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研究生:張秋琪
研究生(外文):chiu-chi chang
論文名稱:風險評估劑量反應模式低相對風險劑量計算模擬
論文名稱(外文):Low excess risk dose computation and simulation of dose-response model in risk assessment
指導教授:陳主智陳主智引用關係
指導教授(外文):chu-chin chen
學位類別:碩士
校院名稱:淡江大學
系所名稱:數學學系
學門:數學及統計學門
學類:數學學類
論文種類:學術論文
論文出版年:1999
畢業學年度:87
語文別:中文
論文頁數:57
中文關鍵詞:風險評估
外文關鍵詞:additive riskexcess riskthresholdBenchmark doseNOAEL
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在環境暴露濃度的規範,以有效降低或防止對人體的危害,常需要倚賴定量的風險評估,藉由動物實驗結果,以建立劑量反應模式,用來探討暴露劑量下產生病變(例如:癌症腫瘤)的機率,並外插到人體,以制定參考劑量(Rfd)或每天可攝取量(ADI)等標準。然而,在動物實驗中,由於餵食的均屬高劑量,而在法定規範的許可發生機率極低(例如: 。因此,又必須由實驗數據所建立模式外插到極低劑量,以計算反應機率,其中最常見的為LED10(lower 95% confidence interval)與NOAEL(Non-observed adverse effect level),近年,美國環保署極力推動Crump(1984)所提Benchmark dose (BD)的方式,以取代NOAEL,本研究根據Crump所提出劑量反應模式 :
其中 。探討在致癌物質時,此模式在LED10與BD的計算值的穩定性與正確性,並且在有閥值 (threshold) 的假設之下,提出一個估算threshold的方法,用以取代NOAEL並與BD做一比較。
我們得到下列結果 :
1 . 隨機選取qi起始值可能導致ED10的值有極大的差異。以聯立方程式解起
始值是較可行的方法。
2 . LR法正確涵蓋理論ED10的機率可能偏低,反之,MLE法可能有極大的機率現LED10為負的現象。
3 .當正確threshold值愈偏離NOAEL值,則不易檢測出真正的NOAEL,但所估計的threshold值較不易受影響。

In quantitative risks assessment , it is often necessary to regulate environmental hazardons chemical exposure limits in order to prevent harmful effects on human heath . Based on animal experiments , dose-response models can be built , and doses such as LED10 (lower 95\% C.I bound for excess risk of 0.1) and NOAEL (no-observed adverse effect level) are estimated ,and extrapolated to human body to regulate Rfd (reference dose ) or ADI (daily allowable intake ) . Recently,U.S EPA has been advocated BD (benchmark dose) in replace of NOAEL . This research discusses the stability of numerical
calculation of the initial paramenter estimates and compares the coverage percentages of ED10 of the MLE ( maximum likelihood) method and the LR (likelihood ratio) method based on the multistage model of Crump et al (1977). Assumming the existence of threshold , we also propose a nonparametric method to estimate the threshold based on the NOAEL
found by serial chi-squared tests . We found that
1.The initial parameter estimates could lead to very unstable LED10 estimates if randomly generated.
2.The coverage percentage of ED10 by the LR method could be very low; while it is quite
possible to have negative estimates of LED10 by the MLE method.
3. When the threshold value is far away from NOAEL , it is difficult to distinguish the true NOAEL . However , the estimated threshold values were less biased.

第一章 簡介 1
第二章 文獻回顧 5
第三章 起始值之研究 8
第四章 MLE法與LR法之比較 19
第五章 NOAEL與BD之研究 28
參考文獻 38
附錄 41

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