| 研究生: |
何信慧 Ho, Hsin-Hui |
|---|---|
| 論文名稱: |
測量老鼠毛髮中鄰苯二甲酸二異壬酯代謝物作為其長期暴露評估之方法 Determination of di-iso-nonylphthalate metabolites in rat hair for the long term exposure assessment |
| 指導教授: |
廖寶琦
Liao, Pao-Chi |
| 學位類別: |
碩士 Master |
| 系所名稱: |
醫學院 - 環境醫學研究所 Department of Environmental and Occupational Health |
| 論文出版年: | 2013 |
| 畢業學年度: | 101 |
| 語文別: | 英文 |
| 論文頁數: | 43 |
| 中文關鍵詞: | 鄰苯二甲酸二異壬酯代謝物 、萃取 、定量 、非侵入性 、頭髮 |
| 外文關鍵詞: | Di-isononyl phthalate metabolites, long term exposure, hair |
| 相關次數: | 點閱:111 下載:0 |
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鄰苯二甲酸二異壬酯(DINP)被當做塑化劑與添加劑使用,並廣泛運用於工業上,如PVC製品。人們會藉由使用這些產品,進而接觸到DINP。在動物實驗中已證實懷孕的母鼠長期暴露DINP造成出生的雄性小鼠乳頭畸形以及生殖力下降。目前評估DINP暴露為量測尿液中的DINP代謝物。DINP的半衰期短在人體中快速被代謝並從尿液排出體外,測定尿液中DINP代謝物僅能反映幾天前的暴露,故先前幾個研究探討流行病學研究時尿液採樣時間點的重要性,但DINP對人體的影響(如荷爾蒙)是由長時間暴露所造成的,利用單泡尿液評估個人長期暴露是不足的,這也使得幾個流行病學研究無法取得DINP影響人體內分泌的結果一致。因此尋找長期暴露的指標對於未來評估DINP的暴露與人類健康影響是有幫助的。相較於其他生物檢體,毛髮可用來反映長時間的暴露,因此本實驗為透過分析毛髮中的八種DINP代謝物,並且去探討是否隨著暴露劑量升高,在毛髮中的八種DINP代謝物訊號強度也隨之升高。實驗中利用動物實驗確認毛髮中含有DINP的代謝物,我們利用單一劑量暴露來證實暴露組與對照組是否有差異,另外劑量效應實驗則是反映代謝物在毛髮的累積量。單一劑量暴露實驗結果,在毛髮中八種代謝物在暴露組與控制組有顯著的差異(p<0.05)。在劑量與反應的組別當中,結果發現毛髮中八種代謝物與暴露劑量有明顯的正相關。我們也討論了暴露DINP一個月後老鼠毛髮與尿液中代謝物之間的相關性,結果發現,MINP、MOINP與MHINP有顯著的相關性(r分別為0.86、0.79 和0.74,p<0.05)。綜合以上的動物實驗的結果證實可在毛髮中量測到DINP的八種代謝物,此外,我們是第一個利用毛髮樣本來評估DINP暴露的研究。
Di-iso-nonyl phthalate (DINP) is a widely used plasticizer in industry. It is a major part of PVC products. People will come in contact with this chemical by using those products. When pregnant rats were exposed to DINP, some male pups displayed female-like nipples and reproductive malformations. So far, DINP metabolites were used as biomarkers to assess human exposure. The most common sample analyzed for these chemicals was urine. Since DINP metabolites are rapidly excreted out of the body, using a single point urine analysis will only represent personal exposure in the past few hours. Several studies have discussed that the sampling timing is important for a meaningful epidemiologic evaluation of the effects of DINP exposure. Human health can be affected by long term DINP exposure. Using a single point urine analysis to assess long term exposure may potentially cause inconsistency in epidemiologic studies. It is thus necessary to find a long term exposure biomarker to be able to accurately assess the correlation between DINP exposure and health. As opposed to biofluid analysis, hair analysis has the potential of being able to determine chemical exposure of several months to years. Our goals in this study were: 1) Detection of the eight DINP metabolites (that were identified from our previous research) in the hair samples and 2) To determine the dose response of the eight DINP metabolites in rat hair after oral administration of varied doses of DINP. In the single-dose study, we wanted to know if the eight metabolite signals were significantly increased in the exposure group. In the dose-dependent study, we tried to determine the correlation between varied doses and varied metabolite signal intensities. Results from the single-dose treatment batch showed that the eight metabolites in hair were significantly higher in the exposed group than in the control group (p<0.05). Moreover, the dose-dependent batch results show that all the analyzed metabolites in the hair had a positive correlation with increasing doses of DINP. We also discussed the metabolite signal correlation between rat urine and hair after one month DINP exposure. The DINP metabolite signals of MINP, MOINP and MHINP (in hair and urine) were significantly correlated (r =0.86, r =0.79 and 0.74, respectively, p<0.05). Thus, our animal experiment proved that DINP metabolites could be detected in exposed rat hair. To our knowledge, we are the first study to analyze hair samples for DINP exposure.
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校內:2018-07-31公開