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研究生: 李芳錦
Lee, Fang-Jin
論文名稱: PVC塑膠皮(布)製造業勞工鄰苯二甲酸二(2-乙基己基) 酯暴露及健康風險評估研究
Exposure and health risk assessment of Di-2-ethylhexyl phthalate of workers in polyvinylchloride leather processing plants
指導教授: 李俊璋
Lee, Ching- Chang
學位類別: 碩士
Master
系所名稱: 醫學院 - 環境醫學研究所
Department of Environmental and Occupational Health
論文出版年: 2010
畢業學年度: 98
語文別: 中文
論文頁數: 134
中文關鍵詞: 鄰苯二甲酸二(2-乙基己基)酯PVC塑膠皮(布)製程業勞工空氣尿液代謝物甲狀腺及生殖荷爾蒙
外文關鍵詞: DEHP, PVC leather processing workers, ambient air, urine metabolites, Thyroid and Reproductive hormone
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  • 鄰苯二甲酸酯類 (Phthalates, PAEs)常添加於PVC塑膠作為塑化劑,依據環保署申報資料顯示,台灣於2005~2007年間鄰苯二甲酸二(2-乙基己基)酯[Di (2-ethylhexyl) phthalate, DEHP]的平均使用量約為20萬公噸、鄰苯二甲酸二丁酯 (Dibutyl phthalate, DBP)為0.5萬公噸,其中從事聚氯乙烯 (Polyvinylchloride, PVC)塑膠製造業的員工約有一萬四千多位。國外研究指出,PVC塑膠製造業勞工為PAEs之高暴露族群,主要暴露途徑尙不明確,可能與職場空氣暴露有關。此外,研究顯示PAEs暴露可能與血液生化測值異常、睪固酮濃度與精蟲數目降低有關。過去,國內對於PVC塑膠皮(布)製造業勞工PAEs暴露評估並未進行完整研究。故為瞭解該作業勞工PAEs暴露程度與途徑,而進行本研究。研究對象為某PVC皮(布)製造廠之30位勞工,並進行一週工作之第一天及第五天,共計二天上班前及下班前尿液共120份之採集,及尿液中DEHP代謝物(一階代謝物MEHP及二階代謝物MEOHP、 MEHHP)分析,以及39處78份作業期間定點空氣中PAEs採樣分析,並進行血液生化與荷爾蒙等檢查及健康、飲食問卷及時間活動模式調查,最後整合各項檢測資料與問卷,進行作業勞工暴露健康風險評估。
    研究結果顯示,第一天作業環境空氣中DEHP濃度以第二條生產線之軋輪區最高達3.91 mg/m3,其次為第三條生產線之軋輪區1.63 mg/m3,而行政人員辦公室內四點空氣中DEHP濃度界於0.011-0.016 mg/m3,皆低於萬馬力機與軋輪區之空氣中DEHP濃度(0.020-3.91 mg/m3 )。至於第五天作業環境空氣中DEHP濃度則以第一條生產線的捲取區最高達1.58 mg/m3,其次為第四條生產線的軋輪區1.1187 mg/m3,至於行政人員辦公室內四點空氣中DEHP濃度(0.005-0.0105 mg/m3)仍為最低。依據作業環境空氣中DEHP濃度、勞工主要職務及時間活動模式調查,將30位員工分成高低暴露組。其中高暴露組為15人,主要為萬馬力機與軋輪機員工;低暴露組為15人,主要為捲取區及辦公室員工。
    在尿液中DEHP代謝物分析結果顯示,第一、五天上班前,高暴露組勞工尿液中MEHHP中位數濃度分別為116.8、151.15μg/g creatinine,下班前則分別為190.53、256.77μg/g creatinine;而在低暴露組方面,勞工第一、五天上班前MEHHP濃度分別為46.03、44.63μg/g creatinine,下班前分別為78.62、63.68μg/g creatinine。高暴露組勞工尿液中MEHHP( P = 0.0327, 0.001)與MEOHP(P=0.0443, 0.005)濃度均顯著高於低暴露組,且達統計上顯著差異。勞工第一天下班前高暴露組尿液中MEOHP、MEHHP的濃度顯著高於低暴露組( P=0.01, 0.008)。第五天下班前高暴露組勞工尿液中MEHP、MEOHP濃度皆顯著高於低暴露組,MEHHP則為臨界差異(P=0.07)。進一步比較個人上、下班前尿液DEHP代謝物濃度之差異,第一天與第五天高暴露組中個人下班前尿液中DEHP代謝物MEHP、MEHHP、MEOHP濃度均較上班前高,且達統計上顯著之差異(P<0.05) ,低暴露組則未有相同情況,因此可推測第一天下班前,高暴露組可能因受到職業暴露之影響,相較於低暴露組有較高的暴露濃度。進一步綜合比較勞工個人第一天及第五天下班後尿液中MEHP、MEOHP、MEHHP的濃度差異,顯示除低暴露組外,MEHP與MEOHP第五天下班後濃度皆顯著高於第一天下班前(P<0.05),而MEHHP則未達統計上顯著差異 (P=0.08),顯示高暴露組勞工可能因暴露高量DEHP而導致有累積之現象。
    進一步檢定區域空氣中DEHP濃度與尿液DEHP二階代謝物MEHHP濃度間之相關性。第一天空氣與尿液濃度分析結果其R2為0.234,為中度相關(P=0.0066);而第五天的R2為0.449,接近高度相關 (P=0.0004)。因此可推測廠內空氣中DEHP為勞工主要暴露來源之一。
    另外,高低暴露組在在甲狀腺荷爾蒙部分,發現高暴露組T3濃度顯著低於低暴露組(median 110.5 vs. 125.1 ng/dL, p=0.0075)。另外高暴露組T4濃度結果亦顯著低於低暴露組(median 6.68 vs. 7.74μg/dL, p=0.0191)。由於血液中FT4的比例約為總T4的0.03%,因此再進一步比較T4與FT4間的比例關係發現,高暴露組T4/FT4比值顯著小於低暴露組(median 5.39 vs. 6.05, p=0.0023),由此可知T4與FT4間之平衡發生變化。
    此外,除依空氣濃度、職掌分成高、低暴露組外,亦發現高暴露組尿液中MEHHP濃度差異過大(Min=13.04, Max=524.24 ng/mg creatinine),顯示高暴露組內,勞工暴露情狀亦有差異,因此進行重新分組,先依職務及暴露之空氣濃度分成高低濃度組後,將高濃度組依照尿液中位數濃度(171.34 ng/mg creatinine)進行分組,再將高濃度組分成高、中濃度組。結果發現,高濃度組之inhibin B平均濃度最低,為68.6 pg/mL,次低為中濃度組74.8 pg/mL,最高為低濃度組102.3 pg/mL,且三組達到統計上顯著之差異(p=0.0275);進行趨勢分析發現,三組亦達顯著之趨勢關係(p=0.006)。
    進一步解析尿液中DEHP代謝物濃度與血中生殖荷爾蒙濃度之關係發現,第五天下班前MEHP%則與雄性荷爾蒙FAI、testosterone、E2呈現顯著的正相關(相關係數=0.405、0.393、0.443, p<0.05)。進行簡單線性迴歸分析後,亦有相同之結果。
    綜合以上資料顯示,勞工確實於作業環境經由空氣途徑暴露DEHP,並導致尿中DEHP代謝物濃度偏高,顯示PVC塑膠皮布作業勞工可能因生產線DEHP的逸散而暴露到高濃度之DEHP。因此建議勞工可配戴呼吸防護具以減少DEHP之暴露。依據作業環境內空氣採樣結果顯示,此兩天空氣中DEHP濃度最高為3.91 mg/m3,雖低於各國所建議的作業環境空氣中容許濃度 5 mg/m3,但從勞工尿液中MEHP回推DEHP濃度顯示,高、低暴露組上班後之日暴露劑量均有上升之趨勢,且高暴露組部分勞工之暴露劑量已經高於歐盟及USEPA建議之參考劑量,且有累積之情形。由此可知,PVC塑膠皮布作業勞工仍屬DEHP高暴露族群。由於DEHP為已知之內分泌干擾物質,因此,建議未來收集更多暴露及健康危害數據以檢討作業環境空氣中容許暴露濃度標準之適當性。

    Phthalates (PAEs) are primarily used as plasticizers in the manufacture of flexible vinyl. According to survey of Taiwan EPA, there are 200 thousand tons of Di (2-ethylhexyl) phthalate (DEHP) and 5 thousand tons of Dibutyl phthalate (DBP) were manufactured or used between 2005 and 2007. And there are about 14 thousand workers working in polyvinylchloride processing industries. Polyvinylchloride (PVC) processing workers may expose to phthalates, the main exposure routes may via ambient air and airborne dust exposure. Some studies revealed that PAEs exposure in male may be resulted in abnormal blood biochemistry, decreased testosterone level and reduced sperm counts. In the past, no comprehensive study conducted for worker exposed to PAEs in PVC leather processing industries. Therefore, we will find out PAEs exposure levels and routes for workers in PVC leather processing industries. Screening criteria such as raw materials, products, used quantities of PAEs, and number of workers were set up to identify the high exposure potential factories. 30 workers in a selected polyvinylchloride leather processing industry were selected as study subjects. The examinations of blood biochemistry and hormones, personal and occupational exposure data, time activity pattern, airborne exposure sampling and DEHP analysis, and urine sampling and urinary DEHP metabolites of pre- and post- workshift analysis for all selected workers has been completed.
    In the first day of working shift, the highest airborne DEHP concentration was 3.91 mg/m3 in mixing roll of the process 2, and followed by 1.63 mg/m3 in mixing roll of the process 3, and the lower airborne DEHP concetrations were found in four airborne samples of office (0.0113 - 0.0157 mg/m3) which were lower than banbury mixer and mixing roll (0.0203-3.9120 mg/m3). In the fifth day of working shift, the highest airborne DEHP concentration was 1.5818 mg/m3 in the winder of process 1, and followed by 1.1187 mg/m3 in mixing roll of the process 4, and the lower airborne DEHP concetrations were found in four airborne samples of office (0.005-0.0105 mg/m3). According to the airborne DEHP concertration, job categories and time activity data, 30 workers were categorized to two groups: high exposure group (banbury mixer and mixing roll workers, n=15), low exposure group (winder workers and officers, n=15).
    The urinary MEHHP levels of high exposure group in the preshift of first and fifth day were 116.8, 151.15μg/g creatinine and in the postshift of first and fifth day were 190.53, 256.77μg/g creatinine. The urinary MEHHP levels of low exposure group in the preshift of first and fifth day were 46.03, 44.63μg/g creatinine and in the postshift of first and fifth day were 78.62, 63.68μg/g creatinine. The urinary MEHHP (P = 0.0327, 0.001) and MEOHP (P=0.0443, 0.005) levels of high exposure group were significant higher than low exposure group in the preshift of first and fifth day. The urinary MEHHP and MEOHP levels of high exposure group were significant higher than low exposure group (P=0.01, 0.008) in the postshift of first day. The urinary MEHP and MEOHP levels of high exposure groupwere significant higher than low exposure group in the postshift of fifth day. And the urinary MEHHP levels of high exposure group were marginal significant higher than low exposure group (P=0.07) in the postshift of fifth day. The urinary MEHP, MEHHP, MEOHP levels of high exposure worker in the postshift of first and fifth day were higher than in the preshift of first and fifth day (P<0.05). But no significant difference was found in urinary DEHP metabolites in low exposure worker. Due to occupational exposue, the urinary DEHP metabolites levels in high exposure group higher than low exposure group. The urinary MEHP, MEOHP levels of high exposure worker in the postshift of fifth day were higher than first day (P<0.05). But no significant difference was found in urinary MEHHP level between the postshift of first day and fifth day. So, the high exposure worker has higher exposure levels, and cause to accumulate.
    In the first day, R-Square of the airborne DEHP concentration and urine MEHHP concentration was 0.205, it’s median correlation. In the fifth day, the R-square was 0.449, it shows to highly correlatied. We concluded the airborne DEHP exposure maybe one of the mainly exposure route.
    We found the T3 concentration of higher exposure group was significant lower than low exposure group (110.5 vs. 125.1 ng/dL, p=0.0075). And we also found the T4/FT4 ratio of higher exposure group was significant lower than low exposure group (median 5.39 vs. 6.05, p=0.0023).
    Beside, the urinary MEHHP levels of high exposure worker have widly range (Min=13.04, Max=524.24 ng/mg creatinine). So, we rechange the group. First, we divide to high and low level group by air levels and job title. Then, according the median of the urinary MEHHP level (171.34 ng/mg creatinine), we divide high exposure to two groups. In the Result, we found the inhibin b concentration in higher exposure group (68.6 pg/ml) were lower than those in the median (74.8pg/ml) and low exposure (102.3 pg/ml) groups (P=0.0275; Ptrend=0.006).
    We analyse the correlation coefficients between with urinary metabolites of DEHP and serum reproductive and thyroid hormone. We found the correlation coefficients were positive significant between in the posshift of fifth day and reproductive hormorne FAI, testosterone, E2(correlation coefficients=0.405, 0.393, 0.443, p<0.05). And there are the same result in the simple regression analysis.
    In conclusion, the workers were truly exposed to higher concentration of DEHP emitted from polyvinylchloride leather processing industry. The usage of personal protective measures was suggested to effectively reduce the concentrations of urinary metabolites of DEHP. Although the hightest airborne DEHP (3.91 mg/m3) was lower than Permissible Exposure Limit (5 mg/m3), the daily expsoure doses of DEHP in 15% workers were higher than the reference doses of EU and US EPA. In addition, DEHP is known endocrine disruptor, further studies are suggested to determine the long-term health effects of DEHP exposure, and to verify the availability of protection of PEL for workers.

    目錄 第一章 序論 1 1.1 研究緣起 1 1.2 研究目的 2 第二章 文獻回顧 3 2.1塑化劑功能與用途 3 2.2 鄰苯二甲酸酯類的物化及環境特性 4 2.3 DEHP毒性分類及毒性研究 5 2.3.1 DEHP毒性分類 5 2.3.2鄰苯二甲酸酯類的毒性 5 2.4鄰苯二甲酸酯類的暴露途徑與代謝 10 2.5 人類PAEs暴露流行病學資料 11 2.6 職業暴露研究 13 2.6.1 職業暴露研究 13 2.6.2 各國PAEs職業暴露管制規範 17 2.7 鄰苯二甲酸二(2-乙基己基)酯及其代謝物採樣與分析方法 19 2.7.1 空氣中DEHP及尿液中DEHP代謝物採樣策略 19 2.7.2 空氣中DEHP採樣及分析方法 19 2.7.3 尿液中DEHP代謝物採樣及分析方法 20 第三章 研究材料與方法 21 3.1 研究架構 21 3.2 研究對象選取 22 3.2.1 PVC皮(布)工廠製程說明 22 3.2.2 工廠篩選原則 22 3.3 問卷設計內容 24 3.3.1 健康及飲食問卷 24 3.3.2 時間-活動模式調查 25 3.4 採樣策略 26 3.4.1 人體試驗委員會規範 26 3.4.2 血液樣本採集及檢查 26 3.4.3 尿液採集 27 3.4.4 空氣採集 27 3.5 樣本分析方法 28 3.5.1 尿液中PAEs代謝物之量測 28 3.5.2 空氣中Phthalates之量測 29 3.5.3 分析方法之品質保證與品質管理 30 3.6 鄰苯二甲酸二(2-乙基己基)每日暴露劑量推估 34 3.6.1 勞工尿液中DEHP代謝物濃度回推DEHP日暴露劑量 34 3.6.2 以作業環境空氣中DEHP濃度推估DEHP日暴露劑量 34 3.7 健康風險評估 35 3.7.1 危害指標 (Hazard Index, HI) 35 3.8 統計方法 36 第四章 結果與討論 37 4.1 品保與品管執行結果 37 4.1.1 空氣樣本品保與品管執行結果 37 4.1.2 尿液樣本品保與品管執行結果 37 4.2 PVC塑膠皮(布)業勞工-職業暴露評估 38 4.2.1 研究對象基本資料 38 4.2.2勞工職業及相關暴露史 39 4.2.3 勞工飲食習慣分布 39 4.2.4 外食使用塑膠產品之情形 40 4.3 空氣及尿液樣本分析結果 41 4.3.1 PVC塑膠皮(布)廠內作業環境空氣中DEHP分析結果 41 4.3.2 勞工尿液中DEHP代謝物濃度分布 42 4.3.3作業場所空氣與尿液代謝物濃度相關比較 43 4.4 勞工DEHP暴露劑量評估 44 4.4.1 以空氣中DEHP分析結果回推DEHP日暴露劑量 44 4. 4.2勞工尿液中DEHP代謝物濃度回推DEHP日暴露劑量 45 4.5 健康風險計算 46 4.5.1 HI (非致癌危害) 46 4.5.2 以尿液DEHP代謝物濃度推算勞工之DEHP日暴露劑量估算HI 46 4.6 健康效應評估 47 4.6.1 勞工血液生化檢查結果 47 4.6.2勞工血液甲狀腺與生殖荷爾蒙檢驗結果 48 第五章 結論與建議 53 5.1 結論 53 5.2 建議 57 第六章 文獻回顧 58 表目錄 表2-1-1、五種鄰苯二甲酸酯類之主要應用產品 64 表3-2-1符合篩選條件之七家工廠資料 72 表3-5-1以GC/MS分析空氣中各PAES及IS之M/Z表 73 表4-1-1 空氣樣本分析方法之品質保證/品質管理表 74 表4-1-2尿液樣本分析方法之品保/品管規範 74 表4-2-1 員工基本資料 75 表4-2-2A 現場與辦公室員工基本資料分布 76 表4-2-2B 第一天作業環境空氣中DEHP濃度分布 76 表4-2-3 高低暴露組基本資料分布 77 表4-2-4 高低暴露組職業史及相關暴露資料分析 78 表4-2-5 員工平日飲食資料 (食用量/月) 79 表4-2-5 員工平日飲食資料 (食用量/月) (續) 80 表4-2-6高低暴露組勞工外食使用塑膠產品結果 81 表4-3-1 7月14日各空氣採樣點空氣中DEHP濃度 (MG/M3)分布 82 表4-3-2 7月18日各空氣採樣點空氣中DEHP濃度 (MG/M3)分布 82 表4-3-3 有無使用DEHP之生產線空氣中DEHP濃度A之比較表 83 表4-3-4 受檢勞工第一天上、下班前尿液中DEHP代謝物濃度分布 84 表4-3-6 第一天與第五天高低暴露組下班前尿中DEHP各代謝物 (MEHP、MEOHP、MEHHP)所占之比例 86 表4-4-1 第一天 PVC塑膠皮(布)廠空氣濃度換算每人每日暴露量 (ΜG/KG/DAY)B 87 表4-4-3 受檢勞工第一天上下班前尿液中DEHP代謝物回推DEHP日暴露劑量 89 表4-4-4 受檢勞工第五天上下班前尿液中DEHP代謝物回推DEHP日暴露劑量 90 表4-5-2第五天 PVC塑膠皮(布)廠勞工直接暴露空氣中DEHP 之 HIB 91 表4-5-3 以尿液結果計算受檢勞工第一天上下班前暴露DEHP之HI 92 表4-5-4 以尿液結果計算受檢勞工第五天 上下班前暴露DEHP之HI 93 表4-6-1 PVC塑膠皮(布)廠高、低暴露組勞工血液生化檢查結果 94 表4-6-3 PVC塑膠皮(布)廠高、低暴露組勞工荷爾蒙分析結果 96 表4-6-4 PVC塑膠皮(布)廠高、中、低濃度組勞工荷爾蒙分析結果 97 表4-6-5 PVC塑膠皮(布)廠高、低暴露組勞工血液荷爾蒙檢查結果異常人數資料分布 98 表4-6-6 30位勞工尿中DEHP代謝物分布狀況 99 表4-6-7 第一天下班前30位勞工尿中DEHP代謝物間經轉換後之CORRELATION COEFFICIENTS表 100 表4-6-8 第五天下班前30位勞工尿中DEHP代謝物間經轉換後之CORRELATION COEFFICIENTS表 101 表4-6-9 第一天下班前30位勞工尿中DEHP代謝物經轉換後濃度與血中荷爾蒙的CORRELATION COEFFICIENTS表 102 表4-6-10 第五天下班前30位勞工尿中DEHP代謝物經轉換後濃度與血中荷爾蒙的CORRELATION COEFFICIENTS表 103 表4-6-11 第一天下班前30位勞工迴歸分析尿中DEHP代謝物間經轉換後之REGRESSION COEFFICIENTS表 104 表4-6-12 第五天下班前30位勞工迴歸分析尿中DEHP代謝物間經轉換後之REGRESSION COEFFICIENTS表 105 表4-6-13 第一天下班前30位勞工迴歸分析尿中DEHP代謝物濃度與荷爾蒙濃度間REGRESSION COEFFICIENTS表 106 表4-6-14 第五天下班前30位勞工迴歸分析尿中DEHP代謝物濃度與荷爾蒙濃度間REGRESSION COEFFICIENTS表 107 圖目錄 圖2-3-1 暴露MEHP後,SERTOLI CELL 上的FASL與 GERM CELL上的FAS受體結合,引發細胞凋亡 108 圖2-3-2 雄性激素的生成 (由膽固醇轉變至睪固酮) 109 圖2-3-3 雄性生殖系統調控機制圖 110 圖2-3-4 甲狀腺荷爾蒙調控機制圖 111 圖2-4-1 DEHP代謝機制圖 112 圖3-1-1 研究架構圖 113 圖3-2-1 PVC皮布工廠製程示意圖 114 圖3-5-1 尿液樣本前處理流程 116 圖3-5-1 尿液樣本前處理流程 (續) 117 圖4-3-2 第五天DEHP空氣濃度與下班後尿液MEHHP濃度之線性相關比較圖 119

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