氯乙烯暴露勞工尿中代謝物（TDGA）分析方法建立及現場驗證

The Analytical Method Development and Field Validation of Urinary Metabolite (TDGA) for Vinyl Chloride Exposure Workers

根據環保署毒性化學物質申報資料庫顯示，台灣氯乙烯單體（Vinyl Chloride Monomer, VCM）平均年產量將近200萬公噸，由於VCM具肝毒性，已在1987年被IARC（International Agency for Research on Cancer）訂為第一類人類致癌物（Group 1）。VCM易經由吸入途徑進入人體，並代謝成主要代謝產物TDGA（Thiodiglycolic Acid, TDGA）由尿液排出。過去研究曾使用氣相層析質譜儀（GC/MS）進行尿中TDGA之分析，但受限於偵測極限偏高（1mg/L），無法對低濃度暴露情境進行完整之生物偵測與暴露評估。因此，本研究之目的為開發一套更精準的VCM尿中代謝物分析技術，降低TDGA之偵測極限，以利職業族群之低劑量VCM暴露及健康風險評估研究。本研究採用液相層析串聯質譜儀（Liquid Chromatography-Tandem Mass, LC-MS/MS）進行尿液樣本中TDGA定性與定量分析方法開發。測試結果顯示，分析方法偵測極限（Method Dete tion Limit, MDL）可達1.34 ng/mL。生物指標驗證方面，本研究選取2間大型VCM製造廠，並完成40名VCM職業暴露勞工之工作前、後尿中TDGA分析。進一步針對無肝腎病史、無每日服用綜合維它命，且工時正常之勞工（n=30），進行TDGA濃度數據解析。研究結果發現，工作後尿中TDGA濃度顯著高於工作前（p=0.03, paired t-test）。本研究建置之分析方法未來應可用於VCM職業暴露之生物偵測評估。

According to the Environmental Protection Administration of Toxic Chemical Database, the production quantity of VCM (Vinly Chloride Monomer) in Taiwan was 2 million tons. VCM exposure has been associated with toxicity of the liver and was classified as a group 1 carcinogen by IARC (1987). Due to the extremely volatile property, the major exposure route is inhalation. The main urinary metabolites is thiodiglycolic acid (TDGA). Urinary TDGA can be detected by GS/MS method, but the higher detection limit (>1 mg/L) was the limitation for low exposure workers in VCM plants. In order to assess the relationship of low exposure level of VCM and health risk, development of a precise and accurate analytical method for measurement of urinary TDGA is needed. The high performance liquid chromatography electro-spray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was used as analytical instrument. The method detection limit (MDL) of developed method is 1.34 ng/mL. Forty workers in two VCM plants were recruited as subjects to measure urinary TDGA in pre- and postshift urine sample for each subject. For biomarker validation, the advanced analysis was complied to compare the measures of urinary TDGA within the thirty subjects without histories of liver or kidney diseases, taking daily vitamin supplements, and standard working hours. Study results showed that the post-shift urinary TDGA levels were significantly higher than those of pre-shift. The results showed that the developed analytical method in this study could be used for the low level VCM exposure assessment.