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研究生： 朱彥澂
Chu, Yen-Cheng
論文名稱： 台灣地區市售食品中吡咯利啶生物鹼及莨菪烷類生物鹼背景含量及國人攝食暴露風險評估
Monitoring of pyrrolizidine alkaloids (PAs) and tropane alkaloids (TAs) in selected foods and dietary risk assessment for Taiwanese population
指導教授： 張偉翔
Chang, Wei-Hsiang
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： 2026
畢業學年度： 114
語文別： 英文
論文頁數： 240
中文關鍵詞： 吡咯利啶生物鹼 、莨菪烷類生物鹼 、食品 、攝食暴露 、健康風險評估
外文關鍵詞： Pyrrolizidine alkaloids, Tropane alkaloids, foods, dietary exposure, health risk assessment
相關次數： 點閱：7  下載：0 
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    • 吡咯利啶生物鹼及莨菪烷類生物鹼為多種植物合成之天然次級代謝物，作為對抗草食性動物與昆蟲的化學防禦物質。植物相關食品可能經由作物採收時共同採收含此毒素植物（或其種子/植株碎片）、食品加工過程及經由土壤水平傳輸而受到污染。人體暴露於吡咯利啶生物鹼可能導致肝臟及肺臟毒性，長期暴露則有致癌的風險，而莨菪烷類生物鹼具有抗膽鹼作用，會干擾中樞及自主神經系統中毒蕈鹼型乙醯膽鹼受體之訊號傳遞，引起急性的神經毒性。人體暴露主要透過攝食受污染的植物性產品，包括穀類食品、食用香草、茶與花草茶、草本膳食補充品及辛香料，另外蜂蜜與花粉中也常被檢出生物鹼的污染。然而，至今國內尚未掌握國人經由飲食暴露於吡咯利啶生物鹼和莨菪烷類生物鹼之健康風險，亦尚未針對此二類污染物訂定管制限量。本研究使用系統性採樣策略，考量食品原料、本土性與加工製程等因素，共於台灣採集11類188件食品樣本中，調查30種吡咯利啶生物鹼和7種莨菪烷類生物鹼之污染情形，並進行國人不同年齡層及性別共14個族群之攝食暴露健康風險評估。以經驗證之超高效率液相層析儀搭載串聯式質譜儀分析方法進行30種吡咯利啶生物鹼及其氮氧化物與7種莨菪烷類生物鹼含量分析，最終利用分析得到的數據，以國家攝食資料庫攝食量資料及蒙地卡羅模擬法估算國人攝食暴露，以危害指數（HI）與邊際暴露限值（MOE）兩種方式進行機率風險評估。結果顯示11 類食品中吡咯利啶生物鹼與莨菪烷類生物鹼平均濃度分別為 2.99–125 ng/g 與 0.19–71.4 ng/g，吡咯利啶生物鹼及莨菪烷類生物鹼最高平均濃度於乾燥茶葉及調味料類檢出，濃度分別為125 ng/g及71.4 ng/g。阿托品（At）與東莨菪鹼（Sc）的總量則介於 0.05–0.63 ng/g 之間。在30件茶與花草茶的平均轉移率測試中，吡咯利啶生物鹼平均轉移率於第一泡中為0.04−7.38%，吡咯利啶生物鹼氮氧化型平均轉移率為0.00–11.7%，莨菪烷類生物鹼平均轉移率為0.00−1.13%。吡咯利啶生物鹼平均轉移率於第二泡中略減為0.00−3.68%，吡咯利啶生物鹼氮氧化型平均轉移率為0.00–9.43%，莨菪烷類生物鹼平均轉移率為0.00−0.03%。14對吡咯利啶生物鹼與其相對應氮氧化型中有9對於氮氧化型之平均轉移率較高，與吡咯利啶生物鹼氮氧化型之極性較高且較易溶於水有關。整體而言，第一泡轉移率高於第二泡，且第二泡中莨菪烷類生物鹼多數未檢出，僅tropine可觀察到轉移（0.03%）。以蒙地卡羅模擬法估算14 個年齡性別族群之吡咯利啶生物鹼每日暴露劑量，男女皆在3–6 歲最高。95 百分位危害指數以3–6歲最高，其次為0–3歲，且皆大於1；而 95 百分位數邊際暴露限值皆 ≥ 10,000，顯示因攝食暴露吡咯利啶生物鹼之風險較低，然而相較於成人，嬰幼兒族群可能具有較高的潛在風險。男女攝食暴露2種莨菪烷類生物鹼生物鹼（At 與 Sc）的每日暴露劑量在3–6 歲最高，95 百分位危害指數在各個年齡層皆大於 1（僅女性 ≥65 歲例外），於3–6 歲最高，結果顯示攝食暴露At和Sc可能具有健康風險。結論為本研究開發並驗證了可同時定量測定30種吡咯利啶生物鹼和7種莨菪烷類生物鹼的分析方法，並應用於檢測涵蓋11類共188件台灣市售食品樣本調查。吡咯利啶生物鹼檢出濃度於乾茶葉中含量最高，莨菪烷類生物鹼於調味料中含量最高。在沖泡茶飲中，吡咯利啶生物鹼氮氧化型的轉移率較其相對應的吡咯利啶生物鹼高，可能原因為氮氧化型極性較高，而莨菪烷類生物鹼的轉移率較低。蒙地卡羅模擬法暴露評估結果顯示，3−6歲的兒童族群暴露程度最高。整體而言，吡咯利啶生物鹼暴露風險較低，但嬰幼兒族群的關注度相較成人及長者族群高；而莨菪烷類生物鹼（尤其是At和Sc）暴露則顯示潛在健康風險，建議持續監測與風險管理。

    Pyrrolizidine alkaloids (PAs) and tropane alkaloids (TAs) are two groups of plant secondary metabolites produced as chemical defenses against herbivores and insects. These natural toxins can enter the food chain through co-harvesting of toxic plants, processing steps, and soil-medited horizontal transfer. Human exposure to PAs is particularly of concern due to potential liver and lung toxicity and an elevated to cancer risk with long-term intake. TA acts as anticholinergic effects by inhibiting muscarinic acetylcholine receptors signaling and may casue acute neurotoxicity. The primary exposure pathway is the consumption of plant-derived products contaminated with PAs and TAs, including cereal-based food, culinary herbs, tea and herbal teas, herbal food supplements and spices; additionally, honey and pollen are also common sources. Information on the estimated daily intake and dietary risk assessment for foodstuffs that might be contaminated with PAs and TAs in the Taiwanese population is remains limited. The study aimed to conduct a nationwide monitoring survey of 30 PAs and 7 TAs levels in 188 food samples collected in Taiwan. A direct analytical method was developed and validated, for the first time, to simultaneously quantify 30 PAs and 7 TAs in selected foods. Dietary exposure and associated health risks to the Taiwanese population were then characterized using a probabilistic risk assessment (hazard index [HI] and margin of exposure [MOE]) based on Monte Carlo simulation. Mean concentrations across 11 food categories ranged from 2.99–125 ng/g for total PAs and 0.19–71.4 ng/g for total TAs, respectively, with the highest levels found in dry tea leaves (125 ng/g) for PAs and seasonings (71.4 ng/g) for TAs. For the sum of atropine (At) and scopolamine (Sc), concentrations ranged from 0.05–0.63 ng/g. Across 30 tea and herbal tea infusions, first-brew transfer rates were 0.04−7.38% for PAs, 0.00–11.7% for PA N-oxides (PANOs), and 0.00–1.13% for TAs; second-brew transfer rates decreased to 0.00–3.68% (PAs), 0.00–9.43% (PANOs), and 0.00–0.03% , respectively. Nine of 14 PANOs showed higher transfer than their corresponding PAs, likely due to higher polarity. Overall, transfer was consistently higher in the first brew, and TAs were largely undetectable in the second brew except for tropine (0.03%). Monte Carlo simulation was used to estimat average daily doses for 14 age-sex groups. The highest PAs intake was observed in the 3−6- age group for both male and female. The 95th-percentile HI was highest in the 3−6 year group, followed by the 0−3 year group. The 95th-percentile MOE for both male and female was above 10,000 across all age groups, indicating low risk concern for PA exposure through dietary exposure in Taiwan; however, infants and toddlers may have relatively higher risk than adults. For the exposure to the sum of At and Sc, the highest TAs intake was observed in the 3−6 year group for both males and females. The 95th-percentile HI exceeded 1 in most age groups (except females ≥ 65 years ), with the highest value in the 3−6 yeargroup, suggesting potential health concern from At and Sc exposure across age groups. In conclusion, this study developed and validated a direct method to simultaneously quantify 30 PAs and 7 TAs and applied it in a nationwide survey of 188 food samples collected in Taiwan across 11 food categories. PAs were highest in dry tea leaves, whereas TAs were highest in seasonings. In tea and herbal tea infusions, PANOs generally showed higher transfer than the corresponding PAs, likely reflecting higher polarity, whereas TAs transfer was minimal. Monte Carlo-based exposure assessment identified children aged 3–6 years as the highest-exposure group. Overall, dietary exposure to PAs indicated low risk, with comparatively higher concern for infants and young children than for adults and the elderly, whereas dietary exposure to TAs (notably At and Sc) suggested potential health concern, supporting continued monitoring and risk management.

    Abstract I 中文摘要 III List of figures IX List of tables XI Chapter 1 Introduction 1 1-1 Background 1 1-2 Research questions 4 1-3 Research purposes 4 Chapter 2 Literature review 5 2-1 Chemistry of PAs and TAs 5 2-1-1 PAs structures and physicochemical properties 5 2-1-2 TAs structures and physicochemical properties 6 2-1-3 Stability of PAs and TAs 7 2-2 Toxicity of PAs and TAs 8 2-2-1 PAs toxicity 8 2-2-2 TAs toxicity 11 2-2-3 Human epidemiology data for PA exposure 12 2-2-4 Human epidemiology data for TA exposure 13 2-3 PAs occurrence in food 14 2-4 TAs Occurrence in food 17 2-5 Health based guidance values 20 2-5-1 Establishment of health-based guidance values for PAs 20 2-5-2 Establishment of health-based guidance values for TAs 21 2-6 Health risk assessment for PAs conducted by different organizations 22 2-6-1 European Food Safety Authority (EFSA) 22 2-6-2 Dutch National Institute for Public Health and the Environment, RIVM 23 2-6-3 UK Food Standards Agency, FSA 24 2-6-4 German Federal Institute for Risk Assessment, BfR 24 2-6-5 Hong Kong The Food and Environmental Hygiene Department, FEHD 24 2-7 Health risk assessment for TAs conducted by different organizations 25 2-7-1 European Food Safety Authority, EFSA 25 2-7-2 Joint FAO/WHO Expert Committee on Food Additives, JECFA 25 2-8 Regulation of PAs and TAs for maximum levels in food 26 2-9 Analytical method for PAs and TAs in foods 27 Chapter 3 Materials and methods 29 3-1 Food sampling strategies 29 3-2 PAs and TAs analysis 30 3-2-1 Chemicals and reagents 30 3-2-2 Sample preparation 33 3-2-3 Plant-based food sample 33 3-2-4 Honey sample 34 3-2-5 Oil-based food sample 34 3-2-6 Liquid sample 35 3-2-7 UHPLC–MS/MS analysis 36 3-2-8 Quality assurance and quality control (QA/QC) 37 3-3 Food consumption data 38 3-4 The calculation of value below the LOQ 38 3-5 Dietary daily intakes calculation 39 3-6 Health risk assessment for PAs and TAs 40 3-7 Uncertainty Analysis of Health Risk Estimation 41 Chapter 4 Results and discussion 42 4-1 Method optimization 42 4-1-1 Chromatography and UHPLC-MS/MS method 42 4-1-2 Optimization of sample preparation and SPE column 43 4-1-3 Optimized extraction and clean-up method for honey 44 4-1-4 Optimized extraction and clean-up method for oil-based food 45 4-1-5 Optimized extraction and clean-up method for plant-based food 46 4-1-6 Matrix effects between labelled internal standard and matrix-matched calibration method 47 4-2 Method validation 47 4-2-1 Linearity 47 4-2-2 Accuracy 48 4-2-3 Sensitivity 49 4-2-4 Precision (repeatability and intermediate precision) 49 4-3 QA/QC for PAs and TAs in foods 51 4-3-1 Method blank sample 51 4-3-2 Quality check sample 51 4-3-3 Duplicate sample 51 4-4 Occurrence of PAs and TAs in food 52 4-4-1 Occurrence of PAs in foods 52 4-4-2 Occurrence of PAs compared with EU regulation 63 4-4-3 Occurrence of TAs in foods 64 4-4-4 Occurrence of TAs compared with EU regulation 72 4-5 Dietary exposure estimation 72 4-5-1 Average dailydoses (ADDs) for individual PAs and TAs 72 4-5-2 Average daily doses (ADDs) for the sum of 30 and 28 PAs 83 4-5-3 Average daily doses (ADDs) for the sum of 7 TAs 83 4-5-4 Average daily doses (ADDs) for the sum of 2 TAs (At+Sc) 84 4-5-5 Lifetime Average daily doses (LADDs) for the sum of 30 and 28 PAs 84 4-5-6 PAs exposure compared to other studies 85 4-5-7 TAs exposure compared to other studies 86 4-6 Health risk estimation 87 4-6-1 Hazard index (HI) for PAs exposure 87 4-6-2 Hazard index (HI) for TAs exposure 88 4-6-3 Margin of exposure (MOE) for PAs exposure 89 4-6-4 Margin of exposure (MOE) for PAs compared to other studies 90 4-6-5 TAs (the sum of At and Sc) exposure compared to ARfD 93 4-7 Sensitivity analysis 94 4-7-1 Sensitivity analysis for the exposure to 30 PAs 94 4-7-2 Sensitivity analysis for the exposure to 7 TAs 96 4-7-3 Sensitivity analysis for the exposure to the sum of At and Sc 97 4-8 Transfer rate from dried tea to tea infusion 99 4-8-1 Transfer rate for PAs from dried tea to tea infusion 99 4-8-2 PAs transfer rate compared to other studies 100 4-8-3 Transfer rate for TAs from dried tea to tea infusion 102 4-8-4 TAs transfer rate compared to other studies 103 Chapter 5 Research limitations 104 Chapter 6 Conclusions 106 Chapter 7 Recommendations 109 Reference 110

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