| 研究生: |
李宜娟 Li, Yi-Chuan |
|---|---|
| 論文名稱: |
以職場勞工與動物實驗探討鉻(VI/III)暴露下尿中鉻之排除情形與動力學 The investigation of urinary chromium and excretory chromium kinetics from occupationally exposed workers and animal experiments |
| 指導教授: |
張火炎
Chang, Ho-Yuan |
| 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: | 2003 |
| 畢業學年度: | 91 |
| 語文別: | 中文 |
| 論文頁數: | 81 |
| 中文關鍵詞: | 動物實驗 、鉻 、價數 、生物偵測 、皮膚暴露 、動力學 |
| 外文關鍵詞: | dermal exposure, valence, chromium, kinetics, animal experiment, biological monitoring |
| 相關次數: | 點閱:122 下載:1 |
| 分享至: |
| 查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報 |
一般在自然界中暴露到鉻的來源除了包括職業場所的工作暴露(空氣暴露、皮膚暴露)外,飲食中的蔬菜、肉類也會有微量鉻的存在,因此鉻也會經由口服的途徑進入到體內。而目前尿中的總鉻濃度往往被當作是鉻的生物暴露指標。文獻中大多假設尿中鉻是以三價型式存在,對於尿中是否有Cr(VI)的存在則尚未有實際量測資料,此外、過去對於鉻暴露之尿中鉻動力學探討有限。因此本研究利用職業暴露與動物實驗探討不同價數鉻(VI/III)暴露下,尿中鉻濃度之分布與動力學資料,因此,本研究目的為:(1)利用離子色層分析儀(IC)來測試高鉻暴露之實驗動物與職業鉻暴露員工之尿中六價鉻的存在與否(2)探討兩種鉻暴露職業(色料及皮革廠)下生物偵測研究及尿中六價鉻是否存在 (3)利用口服途徑的動物實驗方式,來建立不同價數鉻暴露下鼠尿中總鉻的動力學模式,以了解鉻在體內的分佈情形(4)利用皮膚暴露途徑的動物實驗方式,來比較在不同價數鉻暴露下,剃毛與否對皮膚吸收的影響及鼠尿中總鉻的變化情形。
本研究採集了兩種職業(色料及皮革廠)鉻暴露工廠之勞工的空氣、皮膚以及尿液樣本來作為一般職場的監測。另外再利用動物實驗的方式,在兩種價數(Cr(III)及Cr(VI))鉻暴露的情形下,給予口服與皮膚兩種不同途徑的暴露,並以Inductively Coupled Plasma-Mass Spectrometer(ICP-MS)和Ion Chromatography(IC)來進行尿液樣本的分析。結果顯示,兩家工廠空氣中的幾何平均濃度明顯低於法定的容許濃度值(PEL=100μg/m3),而皮膚樣本的幾何平均濃度範圍分別為0.12~0.32μg/cm2(色料廠中)及0.04~0.16μg/cm2(皮革廠中)。經統計分析後發現,皮膚暴露方面以手部的暴露濃度顯著高於身體其他部位(P<0.05)。在尿液總鉻濃度中則發現色料廠皆低於偵測下限(即<0.126μg/L)而皮革廠員工之幾何平均上班前、下班前之濃度分別為6.71 1.78μg/g creatinine及13.84 1.57μg/g creatinine皆低於ACGIH之BEI值(工作前後尿中總鉻的差異量為10 μg/g creatinine)。另外,利用IC來進行尿液分析後發現,在此種暴露情形下,尿中並無可測得之六價鉻。在Wistar rat之實驗中,分別進行皮膚浸泡100 mg/L (分成剃毛及未剃毛兩種)35分鐘及灌食3 mg(口服)方式,給予Cr(VI)、Cr(III)單獨和兩者混合之暴露,結果發現口服Cr(VI)與Cr(III)+Cr(VI),尿中總鉻之排除曲線符合First-order kinetics。並且發現共同Cr(III)+Cr(VI) 暴露與Cr(VI)單獨暴露相較時,在實驗動物體內之尿中總鉻排除曲線之半衰期、AUC與Cl等動力學參數值,前者皆較後者為高,故推論一般人在六價鉻的職業暴露下,同時有其他諸如口服之三價鉻暴露,可能會增加鉻暴露的危險性。而在濃度100 mg/L的皮膚暴露途徑下亦發現,同時暴露到Cr(VI)+Cr(III)時,尿中的總鉻平均濃度明顯的高於未進行實驗前的尿中總鉻濃度,故可推知共同暴露到Cr(VI)+Cr(III)時,可能較個別暴露易於經由皮膚吸收而進入到體內。此外,利用IC來針對高劑量的口服實驗下之尿液測試,結果發現尿中無法測得六價鉻,此與過去文獻的發現一致。
Two main routes of exposure to chromium for humans are from occupation and from diet. Currently, total chromium concentration in urine has been used as the biomarker of chromium exposure. Chromium III was assumed the only form existing in urine. Chromium VI, however, has not been conclusively excluded from its existence in urine. Moreover, very limited studies have been conducted in excretory chromium kinetics. The objectives of this study were : 1. to verify whether there is chromium VI in urine by using ion chromatography (IC), a more sensitive analytical tool; 2. to explore the biological monitoring of occupational exposure to chromium in pigment and leather industries; 3. to establish the kinetics of excretory chromium after oral administration in animal experiments; 4. to compare the dermal absorption between intact skin and stripped skin on the total urinary chromium.
This study was completed by two approaches. First of all, the exposure assessment of air and skin as well as biological monitoring were performed in the workers from pigment and leather industries. Secondly, Wistar rats were exposed to two valance-specific forms of chromium by both oral and dermal routes. The urinary chromium concentrations collected before and after the exposure, along with the airborne and dermal monitoring samples, were determined by Inductively coupled plasma-mass spectrometer (ICP-MS) and IC, respectively. We found the airborne exposure concentrations of chromium in two chromium-exposed manufacturing workers were far below current exposure limit (PEL=100 μg/m3) and the geometric mean of skin exposure concentrations of chromium were 0.12~0.32μg/cm2 (in pigment) and 0.04~0.16μg/cm2 (in leather), respectively. Skin exposure on hands, however, showed significantly higher than that on the rest of other body sites. The total chromium concentration of urine were all below detection limit (<0.126μg/L) in pigment. The urinary chromium concentrations were 6.71 1.78μg/g creatinine and 13.84 1.57μg/g creatinine among pre-shift and post-shift for leather manufacturing workers although all of them were far below the current BEI setting of chromium exposure (= 10 μg/g creatinine). None of any detectable chromium VI forms were found by IC.
In animal experiments, Wistar rats were exposed to chromium III and chromium VI at the dose of 3mg separately and together by oral route, respectively. For dermal exposure, Wistar rats with intact skin and with stripped skin were exposed to chromium III and chromium VI at 100 mg/L separately and together at 100 mg/L, respectively. We found, in oral exposure experiments, the excretory total chromium in urine followed the first-order kinetics curve for the groups of chromium VI and chromium VI+III. The half-life, area under curve (AUC) and clearance (Cl) in urine were higher when simultaneous exposure to chromium VI and chromium III. It suggests that people simultaneously exposed to chromium VI and chromium III might have higher risk of chromium-related diseases.
In skin exposure experiment, we found urinary chromium concentrations in post-exposure overtly higher than that in pre-exposure when Wistar rats were exposed to chromium VI and chromium III at 100 mg/L simultaneously. Moreover, none of any chromium VI could be detected in the urine samples collected from oral exposure at the experimentally highest dose of chromium, indicating the findings of no existing chromium III could not be rejected.
Aitio A. Jarvisalo J. Kiilunen M. Tossavainen A. Vaittinen P. Urinary excretion of chromium as an indicator of exposure to trivalent chromium sulphate in leather tanning. International Archives of Occupational and Environmental Health 1984; 54(3):241-9.
Anderson RA. Kozlovsky AS. Chromium intake, absorption and excretion of subjects consuming self-selected diets. The American Journal of Clinical Nutrition 1985;41(6):1177-83.
ACGIH:Documentation of the threshold limit values and biological exposure indices. Fifth edition 1986;139-141:BEI91-96.
Angerer J. Amin W. Heinrich-Ramm R. Szadkowski D. Lehnert G. Occupational chronic exposure to metals. I. Chromium exposure of stainless steel welders--biological monitoring. International Archives of Occupational and Environmental Health 1987;59(5):503-12.
Accominotti M. Bost M. Haudrechy P. et al. Contribution to chromium and nickel enrichment during cooking of foods in stainless steel utensils. Contact Dermatitis. 1998;38(6):305-10.
Burrows D. Adverse chromate reactions on the skin, Cheomium:Metabolism and Toxicity, Burrowa, D. ed., CRC Press Inc. 1983:p147,.
Baruthio F. Toxic effects of chromium and its compounds. Biological Trace Element Research 1992;32:145-53.
Beere HG. Jones P. Investigation of chromium(III) and chromium(VI) speciation in water by ion chromatography with chemiluminescence detection. Analytica Chimica Acta 1994;293:237-43.
Bittner M. Broekaert JAC. Speciation of chromium by solid-phase extraction coupled to reversed-phase liquid chromatography with UV detection. Analytica Chimica Acta 1998;364:31-40.
Barceloux DG. Chromium. Clinical Toxicology 1999;37(2):173-94.
Chavalitnitikul C. Levin L. A laboratory evaluation of wipe testing based on lead oxide surface contamination. American Industrial Hygiene Association Journal 1984;45(5):311-7,
Cook WA. Occupational exposure limits-wordwide. American Industrial Hygiene Association Journal 1987:p113.
Chen JL, Guo YL, Tsai PJ, Su LF. Use of inhalable Cr6+ exposures to characterize urinary chromium concentrations in plating industry workers. Journal of Occupational Health 2002;44:46-52.
Dionex Technical Note24. Determination of chromium by ion chromatography. 1991
Elias Z. Poirot O. Schneider O. et a;. Cellular uptake, Cytotoxic and mutagenic effects of insoluble chromic oxide in V79 Chinese hamster cells. Mutation Research 1986;169:159.
Fendorf SE, Surface reactions of chromium in soils and waters. Geoderma 1995;67:55-71.
Fowler JF Jr, Kauffman CL, Marks JG Jr, et al. An environmental hazard assessment of low-level dermal exposure to hexavalent chromium in solution among chromium-sensitized volunteers. Journal of Occupational and Environmental Medicine 1999;41(3):150-60.
Gammalgaard B., Fullerton A., Avnstorp C., Menne T. Permeation of chromium salts through human skin in vitro. Contact Dermatitis 1992;27:302-10.
Gao M. Levy LS. Braithwaite RA. Brown SS. Monitoring of total chromium in rat fluids and lymphocytes following intratracheal administration of soluble trivalent or hexavalent chromium compounds. Human and experimental toxicology 1993;12(5):377-82.
Hayes R. Carcinogenic effects of chromium, In Langard S(ed): Biological and environmental spects of chromium. Elsevier Amsterdam, Biomedical Press, 1992;221-47.
International Agency for Research on Cancer (IARC). IARC monographs of the evaluation of the carcinogenic risk of chemicals to humans: Chromium, Nickel and Welding, IARC, Lyon, 1990;p49.
Ladou J. Occupational medicine. Norwalk, Appleton & Lange, 1990:304-306.
Jen JF. Ou-Yang GL. Chen CS. Yang SM. Simultaneous determination of chromium(III) and chromium(VI) with reversed-phase ion-pair high-performance liquid chromatography. Analyst 1993;118:1281-84.
Jeejeebhoy KN. The role of chromium in nutrition and therapeutics and as a potential toxin. Nutrition Reviews 1999;57(11):329-35.
Karita K. Shinozaki T. Tomita K. Yano E. Possible oral lead intake via contaminated facial skin. The Science of the Total Environment 1997; 199(1-2):125-31.
Langard, S. Chromium. In: metals in the environment, Waldron, H.A., Eds, Academic Press, London, 1980;p111.
Langard S. and Norseth T. In L. Friberg. G.F. Nordberg and V.B. Vouk. Handbook on the Toxicology of metals. Vol. 11. Specific Metals. Elsevier. Amsterdam. 2nd ed. 1990;185-210.
Lees PSJ. Chromium and disease, review of epidemiological studies with particular reference to etiological information provided by measure of exposure. Environmental Health Perspectives 1991;92:93-104.
Lumens ME. Ulenbelt P. Geron HM. Herber RF. Hygienic behaviour in chromium plating industries. International Archives of Occupational and Environmental Health 1993;64(7):509-14.
Lin SC. Tai CC. Chan CC. Wang JD. Nasal septum lesions caused by chromium exposure among chromium electroplating workers. American Journal of Industrial Medicine 1994;26(2):221-8.
Lukanova A. Toniolo P. Zhitkovich A. et al. Occupational exposure to Cr(6+): comparison between chromium levels in lymphocytes, erythrocytes, and urine. International Archives of Occupational and Environmental Health 1996;69(1):39-44.
Minoia C. Cavalleri A. Chromium in urine, serum and red blood cells in the biological monitoring of workwes exposed to different chromium valency states. The Science of the Total Environment 1988;71(3):323-27.
McAughey JJ. Samuel AM. Baxter PJ. Smith NJ. Biological monitoring of occupational exposure in the chromate pigment production industry. The Science of the Total Environment 1988;71(3):317-22.
NIOSH:Criteria for a recommended standard-occupational exposure of chromium(VI). DHEW(NIOSH) 1975;76-129.
Nomiyama H. Yotoriyama M. Nomiyama K. Normal chromium levels in urine and blood of Japanese subjects determined by direct flameless atomic absorption spectrophotometry, and valency of chromium in urine after exposure to hexavalent chromium. American Industrial Hygiene Association Journal 1980;41:98-102.
The National Academy of Sciences (NAS, 1980) National research council recommended dietary allowances. National academy of Sciences, Washington, DC, 1980.
Pellerin C. Booker SM. Reflections on hexavalent chromium: health hazards of an industrial heavyweight. Environ health perspect 2000;108(9):402-7.
Rinehart WE. Gad SC. Current concepts in occupational health: metals-chromium. American Industrial Hygiene Association Journal 1986;47(11):696-9.
Richard Lewis. Metals. In :Joseph Ladou. Occupational medicine. Appleton & Lange, Prentice Hall, 1990;297-326.
Robards K. Starr P. Metal determination and metal speciation by liquid chromatography A review. Analyst 1991;116:1247-1273.
Rosenberg J. Fiserova-Bergerova V. Lowry LK. Measurements in urine. In:ACGIH. Topics in biological monitoring. 1995;25-32.
Schneider T, Cherrie JW, Vermeulen R, Kromhout H. Dermal exposure assessment. The Annals of Occupational Hygiene 2000;44:493-9
Sarzanini C. Mentasti E. Determination and speciation of metals by liquid chromatography. Journal of Chromatography A 1997;789:301-21.
Shargel L. Yu A. Applied biopharmaceutics and pharmacokinetics 4/e., McGraw-Hill , New York, 1999;29-66, 607-41.
Sikovec M. Franko M. Novic M. Veber M. Effect of organic solvents in the on-line thermal lens spectrometric detection of chromium(III) and chromium(VI) after ion chromatographic separation. Journal of Chromatography A 2001;920:119-25.
Tossavainen A., Nurminen M., Mutanen P., and Tola S. Application of mathematical modelling for assessing the biological half-times of chromium and nickel in field studies. British Journal of Industrial Medicine 1980;37(3):285-91.
Tupker RA. Measurement of the transepidermal water loss. In:Serup J. Jemec BE. Handbook of non-invasive methods and the skin. Boca Raton, CRC Press, 1994:173-78.
Tsai JC. Sheu HM. Hung PL. Cheng CL. Effect of barrier disruption by acetone treatment on the permeability of compounds with various lipophilicities: implications for the permeability of compromised skin. Journal of Pharmaceutical Sciences 2001;90(9):1242-54.
U.S. Environmental Protection Agency. Integrated Risk Information System (IRIS) on Chromium VI. National Center for Environmental Assessment, Office of Research and Development, Washington, DC. 1999a.
U.S. Environmental Protection Agency. Integrated Risk Information System (IRIS) on Chromium III. National Center for Environmental Assessment, Office of Research and Development, Washington, DC. 1999b.
Wetterhahn KE. Hamilton JW. Molecular basis of hexavalent chromium carcinogenicity: effect on gene expression. The Science of the Total Environment 1989;86(1):113-129.
Wass U. Wahlberg JE. Chromated steel and contact allergy recommendation concerning a “ threshold limit value” for the release of hexavalent chromium. Contact dermatitis 1991;24:114-118.
Wilson K. Guidance on laboratory techniques in occupational medicine. 5th ed, Health and safety executive;1991:23-25.
Zielhuis RL. Exposure cimits to metals for the general population, Proc. Int. Conf. Heavy Metals in the Environment. CEC-WHO, Amsterdam 1981;p429.
行政院勞工委員會,「勞工作業環境空氣中有害物質容許濃度標準」, 1988.
工業衛生技術研究院,物質安全資料表, 1999
行政院勞工委員會勞工安全衛生研究所,勞工鉻暴露生物偵測標準參考方法之建立,1997. 計劃編號:IOSH 85-A308.
蔡靜宜,職業暴露DMF之皮膚吸收與生物偵測,成功大學環境醫學研究所碩士論文,2002.
行政院環境保護署,飲用水水質標準,2003.
行政院環境保護署,毒性化學物質環境流布暴露調查分析與資料庫建立—期末報告,2000. 計劃編號:EPA-89-U1J1-03-1005.