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研究生: 林以馨
Lin, Yi-Hsin
論文名稱: 化妝品銷售員奈米微粒暴露評估與健康影響之相關性研究
The Association between Nanoparticles Exposure and Health Outcomes in Cosmetic Sales Clerk
指導教授: 李俊璋
Lee, Ching-Chang
共同指導教授: 張榮偉
Chang, Jung-Wei
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: 2018
畢業學年度: 106
語文別: 中文
論文頁數: 106
中文關鍵詞: 奈米級化妝品奈米氧化鋅奈米二氧化鈦暴露評估發炎及氧化性壓力指標
外文關鍵詞: Nanocosmetics, Zinc oxide, Titanium dioxide, Exposure assessment, Inflammatory and oxidative stress markers
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  • 奈米科技所產生的相關民生消費產品已逐漸融入我們的日常生活中,但近年來陸續有文獻提出奈米微粒導致不良健康危害的疑慮,使得民眾在使用奈米產品時增加了未知的健康風險。因奈米物質的微小粒徑使得皮膚較易吸收,故廣泛應用於保養品及化妝品中。然而,根據市售奈米級化妝品調查發現,產品中奈米成分時常有標示不清的狀況,導致消費者可能在不知情的狀況下,暴露到奈米微粒。因此,本研究選取較常接觸含氧化鋅或二氧化鈦奈米微粒之化妝品銷售員,進行奈米微粒暴露評估,並探討其可能引發的不良健康效應。
    本研究首先進行含氧化鋅或二氧化鈦奈米微粒之化妝品市場調查,根據調查結果價購專櫃銷售之奈米級化妝品,分析其內容物中奈米氧化鋅及二氧化鈦含量;其次以台南地區百貨公司及一般購物商場,銷售上述奈米級化妝品專櫃銷售員為暴露族群,另以非化妝品專櫃銷售員為對照族群,採集所有銷售員之尿液樣本,分析其發炎(IL-6)及氧化性壓力(8-OHdG)指標;同時亦針對兩族群之化妝品使用量、奈米相關製品使用情形等進行問卷調查,最後整合奈米化妝品中奈米微粒氧化鋅及二氧化鈦之檢測結果,評估化妝品及非化妝品專櫃銷售員暴露奈米微粒中氧化鋅及二氧化鈦之暴露劑量,並透過統計分析探討兩族群奈米級化妝品內奈米微粒中氧化鋅及二氧化鈦之暴露差異,及奈米微粒氧化鋅及二氧化鈦之暴露劑量與尿液中發炎(IL-6)及氧化性壓力指標(8-OHdG)之相關性。
    根據市場調查結果,價購20件產品進行奈米微粒氧化鋅及二氧化鈦含量分析。20件產品皆為乳狀或液態狀且具紫外線防護功效之產品,結果發現所有產品皆含有氧化鋅及二氧化鈦,但部分產品成分及其說明並未標示。奈米氧化鋅分析結果有15件符合歐盟定義之奈米材料(即小於100 nm的粒子大於50% ),眾數粒徑介於48-83 nm之間;奈米二氧化鈦分析結果顯示,20件產品中有19件符合歐盟所定義之奈米材料,眾數粒徑介於52-68 nm之間。本研究共完成40位化妝品專櫃及24位非化妝品專櫃銷售員週四及週日尿液樣本之採集、問卷與個人時間活動模式調查。本研究計算終生平均每日暴露劑量(Life-time Average Daily Dose, LADD)作為暴露指標,將64位銷售員共128件尿液樣本,依照奈米氧化鋅、奈米二氧化鈦及奈米氧化鋅與二氧化鈦共同暴露劑量重新進行分組,並以中位數劃分高、低暴露組。研究結果顯示,奈米二氧化鈦暴露指標高暴露組8-OHdG濃度高於低暴露組,且在原始濃度(5.23 vs. 2.80 ng/mL, p <0.001)及經肌酸酐校正之濃度(6.22 vs. 3.19 μg/g creatinine, p =0.021)皆達統計上差異,奈米氧化鋅及二氧化鈦共同暴露指標分組之結果顯示,高暴露組尿液中8-OHdG濃度高於低暴露組,並於原始濃度達統計上顯著差異(5.13 vs. 2.90 ng/mL, p <0.001)。另選取奈米微粒濃度最高之前三項產品櫃位銷售員作為高暴露組,並挑選濃度最低之三項產品櫃位銷售員作為低暴露組,進行其尿液中IL-6濃度分析,結果發現高暴露組IL-6濃度雖高於低暴露組,但並未達統計上顯著差異。根據奈米消費性產品使用習慣劃分之暴露組及對照組,其尿液中發炎指標IL-6分析結果指出,雖有高暴露組發炎指標IL-6較高之現象,但兩組間並無顯著差異。將暴露指標與氧化壓力指標及發炎指標進行相關性分析,奈米氧化鋅暴露指標與尿液中氧化壓力指標呈負相關,但未達顯著;奈米二氧化鈦暴露指標與尿液中8-OHdG原始濃度(r=0.304,p<0.001)及經creatinine校正後濃度(r=0.222,p=0.012)呈顯著正相關,而三組暴露指標與尿液中IL-6濃度皆無顯著相關。進一步進行年齡、身高、喝酒習慣及喝茶習慣等干擾因子校正後,進行尿液中8-OHdG濃度與暴露指標(取log值)之複迴歸分析,結果顯示奈米二氧化鈦暴露指標(p=0.016)及共同暴露指標(p=0.046)與尿液中8-OHdG濃度呈顯著正相關,表示奈米微粒暴露確實會影響體內氧化壓力指標濃度。
    本研究針對銷售員奈米氧化鋅及奈米二氧化鈦暴露量進行危害指標(Hazard Index, HI)及安全限值(Margin of Safety, MOS)計算,由於低暴露組之奈米氧化鋅暴露指標值受產品濃度影響而趨近於零,故不予計算。結果顯示,高暴露組HI中位數及其範圍為3.72×10-5 (1.02×10-8 - 0.004),危害指標皆小於1;MOS中位數及範圍為7.06×109 (2.28×105 - 9.82×1010),均大於10,顯示無健康危害之疑慮。奈米二氧化鈦風險計算結果指出,無論高或低暴露組,其危害指標皆小於1,中位數及範圍各為6.42×10-6 (8.83×10-9 - 1.41×10-4)及1.50×10-7 (5.19×10-10 – 9.20×10-7);MOS的部分,高暴露組及低暴露組中位數及範圍各為1.58×109 (7.08×107 -1.13×1012)及8.3×1011 (1.35×1011 -1.93×1013),兩組安全限值均大於100,為可接受之風險。
    本研究僅利用液狀及乳態狀之產品進行銷售員健康風險計算,然而,其他固態、膏狀或噴霧型化妝保養品亦可能含有TiO2及ZnO NPs及其他奈米微粒,未來可涵蓋更多類別品項及其他奈米微粒進行整體暴露及風險評估,以更完整了解專櫃銷售員潛在健康危害。由於體內氧化壓力亦受生活習慣及環境因子影響,建議銷售員平時應減少不良習慣,並多補充富含維他命C及維他命E等具抗氧化功效之食品,避免身體長期處於高氧化壓力,而影響身體健康。

    The aims of present study are to evaluate the working exposure and health outcomes of cosmetic sales clerks to the nanoparticles (NPs) such as ZnO and TiO2. 20 cosmetics which may contain titanium dioxide or zinc oxide NPs were purchased and analyzed the content, concentration and size distribution of nanoparticles in products. 40 nanocosmetics sales clerks and 24 clothing sales clerks were recruited in this study, and all were categorized based on the exposure of ZnO and TiO2 NPs. Urinary oxidative stress and inflammatory markers were measured. The analytical results showed that all the products contained ZnO and TiO2. In addition, 19 products meet the EU definition for nanomaterials (i.e., > 50% by number of particles with a size < 100 nm) for TiO2, and 15 products were meet definition for ZnO NPs. Subjects with higher exposure index of TiO2 NPs had significant higher original and creatinine-adjusted level of urinary 8-OHdG. Urinary 8-OHdG original concentration in the high TiO2 and ZnO NPs co-exposure group was significant higher than the low co-exposure group. Urinary inflammatory marker (IL-6) levels of high co-exposure group was higher than low co-exposure group at ZnO/TiO2 NPs and the results were similar to the classification of usage habits of nano consumer products; but no significant differences were observed between both two groups. Multiple regression results showed that the urinary 8-OHdG levels were significantly positive associated with the exposure index of TiO2 NPs and the co-exposure index integrating TiO2 and ZnO NPs. Our results suggested that higher exposure levels of TiO2 and ZnO NPs may result in higher urinary 8-OHdG and IL-6 concentrations. However, no health concerns for sales clerks by applying nanocosmetics according to the results of health risk assessment.

    摘要 I EXTENDED ABSTRACT IV 致謝 VIII 目錄 X 表目錄 XII 圖目錄 XIV 一、 緒論 1 1.1 研究背景 1 1.2 研究目的 2 1.3 研究意義 2 二、 文獻回顧 3 2.1 奈米物質 3 2.1.1 物理化學特性及其與毒性之相關性 3 2.1.2 暴露途徑及健康效應 4 2.1.3 奈米消費性產品 7 2.2 含奈米成分化妝品 10 2.2.1 定義與種類 10 2.2.2 化妝品中氧化鋅及二氧化鈦奈米微粒 11 2.2.3 國際間管理措施 13 2.2.4 國內奈米級化妝品現況 15 2.2.5 奈米級化妝品暴露評估研究 17 2.3 氧化壓力及發炎反應 19 2.3.1 發炎反應、氧化壓力及DNA損傷 19 2.3.2 奈米微粒與氧化壓力及發炎反應 20 三、 研究材料與方法 22 3.1 研究架構 22 3.2 市場調查 22 3.3 研究對象選取 23 3.3.1 採樣地點選取 23 3.3.2 研究對象選取 23 3.3.3 研究對象篩選條件 24 3.3.4 樣本數估算 24 3.4 採樣策略 25 3.4.1奈米級化妝品採集及分析 25 3.4.2尿液樣本之收集 26 3.5 尿液樣本分析 27 3.5.1尿液中氧化損傷標記物 8-OHdG 分析方法 27 3.5.2尿液發炎指標 28 3.6 問卷調查 28 3.7 暴露指標建置 30 3.8 統計分析 31 四、 結果與討論 32 4.1 產品中氧化鋅及二氧化鈦奈米微粒檢測結果 32 4.2 研究族群基本資料、生活習慣及奈米級化妝品使用習慣 32 4.2.1 銷售員基本資料 32 4.2.2 化妝品、保養品及個人衛生用品使用習慣 34 4.3 銷售員尿液分析結果 35 4.3.1 尿液常規檢測結果 35 4.3.2 氧化壓力指標分析結果 37 4.3.3 發炎指標分析結果 40 4.4 暴露指標與健康指標之影響 41 4.5 銷售員個人健康風險評估 43 五、 結論與建議 46 5.1 結論 46 5.2 建議 47 六、 參考文獻 49 七、 附錄 附件一 人體研究說明及同意書 附件二 百貨公司銷售員奈米級化妝品使用調查問卷

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