以尿液中硫代二乙酸評估雲林縣麥寮鄉六輕工業區附近國小學童氯乙烯單體之暴露

Using Urinary Thiodiglycolic Acid to Assess Vinyl Chloride Monomer Exposures for Elementary Students Near a Petrochemical Complex in Yunlin County, Taiwan

劉力瑄(Li-Hsuan Liu)

指導教授 ： 詹長權

國立臺灣大學/公共衛生學院/職業醫學與工業衛生研究所/碩士(2014年)

https://doi.org/10.6342/NTU.2014.02150

摘要

背景：中華民國第六套裂解廠(六輕)的生產過程可能造成各種汙染物之排放，其中氯乙烯及聚氯乙烯廠產生的氯乙烯單體(Vinyl chloride monomer, VCM)為第一級致癌汙染物，其對六輕附近國小學童的風險尚未進行評估。VCM經由人體代謝後會產生硫代二乙酸(Thiodiglycolic acid, TdGA)由尿液排出，然而目前對尿液中TdGA分析的方法不適用於本研究對象。
目的：本研究之目的有二，第一部分為開發一套低偵測極限的TdGA分析方法，第二部分是運用所開發的生物偵測方法評估四所國小學童尿液中TdGA濃度和學校與六輕氯乙烯及聚氯乙烯廠距離之間的關係。
方法：尿液中TdGA分析方法開發分成兩部分進行，分析方法最佳化的過程包含建立儀器分析條件、樣本前處理方法、檢量線準確性及精確性和方法偵測極限，而後透過真實樣本上機進行品質保證與品質管理(QA/QC)程序，其中包括儀器穩定度測試、樣本TdGA的定性及定量以及樣本再現性。優化條件建立完成後，應用所開發方法對雲林縣麥寮鄉與六輕距離0.9公里的許厝分校、2.7公里的豐安國小、5.5公里的橋頭國小及6.9公里的麥寮國小，四所國小學童共268位學童進行尿液中TdGA的偵測，其中尿液偵測結果符合本研究之QA/QC及校正問卷資料都齊全的有242位學童。使用共變數及多重迴歸分析控制TdGA的干擾因子，包括年齡、性別、是否有B肝、是否有服用維生素B之習慣及環境二手菸暴露等影響後，進行242位學童TdGA濃度在四國小間的差異分析。
結果：本方法最佳化結果是將尿液進行30倍稀釋及蛋白質沉澱的前處理，檢量線的準確度介於85-104 %，日內精確度之相對偏準偏差百分比為2-9 %，日間精確度之相對偏準偏差百分比為4-11 %，而本方法之偵測極限為0.259 ng/mL，樣本再現性介於92-106 %。四間國小242位學童的基本人口學資料顯示，麥寮國小學童的父親教育程度顯著高於許厝分校及橋頭國小，豐安國小學童父親在六輕上班的比例顯著低於許厝分校及橋頭國小，許厝分校及豐安國小的學童住家與六輕的距離顯著小於橋頭及麥寮國小，而橋頭國小的學童身體質量指數顯著高於其他三間學校。四間學校242位學童尿液中TdGA濃度平均值，許厝分校為193.06 ± 139.56 μg/g-creatinine，豐安國小為101.05 ± 75.52 μg/g-creatinine，橋頭國小為121.32 ± 81.70 μg/g-creatinine，麥寮國小為113.52 ± 91.86 μg/g-creatinine，其中許厝分校有有4位學童尿液TdGA濃度超過500 μg/g-creatinine。而經共變數分析逐步控制各個干擾因子，許厝分校學童尿液中TdGA濃度都顯著高於麥寮國小。沒有B肝、服用維生素B習慣及二手菸暴露的四間國小共81位學童以共變數分析校正了性別及年齡後，許厝分校與麥寮國小尿液中TdGA濃度呈邊際顯著，以許厝分校學童尿液中TdGA濃度較高。另外，進行回歸分析的結果發現，許厝分校學童尿液中TdGA濃度相對於麥寮國小增加了約80 μg/g-creatinine，且年紀越小的男性學童尿液中TdGA也有較高的現象。
結論：本研究發現，四所學校學童大部分都有尿液中VCM代謝物的檢出，顯示所評估的四所國小可能受到不同程度VCM污染。其中距離六輕氯乙烯及聚氯乙烯廠0.9公里的橋頭國小許厝分校，TdGA濃度高於其他三所國小約80 μg/g-creatinine。從公共衛生的角度，為降低麥寮鄉學童的致癌風險，應採取有效方式降低學童VCM的暴露，其中尤以剛遷校的許厝分校最為迫切。

關鍵字

氯乙烯單體 ； 硫代二乙酸 ； 生物偵測 ； 石化工業 ； 學童

並列摘要

Background: Many industrial processes are taking place in the No.6 Naphtha Cracking Complex. Among them, productions of vinyl chloride and polyvinyl chloride (PVC) could release trace level of vinyl chloride monomer (VCM), a group I carcinogen, to the atmosphere and affect human health. Upon exposure, VCM is metabolized by the cytochrome P450 enzymes and is excreted through urine as thiodiglycolic acid (TdGA). Methods to measure TdGA are available but generally lack the sensitive required for low dose assessment. To our knowledge, no exposure or risk assessment of VCM for the nearby children has been done.
Objectives: The objectives of current study are to 1) develop a TdGA analytical method with lower detection limit, and to 2) assess whether urinary TdGA level found in elementary schoolchildren could be used as a marker to reflect the distance relationships between schools and the vinyl chloride production plants.
Methods: Sensitivity of the TdGA method was mainly improved through optimizing the urine pretreatment conditions and instrument parameters. Quality assurance and quality control (QA/QC) parameters, such as method accuracy, precision, detection limit and instrument stability were characterized with the data obtained from spiked analytical blanks and urine samples. Samples were collected (N=268) from the children attending four elementary schools located in Mailiao, Yunlin. The schools, namely Hsu-Tso, Feng-An, Ciao-Tou and Mai-Liao, were 0.9, 2.7, 5.5 and 6.9 km away from the VCM and PVC plants of the cracking complex respectively. Samples that failed to meet the predefined QA/QC criteria and with incomplete questionnaire information were filtered, and the final inclusion rate for statistical analysis was over 90% (242/268). Analysis of covariance (ANCOVA) and multiple regression models were used to assess the relationship between urinary TdGA level and the school-plant distance. Confounding factors such as age, gender, hepatitis B, intake of vitamin B and exposure to second-handed smoke were controlled in the models.
Results: The urine pretreatment procedure was a 30-fold dilution followed by protein precipitation. The accuracy of the calibration was in the range of 85-104%. The intra-day and inter-day precision was 2-9% and 4-11% respectively (expressed as percentage relative standard deviation, %RSD). Method detection limit was estimated to be 0.259 ng/mL and the reproducibility was 92-106%. The following trends were found from the analysis: Demographic information of the study subjects revealed that the education level of father was significantly higher in Ciao-Tou than Hsu-Tso and Mai-Liao. The proportion of “father currently working at the complex” was significantly lower in Feng-An than Hsu-Tso and Mai-Liao. It was found that the distance between children’s homes and complex was shorter in Hsu-Tso and Feng-An than Ciao-Tou and Mai-Liao. In addition, the body mass index of Ciao-Tou elementary school was significantly higher than the other three schools. Mean urinary TdGA concentrations were: Hsu-Tso, 193.06 ± 139.56 μg/g-creatinine; Feng-An, 101.05 ± 75.52 μg/g-creatinine; Ciao-Tou, 121.32 ± 81.70 μg/g-creatinine and Mai-Liao, 113.52 ± 91.86 μg/g-creatinine. There were 4 students in Hsu-Tso whose urinary TdGA level exceeded 500 μg/g-creatinine. Results from ANCOVA analysis indicated that mean TdGA level of Hsu-Tso was significantly higher than Mai-Liao. Eighty-one children were found to have no hepatitis B, vitamin B intake and exposure to second-handed smoke. From the ANCOVA analysis of these 81 students, the TdGA level was marginally significant in Hsu-Tso elementary school and Mai-Liao elementary school, with a higher level in Hsu-Tso. From the multiple regression model, urinary TdGA was 80 μg/g-creatinine higher in Hsu-Tso than Mai-Liao, and younger male children tended to have a higher TdGA level.
Conclusion: It is found that almost all the children in the study have detectable urinary TdGA, which suggests that VCM exposure can be common. Hsu-Tso elementary school is closest (0.9 km) to the cracking complex among four and has a mean TdGA level about 80 μg/g-creatinine higher than the others. From a public health point of view, appropriate measures are needed to lower VCM exposure to children, especially to those attending the Hsu-Tso elementary school.

並列關鍵字

VCM ； TdGA ； Biomonitoring ； Petrochemical complex ； Elementary Students

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