臺灣博碩士論文加值系統

酞酸酯類（Phthalate esters），為一種環境荷爾蒙，在動物實驗已證實會引發生殖發育毒性。酞酸酯類亦是全球使用最廣的塑化劑。而我國使用塑膠做為食品包裝情形極為普遍，在食品加工保存過程中，塑化劑的溶出、轉移，都可能經由食物進入體內造成危害。
本研究分析食物中的酞酸酯類：DMP、DEP、DBP、DEHP、BBzP以及檢測尿液中各酞酸酯類進入人體代謝所得單酯類：MMP、MEP、MBP、MEHP及MBzP。

本研究第一部份檢測市售塑膠包裝食品，確認塑膠包裝食品中酞酸酯種類及濃度。第二部份提供10名學生三天餐飲，並收集三天每次尿液，以探討膳食攝取與尿中酞酸鹽單酯濃度關係。食物經淨化後固相萃取。尿液則經酵素水解、淨化及衍生，兩者均以GC-MS分析。

國內塑膠包裝食品中DBP及DEHP檢出率為100％，DEP為60％，平均濃度為0.701、0.208及0.029 μg/g，其中以肉類加工品濃度最高。本研究受測者習慣性膳食樣本，DBP、DEHP與DEP檢出率100％。與歐盟毒害與環境科學委員會建議之每日容許攝取量比較，本研究受測者DEHP的攝取佔容許攝取量的10.6％，DBP為29.9％，DEP為 0.005％。且國內市售食品塑膠包裝所含塑化劑可能以DBP含量最高。
本研究受測者尿中酞酸鹽單酯濃度最高為MEP，其次為MBP、MMP、MEHP及MBzP；中位數為0.158、0.070、0.042、0.024 μg/mL及ND。尿液中酞酸鹽單酯濃度在膳食攝取後明顯增加，可見酞酸酯類會經膳食進入人體。尿中單酯與經膳食攝取的酞酸酯類莫耳數比值在DEP為12.949，DBP為0.056，DEHP為0.199，三者的比值差異很大。可能原因為DBP在體內代謝成MBP的比率較低，而DMP與DEP則可能尚有其他暴露來源。而本研究MEHP濃度高於德、美研究的2.4－8倍，可見國人暴露的酞酸酯類仍較國外為高。

Some of Phthalate esters are reported as environmental hormone which are known reproductive and developmental toxicants in animal studies. In Taiwan, plastics are widely used in food contact packaging. During food processing, leaching and migration of plasticizers might result in phthalates residues in food, which might cause health risks for consumers.
In this study, we analyzed five phthalate esters, which are DMP, DEP, DBP, DEHP,and BBzP, in food. We also analyzed five monoester metabolites, including MMP, MEP, MBP, MEHP and MBzP, in urine.
The objective of this study are: (1) Analyzing the species and concentrations of phthalate esters in plastic packaged food in market, and (2)exploring the association of daily phthalate intake and urinary monoesters levels in ten subjects who were provided meals and collected urine samples for three consecutive days. Food samples were purified through extraction, and urine samples were enzymatic deconjugation then purified and derivatized. Then both were analyzed by GC-MS.

DBP and DEHP in plastic packaged food were 100% detected. DEP is 60%. The respective mean concentration were 0.701,0.208,and 0.029 μg/g. The highest was found in processed meat. The DBP, DEP and DEHP in meal food provided to students were 100% detected. Comparing with the tolerable daily intake established by the EU Scientific Committee for Toxicity, Ecotoxicity and the Environment (CSTEE), the daily intake of DEHP, DBP, and DEP for the ten subjects were 10.6%, 29.9%, and 0.005%, respectively. This study found that DBP might be the highest added plasticizer in plastic packaged food in Taiwan.
The highest concentrations detected in the urine samples was MEP, followed by MBP, MMP, MEHP and MBzP. The respective medians were 0.158, 0.070, 0.042, 0.024μg/mL and ND. The concentrations of phthalate monoesters rose significantly after taking the meal, which proved the metabolism of phthalates and the excrection by the metabolites been detected. The molar ratio of phthalate monoesters in urine to those in food intake were 12.949 for DEP, 0.056 for DBP, and 0.199 for DEHP. The ratios varied by different phthalate esters. It implied the relatively low metabolism of DBP to MBP and the multiple exposure sources of DMP and DEP. The urinary MEHP in this study was 2.4 to 8 times higher than those in German and American.

目錄

目錄 I
表目錄 IV
圖目錄 V
附錄 VI
摘要 VII
Abstract VIII

第一章 前言 1
1-1 研究緣起 1
1-2 研究目的 5

第二章 文獻探討 6
2-1 環境荷爾蒙 6
2-1-1 環境荷爾蒙簡介 6
2-1-2 環境荷爾蒙影響機制 7
2-1-3 環境荷爾蒙規範 8
2-2 酞酸酯類 10
2-2-1 物理化學特性 10
2-2-2 來源與用途 10
2-2-3 代謝情形 12
2-2-4 毒性影響 13
2-3 暴露情形 16
2-3-1 環境流布 16
2-3-2 人體暴露 17
2-4 法規規範 19
第三章 材料與方法 21
3-1 研究架構 21
3-2 材料 22
3-2-1 試藥 22
3-2-2 器材 23
3-2-3 儀器 24
3-3 研究設計 24
3-4 分析樣本 25
3-5 實驗方法 26
3-5-1 檢量線配置 26
3-5-2 溶液配置 26
3-5-3 食物樣本前處理方法 28
3-5-4 尿液樣本前處理方法 29
3-5-5 尿液樣本淨化與衍生反應 29
3-5-6 酞酸酯類及酞酸鹽單酯分析方法 30
3-5-7 尿液樣本creatinine測定 31
3-6 分析方法之驗證 33
3-7 樣本資料分析處理 35

第四章 結果 36
4-1 食物樣本 36
4-1-1 塑膠包裝食物之酞酸酯種類及濃度 36
4-1-2 一般大學生食用典型膳食餐盒中酞酸酯類濃度 37
4-1-3 餐盒食物酞酸酯類的濃度之變化 37
4-1-4 塑膠包裝食物與餐點食物濃度之比較 38
4-1-5 經由飲食之酞酸酯類實際攝取量 38

4-2 尿液樣本中酞酸鹽單酯之濃度 40
4-2-1 全體尿液樣本濃度 40
4-2-2 以性別分組來分析尿中酞酸鹽單酯之差異 40
4-2-3 尿中酞酸鹽單酯濃度之變化 41
4-2-4 尿中酞酸鹽單酯濃度與攝取時間關係 41
4-3 經食物實際攝取量與尿中酞酸鹽單酯濃度關係 43
4-4 分析方法之驗證 43
4-4-1 GC-MS分析條件 44
4-4-2 檢量線 44
4-4-3 回收率 44
4-4-4 偵測極限 45

第五章 討論 46
5-1 塑膠包裝食品與膳食餐盒的污染 46
5-1-1 塑膠包裝食物之酞酸酯類污染探討 46
5-1-2 一般學生食用膳食餐盒中酞酸酯類污染探討 47
5-1-3 經由飲食之酞酸酯類實際攝取量探討 47
5-1-4 我國食品中酞酸酯類與國外研究比較 48
5-2 尿液樣本中酞酸鹽單酯濃度 49
5-2-1 本研究尿中酞酸鹽單酯濃度探討 49
5-2-2 本研究尿中酞酸鹽單酯濃度與攝取時間關係探討 49
5-3 國人尿中酞酸鹽單酯濃度與其他研究比較 50
5-4 膳食中酞酸酯類與國人體內酞酸鹽單酯濃度探討 51

第六章 結論與建議 53
參考文獻 55



表目錄


表1 我國法規管理疑似環境荷爾蒙物質情形一覽表 64
表2 本研究酞酸酯類分子結構式 67
表3 市售塑膠包裝食物所含之酞酸酯類及濃度 68
表4 三日之膳食食物中酞酸酯類濃度 70
表5 三餐之餐點食物濃度 71
表6 依日別及餐別比較膳食食物酞酸酯類攝取量 72
表7 男女性經由食物的酞酸酯類攝取量之比較 73
表8 尿液樣本中酞酸鹽單酯濃度 74
表9 尿液樣本中酞酸鹽單酯濃度變化－依日別、餐別 75
表10 食物樣本添加酞酸酯類標準品回收率 76
表11 尿液樣本添加酞酸鹽單酯標準品回收率 77
表12 本研究與各國的食物中酞酸酯類濃度及每日攝取量比較 78
表13 本研究對象之尿中酞酸鹽單酯濃度與其他研究比較 79











圖目錄


圖1 酞酸酯類一般代謝途徑 80
圖2 酞酸酯類及其單酯代謝物之化學結構 81
圖3 食物樣本處理步驟 82
圖4 尿液樣本處理步驟 83
圖5 尿液中酞酸鹽單酯濃度 84
圖6 尿液中酞酸鹽單酯濃度（經creatinine校正） 84
圖7 依性別分組之尿液中酞酸鹽單酯濃度 85
圖8 依性別分組之尿液中酞酸鹽單酯濃度（經creatinine校正） 85
圖9 本研究各受測者尿中酞酸鹽單酯濃度與時間關係 86
圖10 本研究受測者尿中酞酸鹽單酯濃度與時間關係
（經creatinine校正） 90
圖11 十名受測者平均尿中酞酸鹽單酯濃度隨時間之變化 94
圖12 酞酸酯類標準品層析圖 95
圖13 五種酞酸酯類質譜圖 96
圖14 酞酸鹽單酯標準品層析圖 97
圖15 五種酞酸鹽單酯質譜圖 98
圖16 酞酸酯類分析檢量線 99
圖17 酞酸鹽單酯分析檢量線 101






附錄


附件1 本研究受試者三天的餐點食物內容 103
附件2 尿液樣本採集時間 104
附件3 全體受測者尿中酞酸鹽單酯濃度與時間關係 105
附件4 全體受測者尿中酞酸鹽單酯濃度與時間關係
（經creatinine校正） 107

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