(34.228.41.66) 您好!臺灣時間:2018/12/12 20:36
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
本論文永久網址: 
line
研究生:林建宇
研究生(外文):Chien-Yu Lin
論文名稱:探討血清全氟碳化合物與肝功能、甲狀腺功能、血糖調控與心血管疾病危險因子之相關
論文名稱(外文):Investigation of the Associations between Serum Perfluorinated Chemicals, Liver Enzymes, Thyroid Function, Glucose Homeostasis and Cardiovascular Risk Factors
指導教授:陳保中陳保中引用關係
指導教授(外文):Pau-Chung Chen
口試委員:蘇大成陳家揚郭育良陳美蓮洪冠予
口試日期:2010-01-06
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:職業醫學與工業衛生研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文出版年:2011
畢業學年度:99
語文別:英文
論文頁數:121
中文關鍵詞:全氟碳化合物肝功能甲狀腺功能血糖調控心血管疾病
外文關鍵詞:Perfluorinated ChemicalsLiver EnzymesThyroid FunctionGlucose HomeostasisCardiovascular Risk Factors
相關次數:
  • 被引用被引用:0
  • 點閱點閱:556
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
全氟碳化合物是由不同長度的氟化長碳鏈和帶電功能基所組成,全氟化物自1950年代起就被用於商業用途,包括使用於表面活性劑、潤滑劑、紙張與織物的表層塗料、亮光劑、食物包裝與防火泡沫。在動物實驗中,全氟碳化合物與腫瘤、肝毒性、甲狀腺毒性、免疫抑制與身體發展有關。其肝臟毒性的主要機轉是經由活化過氧化物酶體增殖物激活受體α(PPAR-α),活化PPAR-α也能降低老鼠血清中的血脂肪。全氟碳化合物是否會造成人體傷害則還未有定論,且暴露後造成傷害的機轉也都還不清楚;由於全氟碳化合物在人體也可能會活化PPAR-α受體,因此人體血中全氟碳化合物的濃度可能與胰島素抗性,脂肪代謝,進而與代謝症候群的發生率有關,但之前並無相關流行病學的報告。我們最先經由美國食品營養調查(NHANES)所提供的資料進行初步分析,首次發現血中低劑量的全氟碳化物濃度與成人肝功能異常、血糖代謝、高密度脂蛋白濃度有相關,在青少年則與血糖代謝、高密度脂蛋白濃度與代謝症候群有密切相關,結果已發表於國際期刊。在我們的文獻發表後,陸續有文獻發表全氟碳化合物在人體的濃度與膽固醇與尿酸濃度有正相關,但詳細原因還不知。目前除了國人暴露於全氟碳化合物的程度還不清楚外,人體血中全氟碳化合物與甲狀腺功能,脂肪與血糖代謝的詳細機轉甚至動脈硬化之相關性尚還不清楚。為解決上述的問題,我們以之前來自台北與台中自願參與研究的高血壓青少年與年輕成人894人分析其全氟碳化合物於血液中的濃度,結果發現研究對象暴露的全氟碳化合物濃度比美國暴露量稍低,並發現全氟碳化合物其影響血糖代謝可能主要非經由活化過氧化物酶體增殖物激活受體α(PPAR-α),而是經由活化過氧化物酶體增殖物激活受體γ(PPAR-γ)進而刺激肝細胞脂締素(adiponectin)分泌增加而影響血糖的調控,此外我們也首次發現全氟碳化合物與甲狀腺功能有正相關。希望藉由本研究之結果,將有助於了解國人對暴露全氟碳化合物潛在的健康危害風險,以作為未來在環境控制及衛生管理上的依據參考。

The perfluoroalkyl chemicals are a family of perfluorinated chemicals (PFCs) that consist of a carbon backbone. PFCs have been used extensively since the 1950s in commercial applications, including as a component in surfactants, lubricants, paper and textile coatings, polishes, food packaging, and fire-retardant foams. In animal studies, exposure to PFCs are associated with adverse health effects, including tumorigenicity, thyroid toxicity, hepatotoxicity, immune suppression, and developmental toxicity.. The agonistic properties of PFCs on PPAR-α (peroxisome proliferator-activated receptors-α) are well supported and are thought to be a major mechanism leading to PFC-mediated liver damage. PFCs also produced hypolipemia in rodents. Whether PFCs are harmful to humans has remained controversial. The causal biochemical mechanisms leading to the adverse health outcomes after exposure to PFCs are largely unknown. Since activation of PPAR-α can decrease serum triglycerides, normalize low-density lipoprotein cholesterol, and increase HDL-C. We recently analyzed the data from NHANES and found PFCs were associated with abnormal liver function tests, HDL-cholesterol and glucose homeostasis in adults. In adolescents, PFCs level were associated with abnormal glucose homeostasis, HDL-cholesterol and negative associated with metabolic syndrome. These results had been published in international journals. Other reports also demonstrate PFCs were positively associated with total cholesterol and uric acid. However, the extent of PFCs exposure in Taiwan is still unknown. Moreover, the associations between PFCs concentration, thyroid function, mechanism of lipid metabolism and atherosclerosis are still unknown. To solve the above questions, we proposed studies to investigate the association between PFCs concentration and its association with health outcomes. Besides to clarify our previous studies, the goal of the present study is to know the PFCs concentration for people in Taiwan, and we also want to examine associations between PFCs and thyroid function, lipid metabolism and atherosclerosis. Thus, a total 894 subjects from in a community-based sample of adolescents and young adults was enrolled for study. The results showed the PFC exposure in our study group is lower than data from U.S. NHANES. We also found that a higher serum concentration of PFCs was associated with elevated serum adiponectin. It is possible that PFCs increase serum level of adiponectin, decrease serum insulin level by its agonist property to PPARγ instead of PPAR-α. We also conclude that a higher serum concentration of PFCs may cause serum free T4 to increase in this cohort. We hope this study to establish better understandings about PFCs exposure of general household and potential health effect in Taiwan’s population, and used it as a reference for future environmental control and health management program design for public health prevention.

中文摘要ii
英文摘要iv
1: Background 1
1.1: Introduction 1
1.1: Introduction of perfluorinated chemicals (PFCs) 1
1.1.2: The exposure and metabolism of PFCs 2
1.1.3: Toxicity of PFCs 3
1.1.3.1: Human studies: Hepatoxocity 4
1.1.3.2: Human studies: Reproductive and developmental toxicity 4
1.1.3.3: Human studies: Lipid metabolism and atherosclerosis 5
1.1.3.4: Human studies: Glucose metabolism 6
1.1.3.5: Human studies: Thyroid toxicity 7
1.2: Specific aims 9
1.3: References 11
2: Investigation of the associations between low-dose serum perfluorinated chemicals and liver enzymes in US adults 19
2.1: Introduction 19
2.2: Methods 22
2.2.1: Study design and population 22
2.2.2: Potential causes of elevated liver enzymes 24
2.2.3: Assessment of liver enzyme parameters 26
2.2.4: Assessment of PFCs concentration 27
2.2.5: Statistics 28
2.3: Results 29
2.4: Discussion 38
2.5: References 43
3: Association among serum perfluoroalkyl chemicals, glucose homeostasis and metabolic syndrome in adolescents and adults 49
3.1: Introduction 49
3.2: Research design and method 51
3.2.1: Study design and population 51
3.2.2: Anthropometric and biochemical data 51
3.2.3: Definition of metabolic syndrome 53
3.2.4: Assessment of serum PFCs 53
3.2.5: Statistics 54
3.3: Results 55
3.4: Discussion 61
3.5: Conclusion 64
3.6: Study limitations 64
3.7: References 64
4.4: Association Among Serum Perfluoroalkyl Chemicals and Adiponectin in a Young Hypertension Cohort in Taiwan 70
4.1: Introduction 70
4.2: Methods 73
4.2.1: Participants and study design 73
4.2.2: Anthropometric and biochemical data 75
4.2.3 Measurement of PFCs concentration 77
4.2.4: Definition of metabolic syndrome 78
4.2.5: Statistical analysis 79
4.3: Results 81
4.4: Discussion 86
4.5: References 90
5. Associations between Low-dose Serum Perfluorinated Chemicals and Thyroid Function in a Young Hypertension Cohort in Taiwan 96
5.1: Introduction 96
5.2: Research design and methods 99
5.2.1: Participants and study design in baseline 99
5.2.2: Paticipants and study design in follow-up 100
5.2.3: Anthropometric and biochemical data 100
5.2.4: Measurement of PFCs concentration 101
5.2.5: Statistical analysis 103
5.3: Results 104
5.4: Discussion 109
5.5: References 112
6: Conclusion 116
7: Appendix 118


1.: References
1.Houde M, Martin JW, Letcher RJ et al. Biological monitoring of polyfluoroalkyl substances: a review. Environ Sci Technol 2006; 40: 3463–73.
2.Prevedouros K, Cousins IT, Buck RC et al. Sources, fate and transport of perfluorocarboxylates. Environ Sci Technol 2006 ;40 :32-44.
3.Lau C, Anitole K, Hodes C et al. Perfluoroalkyl acids: a review of monitoring and toxicological findings. Toxicol Sci 2007; 99: 366–94.
4.Olsen GW, Burris JM, Ehresman DJ et al. Half-life of serum elimination of perfluorooctanesulfonate, perfluorohexanesulfonate, and perfluorooctanoate in retired fluorochemical production workers. Enviorn Health Perspect 2007; 115.1298-305.
5.Calafat A M, Wong LY, Kuklenyik Z, Reidy JA, Needham LL. Polyfluoroalkyl chemicals in the U.S. population: data from the national health and nutrition examination survey (NHANES) 2003-2004 and comparisons with NHANES 1999-2000. Environ Health Perspect 2007; 115, 1596-1602.
6.Lin AY, Panchangam SC, Lo CC. The impact of semiconductor, electronics and optoelectronic industries on downstream perfluorinated chemical contamination in Taiwanese rivers. Environ Pollut. 2009Apr;157(4):1365-72.
7.Butenhoff J, Costa G, Elcombe C et al. Toxicity of ammonium perfluorooctanoate in male cynomolgus monkeys after oral dosing for 6 months. Toxicol Sci 2002; 69: 244–57.
8.Seacat AM, Thomford PJ, Hansen KJ et al. Sub-chronic dietary toxicity of potassium perfluorooctanesulfonate in rats. Toxicology 2004; 183: 117–31.
9.Seacat A M, Thomford PJ, Hansen KJ et al. Subchronic toxicity studies on perfluorooctanesulfonate potassium salt in cynomolgus monkeys. Toxicol Sci 2002; 68: 249–64.
10.Intrasuksri U, Rangwala SM, O''Brien M et al. Mechanisms of peroxisome proliferation by perfluorooctanoic acid and endogenous fatty acids. Gen Pharmacol 1998; 31: 187–97.
11.Sohlenius AK, Eriksson AM, Hogstrom C et al. Perfluorooctane sulfonic acid is a potent inducer of peroxisomal fatty acid b-oxidation and other activities known to be affected by peroxisome proliferators in mouse liver. Pharmacol Toxicol 2003; 72: 90–3.
12.Klaunig JE, Babich MA, Baetcke KP et al. PPAR agonist-induced rodent tumors: Modes of action and human relevance. Crit Rev Toxicol 2003; 33: 655–780.
13.Kudo N, Bandi N, Suzuki E et al. Induction by perfluorinated fatty acids with different carbon chain length of peroxisomal beta-oxidation in the liver of rats. Chem Biol Interact 2000;124: 119–32,
14.Kudo N, Suzuki-Nakajima E, Mitsumoto A et al. Responses of the liver to perfluorinated fatty acids with different carbon chain length in male and female mice: in relation to induction of hepatomegaly, peroxisomal beta-oxidation and microsomal 1-acylglycerophosphocholine acyltransferase. Biol Pharm Bull 2006; 29: 1952-57
15.Grice MM, Alexander BH, Hoffbeck R et al. Self-reported medical conditions in perfluorooctanesulfonyl fluoride manufacturing workers. J Occup Environ Med 2007; 49: 722–9.
16.Olsen GW, Burris JM, Burlew MM et al. Epidemiologic assessment of worker serum perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) concentrations and medical surveillance examinations. J Occup Environ Med 2003; 45: 260-70.
17.Olsen GW, Burlew MM, Marshall JC et al. Analysis of episodes of care in a perfluorooctanesulfonyl fluoride production facility. J Occup Environ Med 2004;46: 837–46.
18.Olsen GW, Zobel LR. Assessment of lipid, hepatic, and thyroid parameters with serum perfluorooctanoate (PFOA) concentrations in fluorochemical production workers. Int Arch Occup Environ Health 2007;81: 231-46.
19.Sakr CJ, Kreckmann KH, Green JW et al. Cross-sectional study of lipids and liver enzymes related to a serum biomarker of exposure (ammonium perfluorooctanoate or APFO) as part of a general health survey in a cohort of occupationally exposed workers. J Occup Environ Med 2007; 49: 1086–96.
20.Sakr CJ, Leonard RC, Kreckmann KH et al. Longitudinal study of serum lipids and liver enzymes in workers with occupational exposure to ammonium perfluorooctanoate. Occup Environ Med 2007; 49: 872-9.
21.Emmett EA, Zhang H, Shofer FS et al. Community exposure to perfluorooctanoate: Relationships between serum levels and certain health parameters. J Occup Environ Med 2006; 48: 771–9.
22.Apelberg BJ, Witter FR, Herbstman JB, et al. Cord serum concentrations of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in relation to weight and size at birth. Environ Health Perspect. 2007;115(11):1670–1676.
23.Fei C, McLaughlin JK, Tarone RE, et al. Perfluorinated chemicals and fetal growth: a study within the Danish National Birth Cohort. Environ Health Perspect. 2007;115(11):1677–1682.
24.Fei C, McLaughlin JK, Tarone RE, et al. Fetal growth indicators and Perfluorinated chemicals: a study in the Danish National Birth Cohort. Am J Epidemiol. 2008;168(1):66–72.
25.Washino N, Saijo Y, Sasaki S, et al. Correlations Between Prenatal Exposure to Perfluorinated Chemicals and Reduced Fetal Growth. Environ Health Perspect. 2009;117(4):660-667.
26.Joensen UN, Bossi R, Leffers H, et al. Do perfluoroalkyl compounds impair human semen quality? Environ Health Perspect 2009;117(6): 923-7.
27.Stein CR, Savitz DA, Dougan M. Serum levels of perfluorooctanoic acid and perfluorooctane sulfonate and pregnancy outcome. Am J Epidemiol. 2009 Oct 1;170(7):837-46.
28.Nolan LA, Nolan JM, Shofer FS, Rodway NV, Emmett EA. Congenital anomalies, labor/delivery complications, maternal risk factors and their relationship with perfluorooctanoic acid (PFOA)-contaminated public drinking water. Reproductive Toxicology 2010 Apr;29(2):147-55.
29.Steenland K, Tinker S, Frisbee S, Ducatman A, Vaccarino V. Association of perfluorooctanoic acid and perfluorooctane sulfonate with serum lipids among adults living near a chemical plant. Am J Epidemiol 2009; 170: 1268-1278.
30.Nelson, J.W., Hatch E.E., Webster, T.F. 2009. Exposure to Polyfluoroalkyl Chemicals and Cholesterol, Body Weight, and Insulin Resistance in the General U.S. Population. Environ Health Prospect 2010 Feb;118(2):197-202.
31.Steenland K, Tinker S, Shankar A, Ducatman A. Association of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS) with uric acid among adults with elevated community exposure to PFOA. Environ Health Prospect 2010 Feb;118(2):229-33.
32.Leonard RC, Kreckmann KH, Sakr CJ, Symons JM. Retrospective cohort mortality study of workers in a polymer production plant including a reference population of regional workers. Ann Epidemiol. 2008 ;18:15-22.
33.Lundin JI, Alexander BH, Olsen GW, Church TR. Ammonium perfluorooctanoate production and occupational mortality. Epidemiology. 2009 Nov;20(6):921-8.
34.Sakr CJ, Symons JM, Kreckmann KH, Leonard RC. Ischaemic heart disease mortality study among workers with occupational exposure to ammonium perfluorooctanoate. Occup Environ Med. 2009;66:699-703.
35.Ramos RG, Olden K. The prevalence of metabolic syndrome among US women of childbearing age. Am J Public Health 2008; 98(6):1122-1127.
36.Grun F, Blumberg B. Endocrine disrupters as obesogens. Mol Cell Endocrinol 2009; 304(1-2):19-29
37.Paumelle R, Staels B: Cross-talk between statins and PPARalpha in cardiovascular diseases: clinical evidence and basic mechanisms. Trends Cardiovasc Med 18:73–78, 2008.
38.Okochi E, Nishimaki-Mogami T, Suzuki K, Takahashi A. Perfluorooctanoic acid, a peroxisome-proliferating hypolipidemic agent, dissociates apolipoprotein B48 from lipoprotein particles and decreases secretion of very low density lipoproteins by cultured rat hepatocytes. Biochim Biophys Acta. 1999;1437(3):393-401.
39.Díez JJ, Iglesias P. The role of the novel adipocyte-derived hormone adiponectin in human disease. Eur. J. Endocrinol. 2003; 148(3): 293–300.
40.Ukkola O, Santaniemi M. Adiponectin: a link between excess adiposity and associated comorbidities? J. Mol. Med. 2002 ;80(11): 696–702.
41.Renaldi O, Pramono B, Sinorita H, Purnomo LB, Asdie RH, Asdie AH. Hypoadiponectinemia: a risk factor for metabolic syndrome. Acta Med Indones 2009; 41 (1): 20–4.
42.Olsen GW, Gilliland FD, Burlew MM, Burris JM, Mandel JS, Mandel JH. An epidemiologic investigation of reproductive hormones in men with occupational exposure to perfluorooctanoic acid. J Occup Environ Med 1998;40:614–22.
43.Olsen GW, Zobel LR. Assessment of lipid, hepatic, and thyroid parameters with serum perfluorooctanoate (PFOA) concentrations in fluorochemical production workers. Int Arch Occup Environ Health 2007;81:231–46.
44.Bloom MS, Kannan K, Spliethoff HM, Tao L, Aldous KM, Vena JE. Exploratory assessment of perfluorinated compounds and human thyroid function. Physiol Behav. 2010 Feb 9;99(2):240-5.
45.Melzer D, Rice N, Depledge MH, Henley WE, Galloway TS. Association Between Serum Perfluoroctanoic Acid (PFOA) and Thyroid Disease in the NHANES Study. Environ Health Perspect. 2010 May;118(5):686-92.

2: References
1.Houde M, Martin JW, Letcher RJ et al. Biological monitoring of polyfluoroalkyl substances: a review. Environ Sci Technol 2006; 40: 3463–73.
2.Prevedouros K, Cousins IT, Buck RC et al. Sources, fate and transport of perfluorocarboxylates. Environ Sci Technol 2006 ;40 :32-44.
3.Lau C, Anitole K, Hodes C et al. Perfluoroalkyl acids: a review of monitoring and toxicological findings. Toxicol Sci 2007; 99: 366–94.
4.Olsen GW, Burris JM, Ehresman DJ et al. Half-life of serum elimination of perfluorooctanesulfonate, perfluorohexanesulfonate, and perfluorooctanoate in retired fluorochemical production workers. Enviorn Health Perspect 2007; 115.1298-305.
5.Butenhoff J, Costa G, Elcombe C et al. Toxicity of ammonium perfluorooctanoate in male cynomolgus monkeys after oral dosing for 6 months. Toxicol Sci 2002; 69: 244–57.
6.Seacat AM, Thomford PJ, Hansen KJ et al. Sub-chronic dietary toxicity of potassium perfluorooctanesulfonate in rats. Toxicology 2004; 183: 117–31.
7.Seacat A M, Thomford PJ, Hansen KJ et al. Subchronic toxicity studies on perfluorooctanesulfonate potassium salt in cynomolgus monkeys. Toxicol Sci 2002; 68: 249–64.
8.Intrasuksri U, Rangwala SM, O''Brien M et al. Mechanisms of peroxisome proliferation by perfluorooctanoic acid and endogenous fatty acids. Gen Pharmacol 1998; 31: 187–97.
9.Sohlenius AK, Eriksson AM, Hogstrom C et al. Perfluorooctane sulfonic acid is a potent inducer of peroxisomal fatty acid b-oxidation and other activities known to be affected by peroxisome proliferators in mouse liver. Pharmacol Toxicol 2003; 72: 90–3.
10.Klaunig JE, Babich MA, Baetcke KP et al. PPAR agonist-induced rodent tumors: Modes of action and human relevance. Crit Rev Toxicol 2003; 33: 655–780.
11.Kudo N, Bandi N, Suzuki E et al. Induction by perfluorinated fatty acids with different carbon chain length of peroxisomal beta-oxidation in the liver of rats. Chem Biol Interact 2000;124: 119–32,
12.Kudo N, Suzuki-Nakajima E, Mitsumoto A et al. Responses of the liver to perfluorinated fatty acids with different carbon chain length in male and female mice: in relation to induction of hepatomegaly, peroxisomal beta-oxidation and microsomal 1-acylglycerophosphocholine acyltransferase. Biol Pharm Bull 2006; 29: 1952-57
13.Grice MM, Alexander BH, Hoffbeck R et al. Self-reported medical conditions in perfluorooctanesulfonyl fluoride manufacturing workers. J Occup Environ Med 2007; 49: 722–9.
14.Olsen GW, Burris JM, Burlew MM et al. Epidemiologic assessment of worker serum perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) concentrations and medical surveillance examinations. J Occup Environ Med 2003; 45: 260-70.
15.Olsen GW, Burlew MM, Marshall JC et al. Analysis of episodes of care in a perfluorooctanesulfonyl fluoride production facility. J Occup Environ Med 2004;46: 837–46.
16.Olsen GW, Zobel LR. Assessment of lipid, hepatic, and thyroid parameters with serum perfluorooctanoate (PFOA) concentrations in fluorochemical production workers. Int Arch Occup Environ Health 2007;81: 231-46.
17.Sakr CJ, Kreckmann KH, Green JW et al. Cross-sectional study of lipids and liver enzymes related to a serum biomarker of exposure (ammonium perfluorooctanoate or APFO) as part of a general health survey in a cohort of occupationally exposed workers. J Occup Environ Med 2007; 49: 1086–96.
18.Sakr CJ, Leonard RC, Kreckmann KH et al. Longitudinal study of serum lipids and liver enzymes in workers with occupational exposure to ammonium perfluorooctanoate. Occup Environ Med 2007; 49: 872-9.
19.Emmett EA, Zhang H, Shofer FS et al. Community exposure to perfluorooctanoate: Relationships between serum levels and certain health parameters. J Occup Environ Med 2006; 48: 771–9.
20.Calafat AM, Wong LY, Kuklenyik Z, et al. Polyfluoroalkyl chemicals in the U.S. population: data from the National Health and Nutrition Examination Survey (NHANES) 2003–2004 and comparisons with NHANES 1999–2000. Environ Health Perspect 2007;115:1596–602.
21.CDC (Centers for Disease Control and Prevention). National Health and Nutrition Examination Survey Homepage. 2003. Available: http://www.cdc.gov/nchs/nhanes.htm [accessed 1 March 2009].
22.Clark JM, Brancati FL, Diehl AM. The prevalence and etiology of elevated aminotransferase levels in the United States. Am J Gastroenterol 2003; 98: 960–7
23.Ruhl CE, Everhart JE. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States. Gastroenterology 2003; 124: 71–9.
24.Ioannou GN, Weiss NS, Boyko EJ et al. Contribution of metabolic factors to alanine aminotransferase activity in persons with other causes of liver disease. Gastroenterology 2005; 128: 627-35.
25.Weitzman M, Cook S, Auinger P et al. Tobacco smoke exposure is associated with the metabolic syndrome in adolescents. Circulation 2005;112: 862–9.
26.Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care 2004; 27(6): 1487–95.
27.Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection. Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285: 2486-97.
28.Sedlak TW, Snyder SH. Bilirubin benefits: cellular protection by a biliverdin reductase antioxidant cycle. Pediatrics. 2004; 113: 1776-82.
29.Whitfield JB. Gamma glutamyl transferase.Gamma glutamyl transferase. Crit Rev Clin Lab Sci. 2001;38 :263-355.
30.Kuklenyik Z, Needham LL, Calafat AM. Measurement of 18 perfluorinated organic acids and amides in human serum using on-line solid-phase extraction. Anal Chem 2005; 77: 6085-91.
31.Yang Q, Xie Y, Alexson SE et al. Involvement of the peroxisome proliferator-activated receptor alpha in the immunomodulation caused by peroxisome proliferators in mice. Biochem Pharmacol 2002; 63:1893–900.
32.Shipley JM, Hurst CH, Tanaka SS et al. Trans-activation of PPAR and induction of PPAR target genes by perfluorooctane-based chemicals. Toxicol Sci 2004; 80: 151–60.
33.Guruge KS, Yeung LWY, Yamanaka N et al. Gene expression profiles in rat liver treated with perfluorooctaonic acid (PFOA). Toxicol Sci 2006; 89: 93–107.
34.Rosen MB, Thibodeaux JR, Wood CR et al. Gene expression profiling in the lung and liver of PFOA exposed mouse fetuses. Toxicology 2007; 24; 239: 15-33.
35.Peters JM, Hennuyer N, Staels B et al. Alterations in lipoprotein metabolism in peroxisome proliferator-activated receptor alpha-deficient mice. J Biol Chem 1997; 272: 27307-312.
36.Tilg H, Moschen AR. Insulin resistance, inflammation, and non-alcoholic fatty liver disease. Trends Endocrinol Metab 2008; 19: 371-9.
37.Han X, Kemper RA, Jepson GW. Subcellular distribution and protein binding of perfluorooctanoic acid in rat liver and kidney. Drug Chem Toxicol 2005; 28: 197-209.

3: References
1.Lau C, Anitole K, Hodes C, Lai D, Pfahles-Hutchens A, Seed J: Perfluoroalkyl acids: A review of monitoring and toxicological findings. Toxicol Sci 99:366-394, 2007.
2.Calafat AM, Wong LY, Kuklenyik Z, Reidy JA, Needham LL: Polyfluoroalkyl chemicals in the US population: data from the National Health and Nutrition Examination Survey (NHANES) 2003-2004 and comparisons with NHANES 1999-2000. Health Perspect 115:1596-1602, 2007.
3.Kennedy GL Jr, Butenhoff JL, Olsen GW, O''Connor JC, Seacat AM, Perkins RG, Biegel LB, Murphy SR, Farrar DG: The toxicology of perfluorooctanoate. Crit Rev Toxicol 34:351–384, 2004.
4.U.S. Environmental Protection Agency. 2005. Evaluating Human Health Risks from Exposure to Perfluorooctanoic Acid (PFOA): Recommendations to the Science Advisory Board’s PFOA Review Panel; Available: http://www.epa.gov/sab/pdf/kropp-ewg.pdf [last retrieved on September 21, 2008].
5.Butenhoff J, Costa G, Elcombe C, Farrar D, Hansen K, Iwai H, Jung R, Kennedy G Jr, Lieder P, Olsen G, Thomford P: Toxicity of ammonium perfluorooctanoate in male cynomolgus monkeys after oral dosing for 6 months. Toxicol Sci 69:244–257, 2002.
6.Alexander BH, Olsen GW, Burris JM, Mandel JH, Mandel JS: Mortality of employees of a perfluorooctanesulphonyl fluoride manufacturing facility. Occup Environ Med 60:722–729, 2003.
7.Fei C, McLaughlin JK, Tarone RE, Olsen J: Perfluorinated chemicals and fetal growth: a study within the Danish National Birth Cohort. Environ Health Perspect 115:1677–1682, 2007.
8.Intrasuksri U, Rangwala SM, O''Brien M, Noonan DJ, Feller DR: Mechanisms of peroxisome proliferation by perfluorooctanoic acid and endogenous fatty acids. Gen Pharmacol 31:187–197, 1998.
9.Sohlenius AK, Eriksson AM, Hogstrom C, Kimland M, DePierre JW: Perfluorooctane sulfonic acid is a potent inducer of peroxisomal fatty acid β-oxidation and other activities known to be affected by peroxisome proliferators in mouse liver. Pharmacol Toxicol 72:90–93, 2003.
10.The national health and nutrition examination surveys (NAHNES) [online article]. http://www.cdc.gov/nchs/about/major/nhanes/currentnhanes.htm and http://www.cdc.gov/nchs/about/major/nhanes/nhanes2003-2004/current_nhanes_03_04.htm [last retrieved on September 21, 2008].
11.Weitzman M, Cook S, Auinger P, Florin TA, Daniels S, Nguyen M, Winickoff JP. Tobacco smoke exposure is associated with the metabolic syndrome in adolescents. Circulation 112:862–869, 2005.
12.Diabetic Trial Unit, University of Oxford. HOMA calculator. University of Oxford Web site. http://www.dtu.ox.ac.uk/index.php?maindoc=/homa/.december 12, 2007. Accessibility verified October 1, 2008.
13.Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection. Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 285:2486-2497, 2001.
14.Li C, Ford ES, Mokdad AH, Cook S: Recent trends in waist circumference and waist-height ratio among US children and adolescents. Pediatrics 118:e1390-e1398, 2006.
15.Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C: American Heart Association, National Heart, Lung, and Blood Institute: Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American heart Association conference on scientific issues related to definition. Circulation 109:433-438, 2004.
16.National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation and treatment of high blood pressure in children and adolescents. Pediatrics 114:555-576, 2004.
17.Kuklenyik Z, Needham LL, Calafat AM: Measurement of 18 perfluorinated organic acids and amides in human serum using on-line solid-phase extraction. Anal Chem 77:6085-6091, 2005.
18.Inoue K, Okada F, Ito R, Kato S, Sasaki S, Nakajima S, Uno A, Saijo Y, Sata F, Yoshimura Y, Kishi R, Nakazawa H. Perfluorooctane sulfonate (PFOS) and related perfluorinated compounds in human maternal and cord blood samples: Assessment of PFOS exposure in a susceptible population during pregnancy. Environ. Health Perspect 112:1204-1207, 2004.
19.Olsen GW, Church TR, Hansen KJ, Burris JM, Butenhoff JL, Mandel JH. Quantitative evaluation of perfluorooctanesulfonate (PFOS) and other fluorochemicals in the serum of children. J Child Health 2:53–76, 2004.
20.Kudo N, Bandi N, Suzuki E, Katakura M, Kawashima Y. Induction by perfluorinated fatty acids with different carbon chain length of peroxisomal β-oxidation in the liver of rats. Chem. Biol. Interact 124:119–132, 2007.
21.Kudo, N., Suzuki-Nakajima, E., Mitsumoto, A., and Kawashima, Y. Responses of the liver to perfluorinated fatty acids with different carbon chain length in male and female mice: In relation to induction of hepatomegaly, peroxisomal β-oxidation and microsomal 1-acylglycerophosphocholine acyltransferase. Biol Pharm. Bull 29:1952–1957, 2006.
22.Cross-talk between statins and PPARalpha in cardiovascular diseases: clinical evidence and basic mechanisms. Trends Cardiovasc Med 18:73-78, 2008.
23.Luebker DJ, Hansen KJ, Bass NM, Butenhoff JL: Interactions of fluorochemicals with rat liver fatty acid-binding protein. Toxicology 176:175–185, 2002.

4: References
1.Houde, M.; Martin, J. W.; Letcher, R. J.; Solomon, K. R.; Muir, D. C. Biological monitoring of polyfluoroalkyl substances: a review. Environ. Sci. Technol. 2006, 40: 3463–3473.
2.Olsen, G. W.; Burris, J. M.; Ehresman, D. J.; Froehlich, J. W.; Seacat, A. M., Butenhoff, J. L.; Zobel, L. R. Half-life of serum elimination of perfluorooctanesulfonate, perfluorohexanesulfonate, and perfluorooctanoate in retired fluorochemical production workers. Enviorn. Health. Perspect. 2007, 115: 1298-1305.
3.Lau, C.; Anitole, K.; Hodes, C.; Lai, D.; Pfahles-Hutchens, A.; Seed, J. Perfluoroalkyl acids: a review of monitoring and toxicological findings. Toxicol. Sci. 2007, 99: 366–394.
4.Grun, F.; Blumberg, B. Endocrine disrupters as obesogens. Mol. Cell. Endocrinol. 2009, 304:19–29.
5.Olsen, G. W.; Burris, J. M.; Burlew, M. M.; Mandel, J. H. Epidemiologic assessment of worker serum perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) concentrations and medical surveillance examinations. J. Occup. Environ. Med. 2003, 45: 260–270.
6.Olsen, G. W.; Burlew, M. M.; Marshall, J. C.; Burris, J. M.; Mandel, J. H. Analysis of episodes of care in a perfluorooctanesulfonyl fluoride production facility. J. Occup. Environ. Med. 2004, 46: 837– 846.
7.Olsen, G. W.; Zobel, L. R. Assessment of lipid, hepatic, and thyroid parameters with serum perfluorooctanoate (PFOA) concentrations in fluorochemical production workers. Int. Arch. Occup. Environ. Health. 2007, 81: 231– 246.
8.Sakr, C. J.; Kreckmann, K. H.; Green, J. W.; Gillies, P. J.; Reynolds, J. L.; Leonard, R. C. Cross-sectional study of lipids and liver enzymes related to a serum biomarker of exposure (ammonium perfluorooctanoate or APFO) as part of a general health survey in a cohort of occupationally exposed workers. J. Occup. Environ. Med. 2007, 49: 1086 – 1096.
9.Sakr, C. J.; Leonard, R. C.; Kreckmann, K. H.; Slade, M. D.; Cullen, M. R. Longitudinal study of serum lipids and liver enzymes in workers with occupational exposure to ammonium perfluorooctanoate. Occup. Environ. Med. 2007, 49: 872-879.
10.Steenland, K.; Tinker, S.; Frisbee, S.; Ducatman, A.; Vaccarino, V. Association of perfluorooctanoic acid and perfluorooctane sulfonate with serum lipids among adults living near a chemical plant. Am. J. Epidemiol. 2009, 170: 1268-1278.
11.Frisbee, S. J.; Shankar, A.; Knox, S. S.; Steenland, K.; Savitz, D. A.; Fletcher, T.; Ducatman, A. M. Perfluorooctanoic Acid, perfluorooctanesulfonate, and serum lipids in children and adolescents: results from the c8 health project. Arch. Pediatr. Adolesc. Med. 2010, 164: 860-869.
12.Steenland, K.; Tinker, S.; Shankar, A.; Ducatman, A. Association of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS) with uric acid among adults with elevated community exposure to PFOA. Environ. Health. Prospect. 2010, 118: 229-233.
13.Nelson, J.; Hatch, E.; Webster, T. Exposure to Polyfluoroalkyl Chemicals and Cholesterol, Body Weight, and Insulin Resistance in the General U.S. Population. Environ. Health. Perspect. 2010, 118: 197-202.
14.Lin, C. Y.; Chen, P. C.; Lin, Y. C.; Lin, L. Y. Association Among Serum Perfluoroalkyl Chemicals, Glucose Homeostasis and Metabolic Syndrome in Adolescents and Adults. Diabetes. Care. 2009, 32: 702-707.
15.Matsuzawa, Y.; Funahashi, T.; Kihara, S.; Shimomura, I. Adiponectin and metabolic syndrome. Arterioscler. Thromb. Vasc. Biol. 2004, 24: 29-33.
16.Rasouli, N.; Yao-Borengasser, A.; Miles, L. M.; Elbein, S. C.; Kern, P. A. Increased plasma adiponectin in response to pioglitazone does not result from increased gene expression. Am. J. Physiol. Endocrinol. Metab. 2006, 290: E42–E46.
17.Wei, J. N.; Sung, F. C.; Lin, C. C.; Lin, R. S.; Chiang, C. C.; Chuang, L. M. National surveillance for type 2 diabetes mellitus in Taiwanese children. JAMA 2003, 290:1345-1350.
18.Weitzman, M.; Cook, S.; Auinger, P.; Florin, T. A.; Daniels, S.; Nguyen, M.; Winickoff, J. P. Tobacco smoke exposure is associated with the metabolic syndrome in adolescents. Circulation 2005, 112:862–869.
19.Wallace, T. M.; Levy, J. C.; Matthews, D. R. Use and abuse of HOMA modeling. Diabetes. Care. 2004, 27: 1487–1495.
20.Goodfriend, T. L.; Sowers, J. R.; Messerli, F. H.; Cutler, J. A.; Sheps, S. G.; Vidt, D. G. Hypertension Primer: the Essential of High Blood Pressure. Dallas: American Heart Association, 2003.
21.Grundy, S. M.; Brewer, H. B.; Cleeman, J. I.; Smith, S. C.; Lenfant, D. Definition of metabolic syndrome: report of the National, Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 2004, 109:433-438.
22.Jolliffe, C. J.; Janssen, I. Development of age-specific adolescent Metabolic Syndrome Criteria That Are Linked to the Adult Treatment Panel III and International Diabetes Federation Criteria. J. Am. Coll. Cardiol. 2007, 49:891-898.
23.Fang, X.; Zhang, L.; Feng, Y.; Zhao, Y.; Dai, J. Immunotoxic effects of perfluorononanoic acid on BALB/c mice. Toxicol. Sci. 2008, 105: 312–321.
24.Paumelle, R.; Staels, B. Cross-talk between statins and PPARalpha in cardiovascular diseases: clinical evidence and basic mechanisms. Trends. Cardiovasc. Med. 2008, 18: 73–78.
25.Klaunig, J. E.; Babich, M. A.; Baetcke, K. P.; Cook, J. C.; Corton, J. C.; David, R. M.; DeLuca, J. G.; Lai, D.Y.; McKee, R. H.; Peters, J. M.; Roberts, R. A.; Fenner-Crisp, P. A. PPAR agonist-induced rodent tumors: modes of action and human relevance. Crit Rev Toxicol 2003, 33: 655-780.
26.Takacs, M. L.; Abbott, B. D. Activation of mouse and human peroxisome proliferator-activated receptors (alpha, beta/delta, gamma) by perfluorooctanoic acid and perfluorooctane sulfonate. Toxicol. Sci. 2007, 95:108-117.
27.Abbott, B. D. Review of the expression of peroxisome proliferator-activated receptors alpha (PPAR alpha), beta (PPAR beta), and gamma (PPAR gamma) in rodent and human development. Reprod. Toxicol. 2009, 27: 246-257.


5.References
1.Houde M, Martin JW, Letcher RJ et al. Biological monitoring of polyfluoroalkyl substances: a review. Environ Sci Technol 2006;40:3463–73.
2.Lin CY, Lin LY, Chiang CK, Wang WJ, Su YN, Hung KY, Chen PC. Investigation of the associations between low-dose serum perfluorinated chemicals and liver enzymes in US adults. Am J Gastroenterol 2010;105:1354-63.
3.Frisbee SJ, Shankar A, Knox SS, Steenland K, Savitz DA, Fletcher T, Ducatman AM. Perfluorooctanoic acid, perfluorooctanesulfonate, and serum lipids in children and adolescents: results from the c8 health project. Arch Pediatr Adolesc Med. 2010;164:860-9.
4.Lin CY, Chen PC, Lin YC, Lin LY. Association among serum perfluoroalkyl chemicals, glucose homeostasis and metabolic syndrome in adolescents and adults. Diabetes Care 2009; 32: 702-707.
5.Joensen UN, Bossi R, Leffers H, Jensen AA, Skakkebaek NE, Jørgensen N.
Do perfluoroalkyl compounds impair human semen quality? Environ Health Perspect. 2009;117:923-7.
6.Lau C, Anitole K, Hodes C et al. Perfluoroalkyl acids: a review of monitoring and toxicological findings. Toxicol Sci 2007;99:366–94.
7.Egeghy PP, Lorber M. An assessment of the exposure of Americans to perfluorooctane sulfonate: a comparison of estimated intake with values inferred from NHANES data. J Expo Sci Environ Epidemiol 2010 Feb 10. [Epub ahead of print]
8.Lau C, Thibodeaux J, Hanson R, Rogers J, Grey B, Stanton M, Butenhoff J, Stevenson L. Exposure to perfluoroctane sulfonate during pregnancy in rat and mouse II Postnatal evaluation. Toxicol Sci 2003;74:382-392.
9.Seacat AM, Thomford PJ, Hansen KJ, Clemen LA, Eldridge SR, Elcombe CR, et al. Sub-chronic dietary toxicity of potassium perfluorooctanesulfonate in rats. Toxicology 2003;183(1-3):117-131.
10.Butenhoff J, Costa G, Elcombe C, Farrar D, Hansen K, Iwai H, et al. Toxicity of ammonium perfluorooctanoate in male cynomolgus monkeys after oral dosing for 6 months. Toxicol Sci 2002;69:244–57.
11.Liu Y, Wang J, Fang X, Zhang H, Dai J. The thyroid-disrupting effects of long-term perfluorononanoate exposure on zebrafish (Danio rerio). Ecotoxicology. 2010 Oct 13. [Epub ahead of print]
12.Olsen GW, Gilliland FD, Burlew MM, Burris JM, Mandel JS, Mandel JH. An epidemiologic investigation of reproductive hormones in men with occupational exposure to perfluorooctanoic acid. J Occup Environ Med 1998;40:614-22.
13.Olsen GW, Zobel LR. Assessment of lipid, hepatic, and thyroid parameters with serum perfluorooctanoate (PFOA) concentrations in fluorochemical production workers. Int Arch Occup Environ Health 2007;81:231–46.
14.Emmett EA, Zhang H, Shofer FS et al. Community exposure to perfluorooctanoate: Relationships between serum levels and certain health parameters. J Occup Environ Med 2006;48:771–9.
15.Bloom MS, Kannan K, Spliethoff HM, Tao L, Aldous KM, Vena JE. Exploratory assessment of perfluorinated compounds and human thyroid function. Physiol Behav. 2010;99:240-5.
16.Melzer D, Rice N, Depledge MH, Henley WE, Galloway TS. Association Between Serum Perfluoroctanoic Acid (PFOA) and Thyroid Disease in the NHANES Study. Environ Health Perspect. 2010;118:686-92.
17.Steenland K, Fletcher T, Savitz DA. Epidemiologic evidence on the health effects of perfluorooctanoic acid (PFOA). Environ Health Perspect. 2010;118:1100-8.
18.Wei JN, Sung FC, Lin CC, Lin RS, Chiang CC, Chuang LM. National surveillance for type 2 diabetes mellitus in Taiwanese children. JAMA 2003; 290:1345-50.
19.Liao CC, Su TC, Chien KL, Wang JK, Chiang CC, Lin CC, Lin RS, Lee YT, Sung FC. Elevated blood pressure, obesity, and hyperlipidemia. J Pediatr. 2009;155:79-83
20.Weitzman M, Cook S, Auinger P, Florin TA, Daniels S, Nguyen M, Winickoff JP. Tobacco smoke exposure is associated with the metabolic syndrome in adolescents. Circulation 2005;112:862-869.
21.Goodfriend TL, Sowers JR, Messerli FH, Cutler JA, Sheps SG, Vidt DG. Hypertension Primer: the Essential of High Blood Pressure. Dallas: American Heart Association, 2003.
22.Fang X, Zhang L, Feng Y, Zhao Y, Dai J. Immunotoxic effects of perfluorononanoic acid on BALB/c mice. Toxicol Sci 2008;105:312–21.
23.Del Gobbo L, Tittlemier S, Diamond M, et al. Cooking decreases observed perfluorinated compound concentrations in fish. J Agric Food Chem 2008;56:7551–7559.
24.Mundt DJ, Mundt KA, Luippold RS, Schmidt MD, Farr CH. Clinical epidemiological study of employees exposed to surfactant blend containing perfluorononanoic acid. Occup Environ Med. 2007;64:589-94.


QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
系統版面圖檔 系統版面圖檔