近年來發生藥品檢出亞硝胺(N-nitrosamines)不純物事件，使得亞硝胺之致癌性受到民眾高度關注。人體可能藉由飲食與用藥等攝食途徑或化粧品經由皮膚途徑而暴露於亞硝胺之危害。國際間也陸續訂定相關規範，使人體降低暴露於亞硝胺之風險。本研究之目的為針對攝食途徑評估人體暴露於亞硝胺之健康風險。本研究所關注食品中常見之6種亞硝胺，被國際癌症研究中心(International Agency for Research on Cancer)歸類於2A極有可能為致癌因子(Probably Carcinogenic to Humans)的有NDMA (N-nitrosodimethylamine)與NDEA (N-nitrosodiethylamine)；歸類於2B可能為致癌因子(Possibly Carcinogenic to Humans)的有NPYR (N-nitrosopyrrolidine)、NDPA (N-nitrosodipropylamine)、NMEA (N-nitrosomethylethylamine)、及NDBA (N-nitrosodibutylamine)。研究方法分成兩部分，第一部分為健康風險評估，根據文獻彙整食品中亞硝胺濃度來評估食品安全風險，進而篩選出高風險食品；後續再針對高風險食品中貢獻較高之共同來源食品之香腸進行採樣，以及分析NDMA、NDEA、及其前驅物亞硝酸鹽之濃度，再評估各年齡層中一般暴露族群與高暴露族群攝食香腸而攝入亞硝酸鹽之估計每日攝取量(Estimated Daily Intake, EDI)與危害商數(Hazard Quotient, HQ)，以及攝入NDMA與NDEA之EDI與標的致癌風險(Target Cancer Risk, TR)；第二部分為建立每日允許暴露量(Permitted Daily Exposure, PDE)，藉由基準劑量分析軟體模擬基準劑量下限值(Benchmark Dose Lower Bound, BMDL)，再考量不確定性係數(Uncertainty Factor)後計算得之。濃度分析結果顯示，亞硝酸鹽殘留量為0.60–26.59 mg/kg，NDMA與NDEA均未檢出。風險結果顯示，各年齡層中一般暴露族群與高暴露族群因攝食香腸而攝入亞硝酸鹽之HQ均小於1，預期不會有明顯之不良健康影響，表示暴露量低於亞硝酸鹽可能導致之高鐵血紅蛋白血症(Methemoglobinemia)不良反應之閾值，且NDMA與NDEA之TR中僅12歲以下之高暴露族群攝食香腸攝入NDEA之TR略高於10-6，此風險須進行風險管理。而根據BMDL之模擬結果推算NDMA與NDEA之PDE分別為19.2與6.54 ng/kg bw-day，與本研究所計算出各年齡層中一般暴露族群與高暴露族群因攝食香腸而攝入NDMA與NDEA之EDI分別為1.2×10-3－5.3×10-3 ng/kg bw-day與1.1×10-2－9.1×10-3 ng/kg bw-day，EDI結果均低於PDE。但生活中亞硝胺可藉由各種途徑進入人體，因此須持續關注人體經由不同途徑而暴露於亞硝胺之情形，以降低人體暴露於亞硝胺之風險中。

In recent years, the detection of N-nitrosamines as an impurity in pharmaceutical products has led to a high level of public concern about the carcinogenicity of N-nitrosamines. The human body may be exposed to the hazards of N-nitrosamines through the ingestion route, such as via diet and medication, or through the skin route via cosmetics. International regulations have been established to reduce the risk of human exposure to N-nitrosamines. The purpose of this study was to assess the human health risks from dietary exposure to N-nitrosamines. This study focused on the six kinds of N-nitrosamines commonly found in food. The two kinds classified as 2A by the International Agency for Research on Cancer are NDMA (N-nitrosodimethylamine) and NDEA (N-nitrosodiethylamine), which are probably carcinogenic to humans. Classified as 2B are NPYR (N-nitrosopyrrolidine), NDPA (N-nitrosodipropylamine), NMEA (N-nitrosomethylethylamine), and NDBA (N-nitrosodibutylamine), which are possibly carcinogenic to humans. The study method was divided into two parts. The first part was health risk assessment. According to the concentrations of N-nitrosamines in food compiled from the literature, the food safety risk was assessed, and then the high-risk foods were screened out. Subsequently, the sausages of the high-risk foods with high contributions to the common source food were sampled, the concentrations of NDMA, NDEA, and their precursor nitrite were analyzed, and then the sausage consumption of the generally exposed groups and the high-exposure groups in each age group was evaluated. The estimated daily intake (EDI) and hazard quotient (HQ) of ingested nitrite and the EDI and target cancer risk (TR) of the NDMA and NDEA intake were determined. The second part was to establish the permitted daily exposure (PDE), which was calculated by simulating the benchmark dose lower bound (BMDL) and considering the uncertainty factor. The results of the concentration analysis showed that the nitrite residues were 0.60–26.59 mg/kg, and NDMA and NDEA were not detected. The risk results showed that the HQ of the nitrite exposure from sausage consumption was less than 1 for both the general- and high-exposure groups across all age groups, and no significant adverse health effects were expected, indicating that the exposure was below the threshold for Methemoglobinemia, and the TR of NDMA and NDEA was only slightly higher than 10-6 for the high-exposure group under 12 years old. Based on the BMDL modeling results, the PDE of NDMA and NDEA were 19.2 and 6.54 ng/kg bw-day, respectively. The EDI of NDMA and NDEA due to sausage consumption in the average- and high-exposure groups were calculated to be 1.2×10-3 - 5.3×10-3 ng/kg bw-day and 9.1×10-3 - 1.1×10-2 ng/kg bw-day, respectively. Both of them were lower than the PDE. However, N-nitrosamines can enter the human body through various routes in life, so it is necessary to pay attention to the exposure of human bodies to N-nitrosamines through different routes to reduce the risk of human exposure to N-nitrosamines.

摘要 I
Abstract II
索引表 IX
第一章　緒論 1
1.1 研究背景 1
1.2 研究目的 2
第二章　文獻回顧 3
2.1 亞硝胺簡介 3
2.1.1 物化特性 3
2.1.2 亞硝胺來源 4
2.1.3 亞硝胺生成與代謝機制 5
2.1.4 影響亞硝胺生成因素 6
2.2 亞硝胺國際法規 8
2.2.1 食品中亞硝胺之限量 8
2.2.2 飲用水中亞硝胺之限量 8
2.2.3 化粧品中亞硝胺之限量 9
2.2.4 藥品中亞硝胺之限量 9
2.3 健康風險評估 10
2.3.1 健康風險評估架構 10
2.3.2 亞硝酸鹽之毒理參數彙整 11
2.3.3 亞硝胺之毒理參數彙整 11
2.4 亞硝胺風險評估研究 12
2.5 基準劑量法 13
2.5.1 基準劑量法簡介 13
2.5.2 數據型態類型 14
第三章　材料與方法 15
3.1 研究設計 15
3.2 篩選高風險之食品 15
3.2.1 彙整國際間亞硝胺濃度之文獻 15
3.2.2 食品分類原則 16
3.2.3 食品中亞硝胺之暴露量 16
3.2.4 食品中亞硝胺之健康風險評估 16
3.3 規劃採樣策略 17
3.3.1 樣品選擇 17
3.3.2 選擇採樣地點 17
3.3.3 規劃樣品採買、接收、及製備方式 18
3.4 檢驗分析 18
3.4.1 亞硝酸鹽 18
3.4.2 亞硝胺 19
3.5 評估亞硝酸鹽與亞硝胺之食品安全風險 20
3.5.1 香腸中亞硝酸鹽之非致癌風險 20
3.5.2 香腸中亞硝胺之致癌風險 21
3.6 評估每日允許暴露量 21
3.6.1 基準劑量下限量 21
3.6.2 每日允許暴露量 22
第四章　結果 25
4.1 高風險食品之篩選 25
4.1.1 食品中亞硝胺之致癌風險結果 25
4.1.2 主要貢獻食品 25
4.2 濃度分析 27
4.2.1 亞硝酸鹽殘留量 27
4.2.2 亞硝胺 27
4.3 攝食香腸對人體之潛在風險評估 27
4.3.1 攝入亞硝酸鹽對人體之健康風險 27
4.3.2 攝入NDMA與NDEA對人體之健康風險 28
4.4 每日允許暴露量建議 28
4.5 不確定性分析 29
第五章　討論 31
5.1 研究限制 31
5.2 檢驗方法探討 31
5.3 濃度分析結果探討 32
5.4 亞硝酸鹽之潛在健康風險比較 32
5.5 亞硝胺之潛在健康風險比較 33
5.6 每日允許暴露量與估計每日攝取量比較 33
5.7 蔬菜與香腸中亞硝酸鹽含量探討 33
5.8 香腸中還原劑影響亞硝胺生成探討 34
5.9 不同種類之香腸中亞硝胺生成探討 34
第六章　總結 35
第七章　建議 37
參考文獻 39
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