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研究生:王士旻
研究生(外文):Shih-Min Wang
論文名稱:皮革製造業勞工二甲基甲醯胺皮膚暴露評估與二甲基甲醯胺經皮滲透與皮膚滯留之探討
論文名稱(外文):Dermal Exposure Assessment for Workers Exposed to N,N-dimethylformamide (DMF) in Synthetic Leather Industry and An In Vitro Study on Investigating Skin Penetration and Retention
指導教授:蔡朋枝蔡朋枝引用關係
指導教授(外文):Perng-Jy Tsai
學位類別:博士
校院名稱:國立成功大學
系所名稱:環境醫學研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:89
中文關鍵詞:防護具皮膚滯留皮膚穿透皮膚暴露成皮製造業二甲基甲醯胺
外文關鍵詞:protective equipmentreservoir effectskin exposureskin penetrationsynthetic leather industryNN-dimethylformamide
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目前已有許多研究證實DMF對於肝臟及男性精蟲之高毒性,並已知其亦可能經由皮膚吸收進入人體,但事業單位對其之認知與防護卻明顯不足。本研究分為職場研究及實驗室研究兩個部份進行。職場研究的目的在於了解勞工皮膚暴露DMF相對於總暴露劑量之貢獻,及不同個人防護具對皮膚暴露之防護效果。另鑒於以生物偵測的結果推估皮膚吸收量有其不確定性,實驗室研究的目的乃在於利用in vitro的方式,直接量測不同濃度DMF水溶液之皮膚穿透及皮膚滯留量對體內劑量之影響。職場研究係透過連續四天針對相同勞工給予配戴不同個人防護具之研究設計,另以跟隨暴露的方式模擬勞工之暴露情形,再利用尿中代謝物之濃度差異來評估不同個人防護具之防護效果與皮膚暴露之貢獻量。研究結果發現皮膚液體接觸暴露為職業環境中DMF主要暴露來源,因此推論DMF暴露勞工之皮膚防護應較呼吸防護重要。本研究也證實防護霜的防護效果與配戴橡膠手套的防護效果相當。本研究亦發現,皮膚暴露對內在劑量的貢獻達71%,約為呼吸暴露的3.5倍,且若以單一次的尿液樣本來審視之,無法確實反映出體內的總暴露量,亦可能造成對於皮膚暴露量低估的結果。實驗室研究之結果發現,DMF溶液在稀釋後皮膚吸收的能力會大幅降低,其中約有14.1%~34.1%的DMF會滯留於皮膚層中。並發現皮膚在停止暴露後,DMF將慢慢滲透,經由皮膚層進入皮下循環系統而被人體所吸收。鑑於作業現場皮膚採樣大多只能測量到皮膚表面殘留的劑量加上本研究所發現皮膚滯留的影響,故在現階段尚難以透過皮膚採樣的結果直接推估實際皮膚吸收劑量。因此,本研究所提供的DMF皮膚穿透能力及皮膚滯留影響的量化資料,未來亦可作為推估勞工暴露劑量及風險評估的參考依據。
It has been demonstrated that N-dimethylformamide (DMF) is toxic to liver and male sperms and known that DMF is also a skin penetrator. However, regarding the recognition and protection of skin exposure to DMF for industries are still inadequate. Both field study and laboratory study were executed in this study. The field study attempts to quantitatively determine the relative contribution of DMF vapor exposure via skin and inhalation route and to evaluate the protective effectiveness of various personal protective equipments (PPE). Laboratory study is aimed to determine the skin permeability of neat DMF and DMF/water mixtures and to assess their skin reservoir effects on systemic absorption by using the in vitro flow-through diffusion cell. For the field study the effectiveness of various PPE were evaluated through a four-consecutive-workday sampling on DMF exposures to workers. The workers were requested to wear different type of PPE and not wear any PPE across four consecutive days. Moreover the internal dose contribution of DMF vapor skin exposure was determined by using a semi-actual exposure approach. Urinary N-methylformamide (NMF) was determined as biological exposure marker for DMF exposure. We found that the contribution of skin contact to DMF was more significant than that of through the respiratory exposure in the total DMF internal dose. Therefore, the use of skin protective equipment could be more important than that of the respiratory protective equipment. The application of barrier cream can serve as a good measure to effectively diminish the skin absorption of DMF in the occupational setting, particularly it is more convenient to the workers. About 71% of internal dose was contributed from skin vapor exposure (it is about 3.5-fold higher than that from inhalation route). Therefore, internal burden contribution on the basis of spot urine was not able to reflect the actual internal burden of cumulative exposure dose in the comparison of the basis of consecutive urine monitoring. The results obtained from the laboratory study indicate that the presence of water would significantly reduce the permeability of DMF. We also found that the estimated reservoir effect for neat DMF (= 34.1%) was higher than that of 50% and 10% DMF/water mixtures (=27.1% and 14.1%, respectively). The above results suggest that the impact associated with the internal burden of DMF could be prolonged even the external exposure of DMF is terminated, particularly for those dermal contact with DMF/water mixtures with a high DMF content. Due to the difficulty in accurately evaluate the skin absorption dose by using skin exposure data in occupational environment, the quantitative data of DMF skin penetration and retention provided by this study would be the useful information for internal dose estimation and risk assessment.
目錄
摘 要 I
Abstract II
致 謝 IV
目錄 VI
表目錄 VII
圖目錄 VIII
第一章 緒論 1
1-1 研究緣起 1
1-2 研究目的 6
第二章 文獻回顧 7
2-1 DMF與人造合成皮製程之介紹 7
2-1-1 DMF的物化特性與應用 7
2-1-2 DMF暴露之健康危害 7
2-1-3 DMF的代謝路徑 8
2-1-4 DMF之生物偵測 8
2-1-5 DMF之皮膚吸收 9
2-1-6 人造合成皮製程介紹 11
2-2 皮膚吸收介紹 12
2-2-1 皮膚的構造 12
2-2-2 皮膚的功能 12
2-2-3皮膚滲透機制 14
2-2-4皮膚吸收的定義 14
2-2-5影響皮膚吸收的因素 15
2-2-6 體外經皮吸收試驗 15
2-3 防護霜介紹 17
第三章 研究架構、對象、材料、方法與步驟 18
3-1 研究架構 18
3-2實驗材料、試劑與儀器設備 18
3-3 實驗方法與步驟 20
3-3-1 實驗設計 20
3-3-2 樣本分析方法 28
第四章 研究結果與討論 31
第五章 結論與建議 41
第六章 參考文獻 43

表目錄
表2-1.DMF基本物化特性 50
表2-2.影響皮膚吸收的因子 51
表3-1.合成皮製造業勞工基本資料及從事高、低暴露作業之時間比例 52
表3-2.從事、高低作業之勞工在使用各式防護具後DMF的暴露途徑及體內總暴露劑量的貢獻來源 53
表4-1.合成皮製造業勞工連續四天使用不同防護具的配戴方式及勞工尿中NMF的濃度值 (mg/L) 54
表4-2.校正空氣中DMF暴露濃度後之防護具防護係數指標 (Adjusted protective effectiveness index, PEIadj) 55
表4-3.不同暴露途徑對於DMF總暴露劑量的貢獻百分比 56
表4-4.結合紅外線氣體即時偵測器與時間活動模式紀錄計算之兩階段採樣工作中(暴露4小時)及工作後(暴露8小時)個人空氣中DMF暴露濃度值 58
表4-5.跟隨暴露之志願受試者於工作中(暴露4小時)及工作後(暴露8小時)尿中NMF的濃度值(mg/L)及不同暴露途徑對於總暴露劑量的貢獻百分比 59
表4-6.以連續24小時尿液樣本推估之內在暴露劑量及不同暴露途徑對於總暴露劑量的貢獻百分比 60
表4-7.不同濃度DMF水溶液滲透皮膚層後的分布情形與質量平衡的結果 61
表4-8.不同濃度DMF水溶液皮膚滲透參數值(暴露24小時) 62
表4-9.不同濃度DMF水溶液皮膚滲透參數值(暴露12小時) 63
表4-10.不同濃度DMF水溶液在暴露24小時後DMF在皮膚滲透、皮膚滯留及未吸收部分的分布比例 64
表4-11.不同濃度DMF水溶液皮膚滯留量佔總滲透量之百分比 65

圖目錄
圖2-1.DMF在人體內代謝流程圖 66
圖2-2.人造合成皮乾式製程流程圖 67
圖2-3.人造合成皮濕式製程流程圖 67
圖2-4.物質穿透角質層之滲透路徑. 68
圖3-1.研究架構 69
圖3-2.累積滲透量曲線圖 70
圖4-1.合成皮製造業勞工連續四天空氣中DMF暴露濃度值 71
圖4-2.合成皮製造業勞工配戴不同防護具後尿中NMF濃度值相對於未使用任何防護具之尿中NMF濃度值的差異量。 72
圖4-3.不同暴露途徑尿中NMF代謝的一階動力學曲線 73
圖4-4.暴露24小時後不同濃度DMF水溶液的皮膚穿透速率。 74
圖4-5.暴露24小時後不同濃度DMF溶液皮膚穿透的累積滲透量。 75
圖4-6.停止暴露後滯留於皮膚層中的DMF排除出皮膚層的滲透速率。 76
圖4-7.停止暴露後滯留於皮膚層中的DMF的濃度及排除出皮膚層的半衰期。 77
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