國人順丁烯二酸及反丁烯二酸暴露之初探

Abstract

順丁烯二酸酐(Maleic anhydride)，工業上常用於製造船隻、汽車、水管和家電之聚酯樹酯的原料。2013年，台灣爆發「順丁烯二酸酐化製澱粉」事件，為非法添加順丁烯二酸酐化製澱粉於澱粉製品中，以增加澱粉製品的Q彈口感並降低產品成本，其製品包括粉圓、肉圓、粄條、黑輪和米粉等等。順丁烯二酸酐在水中極易形成順丁烯二酸(Maleic acid)，而順丁烯二酸在大鼠和狗身上會出現類似人類范可尼氏症候群(Fanconi syndrome)的症狀，包括糖尿(Glucosuria)、胺基酸尿(Aminoaciduria)、磷酸鹽尿(Phosphaturia)，並且會影響腎臟的酸鹼平衡和近端腎小管的再吸收功能，推測其原因是由於順丁烯二酸的暴露導致刷狀緣上柱狀細胞離子傳輸的功能受損所致，特別是在腎臟皮質的髓射線以及腎臟髓質的外條紋部分，但其在人體中的影響機制仍有待確認。美國國家環境保護局(United Sates Environmental Protection Agency, U.S. EPA)以兩年毒理試驗的數據定訂順丁烯二酸酐的參考劑量(Reference dose, RfD)為0.1 mg/kg/day。 反丁烯二酸(Fumaric acid)為順丁烯二酸的幾何異構物，早在1946年便開始作為食品添加物，美國藥物食品管理局(U.S. Food and Drug Administration, U.S. FDA)和台灣衛生福利部食品藥物管理署(Taiwan Food and Drug Administration, TFDA)亦將其歸類為食品添加物，可適量添加在食品和食品包裝材中。世界衛生組織食品添加劑專家聯合委員會(The Joint FAO/WHO Expert Committee on Food Additives, JECFA)定訂反丁烯二酸的每日容許攝取量(Acceptable daily intake, ADI)為6 mg/kg bw。因此，本研究的研究目的在於建立以液相串聯式質譜儀搭配同素稀釋法分析食品中順丁烯二酸和反丁烯二酸的分析方法，並對台灣19到65歲的成人進行暴露劑量的估算。 食品樣本是自2015年4月開始收集，購買自台北市傳統市場、手搖杯飲料店和量販通路，樣本種類包含米粉、冬粉、肉圓、黑輪、太白粉、木薯粉、在來米粉、果凍、年糕、粉圓以及咖啡等十一個品項，樣本均質後經萃取、鹼水解、除油、離心、取上清液、過濾等過程後再上機進行分析。分析管柱是使用C18管柱，並以同位素內標準品定量，有良好的線性(r2>0.995)，同日(Intra-day)和異日(Inter-day)的精密度(Precision)和準確度(Accuracy)之變異皆落在15 %的誤差範圍之內。順丁烯二酸的LOD(Limit of detection)和LOQ(Limit of quantitation)分別為0.5 ng/g和1 ng/g，而反丁烯二酸的LOD和LOQ分別為10 ng/g和25 ng/g。在66個樣本中，有60個樣本測到的順丁烯二酸是可以定量的，有39個樣本測到的反丁烯二酸是可以定量的。 暴露評估的部分是使用貝氏統計馬可夫鏈蒙地卡羅(Bayesian Statistic Markov chain Monte Carlo, BSMCMC)的抽樣方法進行模擬，並利用國家攝食資料庫之攝食量數據估算終生平均每日暴露劑量(Life average daily dose, LADD)和危害商數(Hazard index, HI)，結果顯示目前台灣19至65歲成人對於順丁烯二酸和反丁烯二酸的暴露劑量並不會對人體造成不良效應。

Maleic anhydride, mainly used in the manufacture of polyester resins for boats, autos, piping, and electrical goods. However, in 2013, maleic anhydride was found to be illegally adulterated into starch in Taiwanese traditional delicacies such as tapioca balls, Taiwanese meatballs and rice noodles. Once consumed, maleic anhydride will form maleic acid which may cause tubular injury and necrosis in the proximal tubules, primarily in the medullary rays, outer strip of the medulla. In dogs and rats, maleic acid produces a condition analogous to the human Fanconi syndrome, characterized by increasing urinary elimination of glucose, amino acids and other biochemical, resulting from impaired tubular reabsorption of these materials. On the other hand, fumaric acid, which is an isomer of maleic acid, has been used as a food acidulent since 1946. In this case, the aim of this study is to develop an analytical method to determine the total amount of maleic acid and fumaric acid in foods with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and assess the exposure in adults in Taiwan. Food samples were collected from supermarkets, chain supermarkets and custom-made beverages stores. Including instant coffee, tapioca starch, rice cake, fish cake, Taiwanese meatballs, tapioca balls, potato starch, chai lai rice flour, jelly bean, vermicelli and rice noodles. Samples were analyzed with C18 column after homogenization, addition of internal standards, base hydrolysis, absorption of lipid and filtration. This method provide good accuracy, precision and linearity. In 66 samples, 60 samples were found quantifiable residue of maleic acid and 39 samples were found quantifiable residue of fumaric acid. By using the residues and the intake rates collected from National food consumption database, life average daily dose (LADD) and hazard index (HI) were simulated by Bayesian Statistic Markov chain Monte Carlo (BSMCMC). As the result, we can suggest that the exposures to Maleic acid and fumaric acid through food consumption is unlikely to cause adverse health effect for 19-65 years-old adults in Taiwan.