合成皮製造業勞工丁酮混合暴露對於二甲基甲醯胺生物偵測之影響

The Effects of Mixture Exposure to Methyl Ethyl Ketone on Urinary Biomarkers of N,N- methylformamide Exposure among Synthetic Leather Workers2

在一般的環境或職場中，人類暴露到化學物質通常為混合物暴露，隨著化學物質的組成與強度不同，混合物暴露可能會導致其毒性降低或是增加。在職場環境中極易同時暴露到二甲基甲醯胺（DMF）與丁酮（MEK），本研究主要目的是探討共同暴露丁酮不同濃度時，對於DMF暴露生物指標即尿中DMF（U-DMF）與尿中NMF（U-NMF）的影響。研究上採二階段現場採樣策略，第一階段對於選定之一家合成皮工廠所有可能暴露DMF的勞工（n=65）進行個人空氣樣本採樣，依據DMF與MEK共同暴露濃度高低來分成四組後，再選取其中35 位勞工進行第二階段採樣，環境偵測包括個人空氣DMF 與MEK及皮膚DMF 暴露濃度測定，而生物偵測則收集勞工下班尿液樣本以分析U-DMF 及U-NMF 濃度。高DMF 暴露組的U-DMF 濃度，無論MEK 共同暴露高低均一致，較低DMF 暴露組的U-DMF 濃度顯著為高（p＜0.05），此與四組DMF空氣暴露濃度趨勢呈現一致；然而在U-NMF方面則顯示不同的結果，DMF 與MEK 共同暴露皆為高暴露組，其U-NMF 較DMF 高暴露，且低共同暴露組的U-NMF 顯著為低。由代謝指標比（metabolic index, MI）在四組分布情況可發現，高濃度共同暴露會在DMF高暴露時，對DMF生化轉換成NMF產生顯著之抑制作用（p＜0.001）；再進一步以簡單線性迴歸可得知，高DMF暴露（＞7.8 ppm）時增加一個自然指數單位的MEK可對MI降低為原來的0.78倍。本研究的結論是當在高DMF暴露時，MEK共同暴露會抑制NMF的產生，因為DMF暴露的職業現場之MEK共同暴露是十分普遍，我們建議未來在相關職場進行生物偵測時需同時考量共同暴露的濃度，以對生物暴露指標進行適當調整，以免對現場作業員工的DMF之暴露產生低估。

Exposure to chemical mixtures is very common in the general environment as well as in most occupational settings. Toxicity of the mixtures depends on their constituents and potencies. It is very likely that the workers could be exposed to N,N-dimethylformamide (DMF) and methyl ethyl ketone (MEK) in the occupational environment simultaneously. This study was aimed to investigate the effects of the different MEK co-exposure levels and different DMF on two biomarkers of DMF exposure metabolism-free form (U-DMF) and biotransformation-required form (U-NMF), respectively. A two-stage field investigation strategy was implemented. Sixty-five workers with possible exposure to DMF in a synthetic leather factory were assessed for DMF and MEK co-exposure. Thirty-five workers were then classified into four subgroups based on their DMF exposure and MEK co-exposure levels determined in the second stage. Personal exposure monitoring of airborne DMF and MEK as well as dermal DMF exposure was performed. Post-shift urine for each individual was collected and was analyzed for U-NMF and U-DMF levels, respectively. U-DMF concentrations in the high DMF subgroups were significantly higher than those in the low DMF subgroups (p＜0.05). On the other hand, U-NMF concentrations in high DMF with low MEK co-exposure subgroup but not for the high DMF with high MEK co-exposure subgroup, were significantly higher than those in the low DMF subgroups. Metabolic index (MI) showed the biotransformation from DMF to NMF was suppressed while MEK co-exposure levels were high (p＜0.001). Based on regression model estimates, per ppm increment of airborne MEK co-exposure (ppm) could suppress MI to 0.78-fold while the workers occupationally exposed to DMF at about 7.8 ppm. It is concluded that co-exposure to high MEK could suppress the NMF generation in high levels of DMF exposure. It is also suggested that due to the ubiquity of co-exposure to MEK in DMF-exposed occupational settings, biological exposure index for occupational DMF exposure should be adjusted while the co-exposure levels are substantial.