勞工甲苯暴露及健康危害之探討

Abstract

甲苯為國內工業界常用之溶劑，甲苯過量暴露會對人類造成可能會造成人類神經系統、肝和腎臟危害和聽力損失等，且由文獻已知甲苯具有皮膚吸收之特性，皮膚直接接觸或暴露於作業環境空氣中甲苯，均可造成甲苯自皮膚滲透吸收，因此職業性甲苯暴露危害是不容忽視。 本研究規劃分成三部份進行，第一部份：建立以液相層析/離子電灑法之串聯質譜儀檢測尿中的甲苯代謝物（芐基硫醇酸；benzylmercapturic acid）之新方法。方法首先運用固相萃取技術進行尿液樣品萃取，再以C18逆向層析管柱進行樣品分離，負離子電灑法和多重反應監測模式分析尿中的芐基硫醇酸。尿液樣品之檢量線（濃度範圍：0.5–120.0 ng/mL）是由芐基硫醇酸濃度與其和內標準品（13C6-芐基硫醇酸）之質譜強度比計算而得。同日及異日精密度範圍分別為2.32%–2.95% 和2.24%–4.97%。分析方法之可量化偵測極限為0.5 ng/mL。芐基硫醇酸之添加回收率為97.56%。 第二部份為探討勞工甲苯暴露濃度及其尿中代謝物相關性，以了解職場之甲苯經皮膚吸收之情形。研究結果顯示，109位勞工的9個不同皮膚部位（左右手的手掌心、手掌背、手臂內側、手臂外側和後頸部）之甲苯暴露濃度，並無統計上的差異性存在。複迴歸分析知空氣中和皮膚中甲苯濃度值與尿中馬尿酸/肌酐酸、鄰-甲酚、鄰-甲酚/肌酐酸、鄰-甲酚/尿比重、芐基硫醇酸、芐基硫醇酸/肌酐酸和芐基硫醇酸濃度/尿比重具顯著相關性（p＜0.05）。 第三部份係收集國內膠帶廠作業283位勞工之健康檢查資料，並針對勞工健康檢查項目進行統計分析。研究結果發現暴露組（噪音和甲苯共同暴露）、對照組（噪音暴露）和控制組（行政人員）勞工之紅血球數、血色素、血球容積比和血清丙胺酸轉胺酶檢查結果有差異。在聽力損失方面，膠帶業作業環境之噪音暴露均低於法令標準（<90dBA），但勞工同時暴露於噪音（82.8±2.6dBA）和甲苯溶劑（35.8±25.2 ppm）時，甲苯仍會加強噪音對聽力損失的影響。 本研究已成功建立靈敏、簡單且可靠之勞工尿中甲苯暴露指標芐基硫醇酸分析方法，提供職場上甲苯蒸氣經皮膚吸收之實驗數據，並由勞工健康檢查資料，知勞工長期職業性甲苯暴露，對其聽力損失有影響。

Toluene is a widely used solvent in Taiwan. It is a human central nervous system (CNS) depressant. Long-term occupational exposure to toluene is associated with liver and kidney damage, and hearing loss in humans. A number of studies have recognized dermal absorption of toluene. Therefore, prevention of dermal absorption might be required for occupations which involve toluene exposure. This study was comprised of three parts. Part I: A method based on liquid chromatography (reversed phase)-electrospray (negative) ionization-tandem triple quadrupole mass spectrometry (LC-ES(–)-MS/MS), in the multiple reaction monitoring mode, was developed for determination of urinary benzylmercapturic acid (BMA). Isotope dilution through introduction of 13C6-labeled BMA was employed as an internal standard, achieving intra- and inter-run precision ranges of 2.32%–2.95% and 2.24%–4.97%, respectively. The calibration curve obtained with BMA-spiked blank human urine was linear from 0.5–120.0 ug/L; the correlation coefficient of the calibration curve was 0.999. The method limit of quantification was 0.5 ng/mL; mean BMA recovery was 97.56%. Part II: Exposure via respiratory and dermal routes was assessed on an individual basis for 109 workers employed in eighteen factories which manufactured adhesive tape who were directly exposed to toluene. Respiratory exposure was determined by breathing-zone sampling for a full-work shift, and dermal exposure was assessed on nine skin areas (the palms, forearms of both hands and the paravertebral area of the seventh cervical spine process) by a hand wipe sampling method. Each worker provided a post-shift urine sample and urinary hippuric acid, o-cresol and BMA were measured. Toluene concentrations on the nine skin areas showed no statistical differences. In multiple linear regression tests, airborne toluene and toluene on the skin remained significantly (P<0.05) associated with urinary happuric acid/creatinine (g/g),o-cresol (ug/L), o-cresol/creatinine (ug/g), o-cresol/specific gravity (ug/L), BMA (ug/L), BMA/creatinine (ug/g) and BMA/specific gravity (ug/L). Part III: A total of 283 workers in adhesive-tape production factories in Taiwan were recruited for this study. Each participant read and signed consent forms. The participants had clinical examinations which they were different included red blood cell count, hemoglobin, hematocrit and alanine aminotransferase. Comparisons were made among the exposed (noise and toluene), contrast (noise) and control groups (administrative personnel, unexposed) and between genders. The average noise exposure in the working environment was lower than 90 dBA, but workers who were exposed to both noise (82.8±2.6 dBA) and toluene (35.8±25.2 ppm) had enhanced hearing loss. The present study established a sensitive, specific and reliable testing method to determine urinary BMA in urine samples collected from workers who had been exposed to toluene. We found that dermal exposure provides a substantial contribution to the total body burden of toluene, and workers experience hearing loss after long-term exposure to toluene.