健康風險評估於食品加工之應用－以高粱酒中乙醛為例

Abstract

國際癌症研究機構 (International Agency for Research on Cancer, IARC) 於 2012年將酒精飲料及存在其中的乙醛(Acetaldehyde) 列為1級致癌物(IARC 1)。目前國外已有針對酒精飲料中乙醛之致癌風險進行評估，評估酒品項目包括啤酒、葡萄酒、威士忌、白蘭地等常見洋酒。高粱酒為華人文化中十分常見的中式白酒品項之一，中式白酒因屬酒精濃度高的蒸餾酒類，且製程相比其他蒸餾酒類更為複雜，故乙醛含量普遍高於國外蒸餾酒，惟目前國內外皆未有針對中式白酒進行風險評估的研究。本論文藉由模擬高粱酒製程預測乙醛在其最終產品中的含量，並針對國內男性、女性及全體國民因飲用高粱酒而暴露到乙醛致使產生不良健康反應之風險進行評估。 本研究將高粱酒製程分成發酵、蒸餾、熟成三階段，探討各階段製程條件對乙醛濃度之影響，並分析各階段之乙醛濃度，得結果分別為72、295、471 mg/L，後續利用拉丁超立體取樣(Latin Hypercube Sampling, LHS)技術及部分排序相關係數(Partial ranked correlation coefficient, PRCC)執行製程條件敏感度分析，以得知各製程參數對乙醛生成的影響程度。另採用Sprague-Dawley大鼠進行為期104周的慢性毒性實驗結果以Benchmark Dose Software進行運算，經過體重比例調整後得基準劑量10％下限值(BMDL10)為16.91 mg/kg/day。利用Crystal Ball軟體對各參數進行50000次蒙地卡羅抽樣進行風險值評估，計算國內高粱酒消費者(Consumer only)透過攝食高粱酒而暴露乙醛之致癌風險(Cancer risk)及暴露限值(Margin of exposure, MOE)。全體國人高粱酒消費者致癌風險(Cancer risk)中位數為5.35×10-3，95%的信賴區間上限為2.72×10-2，男性及女性高粱酒消費者致癌風險中位數則分別為4.68×10-3及1.43×10-2；全體國人、男性及女性之暴露限值中位數分別為18.5、21.2、6.94。致癌風險高於10-4或暴露限值低於104表示透過攝食高粱酒而攝取到乙醛並產生不良健康影響的風險需要特別關注。本研究亦對致癌風險進行敏感度分析，發現影響最大的影響因素為高粱酒的攝食量，與致癌風險呈正相關且影響程度約占94％。 本論文希望建立可作為未來產品生產前預測最終產品之特定有害物質的濃度並進行風險評估之方法，讓產品在生產前即可預測特定化學物質之風險，供業者作為製程改良及消費者購買之參考。

Acetaldehyde (ethanol, CHCHO, CAS # 75-07-0) is a metabolite of ethanol which occurs in the human body after the consumption of alcoholic beverages. Additionally, it is widely exists in foods, beverages and industry as well as in the environment. It is known as a carcinogenic substance. In 2012, International Agency for Research on Cancer (IARC) listed acetaldehyde in alcoholic beverages as a Class 1 carcinogen. Foreign research has already assessed the risk of acetaldehyde in many kinds of alcoholic beverages included beer, wine, whiskey, brandy and other common alcohols. However, there is no research on risk assessment for Chinese liquor at present. We simulated the production process of sorghum liquor to predict the amount of acetaldehyde in the final product, and then evaluate the health risk for domestic men, women and all citizens who exposure to acetaldehyde due to drinking sorghum liquor. According to the results from this study, we knew the predicted concentration of acetaldehyde after the end of the three stages of fermentation, distillation and aging is 72、295、471 mg/L respectively. In addition, we used Latin Hypercube Sampling (LHS) method and Partial ranked correlation coefficient (PRCC) to perform sensitivity analysis to know the influence of each manufacturing parameter. On the other hand, we used the results from chronic animal experiment in Sprague-Dawley rats for a period of 104 weeks to establish dose-response relationship and obtain the baseline dose 10% lower limit (BMDL10). After adjusting the body weight, BMDL10 is 16.91 mg/kg/day. The risk exposed acetaldehyde due to consume sorghum liquor is evaluated by using the Crystal Ball software to perform 50,000 Monte Carlo sampling of each parameter to calculate the cancer risk and margin of exposure (MOE).The median of cancer risk and MOE for all citizens drinking sorghum liquor are 5.35×10-3 and 18.5, respectively. The result indicated that adverse health effects from exposure through consuming sorghum liquor requires attention. The study also analyzed the sensitivity of cancer risk and MOE, and find that the most influential factor is the intake of sorghum liquor, which was positively correlated with cancer risk, but negatively with MOE, both influence accounts for about 94%. This study hopes to establish a method for predicting the concentration of specific hazardous substances in the final product before production and conduct the risk assessment to provide the industry a reference for process improvement and consumer purchase.