binding protein)結合累積於肝臟之中，因而推算出較高的肝臟/血清分配係數(PCLiver/plasma)，另外，隨著碳鏈長度增加PFHxS(6C)相較於PFBS(4C)其肝臟/血清分配係數(PCLiver/plasma)則有增加之現象發生。 | zh_TW |
| dc.description.abstract | The widespread environmental distribution of Perflourinated chemicals (PFCs) has been considered as a public health issue for a long time. Most of the current reserch focus on perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) compare to other PFCs. In order to know the metabolism progress of the chemical in biota. Physiologically based pharmacokinetic model (PBPK model) is a well-known method. Among numerous parameters, the paeririon coefficient (PC) for each of the organ in biota is indispensable. The male SD rats(N=40) were treated with a single dose of PFBA、PFBS、PFPeA、PFHxA、PFHxS、PFHpA by oral gavage at 500μg/kg. Subsequently, the SD rats were classified into exposure group (N=3) and control group (N=1) in each of the sacrified time point (2, 4, 8, 12, 24, 48, 96, 144, 196, 240 hour). Serum, liver, kidney, small intestine, epididymis fat were collected. After pre-treatment, the samples were analyzed for these PFCs via liquid chromatograph tandem mass spectrometer (LC-MS/MS). The aims of this study are finding out how the influences for partition coefficient of different carbon chain length and different fuction groups in male SD rats. After the gavage exposure, results shows that apart form PFHxS, most of the PFCs were quickly absorb from small intestine into blood circulation.Then distribute into other organs, at last exceret out of the body via kidney in 48 hours. On the other hand, PFHxS keep exist in biota after 240 hours. PFCs with carboxyl group (-COOH), such as PFBA, PFPeA, PFHxA, PFHpA. The descending order of partition coefficient is kidney, liver, small intestine, epididymis fat. As the carbon chain length increase, the partition coefficient for each of the organ does not change significantly. PFCs with sulfur trioxide group (-SO3), such as PFBS and PFHxS. The descending order of partition coefficient is liver, kidney, small intestine, epididymis fat. These differences attribute to PFCs with sulfur trioxide group (-SO3) are likely combined with hepatic fatty acid-binding protein in hepatic cells. Therefore, we can estimate a higher value of partition coefficient in liver. | en |
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| dc.description.tableofcontents | 口委審定書………………………………………………………………………i
中文摘要…………………………………………………………………………ii 英文摘要……………………………………………………………………………iv 第一章 文獻回顧………………………………………………………………1 1.1. 全氟碳化物的物理及化學特性……………………………………1 1.2. 全氟碳化物的環境流佈……………………………………………1 1.2.1. 水……………………………………………………………2 1.2.2. 大氣…………………………………………………………4 1.2.3. 食物…………………………………………………………4 1.2.4. 動物…………………………………………………………4 1.3. 全氟碳化物的毒理資料……………………………………………5 1.3.1. 全氟碳化物的致癌性………………………………………8 1.3.2. 全氟碳化物的生殖發育毒性………………………………9 1.3.3. 全氟碳化物的肝毒性………………………………………10 1.3.4. 全氟碳化物造成荷爾蒙失調………………………………11 1.4. 全氟碳化物人體的暴露途徑以及暴露程度………………………12 1.5. 全氟碳化物的代謝機制……………………………………………13 1.6. 全氟碳化物的藥物動力學研究……………………………………15 1.7. 全氟碳化物的分析方法……………………………………………17 1.8. 全氟碳化物的分析儀器介紹………………………………………18 1.8.1. 線上固相萃取，On-Line SPE……………………………18 1.8.2. 液相層析串聯質譜儀，LC-MS-MS…………………………18 1.8.3. 同位素稀釋法搭配液相層析串聯質譜儀…………………19 1.9. 藥物動立學概述……………………………………………………20 1.9.1. 房室模式(Compartment Model) …………………………20 1.9.2. 非室模式(Non-Compartment model) ……………………21 1.9.3. 生理藥物動力學模式(Physiological-Based Pharmacokinetic Model)……21 1.9.4. 藥物動力學模式的選擇……………………………………21 1.9.5. 分配係數(Partition-Coefficient) ……………………22 第二章 研究方法………………………………………………………………26 2.1. 研究目的……………………………………………………………26 2.2. 樣品來源……………………………………………………………27 2.2.1. 化學標準品…………………………………………………27 2.2.2. 實驗動物……………………………………………………29 2.3. 動物實驗……………………………………………………………29 2.3.1. 暴露方式……………………………………………………29 2.3.2. 犧牲間隔……………………………………………………30 2.3.3. 器官檢體採集………………………………………………30 2.3.4. 樣本保存處理………………………………………………30 2.4. 檢體前處理…………………………………………………………30 2.4.1. 血清檢體前處理……………………………………………30 2.4.2. 器官檢體前處理……………………………………………32 2.5. 儀器分析流程………………………………………………………33 2.5.1. 血漿檢體層析、線上固相萃取OnLine-SPE……………33 2.5.2. 器官檢體層析方法…………………………………………34 2.5.3. 校正曲線配置………………………………………………35 2.5.4. 基值效應、回收率、分析方法確效………………………36 2.5.5. 統計分析軟體與方法………………………………………38 3.1. 樣本分析……………………………………………………………39 3.1.1. 全氟碳化物於血液中之分析圖譜…………………………39 3.1.2. 全氟碳化物於器官中之分析圖譜…………………………40 3.1.3. 全氟碳化物於各基質中之檢量線…………………………41 3.1.4. 精密度、準確度與回收率分析……………………………44 3.2. 全氟碳化物於血清中之濃度變化…………………………………48 3.2.1. PFPeA、PFBS與PFHxA……………………………………48 3.2.2. PFBA與PFHpA………………………………………………49 3.2.3. PFHxS………………………………………………………49 3.2.4. 小結…………………………………………………………50 3.3. 全氟碳化物於各臟器中之分配係數………………………………50 3.3.1. PFBA之分配係數…………………………………………51 3.3.2. PFBS之分配係數…………………………………………55 3.3.3. PFPeA之分配係數…………………………………………57 3.3.4. PFHxA之分配係數…………………………………………59 3.3.5. PFHpA之分配係數…………………………………………61 3.3.6. PFHxS之分配係數…………………………………………65 3.3.7. 小結…………………………………………………………69 3.4. 碳鏈長度與官能基對全氟碳化物之分配係數影響………………72 3.4.1. 肝臟分配係數之比較………………………………………74 3.4.2. 腎臟分配係數之比較………………………………………74 3.4.3. 脂肪分配係數之比較………………………………………75 3.4.4. 小腸分配係數之比較………………………………………76 第四章 結論與建議……………………………………………………………77 參考文獻…………………………………………………………………………79 | |
| dc.language.iso | zh-TW | |
| dc.subject | 大鼠 | zh_TW |
| dc.subject | 全氟碳化物 | zh_TW |
| dc.subject | 藥物動力學 | zh_TW |
| dc.subject | 分配係數 | zh_TW |
| dc.subject | Perflourinated chemical | en |
| dc.subject | SD rat | en |
| dc.subject | Pharmacokinetics | en |
| dc.subject | Partition coefficient | en |
| dc.title | 全氟碳化物於大鼠中分配係數之研究 | zh_TW |
| dc.title | Partition Coefficient of Perfluorinated Chemical in Rats | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳保中,蔡東湖 | |
| dc.subject.keyword | 全氟碳化物,藥物動力學,分配係數,大鼠, | zh_TW |
| dc.subject.keyword | Perflourinated chemical,Pharmacokinetics,Partition coefficient,SD rat, | en |
| dc.relation.page | 86 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2015-08-20 | |
| dc.contributor.author-college | 公共衛生學院 | zh_TW |
| dc.contributor.author-dept | 職業醫學與工業衛生研究所 | zh_TW |
| 顯示於系所單位： | 職業醫學與工業衛生研究所 | |
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|---|---|---|---|
| ntu-104-1.pdf | 3.57 MB | Adobe PDF | 檢視/開啟 |
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