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  • 學位論文

自行車貼標作業勞工乙二醇丁醚暴露調查及健康效應評估研究

2-Butoxyethanol Exposures and Health Effect Assessment for Decal Transfer Workers in Bicycle Manufacturing Factories

指導教授 : 蔡詩偉
共同指導教授 : 劉紹興

摘要


由於乙二醇醚類(glycol ethers)溶劑的物理及化學特性,其被廣泛地使用於工業及家庭中,如轉印高級自行車的車身圖騰時就需要使用乙二醇丁醚(2-butoxyethanol, 2-BE)溶劑。為了要讓產品更為精良,自行車貼標工人是以手工、未穿戴防護手套的方式工作,且需直接以雙手接觸約10%(v/v) 2-BE稀釋溶液,並控制2-BE溶液的溫度,在此種作業條件下,可能會大大地增加勞工2-BE攝入體內的風險,而2-BE的健康效應,主要是在紅血球細胞(red blood cells)的不良效應上。 本研究即是以較高2-BE攝入風險的自行車2-BE貼標工為採樣對象,分析其尿中總BAA濃度,來探討使用2-BE之職場勞工實際總攝入2-BE的情形,以及體內累積情形,並以血紅素濃度値評估2-BE對職場勞工造血系統的危害情形;進一步探討2-BE可能的氧化壓力及視覺功能影響,此外亦評估CYP 2E1的基因多形性對於2-BE代謝可能的影響。 研究總計有80位受測者,包括31位自行車2-BE貼標作業的勞工、25位主要黏貼一般標籤勞工及24位裝配工。在休假後的第1天及連續工作第5天時,進行作業環境空氣個人採樣及工作前後的尿液收集,之後以(gas chromatograph/flame ionization detector, GC/FID)進行空氣樣本2-BE、以(gas chromatography/mass spectrometry, GC/MS)進行尿中總丁氧基乙酸(total butoxyacetic acid, total BAA)的分析。除了進行受測者作業環境2-BE及其生物指標濃度的測定外,本研究亦進行問卷調查,並於連續工作第5天時抽血進行評估受測者的血紅素濃度、氧化性壓力程度、抗氧化能力、基因多型性及視覺功能情形。 結果顯示,31位自行車2-BE貼標作業的勞工,2天採樣的個人暴露環境2-BE濃度分別為1.89及1.57 ppm,工作後的尿中總丁氧基乙酸濃度分別為446.8及619.4 mg/g creatinine,勞工暴露2-BE的空氣濃度與工作後尿中total BAA濃度相關性不佳。雖然本研究勞工個人暴露2-BE的濃度約只有ACGIH建議濃度的8.5%,但是,採樣2天工作後的尿中總BAA濃度卻分別超出ACGIH建議BEI値的123%及210%,但尚未發現造成勞工血色素降低的造血系統不良效應。本研究亦推測在自行車2-BE貼標作業條件下,皮膚直接接觸2-BE水溶液是造成勞工2-BE吸收的主要原因,且2-BE在此職場環境中有明顯的體內累積現象。因此建議在工作週最後一天的工作後進行尿液採樣,為進行2-BE生物偵測的較佳時機點。 雖然過去文獻建議可將視力異常做為有機溶劑中毒損傷的早期指標,但本研究中在顏色混亂指數(color confusion index, CCI)及對比敏感度(contrast sesitivity)項目,2-BE的貼標工和裝配工(未暴露任何溶劑)均無顯著差異,顯示暴露在約1.7ppm乙二醇單丁醚,並直接以雙手接觸約10%(v/v) 2-BE稀釋溶液的作業方式,似未造成視覺功能的異常。 使用2-BE的貼標工和裝配工,在採樣週第5天工作後尿中8-OhdG濃度値、血中骨髓過氧化酵素(MPO)濃度値平均值並沒有呈現顯著差異。由於受測者大都無抽煙和喝酒習慣,此意味著暴露在此濃度的乙二醇單丁醚,並未造成DNA氧化傷害和體內發炎異常的情形。 過去曾有研究發現CYP 2E1基因多型性,可能與造成尿中較低濃度free BAA有可能的相關性。在本研究中利用複回歸分析2-BE貼標工星期五工作後尿中BAA和CYP 2E1基因多型性、空氣中2BE濃度的相關性,結果發現在控制空氣中2BE濃度後,CYP 2E1基因多型性(Rsa I和 Dra I)和工作後尿中BAA並無顯著相關。因此依據本研究的結果,初步推測CYP 2E1基因多型性,可能並非2BE代謝的一個調節因子(modifying factor)。但是由於本研究並未估算2-BE貼標工皮膚暴露的情形,僅由空氣中2-BE濃度納入分析,並無法完全代表其暴露程度,此外alcohol dehydrogenase 2和aldehyde dehydrogenase 2在本研究中亦未進行分析,因此CYP 2E1基因多型性,對於2-BE代謝的可能影響仍有待進一步研究釐清。

並列摘要


Glycol ethers are widely used in industrial and household applications because of their chemical and physical properties. During the manufacturing process of bicycles, the dilute aqueous solution of 2-butoxyethanol (2-BE) is used to transfer decals to the frames. Workers usually transfer the decals by hand without using protective gloves. The concentration of dilute aqueous solution of 2-BE is about 10% (vol/vol), and the temperature is kept at around 25-30℃. Such work pattern will increase the exposure risk of 2-BE. Various animal studies using different routes of exposure (oral, inhalation, and dermal) have shown 2-BE to cause decreases in red blood cell counts and hemoglobin concentration, as well as red blood cell hemolysis, hemolytic anemia, and red blood cell osmotic fragility. The objectives of this study were to evaluate the 2-BE exposure and hydrolyzed 2-butoxyacetic acid of the 2-BE transfer workers, 2-BE effect on oxidative stress and visual function, and to test the effects of the CYP2E1 genetic polymorphism on metabolism of 2-BE. In the current study, 80 workers (including 31 2-BE transfer workers, 25 self-adhesive decals workers, and 24 assembly workers) were comprised at two bicycle manufacturing factories. Sociodemographics, work history, lifestyle factors, medical history, and subjective symptom were investigated by questionnaires. Subject 2-BE in personal air, pre- and post-work urines were sampled on the first (W1) and the fifth (W5) workday after a holiday. These samples were analyzed by gas chromatograph/flame ionization detector (2-BE in air) and gas chromatography/mass spectrometry (hydrolyzed 2-butoxyacetic acid, total BAA). Further, Subject blood was drawn from a vein for hemoglobin, oxidative stress, and polymorphism analysis. Color vision and contrast sensitivity were also conducted to evaluate the visual function of the subjects. Of the 31 2-BE transfer subjects, mean 2-BE air level was 1.89 (W1) and 1.57 ppm (W5), and average postshift urinary total BAA was 446.8 (W1) and 619.4 mg/g creatinine (W5). Correlation of 2-BE air levels and postshift urinary BAA levels on these two workdays was poor. Although 2-BE air level was around 8.5% of the current TLV–TWA, the postshift BAA in urine of W1 and W5 was 123% and 210% more than the value of BEI, respectively. No hematopoietic effect was found for the study subjects.We speculated that the main reason for 2-BE absorption of them could be ascribed to the direct dermal contact. The evidence of accumulation also appeared in current research with the exposures of low-level 2-BE. Therefore, for the biological monitoring, it is highly recommended that the urine sample should be collected at the end of the workweek. Many researches have already examined the effects of organic solvents on visual function. The color confusion index and visual contrast sensitivity test are some of the techniques purported to be a sensitive indicator. However, there was no significant difference between 2-BE transfer workers and assembly workers on these two indices. No visual dysfunction was found in the study subjects performed their tasks with hands direct contact to dilute aqueous solution of 2-BE (10%). Of the oxidative stress, such as 8-OhdG and myeloperoxidase, there was also no significant difference between 2-BE transfer workers and assembly workers. Most of the subjects did not have alcoholic drinking and smoking habits. It seemed that exposure to low-level 2-BE did not cause significant difference of oxidative stress. Previous study has reported a possible connection between mutant CYP2E1 genotype and low urinary excretion of free BAA in exposure to 2-BE. Our results showed that, after adjustment for 2-BE concentrations in personal air, neither Rsa I site polymorphism nor Dra I site polymorphism was significantly associated with the urinary BAA. This indicates that the CYP2E1 polymorphism may not be a modifying factor of 2-BE metabolism to modulate the excretion of urinary total BAA in our study population. Since 2-BE exposure from dermal route, alcohol dehydrogenase 2 and aldehyde dehydrogenase 2 were not evaluated in our study, the influence of the genetic polymorphism for CYP2E1 deserves further investigation for the interpretation of urinary BAA measurements.

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