工業的發展為人類生活帶來許多便利，然而民生、工業、農業及畜牧業的廢棄物排放，為環境帶來許多污染。人類活動排放的污染物質種類複雜，其中含有類(抗)雌激素與類(抗)雄激素物質，這些化合物具有能模擬或拮抗荷爾蒙之特性，能與生物體中的雌(雄)激素受體結合，干擾生物體內分泌系統的運作，使生物體外觀發生變化、影響繁殖能力或子代發育。
本研究利用基因重組酵母菌生物試驗法、高效液相層析儀與液相層析串聯式質譜儀，來探討臺灣受污染之河川水體的內分泌干擾活性以及內分泌干擾物質之濃度，並以生物試驗與儀器分析之結果探討污染物與內分泌干擾活性之間的關聯。研究中採集臺灣西半部河川水樣，由北至南分別為淡水河、中港溪、後龍溪、大甲溪、濁水溪、北港溪、八掌溪、二仁溪以及阿公店溪，共九條河川之水相與懸浮固體相樣本，以生物試驗法分析樣本之類(抗)雌(雄)激素活性，挑選具顯著活性樣本以液相層析分離後，探討其類雌激素物質含量和活性。生物試驗結果指出二仁溪與北港溪皆測得顯著類雌激素活性與抗雄激素活性。經液相層析儀分離後，其類雌激素活性來源多為已知之類雌激素物質，然而北港溪測得具類雌激素活性之未知物。
液相層析串聯式質譜儀分析結果顯示，九條河川中可廣泛測得合成類雌激素雙酚A(ND~28874.7 ng/L)、壬基酚(ND~2381.8 ng/L)和雙酚A氯化衍生物(ND~1863.4 ng/L)，其中以二仁溪流域平均測得之濃度最高。生物試驗類雌激素活性當量濃度大於儀器分析之當量濃度，其原因為雙酚A、壬基酚等物質對類雌激素活性之貢獻度低，主要貢獻推測來自天然雌激素。生物試驗抗雄激素活性當量濃度亦高於儀器分析之當量濃度，其原因可能為環境樣本內物質間產生複合效應使生物試驗之當量濃度提高或存在未知抗雄激素物質。

Pollutant emissions from human activities, which contain (anti-)estrogenic and (anti-)androgenic endocrine disrupting chemicals (EDCs) are discharged into rivers. EDCs have the ability to combine with the hormone receptors and interfere the endocrine system of organisms. To evaluate the concentrations of EDCs in the water and suspended solids (SS) of Taiwanese rivers, yeast-based bioassays, high performance liquid chromatography (HPLC) and liquid chromatography tandem mass spectrometry (LC-MS/MS) were used to detect EDCs in water and SS phase samples. The results of bioassays showed that (anti-)estrogenic activities were detected in some samples, and anti-androgenic activities were detected in a few samples. According to the results of chemical analysis, natural estrogens like estrone, and synthetic compounds, such as bisphenol A, chlorinated bisphenol A and nonylphenol were widely detected in most of the water phase samples by LC-MS/MS. The relationship between estrogenic and anti-androgenic equivalent concentrations of bioassays and LC-MS/MS demonstrated that natural estrogens were major contributors for estrogenic activities in river samples, and combined effects of EDCs might play an important role on the evaluation of estrogenic and anti-androgenic activities.

參考文獻

(1) Colborn, T., vom Saal, F. S., and Soto, A. M. (1993). Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environmental Health Perspectives, 101(5), 378.
(2) Eertmans, F., Dhooge, W., Stuyvaert, S., and Comhaire, F. (2003). Endocrine disruptors: effects on male fertility and screening tools for their assessment.Toxicology in vitro, 17(5), 515-524.
(3) Guo, Y. L., Hsu, P. C., Hsu, C. C., and Lambert, G. H. (2000). Semen quality after prenatal exposure to polychlorinated biphenyls and dibenzofurans. The Lancet, 356(9237), 1240-1241.
(4) Dallinga, J. W., Moonen, E. J., Dumoulin, J. C., Evers, J. L., Geraedts, J. P., and Kleinjans, J. C. (2002). Decreased human semen quality and organochlorine compounds in blood. Human Reproduction, 17(8), 1973-1979.
(5) Li, J., Wang, Z., Ma, M., and Peng, X. (2010). Analysis of environmental endocrine disrupting activities using recombinant yeast assay in wastewater treatment plant effluents. Bulletin of Environmental Contamination and Toxicology, 84(5), 529-535.
(6) Liscio, C., Magi, E., Di Carro, M., Suter, M. F., and Vermeirssen, E. L. M. (2009). Combining passive samplers and biomonitors to evaluate endocrine disrupting compounds in a wastewater treatment plant by LC/MS/MS and bioassay analyses. Environmental pollution, 157(10), 2716-2721.
(7) Ma, M., Rao, K., and Wang, Z. (2007). Occurrence of estrogenic effects in sewage and industrial wastewaters in Beijing, China. Environmental Pollution, 147(2), 331-336.
(8) Nakada, N., Shinohara, H., Murata, A., Kiri, K., Managaki, S., Sato, N., and Takada, H. (2007). Removal of selected pharmaceuticals and personal care products (PPCPs) and endocrine-disrupting chemicals (EDCs) during sand filtration and ozonation at a municipal sewage treatment plant. Water Research, 41(19), 4373-4382.
(9) Liu, Z. H., Kanjo, Y., and Mizutani, S. (2009). Removal mechanisms for endocrine disrupting compounds (EDCs) in wastewater treatment—physical means, biodegradation, and chemical advanced oxidation: a review. Science of the Total Environment, 407(2), 731-748.
(10) Blair, I. A. (2010). Analysis of estrogens in serum and plasma from postmenopausal women: past present, and future. Steroids, 75(4), 297-306.
(11) Ternes, T. A., Kreckel, P., and Mueller, J. (1999). Behaviour and occurrence of estrogens in municipal sewage treatment plants—II. Aerobic batch experiments with activated sludge. Science of the Total Environment, 225(1), 91-99.
(12) Shappell, N. W., Billey, L. O., Forbes, D., Matheny, T. A., Poach, M. E., Reddy, G. B., and Hunt, P. G. (2007). Estrogenic activity and steroid hormones in swine wastewater through a lagoon constructed-wetland system. Environmental Science and Technology, 41(2), 444-450.
(13) Su, S. J., Yeh, T. M., Chuang, W. J., Ho, C. L., Chang, K. L., Cheng, H. L., et al. (2005). The novel targets for anti-angiogenesis of genistein on human cancer cells. Biochemical Pharmacology, 69(2), 307-318.
(14) Kang, X., Zhang, Q., Wang, S., Huang, X., and Jin, S. (2010). Effect of soy isoflavones on breast cancer recurrence and death for patients receiving adjuvant endocrine therapy. Canadian Medical Association Journal, 182(17), 1857-1862.
(15) Yamamoto, S., Sobue, T., Kobayashi, M., Sasaki, S., and Tsugane, S. (2003). Soy, isoflavones, and breast cancer risk in Japan. Journal of the National Cancer Institute, 95(12), 906-913.
(16) Marini, H., Minutoli, L., Polito, F., Bitto, A., Altavilla, D., Atteritano, M., et al. (2007). Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial. Annals of Internal Medicine, 146(12), 839-847.
(17) Vom Saal, F. S., and Hughes, C. (2005). An extensive new literature concerning low-dose effects of bisphenol A shows the need for a new risk assessment. Environmental Health Perspectives, 926-933.
(18) Nikaido, Y., Yoshizawa, K., Danbara, N., Tsujita-Kyutoku, M., Yuri, T., Uehara, N., and Tsubura, A. (2004). Effects of maternal xenoestrogen exposure on development of the reproductive tract and mammary gland in female CD-1 mouse offspring. Reproductive Toxicology, 18(6), 803-811.
(19) Lee, H. J., Chattopadhyay, S., Gong, E. Y., Ahn, R. S., and Lee, K. (2003). Antiandrogenic effects of bisphenol A and nonylphenol on the function of androgen receptor. Toxicological Sciences, 75(1), 40-46.
(20) Jonkers, N., Laane, R. W., and de Voogt, P. (2003). Fate of nonylphenol ethoxylates and their metabolites in two Dutch estuaries: evidence of biodegradation in the field. Environmental Science and Technology, 37(2), 321-327.
(21) Kannan, K., Keith, T. L., Naylor, C. G., Staples, C. A., Snyder, S. A., and Giesy, J. P. (2003). Nonylphenol and nonylphenol ethoxylates in fish, sediment, and water from the Kalamazoo River, Michigan. Archives of Environmental Contamination and Toxicology, 44(1), 0077-0082.
(22) Laws, S. C., Carey, S. A., Ferrell, J. M., Bodman, G. J., and Cooper, R. L. (2000). Estrogenic activity of octylphenol, nonylphenol, bisphenol A and methoxychlor in rats. Toxicological Sciences, 54(1), 154-167.
(23) Rogers, S. M., Back, D. J., Stevenson, P. J., Grimmer, S. F., and Orme, M. L. (1987). Paracetamol interaction with oral contraceptive steroids: increased plasma concentrations of ethinyloestradiol. British Journal of Clinical Pharmacology, 23(6), 721-725.
(24) Newman, M. C. (2009). Fundamentals of ecotoxicology. CRC press.
(25) Parrott, J. L., and Blunt, B. R. (2005). Life‐cycle exposure of fathead minnows (Pimephales promelas) to an ethinylestradiol concentration below 1 ng/L reduces egg fertilization success and demasculinizes males. Environmental Toxicology, 20(2), 131-141.
(26) Murphy, G. P., Beckley, S., Brady, M. F., Ming Chu, T., Dekernion, J. B., Dhabuwala, C, et al. (1983). Treatment of newly diagnosed metastatic prostate cancer patients with chemotherapy agents in combination with hormones versus hormones alone. Cancer, 51(7), 1264-1272.
(27) Titus-Ernstoff, L., Hatch, E. E., Hoover, R. N., Palmer, J., Greenberg, E. R., Ricker, W., et al. (2001). Long-term cancer risk in women given diethylstilbestrol (DES) during pregnancy. British Journal of Cancer, 84(1), 126.
(28) Herbst, A. L., Ulfelder, H., and Poskanzer, D. C. (1971). Adenocarcinoma of the vagina: association of maternal stilbestrol therapy with tumor appearance in young women. New England Journal of Medicine, 284(16), 878-881.
(29) Vom Saal, F. S., Timms, B. G., Montano, M. M., Palanza, P., Thayer, K. A., Nagel, S. C., et al. (1997). Prostate enlargement in mice due to fetal exposure to low doses of estradiol or diethylstilbestrol and opposite effects at high doses. Proceedings of the National Academy of Sciences, 94(5), 2056-2061.
(30) Newbold, R. R., and McLachlan, J. A. (1982). Vaginal adenosis and adenocarcinoma in mice exposed prenatally or neonatally to diethylstilbestrol.Cancer Research, 42(5), 2003-2011.
(31) Newbold, R. R., and McLachlan, J. A. (1982). Vaginal adenosis and adenocarcinoma in mice exposed prenatally or neonatally to diethylstilbestrol.Cancer Research, 42(5), 2003-2011.
(32) Osborne, C. K., Coronado-Heinsohn, E. B., Hilsenbeck, S. G., McCue, B. L., Wakeling, A. E., McCleland, R. A., et al. (1995). Comparison of the effects of a pure steroidal antiestrogen with those of tamoxifen in a model of human breast cancer. Journal of the National Cancer Institute, 87(10), 746-750.
(33) Oefelein, M. G., Ricchuiti, V., Conrad, W., Seftel, A., Bodner, D., Goldman, H., and Resnick, M. (2001). Skeletal fracture associated with androgen suppression induced osteoporosis: the clinical incidence and risk factors for patients with prostate cancer. The Journal of Urology, 166(5), 1724-1728.
(34) Vendola, K. A., Zhou, J., Adesanya, O. O., Weil, S. J., and Bondy, C. A. (1998). Androgens stimulate early stages of follicular growth in the primate ovary.Journal of Clinical Investigation, 101(12), 2622.
(35) Rainey, W. E., Carr, B. R., Sasano, H., Suzuki, T., and Mason, J. I. (2002). Dissecting human adrenal androgen production. Trends in Endocrinology and Metabolism, 13(6), 234-239.
(36) Geens, T., Roosens, L., Neels, H., and Covaci, A. (2009). Assessment of human exposure to Bisphenol-A, Triclosan and Tetrabromobisphenol-A through indoor dust intake in Belgium. Chemosphere, 76(6), 755-760.
(37) Ye, X., Bishop, A. M., Needham, L. L., and Calafat, A. M. (2008). Automated on-line column-switching HPLC-MS/MS method with peak focusing for measuring parabens, triclosan, and other environmental phenols in human milk. Analytica Chimica Acta, 622(1), 150-156.
(38) Chen, J., Ahn, K. C., Gee, N. A., Gee, S. J., Hammock, B. D., and Lasley, B. L. (2007). Antiandrogenic properties of parabens and other phenolic containing small molecules in personal care products. Toxicology and Applied Pharmacology, 221(3), 278-284.
(39) Santos, M. M., Castro, L. F. C., Vieira, M. N., Micael, J., Morabito, R., Massanisso, P., and Reis-Henriques, M. A. (2005). New insights into the mechanism of imposex induction in the dogwhelk Nucella lapillus. Comparative Biochemistry and Physiology Part C: Toxicology and Pharmacology, 141(1), 101-109.
(40) Gibbs, P. E., Bryan, G. W., Pascoe, P. L., and Burt, G. R. (1987). The use of the dog-whelk, Nucella lapillus, as an indicator of tributyltin (TBT) contamination.Journal of the Marine Biological Association of the United Kingdom, 67(03), 507-523.
(41) Ishijima, S., Nochide, A., Kawamoto, K., Shirakawa, D., and Ohnishi, M. (2005). Effects of tributyltin, triphenyltin and atrazine on plasma vitellogenin concentration in Japanese medaka fish Oryzias latipes. J. Biol. Macromol, 5, 39-44.
(42) Anway, M. D., Rekow, S. S., and Skinner, M. K. (2008). Comparative anti-androgenic actions of vinclozolin and flutamide on transgenerational adult onset disease and spermatogenesis. Reproductive Toxicology, 26(2), 100-106.
(43) Halden, R. U., and Paull, D. H. (2005). Co-occurrence of triclocarban and triclosan in US water resources. Environmental Science and Technology, 39(6), 1420-1426.
(44) Perencevich, E. N., Wong, M. T., and Harris, A. D. (2001). National and regional assessment of the antibacterial soap market: a step toward determining the impact of prevalent antibacterial soaps. American Journal of Infection Control, 29(5), 281-283.
(45) Dimitrov, S. D., Dimitrova, N. C., Walker, J. D., Veith, G. D., and Mekenyan, O. G. (2003). Bioconcentration potential predictions based on molecular attributes–an early warning approach for chemicals found in humans, birds, fish and wildlife. QSAR and Combinatorial Science, 22(1), 58-68.
(46) Gledhill, W. E. (1975). Biodegradation of 3, 4, 4′-trichlorocarbanilide, TCC®, in sewage and activated sludge. Water Research, 9(7), 649-654.
(47) Nolen, G. A., and Dierckman, T. A. (1979). Reproduction and teratogenic studies of a 2: 1 mixture of 3, 4, 4′-trichlorocarbanilide and 3-trifluoromethyl-4, 4′-dichlorocarbanilide in rats and rabbits. Toxicology and Applied Pharmacology, 51(3), 417-425.
(48) Chen, J., Ahn, K. C., Gee, N. A., Ahmed, M. I., Duleba, A. J., Zhao, L., et al. (2013). Triclocarban enhances testosterone action: a new type of endocrine disruptor?. Endocrinology.
(49) Burgess, R. M., Ho, K. T., Brack, W., and Lamoree, M. (2013). Effects‐directed analysis (EDA) and toxicity identification evaluation (TIE): Complementary but different approaches for diagnosing causes of environmental toxicity. Environmental Toxicology and Chemistry, 32(9), 1935-1945.
(50) Sanderson, H., Johnson, D. J., Wilson, C. J., Brain, R. A., and Solomon, K. R. (2003). Probabilistic hazard assessment of environmentally occurring pharmaceuticals toxicity to fish, daphnids and algae by ECOSAR screening.Toxicology Letters, 144(3), 383-395.
(51) Swartz, R. C., Cole, F. A., Lamberson, J. O., Ferraro, S. P., Schults, D. W., Deben, W. A., et al. (1994). Sediment toxicity, contamination and amphipod abundance at a DDT‐and dieldrin‐contaminated site in San Francisco Bay. Environmental Toxicology and Chemistry, 13(6), 949-962.
(52) Lukasewycz, M., and Durhan, E. (1992). Strategies for the identification of non-polar toxicants in aqueous environmental samples using toxicity-based fractionation and gas chromatography—mass spectrometry. Journal of Chromatography B: Biomedical Sciences and Applications, 580(1), 215-228.
(53) Brack, W. (2003). Effect-directed analysis: a promising tool for the identification of organic toxicants in complex mixtures? Analytical and Bioanalytical Chemistry, 377(3), 397-407.
(54) Schmitt, C., Streck, G., Lamoree, M., Leonards, P., Brack, W., and de Deckere, E. (2011). Effect directed analysis of riverine sediments—the usefulness of Potamopyrgus antipodarum for in vivo effect confirmation of endocrine disruption. Aquatic Toxicology, 101(1), 237-243.
(55) Chinathamby, K., Allinson, M., Shiraishi, F., Lopata, A. L., Nugegoda, D., Pettigrove, V., and Allinson, G. (2013). Screening for potential effects of endocrine-disrupting chemicals in peri-urban creeks and rivers in Melbourne, Australia using mosquitofish and recombinant receptor–reporter gene assays. Environmental Science and Pollution Research, 20(3), 1831-1841.
(56) Flores-Valverde, A. M., Horwood, J., and Hill, E. M. (2010). Disruption of the steroid metabolome in fish caused by exposure to the environmental estrogen 17α-ethinylestradiol. Environmental Science and Technology, 44(9), 3552-3558.
(57) Judy, B. M., Nagel, S. C., Thayer, K. A., Vom Saal, F. S., and Welshons, W. V. (1999). Low-dose bioactivity of xenoestrogens in animals: fetal exposure to low doses of methoxychlor and other xenoestrogens increases adult prostate size in mice. Toxicology and Industrial Health, 15(1-2), 12-25.
(58) Matsumoto, T., Kobayashi, M., Moriwaki, T., Kawai, S. I., and Watabe, S. (2004). Survey of estrogenic activity in fish feed by yeast estrogen-screen assay. Comparative Biochemistry and Physiology Part C: Toxicology and Pharmacology, 139(1), 147-152.
(59) Engvall, E., and Perlmann, P. (1971). Enzyme-linked immunosorbent assay (ELISA) quantitative assay of immunoglobulin G. Immunochemistry, 8(9), 871-874.
(60) Loizou, S., McCrea, J. D., Rudge, A. C., Reynolds, R., Boyle, C. C., and Harris, E. N. (1985). Measurement of anti-cardiolipin antibodies by an enzyme-linked immunosorbent assay (ELISA): standardization and quantitation of results.Clinical and Experimental Immunology, 62(3), 738.
(61) Vidal, M. L., Gautron, J., and Nys, Y. (2005). Development of an ELISA for quantifying lysozyme in hen egg white. Journal of Agricultural and Food Chemistry, 53(7), 2379-2385.
(62) Schubert, D., Maier, B., Morawietz, L., Krenn, V., and Kamradt, T. (2004). Immunization with glucose-6-phosphate isomerase induces T cell-dependent peripheral polyarthritis in genetically unaltered mice. The Journal of Immunology, 172(7), 4503-4509.
(63) Soto, A. M., Sonnenschein, C., Chung, K. L., Fernandez, M. F., Olea, N., and Serrano, F. O. (1995). The E-SCREEN assay as a tool to identify estrogens: an update on estrogenic environmental pollutants. Environmental Health Perspectives, 103(Suppl 7), 113.
(64) Legler, J., van den Brink, C. E., Brouwer, A., Murk, A. J., van der Saag, P. T., Vethaak, A. D., and van der Burg, B. (1999). Development of a stably transfected estrogen receptor-mediated luciferase reporter gene assay in the human T47D breast cancer cell line. Toxicological Sciences, 48(1), 55-66.
(65) Martin, C. S., Wight, P. A., Dobretsova, A., and Bronstein, I. (1996). Dual luminescence-based reporter gene assay for luciferase and beta-galactosidase.Biotechniques, 21(3), 520-524.
(66) Naylor, L. H. (1999). Reporter gene technology: the future looks bright.Biochemical pharmacology, 58(5), 749-757.
(67) NORDEEN, S. K., GREEN III, P. P., and FOWLKES, D. M. (1987). A rapid, sensitive, and inexpensive assay for chloramphenicol acetyltransferase. Dna, 6(2), 173-178.
(68) Martin, C. S., Wight, P. A., Dobretsova, A., and Bronstein, I. (1996). Dual luminescence-based reporter gene assay for luciferase and beta-galactosidase.Biotechniques, 21(3), 520-524.
(69) Charles, G. D., Bartels, M. J., Zacharewski, T. R., Gollapudi, B. B., Freshour, N. L., and Carney, E. W. (2000). Activity of benzo [a] pyrene and its hydroxylated metabolites in an estrogen receptor-α reporter gene assay. Toxicological Sciences, 55(2), 320-326.
(70) Denison, M. S., Zhao, B., Baston, D. S., Clark, G. C., Murata, H., and Han, D. (2004). Recombinant cell bioassay systems for the detection and relative quantitation of halogenated dioxins and related chemicals. Talanta, 63(5), 1123-1133.
(71) Liscio, C., Magi, E., Di Carro, M., Suter, M. F., and Vermeirssen, E. L. M. (2009). Combining passive samplers and biomonitors to evaluate endocrine disrupting compounds in a wastewater treatment plant by LC/MS/MS and bioassay analyses. Environmental Pollution, 157(10), 2716-2721.
(72) WANG, X. Z., WANG, Q. Q., SONG, H. F., and LI, W. P. (2010). Application progress of derivatization technology in amino acids analysis. Chinese Journal of Pharmaceutical Analysis, 6, 064.
(73) Snyder, L. R., Kirkland, J. J., and Dolan, J. W. (2011). Introduction to Modern Liquid Chromatography. John Wiley and Sons.
(74) Striegel, A., Yau, W. W., Kirkland, J. J., and Bly, D. D. (2009). Modern Size-Exclusion Liquid Chromatography: Practice of Gel Permeation and Gel Filtration Chromatography. John Wiley and Sons.
(75) Ghislain, T., Faure, P., and Michels, R. (2012). Detection and monitoring of PAH and Oxy-PAHs by high resolution mass spectrometry: comparison of ESI, APCI and APPI source detection. Journal of the American Society for Mass Spectrometry, 23(3), 530-536.
(76) Byrdwell, W. C., and Emken, E. A. (1995). Analysis of triglycerides using atmospheric pressure chemical ionization mass spectrometry. Lipids, 30(2), 173-175.
(77) Lemaire, R., Tabet, J. C., Ducoroy, P., Hendra, J. B., Salzet, M., and Fournier, I. (2006). Solid ionic matrixes for direct tissue analysis and MALDI imaging.Analytical Chemistry, 78(3), 809-819.
(78) Perry, R. H., Cooks, R. G., and Noll, R. J. (2008). Orbitrap mass spectrometry: instrumentation, ion motion and applications. Mass Spectrometry Reviews, 27(6), 661-699.
(79) 經濟部水利署 [http://www.wra.gov.tw/ct.asp?xItem=12955&CtNode=4349]
(80) Chen, C. Y., Wen, T. Y., Wang, G. S., Cheng, H. W., Lin, Y. H., and Lien, G. W. (2007). Determining estrogenic steroids in Taipei waters and removal in drinking water treatment using high-flow solid-phase extraction and liquid chromatography/tandem mass spectrometry. Science of the Total Environment, 378(3), 352-365.
(81) 環境資源資料庫 [http://erdb.epa.gov.tw/ERDBIndex.aspx]
(82) 行政院環保署環境品質資料倉儲系統 [http://edw.epa.gov.tw/default1.aspx]
(83) 水利署第二河川局 [http://www.wra02.gov.tw/mp.asp?mp=02]
(84) 行政院環境保護署(2008)，應用生態工法整治河川污染調查研究計畫-以北港溪為例[http://sta.epa.gov.tw/report/Files/EPA-97-U1G1-02-104.pdf]
(85) 王漢泉. 河川魚類指標評估南崁溪、客雅溪、中港溪、
北港溪、將軍溪、典寶溪等河川水質之研究. 環保署2002年調查研究年報。[http://www.niea.gov.tw/analysis/protect/2002/2002-11.htm]
(86) 行政院環保署 八掌溪產業結構 [http://ivy1.epa.gov.tw/runlet/env/env225.asp]
(87) 環保署二仁溪再生願景整治管理系統 [http://ivy1.epa.gov.tw/runlet/entry/]
(88) 高雄市環保局河川水質統計與優劣探討[http://kses.ksepb.gov.tw/kses/project_analy.aspx?tpid=3]
(89) Routledge, E. J., and Sumpter, J. P. (1996). Estrogenic activity of surfactants and some of their degradation products assessed using a recombinant yeast screen. Environmental Toxicology and Chemistry, 15(3), 241-248.
(90) Luccio-Camelo, D. C., and Prins, G. S. (2011). Disruption of androgen receptor signaling in males by environmental chemicals. The Journal of Steroid Biochemistry and Molecular Biology, 127(1), 74-82.
(91) Zhao, J. L., Ying, G. G., Chen, F., Liu, Y. S., Wang, L., Yang, B., et al. (2011). Estrogenic activity profiles and risks in surface waters and sediments of the Pearl River system in South China assessed by chemical analysis and in vitro bioassay. Journal of Environmental Monitoring, 13(4), 813-821.
(92) 陳廣育. 臺灣河川中內分泌干擾物質之流布及其複合效應之評估. 成功大學環境工程學系學位論文 (2013): 1-197.
(93) 葉奕伯. 以生物試驗法及液相層析串聯式質譜儀分析污水處理廠中內分泌干擾物質及其衍生物之變化. 成功大學環境工程學系學位論文 (2014): 1-159.
(94) Vermeirssen, E. L., Burki, R., Joris, C., Peter, A., Segner, H., Suter, M. J. E., and Burkhardt‐Holm, P. (2005). Characterization of the estrogenicity of Swiss midland rivers using a recombinant yeast bioassay and plasma vitellogenin concentrations in feral male brown trout. Environmental Toxicology and Chemistry, 24(9), 2226-2233.
(95) Cargouet, M., Perdiz, D., Mouatassim-Souali, A., Tamisier-Karolak, S., and Levi, Y. (2004). Assessment of river contamination by estrogenic compounds in Paris area (France). Science of the Total Environment, 324(1), 55-66.
(96) Krein, A., Pailler, J. Y., Guignard, C., Gutleb, A. C., Hoffmann, L., Meyer, B., et al. (2012). Determination of estrogen activity in river waters and wastewater in Luxembourg by chemical analysis and the yeast estrogen screen assay. Environment and Pollution, 1(2), p86.
(97) Ra, J. S., Lee, S. H., Lee, J., Kim, H. Y., Lim, B. J., Kim, S. H., and Kim, S. D. (2011). Occurrence of estrogenic chemicals in South Korean surface waters and municipal wastewaters. Journal of Environmental Monitoring, 13(1), 101-109.
(98) Witters, H., Vangenechten, C., and Berckmans, P. (2001). Detection of estrogenic activity in Flemish surface waters using anin vitro recombinant assay with yeast cells. Water Science and Technology, 43(2), 117-123.
(99) 彭柏頤. 結合生物試驗法與 LC-MS/MS 檢測臺灣河川中類雌激素物質之分布. 成功大學環境工程學系學位論文 (2011): 1-103.
(100) 林依鈴. 臺灣環境水體中類雌激素/類雄激素物質之流布. 成功大學環境工程學系學位論文 (2012): 1-123.
(101) 蔡宗亞. 應用基因重組酵母菌結合液相層析串聯質譜儀檢測臺灣河川中類 (抗) 雌激素及類 (抗) 雄激素之分布. 成功大學環境工程學系學位論文 (2013): 1-111.
(102) Jung, J., Ishida, K., and Nishihara, T. (2004). Anti-estrogenic activity of fifty chemicals evaluated by in vitro assays. Life Sciences, 74(25), 3065-3074.
(103) Heath, R. J., Li, J., Roland, G. E., and Rock, C. O. (2000). Inhibition of the staphylococcus aureusNADPH-dependent enoyl-acyl carrier protein reductase by triclosan and hexachlorophene. Journal of Biological Chemistry, 275(7), 4654-4659.
(104) Kimbrough, R. D. (1971). Review of the toxicity of hexachlorophene. Archives of Environmental Health: An International Journal, 23(2), 119-122.
(105) Holbrook, R. D., Love, N. G., and Novak, J. T. (2004). Sorption of 17β-estradiol and 17α-ethinylestradiol by colloidal organic carbon derived from biological wastewater treatment systems. Environmental Science and Technology, 38(12), 3322-3329.
(106) Janošek, J., Bittner, M., Hilscherová, K., Bláha, L., Giesy, J. P., and Holoubek, I. (2007). AhR-mediated and antiestrogenic activity of humic substances.Chemosphere, 67(6), 1096-1101.
(107) Wu, Q. Y., Tang, X., Huang, H., Li, Y., Hu, H. Y., Ding, Y. N., and Shao, Y. R. (2014). Antiestrogenic activity and related disinfection by-product formation induced by bromide during chlorine disinfection of sewage secondary effluent.Journal of Hazardous Materials, 273, 280-286.
(108) Schlautman, M. A., and Morgan, J. J. (1993). Effects of aqueous chemistry on the binding of polycyclic aromatic hydrocarbons by dissolved humic materials. Environmental Science and Technology, 27(5), 961-969.
(109) Rav-Acha, C., and Rebhun, M. (1992). Binding of organic solutes to dissolved humic substances and its effects on adsorption and transport in the aquatic environment. Water Research, 26(12), 1645-1654.
(110) Steinberg, C. E., Paul, A., Pflugmacher, S., Meinelt, T., Klöcking, R., and Wiegand, C. (2003). Pure humic substances have the potential to act as xenobiotic chemicals-A review. Fresenius Environmental Bulletin, 12(5), 391-401.
(111) Zsolnay, A. (1996). Dissolved humus in soil waters. Humic Substances in Terrestrial Ecosystems, 171-223.
(112) Neale, P. A., Escher, B. I., and Leusch, F. D. (2015). Understanding the implications of dissolved organic carbon when assessing antagonism in vitro: An example with an estrogen receptor assay. Chemosphere, 135, 341-346.
(113) Lambropoulou, D. A., and Albanis, T. A. (2004). Sensitive trace enrichment of environmental andiandrogen vinclozolin from natural waters and sediment samples using hollow-fiber liquid-phase microextraction. Journal of Chromatography A, 1061(1), 11-18.
(114) Hou, L., Xie, Y., Ying, G., and Fang, Z. (2011). Developmental and reproductive characteristics of western mosquitofish (Gambusia affinis) exposed to paper mill effluent in the Dengcun River, Sihui, South China. Aquatic Toxicology, 103(3), 140-149.
(115) Soto, A. M., Calabro, J. M., Prechtl, N. V., Yau, A. Y., Orlando, E. F., Daxenberger, A., et al. (2004). Androgenic and estrogenic activity in water bodies receiving cattle feedlot effluent in Eastern Nebraska, USA. Environmental Health Perspectives, 112(3), 346.
(116) Rostkowski, P., Horwood, J., Shears, J. A., Lange, A., Oladapo, F. O., Besselink, H. T., et al. (2011). Bioassay-directed identification of novel antiandrogenic compounds in bile of fish exposed to wastewater effluents. Environmental Science and Technology, 45(24), 10660-10667.
(117) Chen, J., Ahn, K. C., Gee, N. A., Gee, S. J., Hammock, B. D., and Lasley, B. L. (2007). Antiandrogenic properties of parabens and other phenolic containing small molecules in personal care products. Toxicology and Applied Pharmacology, 221(3), 278-284.
(118) Kelce, W. R., Monosson, E., Gamcsik, M. P., Laws, S. C., and Gray, L. E. (1994). Environmental hormone disruptors: evidence that vinclozolin developmental toxicity is mediated by antiandrogenic metabolites. Toxicology and Applied Pharmacology, 126(2), 276-285.
(119) Grover, D. P., Balaam, J., Pacitto, S., Readman, J. W., White, S., and Zhou, J. L. (2011). Endocrine disrupting activities in sewage effluent and river water determined by chemical analysis and in vitro assay in the context of granular activated carbon upgrade. Chemosphere, 84(10), 1512-1520.
(120) Jobling, S., Burn, R. W., Thorpe, K., Williams, R., and Tyler, C. (2009). Statistical modeling suggests that antiandrogens in effluents from wastewater treatment works contribute to widespread sexual disruption in fish living in English rivers.
(121) Urbatzka, R., Van Cauwenberge, A., Maggioni, S., Viganò, L., Mandich, A., Benfenati, E., et al. (2007). Androgenic and antiandrogenic activities in water and sediment samples from the river Lambro, Italy, detected by yeast androgen screen and chemical analyses. Chemosphere, 67(6), 1080-1087.
(122) Rostkowski, P., Horwood, J., Shears, J. A., Lange, A., Oladapo, F. O., Besselink, H. T., et al. (2011). Bioassay-directed identification of novel antiandrogenic compounds in bile of fish exposed to wastewater effluents. Environmental Science and Technology, 45(24), 10660-10667.
(123) Belfroid, A. C., Van der Horst, A., Vethaak, A. D., Schäfer, A. J., Rijs, G. B. J., Wegener, J., and Cofino, W. P. (1999). Analysis and occurrence of estrogenic hormones and their glucuronides in surface water and waste water in The Netherlands. Science of the Total Environment, 225(1), 101-108.
(124) Ternes, T. A., Stumpf, M., Mueller, J., Haberer, K., Wilken, R. D., and Servos, M. (1999). Behavior and occurrence of estrogens in municipal sewage treatment plants—I. Investigations in Germany, Canada and Brazil. Science of the Total Environment, 225(1), 81-90.
(125) Williams, R. J., Johnson, A. C., Smith, J. J., and Kanda, R. (2003). Steroid estrogens profiles along river stretches arising from sewage treatment works discharges. Environmental Science and Technology, 37(9), 1744-1750.
(126) Johnson, A. C., Belfroid, A., and Di Corcia, A. (2000). Estimating steroid oestrogen inputs into activated sludge treatment works and observations on their removal from the effluent. Science of the Total Environment, 256(2), 163-173.
(127) Pawlowski, S., Ternes, T. A., Bonerz, M., Rastall, A. C., Erdinger, L., and Braunbeck, T. (2004). Estrogenicity of solid phase-extracted water samples from two municipal sewage treatment plant effluents and river Rhine water using the yeast estrogen screen. Toxicology in Vitro, 18(1), 129-138.
(128) Furuichi, T., Kannan, K., Giesy, J. P., and Masunaga, S. (2004). Contribution of known endocrine disrupting substances to the estrogenic activity in Tama River water samples from Japan using instrumental analysis and in vitro reporter gene assay. Water Research, 38(20), 4491-4501.
(129) Wu, J. L., Lam, N. P., Martens, D., Kettrup, A., and Cai, Z. (2007). Triclosan determination in water related to wastewater treatment. Talanta, 72(5), 1650-1654.
(130) Zhao, J. L., Ying, G. G., Liu, Y. S., Chen, F., Yang, J. F., and Wang, L. (2010). Occurrence and risks of triclosan and triclocarban in the Pearl River system, South China: from source to the receiving environment. Journal of Hazardous Materials, 179(1), 215-222.

(131) Nishi, I., Kawakami, T., and Onodera, S. (2008). Monitoring of triclosan in the surface water of the Tone Canal, Japan. Bulletin of Environmental Contamination and Toxicology, 80(2), 163-166.
(132) Zhang, S., Zhang, Q., Darisaw, S., Ehie, O., and Wang, G. (2007). Simultaneous quantification of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and pharmaceuticals and personal care products (PPCPs) in Mississippi river water, in New Orleans, Louisiana, USA. Chemosphere, 66(6), 1057-1069.
(133) Hua, W., Bennett, E. R., and Letcher, R. J. (2005). Triclosan in waste and surface waters from the upper Detroit River by liquid chromatography-electrospray-tandem quadrupole mass spectrometry. Environment International, 31(5), 621-630.
(134) Kantiani, L., Farré, M., Asperger, D., Rubio, F., González, S., de Alda, M. J. L., et al. (2008). Triclosan and methyl-triclosan monitoring study in the northeast of Spain using a magnetic particle enzyme immunoassay and confirmatory analysis by gas chromatography–mass spectrometry. Journal of Hydrology, 361(1), 1-9.
(135) Bester, K. (2005). Fate of triclosan and triclosan-methyl in sewage treatmentplants and surface waters. Archives of Environmental Contamination and Toxicology, 49(1), 9-17.
(136) Fukazawa, H., Hoshino, K., Shiozawa, T., Matsushita, H., and Terao, Y. (2001). Identification and quantification of chlorinated bisphenol A in wastewater from wastepaper recycling plants. Chemosphere, 44(5), 973-979.
(137) Zafra, A., del Olmo, M., Suárez, B., Hontoria, E., Navalón, A., and Vı́lchez, J. L. (2003). Gas chromatographic–mass spectrometric method for the determination of bisphenol A and its chlorinated derivatives in urban wastewater. Water Research, 37(4), 735-742.
(138) Fernandez, M. F., Arrebola, J. P., Taoufiki, J., Navalón, A., Ballesteros, O., Pulgar, R., et al. (2007). Bisphenol-A and chlorinated derivatives in adipose tissue of women. Reproductive Toxicology, 24(2), 259-264.
(139) Diehl, J., Johnson, S. E., Xia, K., West, A., and Tomanek, L. (2012). The distribution of 4-nonylphenol in marine organisms of North American Pacific Coast estuaries. Chemosphere, 87(5), 490-497.
(140) Loyo-Rosales, J. E., Schmitz-Afonso, I., Rice, C. P., and Torrents, A. (2003). Analysis of octyl-and nonylphenol and their ethoxylates in water and sediments by liquid chromatography/tandem mass spectrometry. Analytical Chemistry, 75(18), 4811-4817.
(141) Jonkers, N., Knepper, T. P., and De Voogt, P. (2001). Aerobic biodegradation studies of nonylphenol ethoxylates in river water using liquid chromatography-electrospray tandem mass spectrometry. Environmental Science and Technology, 35(2), 335-340.
(142) Ahel, M., McEvoy, J., and Giger, W. (1993). Bioaccumulation of the lipophilic metabolites of nonionic surfactants in freshwater organisms. Environmental Pollution, 79(3), 243-248.
(143) da Silva, B. F., Jelic, A., López-Serna, R., Mozeto, A. A., Petrovic, M., and Barceló, D. (2011). Occurrence and distribution of pharmaceuticals in surface water, suspended solids and sediments of the Ebro river basin, Spain.Chemosphere, 85(8), 1331-1339.
(144) Kizu, R., Okamura, K., Toriba, A., Mizokami, A., Burnstein, K. L., Klinge, C. M., and Hayakawa, K. (2003). Antiandrogenic activities of diesel exhaust particle extracts in PC3/AR human prostate carcinoma cells. Toxicological Sciences, 76(2), 299-309.
(145) Yang, W., Mu, Y., Giesy, J. P., Zhang, A., and Yu, H. (2009). Anti-androgen activity of polybrominated diphenyl ethers determined by comparative molecular similarity indices and molecular docking. Chemosphere, 75(9), 1159-1164.
(146) Thomas, K. V., Langford, K., Petersen, K., Smith, A. J., and Tollefsen, K. E. (2009). Effect-directed identification of naphthenic acids as important in vitro xeno-estrogens and anti-androgens in North Sea offshore produced water discharges. Environmental Science and Technology, 43(21), 8066-8071.
(147) 李信佳. 含環烷酸煉油廢水之化學氧化處理研究. 國立中山大學環境工程研究所學位論文 (2012):1-71.