臺灣國人尿液中鄰苯二甲酸酯類及其替代品之代謝產物基線值之建立：2019臺灣全國代表性樣本及其分析

Abstract

自2011年發生食品鄰苯二甲酸鹽事件後中，di-(2-ethylhexyl) phthalate (DEHP) and di-isononyl phthalate (DiNP) 被非法添加到食品和藥物中，臺灣民眾開始關注食品安全，在這件事發生後，儘管使用上已有諸多政策的相關限制，但臺灣民眾仍會接觸到一定程度的鄰苯二甲酸酯類。DEHP 和 DiNP 作為廣泛使用的塑化劑，被諸多研究證實是內分泌干擾物質的一種，對人類的生殖、內分泌系統具有毒理作用。 許多國家多年來都持續進行著全國性的監測調查，像從1960年代初開始的美國，開始了名為National Health and Nutrition Examination Survey (NHANES)；1985年在德國，German Environmental Survey (GerES) 開始在西德進行生物監測研究；韓國於2005年也開始了Korean National Environmental Health Survey (KoNEHS)，旨在製定和支持環境相關的政策；最後是加拿大，他們建立了Canadian Health Measures Survey (CHMS)，從2007年開始收集人體生物監測數據。但是，我們國家卻遲遲沒有進行全國性的人體生物監測調查，來收集有關鄰苯二甲酸酯類的代謝產物及其替代產品之暴露水平與濃度基線值的資料。 我們旨在建立一個具有全國代表性的人體生物監測研究，並利用此資料建立鄰苯二甲酸酯類及其替代品的尿中代謝產物，有關臺灣國人的濃度基線值與其分布狀況。我們從2019年進行的臺灣國民營養健康調查中招募了1748名7歲及以上的參與者，方法是使用PPS (probability proportional to size)法抽出村里PSU (Primary sampling unit)進行分層多階段集束抽樣，覆蓋臺灣20個城市或縣。每個鄉鎮和市區依人口密度和都市化程度各分2小層。我們收集了參與者的尿液和血液，並同時收集了有關生活環境和飲食習慣的問卷調查。於尿液檢體的分析上使用超高效液相色譜-串聯式質譜儀測定每個參與者尿液樣本中12種不同鄰苯二甲酸酯類及其替代品之代謝產物(MEHP、MECPP、MiBP、MnBP、MEP、MHINP、MCINP、MBzP、MnOP、oxo-MPHP、OH-MINCH、MECPTP)。我們將臺灣國人之鄰苯二甲酸酯及其替代品之代謝產物分佈的結果與其他國家代表性樣本進行了比較，提供了對各種健康相關主題的國家級估計，在2019年的數據中我們發現，大部分的代謝產物濃度在低年齡層組別（7-12歲）都顯著高於其他年齡層組別（除MEP、MnOP、MBzP），且在與其他國家進行比較時，同時也發現我國在與他國全國性代表資料比較之下，我們國民在MEHP、MECPP、MnBP、MiBP幾種代謝產物之濃度仍明顯高於其他國家，而在替代產物oxo-MPHP、OH-MINCH、MECPTP的濃度則明顯低於其他過家的狀況出現。我們同時使用國人的鄰苯二甲酸酯類及其替代品之代謝產物之基線值與Human biomonitoring initiative (HBM4EU)所公佈的HBM guidance values (HBM-GVs)及HBM-I Value進行比較，其中發現我國國民在兒童組於MnBP、MiBP兩組均有出現超標狀況，超標情形分別為0.42%、0.83%，利用外插法推估至全國人民時則有約5892至11784名兒童有超過健康風險指標值的狀況；而在青少年及成人組的部分，則是發現MnBP、MiBP及oxo-MPHP等三組有出現超標情形，其比例分別為0.13%、0.07%、0.20%，利用外插法推估至全國人民時則有約13791至41373名國人有超過健康風險指標值的狀況。由於監測資料我們得知目前我們鄰苯二甲酸酯類及其替代品的暴露水平依然有高於其他國家且高於健康風險指標值的情形存在，且在塑化劑相關政策管控上仍尚未進行替代品之管制，因此預計持續使用這一項具有全國代表性的人體生物監測研究，以評估臺灣國人對於這些內分泌干擾物質的暴露水平，用以確保我們臺灣民眾每一階段鄰苯二甲酸酯類及其替代品的暴露水平是處在一個安全的生活環境之中。

Since 2011, there was an incident involving phthalate-tainted food, Taiwanese people have become concerned about food safety. Although after this incident happened, people in Taiwan are still being exposed to certain levels of phthalates esters. At that incident, di-(2-ethylhexyl) phthalate (DEHP) and di-isononyl phthalate (DiNP) were illegally added to foodstuffs and medications. DEHP and DiNP, as widespread plasticizers, are considered endocrine disrupting chemicals (EDCs) with main toxicological effects on reproductive and metabolic systems. We like to start a nationwide Human biomonitoring (HBM) studies to evaluate the background exposure levels of these EDCs in Taiwan. Nationwide monitoring surveys have been conducted in many countries. Like the United States beginning in the early 1960s, which call the National Health and Nutrition Examination Survey (NHANES); and in 1985 in Germany, the German Environmental Survey (GerES) began biomonitoring in West Germany; other like the Korea, they also started their Korean National Environmental Health Survey (KoNEHS), which began in 2005 to establish and support environmental policies; and the last but not the least is Canada, they conducted Canadian Health Measures Survey (CHMS) beginning to collect human biomonitoring data in 2007. However, there is no nationwide human biomonitoring survey had been conducted to gather information on levels or reference values (RVs) of phthalates in the Taiwanese population in recent years. We aimed to establish the urinary levels and RVs of phthalate metabolites and identify exposure characteristics among Taiwan’s population. We enrolled 1748 participants 7 years of age and older from the Nutrition and Health Survey in Taiwan (NAHSIT) conducted in 2019 by using probability proportional to size (PPS) and primary sampling unit (PSU) sampling covering 20 cities or counties of Taiwan. Each township and city district were classified into one of two groups according to its population density and urbanization level. We collected participant’s urine and blood, and did the environmental and lifestyle questionnaires. Levels of 12 different phthalate metabolites (MEHP, MECPP, MiBP, MnBP, MEP, MHINP, MCINP, MBzP, MnOP, oxo-MPHP, OH-MINCH, MECPTP) in each participant’s urine samples were determined using Ultra Performance Liquid Chromatography-tandem mass spectrometry (UPLC-MS/MS) for analysis. The results of phthalate esters distribution in Taiwan were compared with other national representative samples that provide national estimates on various health-related topics. Data from 2019 show that concentrations of most metabolites in younger age groups (7–12 years) are significantly higher than in other age groups (except MEP, MnOP and MBzP). According to representative data from other countries, the concentrations of metabolites of MEHP, MECPP, MnBP, and MiBP in our country are still significantly higher than those of other countries; while the concentrations of alternative products, oxo-MPHP, OH-MINCH and MECPTP are significantly lower than others. And we also used our RVs of urinary phthalate metabolites compared with HBM guidance values (HBM-GVs) and HBM-I Value announced from Human biomonitoring initiative (HBM4EU). Of these, in the children group, both the MnBP group and the MiBP group exceeded the criteria, and it was found that the cases exceeding the criteria were 0.42% and 0.83%, respectively. Using extrapolation to estimate the national population, there were approximately 5,892 to 11,784 children who exceeded the threshold which is the status of the risk index value. Among adolescents and adults, three groups were found to exceed the norm: MnBP, MiBP, and Oxo-MPHP, at rates of 0.13%, 0.07%, and 0.20%, respectively. Using extrapolation to estimate the national population that about 13,791 to 41,373 people are above the health risk index values. Monitoring data shows that our exposure to phthalates remains higher than in other countries, and some phthalates and their substitutes were above health risk indicators. Our political restrictions on plasticizers substitutes have not yet been implemented well. Therefore, this national representative human biomonitoring study will continue to be conducted to ensure that Taiwan's phthalates exposure level every year are safe and make some recommendation to our government. In order to make sure our Taiwanese general population keep in a safe living environment.