臺灣博碩士論文加值系統

近年來由於半導體業的興盛，砷因為其類金屬元素的特性被大量使用在製程當中，使得員工有暴露於砷的疑慮。為了研究其員工是否有職業性無機砷暴露，本研究使用唾液做為生物檢體，研究唾液中砷濃度與職等之間的關係，並探討影響唾液砷之因子。
本研究配合某一LED製造公司之年度健檢，在該公司南部廠區及北部廠區共招募355名受試者，並利用問卷記錄各項人口學變項、生活習慣，及海鮮攝食量等因素。唾液砷濃度與職等之統計分析分成兩部分，第一部分使用廠方醫護人員提供之職業砷暴露情形分為暴露組、對照組(一)及對照組(二)，第二部分使用受試者問卷自答是否有職業性砷暴露以及所在職等是否有過半人數有職業砷暴露進行分組，分成暴露組、低暴露組及行政組。本研究使用感應耦合電漿質譜儀(ICP-MS)分析受試者唾液中的砷濃度。結果發現，全體受試者唾液平均砷濃度為 0.66 μg/L，問卷中回答有及無職業砷暴露的受試者平均唾液中砷濃度分別為0.65 μg/L、0.60 μg/L。本研究沒有看到唾液中砷濃度與職等之關係。唾液中的砷濃度與年資、年齡之Pearson’s相關係數分別為0.158 (p < 0.01)、0.126 (p < 0.05)，唾液中砷濃度與飲酒習慣、檳榔食用習慣之Spearman’s相關係數分別為0.142 (p < 0.01)、0.146 (p < 0.01)。唾液中的砷濃度也會隨著教育程度的提高而降低(p < 0.001)。
本研究結果顯示唾液中砷濃度與年齡、年資顯著正相關，表示年紀為影響唾液中砷濃度重要的因子。而唾液中砷濃度隨著教育程度提高而下降，則可能是由於教育程度會決定受試者之職等進而影響職業砷暴露情形。唾液中砷濃度與抽菸、喝酒及食用檳榔等生活習慣因子的正相關關係與過往文獻研究結果相
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同。唾液中砷濃度與職等之間的關係在本研究中沒有看到，推測可能是同樣職等下不同工作內容會有不同程度之職業砷暴露，以致難以從職等看出唾液中砷濃度變化情形。建議之後類似的研究應更詳細記錄工作內容，以進一步釐清受試者唾液中砷濃度作為生物指標與工作環境中砷暴露的關聯性。

As the blossom of semiconductor industry, arsenic was used widely in the fab manufacturing process due to its metalloid properties, which therefore led to the concern of exposure hazard to workers on site. In order to characterize the association between inorganic arsenic exposure and work task, this study was conducted using saliva arsenic as biomarker to explore its association with the affecting factors. This study was incorporated into a LED manufacturing company’s annual physical examination program, and recruited a total of 355 subjects from this company’s northern and southern factories. Questionnaire was used to collect information on demographics, living habits, and seafood consumption. There were two parts in statistical analysis for the association between saliva arsenic concentration and job title. In the first part, study subjects were grouped as exposed group, control I, and II groups, based on the judgement of the occupational nurse of this company. In the second part, we combined job title along with arsenic exposure information collected using questionnaire to divide the study subjects into exposed group, low exposed group, and administration group. This study used inductively coupled plasma mass spectrometry (ICP-MS) to analyze arsenic concentration in the saliva samples of the study subjects. Results showed that average saliva arsenic concentration of all subjects was 0.66 μg/L, average saliva arsenic concentration of subjects with and without occupational arsenic exposure was 0.65 μg/L, and 0.60 μg/L, respectively. Though there was no significant association between saliva arsenic level and job title, there were positive correlations of saliva arsenic concentration with work seniority (r= 0.158, p< 0.01), workers’ age (r= 0.126, p< 0.05), alcohol drinking (r= 0.142, p<
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0.01), and betel nut chewing (r= 0.146, p< 0.01), respectively. However, saliva arsenic concentration significantly decreased with higher education level. In this study, significantly positive association of saliva arsenic level with work seniority and workers’ age suggested age-related factors were important to saliva arsenic concentration. Besides, negative association of saliva arsenic concentration with higher education level could be attributed to that study subjects with higher education level would work at higher job title, with relatively low arsenic exposure. Positive relationship between saliva arsenic concentration and living habits such as smoking, alcohol drinking, betel nut chewing was in accordance with previous studies’ finding. No significant association between saliva arsenic concentration and job title could probably be attributed to that various work tasks under the same job title might cause the misclassification of arsenic exposure based on job title. Further study with
precise and detailed arsenic exposure history is anticipated in order to classify the relationship of saliva arsenic concentration, as biological marker, with worker’s occupational arsenic exposure.

口試委員會審定書…………………………………………………………………... I
中文摘要…………………………………………………………………………….. II
英文摘要……………………………………………………….…………………… IV
目錄………………………………………………………………………………..... VI
表目錄…………………………………………………………………………….. VIII
圖目錄………………………………………………………………………………. IX
第一章 前言…………………………………………………………………………. 1
1-1 研究背景…………………………………………………………………… 1
1-2 研究目的及假說…………………………………………………………… 1
第二章 文獻探討……………………………………………………………………. 3
2-1 砷之物化特性及環境與健康危害………………………………………… 3
2-1-1 砷的環境傳播與流布……………………………………………… 4
2-1-2 砷的環境濃度及人體暴露………………………………………… 5
2-1-3 砷的使用…………………………………………………………… 6
2-1-4 砷的藥物動力學及代謝…………………………………………… 7
2-1-5 砷毒性……………………………………………………………… 8
2-1-6 砷暴露的生物指標………………………………………………… 8
2-2 唾液的基本特性…………………………………………………………... 9
2-2-1 唾液的分泌……………………………………………………….. 10
2-2-2 唾液作為生物偵測介質………………………………………….. 11
2-2-3 唾液中的砷……………………………………………………….. 12
2-3 砷含量檢測儀器分析原理- 感應耦合電漿質譜儀…………………….. 13
第三章 材料與方法………………………………………………………………... 17
3-1 研究架構………………………………………………………………….. 17
3-2 研究對象………………………………………………………………….. 17
3-3 問卷……………………………………………………………………….. 18
3-3-1 問卷設計………………………………………………………….. 18
3-3-2 問卷填答………………………………………………………….. 18
3-4 採樣……………………………………………………………………….. 19
3-4-1 採樣時間………………………………………………………….. 19
3-4-2 採樣流程………………………………………………………….. 19
VII
3-4-3 唾液採集………………………………………………………….. 19
3-5 樣品保存與實驗前處理…………………………………………………. 20
3-5-1 樣品保存………………………………………………………….. 20
3-5-2 樣品解凍………………………………………………………….. 20
3-5-3 樣品上機前處理………………………………………………….. 20
3-6 砷濃度檢測分析…………………………………………………………. 20
3-7 品質控管…………………………………………………………………. 21
3-7-1 檢量線配製……………………………………………………….. 21
3-7-2 方法空白樣本…………………………………………………….. 22
3-7-3 重複分析樣品…………………………………………………….. 22
3-7-4 偵測極限………………………………………………………….. 22
3-8 統計分析……………………………………………………………….…. 22
3-9 實驗器材……………………………………………………………….…. 23
第四章 結果…………………………………………………………………….….. 24
4-1 受試者基本資料………………………………………………………….. 24
4-2 受試者依照廠方分組後之基本資料…………………………………….. 24
4-3 受試者唾液砷濃度分布情形………………………………………….…. 25
4-4 更新分組後之基本資料………………………………………………….. 26
4-5 更新分組後受試者唾液砷濃度分布情形……………………….............. 28
4-6 各人口學變向別之間唾液砷濃度差異性檢定…………………….……. 28
4-7 唾液砷濃度及各變項間之相關係數…………………….………………. 29
第五章 討論………………………………………………………………….…….. 39
5-1 唾液中砷作為職業性砷暴露指標之評估…………………………….…. 39
5-2 唾液中砷濃度與人口學變項……………………………………….……. 40
5-3 唾液中砷濃度與職等之關係……………………………………….……. 41
5-4 唾液中砷濃度與生活習慣之關係………………………………….……. 43
5-5 唾液中砷濃度與採樣前三日內是否有食用海鮮之關係…………….…. 44
5-6 唾液中砷濃度與疾病之關係………………………………………….…. 45
5-7 研究限制……………………………………………………………….…. 46
第六章 結論………………………………………………………………….…….. 47
參考文獻……………………………………………………………………….…… 48
附錄、砷暴露調查問卷………………………………………………………….… 55

Abass K, Koiranen M, Mazej D, Tratnik JS, Horvat M, Hakkola J, Järvelin M, Rautio A. Arsenic, cadmium, lead and mercury levels in blood of Finnish adults and their relation to diet, lifestyle habits and sociodemographic variables. Environ Sci Pollut Res 2017;24: 1347–1362.
Agilent. Agilent 7500 series ICP-MS hardware manual. Tokyo, Japan: Agilent Technologies, Inc; 2008; 334p.
Agilent. Agilent 7500 Inductively Coupled Plasma Mass Spectrometry course number H8974A student manual. Tokyo, Japan: Agilent Technologies, Inc; 2001; 408p.
Aguilera I, Daponte A, Gil F, Hernández AF, Godoy P, Pla A, Ramos JL. Biomonitoring of urinary metals in a population living in the vicinity of industrial sources: a comparison with the general population of Andalusia, Spain. Sci Total Environ 2008;407: 669-678.
Allard P, Aiuppa A, Loyer H, Carrot F, Gaudry A, Pinte G, Michel A, Dongarra G. Acid gas and metal emission rates during long-lived basalt degassing at Stromboli volcano. Geophysical Research Letters 2000;27(8): 1207-1210.
Argos M, Kalra T, Rathouz PJ, Chen Y, Pierce B, Parvez F, Islam, T, Ahmed A, Rakibuz-Zaman M, Hasan R, Sarwar G, Slavkovich V, Van Geen A, Graziano J, Ahsan H. Arsenic exposure from drinking water, and all-cause and chronic-disease mortalities in Bangladesh (HEALS): a prospective cohort study. Lancet 2010;376(9737): 252–258.
Arnold RG, Carpenter DO, Kirk D, Koh D, Armour MA, Cebrian M, Cifuentes L, Khwaja M, Ling B, Makalinao I, pza-y-Miño C, Peralta G, Prasad R, Singh K, Sly P, Tohyama C, Woodward A, Zheng B, Maiden T. Meeting report: threats to human health and environmental sustainability in the pacific basin. Environmental Health Perspectives 2007;115(12): 1770-1775.
An Y, Wang PD, Shimoda Y, Wang XS, Wang HZ, Liu J, Liu X, Jin HY, Gao FF, Tong J. Total arsenic and speciation analysis of saliva and urine samples from individuals living in a chronic arsenicosis area in China. Toxicology Letters 2016;258.
Al-Rmalli SW, Jenkins RO, Haris PI. Betel quid chewing elevates human exposure to arsenic, cadmium and lead. J Hazard Mater 2011;190: 69–74.
ATSDR. Public health statement for arsenic 2007. Atlanta, GA: Agency for Toxic Substances and Disease Registry; Retrived on December 10, 2016, from: URL:http://www.atsdr.cdc.gov/phs/phs.asp?id=18&tid=3
Bali I, Bilir B, Emir S, Turan F, Yilmaz A, Gokkus T, Aydin M. The effects of melatonin on liver functions in arsenic-induced liver damage. Turk J Surg 2016;32: 233–237.
Ball AL, Rom, WN, Glenne B. Arsenic distribution in soils surrounding the Utah copper smelter. AIHAJ 1983;44(5): 341-348.
Bertoldi D, Villegas TR, Larcher R, Santato A, Nicolini G. Arsenic present in the soil-vine-wine chain in vineyards situated in an old mining area in Trentino, Italy. Environmental Toxicology and Chemistry 2013;32(4): 773-779.
Bhowmick S, Halder D, Kundu AK, Saha D, Chatterjee D, Iglesias M, Nriagu J, Roman-Ross G. Is saliva a potential biomarker of arsenic exposure? A case-control study in West Bengal, India. Environ Sci Technol 2013;47(7): 3326-3332.
Bhowmick S, Halder D, Nriagu J, Guha Mazumder DN, Roman-Ross G, Chatterjee D, Iglesias M. Speciation of arsenic in saliva samples from a population of West Bengal, India. Environ Sci Technol 2014;48: 6973–6980.
Cui C, Liu Z. Chemical speciation and distribution of arsenic in water, suspended solids and sediment of Xiangjiang River, China. Science of the Total Environment 1988;77(1): 69-82.
Dabeka RW, McKenzie AD, Lacroix GM. Dietary intakes of lead, cadmium, arsenic and fluoride by Canadian adults: a 24-hour duplicate diet study. Food Additives and Contaminants 1987;4(1): 89-101.
Dixon HB. The biochemical action of arsonic acids especially as phosphate analogues. Adv Inorg Chem 1997;44: 191–228.
Díaz-Barriga F, Santos MA, Mejía JJ, Batres L, Yáñez L, Carrizales L, Vera E, Del Razo LM, Cebrián ME. Arsenic and cadmium exposure in children living near a smelter complex in San Luis Potosí, Mexico. Environ Res 1993;62(2):242–250.
Ettinger AS, Arbuckle TE, Fisher M, Liang CL, Davis K, Cirtiu CM, Belanger P, LeBlanc A, Fraser WD. Arsenic levels among pregnant women and newborns in Canada: results from the maternal-infant research on environmental chemicals (MIREC) cohort. Environ Res 2016;153: 8–16.
Garrett JR, Kidd A. The innervation of salivary glands as revealed by morphological methods. Microscopy Research and Technique 1993;26(1): 75-91.
Gartrell MJ, Craun JC, Podrebarac DS, Gunderson EL. Pesticides, selected elements, and other chemicals in adult total diet samples, October 1980-March 1982. Journal - Association of Official Analytical Chemists 1986;69: 146-159.
Gemba H, Teranaka A, Takemura K. Influences of emotion upon parotid secretion in human. Neuroscience Letters 1996;211(3): 159-162.
Gordon BP. The physiology of salivary secretion. Periodontol 2000 2016;70: 11–25.
Grund SC, Hanusch K, Wolf HU. Arsenic and arsenic compounds. Ullmann’s encyclopaedia of industrial chemistry. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA; 2008.
Hazell T. Minerals in foods: dietary sources, chemical forms, interactions, bioavailability. World Review of Nutrition and Dietetics 1985;46: 1-123.
Health and Welfare Canada. Guidelines for Canadian drinking water quality: guideline technical document – arsenic. Ottawa, Ontario: Department of National Health and Welfare, Bureau of Chemical Safety; 1983: 6-7.
Hector MP, Linden RWA. Reflexes of salivary secretion. Neural mechanisms of salivary gland secretion. Basel, Switzerland: Karger, 1999: 196–217.
Hindmarsh JT, McCurdy RF. Clinical and environmental aspects of arsenic toxicity. CRC Critical Reviews in Clinical Laboratory Sciences 1986;23: 315–347.
Hsueh YM, Huang YL, Huang, CC, Wu WL, Chen HM, Yang MH, Lue LC, Chen CJ. Urinary levels of inorganic and organic arsenic metabolites among residents in an arseniasis-hyperendemic area in Taiwan. Journal of Toxicology and Environmental Health 1998;54(6): 431-444.
Hughes MF, Beck BD, Chen Y, Lewis AS, Thomas DJ. Arsenic exposure and toxicology: a historical perspective. Toxicol Sci 2011;123: 305–332.
Inoue H, Ono K, Masuda W, Morimoto Y, Tanaka T, Yokota M, Inenaga K. Gender difference in unstimulated whole saliva flow rate and salivary gland sizes. Arch Oral Biol 2006;51: 1055–1060.
IPCS. Arsenic and arsenic compounds. World Health Organization, International Programme on Chemical Safety (Environmental Health Criteria 224). Geneva, Switzerland: World Health Organization; 2001.
IPCS. Arsenic. World Health Organization, International Programme on Chemical Safety (Environmental Health Criteria 18). Geneva, Switzerland: World Health Organization; 1981.
Irgolic KJ, Health Effects Research Laboratory. Speciation of arsenic compounds in water supplies. Washington, D.C., U.S.: USEPA; 1982.
Lee VM, Linden RWA. An olfactory submandibular salivary reflex in humans. Exp Physiol 1992;77: 221–224.
Lee YH, Wong DT. Review article - Saliva: An emerging biofluid for early detection of diseases. American Journal of Dentistry 2009;22(4): 241-248.
Lemmo NV, Faust SD, Belton T, Tucker R. Assessment of the chemical and biological significance of arsenical compounds in a heavily contaminated watershed. Part 1. The fate and speciation of arsenical compounds in aquatic environments — a literature review. Journal of Environmental Science and Health Part A 1983;18: 335-387.
Liu J, Waalkes MP. Liver is a target of arsenic carcinogenesis. Toxicological Sciences 2008;105(1): 24-32.
Mandal BK, Suzuki KT. Arsenic around the world: A review. Talanta 2002; 58: 201-235.
Michalke B, Rossbach B, Göen T, Schäferhenrich A, Scherer G. Saliva as a matrix for human biomonitoring in occupational and environmental medicine. International Archives of Occupational and Environmental Health 2015;88(1): 1-44.
Monnot AD, Tvermoes BE, Gerads R, Gurleyuk H, Paustenbach DJ. Risks associated with arsenic exposure resulting from the consumption of California wines sold in the United States. Food Chem 2016;211: 107−113.
Nadakavukaren JJ, Ingermann RL, Jeddeloh G, Falkowski SJ. Seasonal variation of arsenic concentration in well water in Lane County, Oregon. Bulletin of Environmental Contamination and Toxicology 1984;33(1): 264-269.
Percival RS, Challacombe SJ, Marsh PD. Flow rates of resting whole and stimulated parotid saliva in relation to age and gender. Journal of Dental Research 1994;73: 1416–1420.
Pflaum T, Hausler T, Baumung C, Ackermann S, Kuballa T, Rehm J, Lachenmeier DW. Carcinogenic compounds in alcoholic beverages: An update. Arch Toxicol 2016;90: 2349–2367.
Roussa E. Channels and transporters in salivary glands. Cell and Tissue Research 2011;343(2): 263-287.
Serrano IN, Ballesteros MTL, Pacheco SSF, Álvarez SI, Colón JLL. Total and speciated urinary arsenic levels in the Spanish population. Sci Total Environ 2016;571: 164-171.
Shen S, Li XF, Cullen WR, Weinfeld M, Le XC. Arsenic Binding to Proteins. Chemical Reviews 2013;113(10): 7769-7792.
Slooff W, Haring BJA, Hesse JM, Janus JA, Thomas R, van Beelen P, de Boer JLM. Integrated criteria document arsenic. Bilthoven, Netherlands: National Institute of
Public Health and Environmental Protection; 1990.
Spinazzè A, Cattaneo A, Monticelli D, Recchia S, Rovelli S, Fustinoni S, Cavallo D. Occupational exposure to arsenic and cadmium in thinfilm solar cell production. Ann Occup Hyg 2015;59: 572–585.
Tseng CH, Huang YK, Huang YL, Chung CJ, Yang MH, Chen CJ, Hsueh YM. Arsenic exposure, urinary arsenic speciation, and peripheral vascular disease in blackfoot disease-hyperendemic villages in Taiwan. Toxicol Appl Pharmacol 2005;206, 299-308.
UNICEF. Bangladesh national drinking water quality survey of 2009. Dhaka, Bangladesh: Bangladesh Bureau of Statistics; 2011.
USEPA. Special report on ingested inorganic arsenic: Skin cancer, nutritional essentiality. Washington, DC: Risk Assessment Forum, U.S. Environmental Protection Agency; 1988.
USNRC. Arsenic in drinking water: 2001 update. Washington, DC: National Academies Press; 2001.
Vahter M, Concha G, Nermell B, Dulout F, Natarajan AT. A unique metabolism of inorganic arsenic in native Andean women. Eur J Pharmacol 1995;293: 455-462.
Wang D, Shimoda Y, Kurosawa H, Liu J, Xu X, Liu X, Jin H, Tong J, Yamanaka K, An Y. Excretion patterns of arsenic and its metabolites in human saliva and urine after ingestion of Chinese seaweed. Int J Environ Anal Chem 2015;95: 379–389
Welch AH, Lico MS, Hughes JL. Arsenic in ground water of the western United States. Ground Water 1988;26(3): 333-347.
WHO. Air quality guidelines for Europe. Geneva, Switzerland: World Health Organization; 2001.
Yeh H. Evaluation of the use of arsenic species and heavy metals in saliva as biological marker of inorganic arsenic and heavy metals exposure. Taipei, Taiwan: National Taiwan University[Thesis]; 2016; 142p.
Yost LJ, Schoof RA, Aucoin R. Intake of inorganic arsenic in the north American diet. Human and Ecological Risk Assessment 1998;4(1): 137-152.
Yuan CG, Lu XF, Oro N, Wang ZW, Xia YJ, Wade TJ, Mumford J, Le XC. Arsenic speciation analysis in human saliva. Clin Chem 2008;54: 163-171.