隨著科技迅速發展，我們的日常生活變得更加便利，但這也導致了大量新興污染物，如藥物與個人保健用品被釋放到環境中。然而，傳統污水處理廠的處理過程可能不足以完全去除這些新興污染物，從而使其通過水相、懸浮固體或廢棄污泥進入環境。此外，持續的COVID-19大流行顯著影響了我們的生活，可能導致治療或緩解症狀所使用的藥物用量增加，從而加劇了藥物對環境的影響。
本研究以臺灣的臺北、臺中及臺南三大城市中共五座污水處理廠為研究對象，涵蓋三座民生與兩座醫院污水處理廠，採集各污水處理單元之出流水及污水廠之廢棄污泥，使用報導基因酵母菌試驗法檢測目標物質及污水廠樣本之內分泌干擾活性，並以液相層析串聯式質譜儀分析目標物質於各污水廠樣本之濃度。內分泌干擾試驗結果顯示抗糖皮質激素與抗鹽皮質激素活性仍可於污水廠放流中測得，並可吸附於懸浮固相與污泥樣本中，顯示抗糖皮質激素與抗鹽皮質激素物質無法經二級生物處理便有效去除，並可能直接或間接進入到環境水體中。
液相層析串聯式質譜儀分析結果顯示有數種目標藥物於污水廠進流水中測得較高濃度，如乙醯胺酚 (Acetaminophen, ACE) (3.8×103 – 3.6×104 ng/L)、布洛芬 (Ibuprofen, IBU) (1.1×103 – 2.3×103 ng/L)、雙氯芬酸 (Diclofenac, DIC) (124.7 – 664.1 ng/L)、環丙沙星 (Ciprofloxacin, CIP) (21.2 – 1995.7 ng/L)、替米沙坦 (Telmisartan, TEL) (173.2 – 1528.4 ng/L)及卡馬西平 (Carbamazepine, CBM) (57.8 – 656.9 ng/L)。在放流水中仍被測得較高濃度的如DIC (16.2 – 545.5 ng/L)、CIP (12.6 – 459.8 ng/L)、TEL (85.6 – 614.9 ng/L)及CBM (48.2 – 171.4 ng/L)，顯示許多藥物仍無法經污水處理程序而妥善去除。此外，各物質於醫院污水處理廠樣本中之含量普遍高於民生污水處理廠，而相較於COVID-19疫情前，止痛藥物與抗生素等常用藥物未因疫情影響而在污水廠中測得明顯之濃度增長。
污水廠樣本中目標物質濃度及內分泌干擾活性之相關性顯示，目標物質濃度換算之內分泌干擾活性與樣本測得之內分泌干擾活性間有著數千倍之差距，具內分泌干擾活性之物質於樣本中僅為一小部分，仍有許多未被選定之內分泌干擾物質存在樣本中，加上污水廠樣本中基質複雜，各類污染物之間亦可能產生協同效應而使活性增加。風險評估之結果顯示DIC、CBM、TEL、AZI、RTV及TCS於放流水中呈現中度或高度風險，即使排放至環境水體後會受到稀釋，仍可能對水生環境及生物造成影響，長期下來甚至可能造成藥物抗藥性的發生。因此，若能改善污水處理流程以提高其去除效率，才能有效降低放流水造成之危害。

With the rapid development of technology, our daily lives have become more convenient, but this has also led to the release of many emerging pollutants into the environment. Pharmaceuticals and personal care products (PPCPs) may be discharged into domestic or hospital wastewater treatment plants (WWTPs) through various pathways after using. Additionally, the ongoing COVID-19 pandemic has significantly impacted our lives and may lead to increased use of medications for treatment or symptom relief, thereby exacerbating the impact of pharmaceuticals on the environment.
In this study, endocrine-disrupting activities of target PPCPs and WWTP samples were assessed using yeast-based reporter gene assays, and the occurrence of selected PPCPs in WWTPs were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Bioassay results indicated that anti-glucocorticoid and anti-mineralocorticoid activities were still detectable in the effluents and could be adsorbed onto suspended solids and sludge samples, indicating that endocrine disrupting substances cannot be effectively removed through secondary biological treatment and may enter the aquatic environment.
LC-MS/MS analysis indicated that several target PPCPs were detected at higher concentrations in the WWTP samples. For example, acetaminophen, ibuprofen, diclofenac, ciprofloxacin, telmisartan, and carbamazepine were detected at relatively high concentrations in the influent water. Higher concentrations of diclofenac (16.2-545.5 ng/L), ciprofloxacin (12.6-459.8 ng/L), telmisartan (85.6-614.9 ng/L), and carbamazepine (48.2-630.33 ng/L) were still detected in the effluents, indicating that many PPCPs cannot be effectively removed by wastewater treatment processes.
The results of the risk assessment also demonstrated medium to high risks associated with several PPCPs (diclofenac, carbamazepine, telmisartan, azithromycin, ritonavir, and triclosan) in the effluents. Even after dilution in the receiving water bodies, these compounds may still have an impact on the aquatic environment and organisms, and over time, they may contribute to the development of drug resistance. Therefore, our study suggested that it’s necessary to pay more attention to the distribution of PPCPs discharged into environment.

Abafe, O. A., Späth, J., Fick, J., Jansson, S., Buckley, C., Stark, A., Pietruschka, B., & Martincigh, B. S. (2018). LC-MS/MS determination of antiretroviral drugs in influents and effluents from wastewater treatment plants in KwaZulu-Natal, South Africa. Chemosphere, 200, 660-670.
Abibu, W. A., Bamigbade, G., Kolawole, A. O., Ajayi, T., & Sakariyau, A. W. (2021). Current trends in steroidal 17α-ethynylestradiol (EE2) removal from the environment: A Review. Applied Environmental Research, 43(2), 130-158.
Ahn, K. C., Zhao, B., Chen, J., Cherednichenko, G., Sanmarti, E., Denison, M. S., Lasley, B., Pessah, I. N., Kültz, D., & Chang, D. P. (2008). In vitro biologic activities of the antimicrobials triclocarban, its analogs, and triclosan in bioassay screens: receptor-based bioassay screens. Environmental Health Perspectives, 116(9), 1203-1210.
Alwan, S., Polifka, J., & Friedman, J. (2005). Angiotensin II receptor antagonist treatment during pregnancy. Birth Defects Research Part A: Clinical and Molecular Teratology, 73(2), 123-130.
Alygizakis, N. A., Besselink, H., Paulus, G. K., Oswald, P., Hornstra, L. M., Oswaldova, M., Medema, G., Thomaidis, N. S., Behnisch, P. A., & Slobodnik, J. (2019). Characterization of wastewater effluents in the Danube River Basin with chemical screening, in vitro bioassays and antibiotic resistant genes analysis. Environment International, 127, 420-429.
Aminoshariae, A., & Khan, A. (2015). Acetaminophen: old drug, new issues. Journal of Endodontics, 41(5), 588-593.
Archer, E., Petrie, B., Kasprzyk-Hordern, B., & Wolfaardt, G. M. (2017). The fate of pharmaceuticals and personal care products (PPCPs), endocrine disrupting contaminants (EDCs), metabolites and illicit drugs in a WWTW and environmental waters. Chemosphere, 174, 437-446.
Ashfaq, M., Khan, K. N., Rasool, S., Mustafa, G., Saif-Ur-Rehman, M., Nazar, M. F., Sun, Q., & Yu, C.-P. (2016). Occurrence and ecological risk assessment of fluoroquinolone antibiotics in hospital waste of Lahore, Pakistan. Environmental Toxicology and Pharmacology, 42, 16-22.
Baalbaki, Z., Sultana, T., Metcalfe, C., & Yargeau, V. (2017). Estimating removals of contaminants of emerging concern from wastewater treatment plants: The critical role of wastewater hydrodynamics. Chemosphere, 178, 439-448.
Bayer, A., Asner, R., Schüssler, W., Kopf, W., Weiß, K., Sengl, M., & Letzel, M. (2014). Behavior of sartans (antihypertensive drugs) in wastewater treatment plants, their occurrence and risk for the aquatic environment. Environmental Science and Pollution Research, 21(18), 10830-10839.
Beard Jr, E. L. (2001). The american society of health system pharmacists. JONA'S Healthcare Law, Ethics and Regulation, 3(3), 78-79.
Behera, S. K., Kim, H. W., Oh, J.-E., & Park, H.-S. (2011). Occurrence and removal of antibiotics, hormones and several other pharmaceuticals in wastewater treatment plants of the largest industrial city of Korea. Science of the Total Environment, 409(20), 4351-4360.
Bengtsson-Palme, J., & Larsson, D. J. (2016). Concentrations of antibiotics predicted to select for resistant bacteria: proposed limits for environmental regulation. Environment International, 86, 140-149.
Bergman, Å., Heindel, J. J., Jobling, S., Kidd, K., Zoeller, T. R., & Organization, W. H. (2013). State of the Science of Endocrine Disrupting Chemicals 2012. World Health Organization.
Bernal, J. (2002). Action of thyroid hormone in brain. Journal of Endocrinological Investigation, 25, 268-288.
Blieden, M., Paramore, L. C., Shah, D., & Ben-Joseph, R. (2014). A perspective on the epidemiology of acetaminophen exposure and toxicity in the United States. Expert Review of Clinical Pharmacology, 7(3), 341-348.
Brinton, R. D., Thompson, R. F., Foy, M. R., Baudry, M., Wang, J., Finch, C. E., Morgan, T. E., Pike, C. J., Mack, W. J., & Stanczyk, F. Z. (2008). Progesterone receptors: form and function in brain. Frontiers in Neuroendocrinology, 29(2), 313-339.
Caldas, S. S., Arias, J. L. O., Rombaldi, C., Mello, L. L., Cerqueira, M. B., Martins, A. F., & Primel, E. G. (2019). Occurrence of pesticides and PPCPs in surface and drinking water in southern Brazil: Data on 4-year monitoring. Journal of the Brazilian Chemical Society, 30, 71-80.
Cappelli, F., Longoni, O., Rigato, J., Rusconi, M., Sala, A., Fochi, I., Palumbo, M. T., Polesello, S., Roscioli, C., & Salerno, F. (2022). Suspect screening of wastewaters to trace anti-COVID-19 drugs: Potential adverse effects on aquatic environment. Science of the Total Environment, 824, 153756.
Carranco, E., Kareus, J., Peak, V., & Al-Rajeh, S. (1985). Carbamazepine toxicity induced by concurrent erythromycin therapy. Archives of Neurology, 42(2), 187-188.
Chen, X., Lei, L., Liu, S., Han, J., Li, R., Men, J., Li, L., Wei, L., Sheng, Y., & Yang, L. (2021). Occurrence and risk assessment of pharmaceuticals and personal care products (PPCPs) against COVID-19 in lakes and WWTP-river-estuary system in Wuhan, China. Science of the Total Environment, 792, 148352.
Clark, M. F., Lister, R. M., & Bar-Joseph, M. (1986). ELISA techniques. In Methods in Enzymology (Vol. 118, pp. 742-766). Elsevier.
Colson, P., Rolain, J.-M., Lagier, J.-C., Brouqui, P., & Raoult, D. (2020). Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. In International Journal of Antimicrobial Agents, 55(4), 105932..
Cvetkovic, R. S., & Goa, K. L. (2003). Lopinavir/ritonavir: a review of its use in the management of HIV infection. Drugs, 63(8), 769-802.
D'Alessio, M., Onanong, S., Snow, D. D., & Ray, C. (2018). Occurrence and removal of pharmaceutical compounds and steroids at four wastewater treatment plants in Hawai'i and their environmental fate. Science of the Total Environment, 631, 1360-1370.
Décima, M. A., Marzeddu, S., Barchiesi, M., Di Marcantonio, C., Chiavola, A., & Boni, M. R. (2021). A review on the removal of carbamazepine from aqueous solution by using activated carbon and biochar. Sustainability, 13(21), 11760.
del Carmen Ramírez-Montero, M., Gómez-Oliván, L. M., Gutiérrez-Noya, V. M., Orozco-Hernández, J. M., Islas-Flores, H., Elizalde-Velázquez, G. A., SanJuan-Reyes, N., & Galar-Martínez, M. (2022). Acute exposure to 17-α-ethinylestradiol disrupt the embryonic development and oxidative status of Danio rerio. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology, 251, 109199.
Domingo-Echaburu, S., Irazola, M., Prieto, A., Rocano, B., de Torre-Querejazu, A. L., Quintana, A., Orive, G., & Lertxundi, U. (2022). Drugs used during the COVID-19 first wave in Vitoria-Gasteiz (Spain) and their presence in the environment. Science of the Total Environment, 820, 153122.
Echeverría-Esnal, D., Martin-Ontiyuelo, C., Navarrete-Rouco, M. E., De-Antonio Cuscó, M., Ferrández, O., Horcajada, J. P., & Grau, S. (2021). Azithromycin in the treatment of COVID-19: a review. Expert Review of Anti-infective Therapy, 19(2), 147-163.
Engvall, E., Jonsson, K., & Perlmann, P. (1971). Antiserum, immunoglobulin fraction, and specific antibodies Iodinated proteins. Biochim. Biophys. Acta, 251, 427-434.
Enners, S., Gradl, G., Kieble, M., Böhm, M., Laufs, U., & Schulz, M. (2021). Utilization of drugs with reports on potential efficacy or harm on COVID‐19 before, during, and after the first pandemic wave. Pharmacoepidemiology and Drug Safety, 30(11), 1493-1503.
Escher, B. I., Baumgartner, R., Koller, M., Treyer, K., Lienert, J., & McArdell, C. S. (2011). Environmental toxicology and risk assessment of pharmaceuticals from hospital wastewater. Water Research, 45(1), 75-92.
Ezechiáš, M., Janochová, J., Filipová, A., Křesinová, Z., & Cajthaml, T. (2016). Widely used pharmaceuticals present in the environment revealed as in vitro antagonists for human estrogen and androgen receptors. Chemosphere, 152, 284-291.
Fang, T.-H., Nan, F.-H., Chin, T.-S., & Feng, H.-M. (2012). The occurrence and distribution of pharmaceutical compounds in the effluents of a major sewage treatment plant in Northern Taiwan and the receiving coastal waters. Marine Pollution Bulletin, 64(7), 1435-1444.
Fernandez-Fontaina, E., Omil, F., Lema, J., & Carballa, M. (2012). Influence of nitrifying conditions on the biodegradation and sorption of emerging micropollutants. Water Research, 46(16), 5434-5444.
Fernández-López, C., Guillén-Navarro, J. M., Padilla, J. J., & Parsons, J. R. (2016). Comparison of the removal efficiencies of selected pharmaceuticals in wastewater treatment plants in the region of Murcia, Spain. Ecological Engineering, 95, 811-816.
Fiege, H., Voges, H. W., Hamamoto, T., Umemura, S., Iwata, T., Miki, H., Fujita, Y., Buysch, H. J., Garbe, D., & Paulus, W. (2000). Phenol derivatives. Ullmann's Encyclopedia of Industrial Chemistry.
Food, U., & Administration, D. (2022). Drug safety communication: FDA warns about increased risk of ruptures or tears in the aorta blood vessel with fluoroquinolone antibiotics in certain patients. 2018.
Forrest, J. A., Clements, J., & Prescott, L. (1982). Clinical pharmacokinetics of paracetamol. Clinical Pharmacokinetics, 7, 93-107.
Franklyn, J. A., & Boelaert, K. (2012). Thyrotoxicosis. The Lancet, 379(9821), 1155-1166.
Freel, E. M., & Connell, J. M. (2004). Mechanisms of hypertension: the expanding role of aldosterone. Journal of the American Society of Nephrology, 15(8), 1993-2001.
Goyal, S., Bharti, S., Bhatia, J., Nag, T., Ray, R., & Arya, D. (2011). Telmisartan, a dual ARB/partial PPAR‐γ agonist, protects myocardium from ischaemic reperfusion injury in experimental diabetes. Diabetes, Obesity and Metabolism, 13(6), 533-541.
Gracia-Lor, E., Sancho, J. V., Serrano, R., & Hernández, F. (2012). Occurrence and removal of pharmaceuticals in wastewater treatment plants at the Spanish Mediterranean area of Valencia. Chemosphere, 87(5), 453-462.
Guerra, P., Kim, M., Shah, A., Alaee, M., & Smyth, S. (2014). Occurrence and fate of antibiotic, analgesic/anti-inflammatory, and antifungal compounds in five wastewater treatment processes. Science of the Total Environment, 473, 235-243.
Guerra, P., Teslic, S., Shah, A., Albert, A., Gewurtz, S. B., & Smyth, S. A. (2019). Occurrence and removal of triclosan in Canadian wastewater systems. Environmental Science and Pollution Research, 26, 31873-31886.
Gurke, R., Rößler, M., Marx, C., Diamond, S., Schubert, S., Oertel, R., & Fauler, J. (2015). Occurrence and removal of frequently prescribed pharmaceuticals and corresponding metabolites in wastewater of a sewage treatment plant. Science of the Total Environment, 532, 762-770.
Hoeger, B., Köllner, B., Dietrich, D. R., & Hitzfeld, B. (2005). Water-borne diclofenac affects kidney and gill integrity and selected immune parameters in brown trout (Salmo trutta f. fario). Aquatic Toxicology, 75(1), 53-64.
Horby, P., Mafham, M., Linsell, L., Bell, J., Staplin, N., & Emberson, J. (2020). & Landray, MJ (2020). Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial. MedRxiv.
Iatrou, E. I., Stasinakis, A. S., & Thomaidis, N. S. (2014). Consumption-based approach for predicting environmental risk in Greece due to the presence of antimicrobials in domestic wastewater. Environmental Science and Pollution Research, 21, 12941-12950.
Ito-Harashima, S., Matano, M., Onishi, K., Nomura, T., Nakajima, S., Ebata, S., Shiizaki, K., Kawanishi, M., & Yagi, T. (2020). Construction of reporter gene assays using CWP and PDR mutant yeasts for enhanced detection of various sex steroids. Genes and Environment, 42, 1-19.
Ito-Harashima, S., Shiizaki, K., Kawanishi, M., Kakiuchi, K., Onishi, K., Yamaji, R., & Yagi, T. (2015). Construction of sensitive reporter assay yeasts for comprehensive detection of ligand activities of human corticosteroid receptors through inactivation of CWP and PDR genes. Journal of Pharmacological and Toxicological Methods, 74, 41-52.
Jacobs, M., Janssens, W., Bernauer, U., Brandon, E., Coecke, S., Combes, R., Edwards, P., Freidig, A., Freyberger, A., & Kolanczyk, R. (2008). The use of metabolising systems for in vitro testing of endocrine disruptors. Current Drug Metabolism, 9(8), 796-826.
Jelic, A., Gros, M., Ginebreda, A., Cespedes-Sànchez, R., Ventura, F., Petrovic, M., & Barcelo, D. (2011). Occurrence, partition and removal of pharmaceuticals in sewage water and sludge during wastewater treatment. Water Research, 45(3), 1165-1176.
Jia, Z., Sun, Y., Yang, G., Zhang, A., Huang, S., Heiney, K. M., & Zhang, Y. (2014). New insights into the PPARγ agonists for the treatment of diabetic nephropathy. PPAR Research, 2014.
Juksu, K., Zhao, J.-L., Liu, Y.-S., Yao, L., Sarin, C., Sreesai, S., Klomjek, P., Jiang, Y.-X., & Ying, G.-G. (2019). Occurrence, fate and risk assessment of biocides in wastewater treatment plants and aquatic environments in Thailand. Science of the Total Environment, 690, 1110-1119.
König, A., Weidauer, C., Seiwert, B., Reemtsma, T., Unger, T., & Jekel, M. (2016). Reductive transformation of carbamazepine by abiotic and biotic processes. Water Research, 101, 272-280.
Kabir, E. R., Rahman, M. S., & Rahman, I. (2015). A review on endocrine disruptors and their possible impacts on human health. Environmental Toxicology and Pharmacology, 40(1), 241-258.
Kavlock, R. J., Daston, G. P., DeRosa, C., Fenner-Crisp, P., Gray, L. E., Kaattari, S., Lucier, G., Luster, M., Mac, M. J., & Maczka, C. (1996). Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the US EPA-sponsored workshop. Environmental Health Perspectives, 104(suppl 4), 715-740.
Kenda, M., Karas Kuželički, N., Iida, M., Kojima, H., & Sollner Dolenc, M. (2020). Triclocarban, triclosan, bromochlorophene, chlorophene, and climbazole effects on nuclear receptors: an in silico and in vitro study. Environmental Health Perspectives, 128(10), 107005.
Klopčič, I., Markovič, T., Mlinarič-Raščan, I., & Dolenc, M. S. (2018). Endocrine disrupting activities and immunomodulatory effects in lymphoblastoid cell lines of diclofenac, 4-hydroxydiclofenac and paracetamol. Toxicology Letters, 294, 95-104.
Koh, Y., Chiu, T., Boobis, A., Cartmell, E., Scrimshaw, M., & Lester, J. (2008). Treatment and removal strategies for estrogens from wastewater. Environmental Technology, 29(3), 245-267.
Krenzelok, E. P. (2009). The FDA Acetaminophen Advisory Committee Meeting–what is the future of acetaminophen in the United States? The perspective of a committee member. Clinical Toxicology, 47(8), 784-789.
Kruglova, A., Ahlgren, P., Korhonen, N., Rantanen, P., Mikola, A., & Vahala, R. (2014). Biodegradation of ibuprofen, diclofenac and carbamazepine in nitrifying activated sludge under 12 C temperature conditions. Science of the Total Environment, 499, 394-401.
Langford, K., & Lester, J. N. (2002). Fate and behavior of endocrine disrupters in wastewater treatment processes. In Endocrine Disrupters in Wastewater and Sludge Treatment Processes (pp. 99-159). CRC Press.
Laue, L., Kawai, S., Brandon, D. D., Brightwell, D., Barnes, K., Knazek, R. A., Loriaux, D. L., & Chrousos, G. P. (1988). Receptor-mediated effects of glucocorticoids on inflammation: enhancement of the inflammatory response with a glucocorticoid antagonist. Journal of Steroid Biochemistry, 29(6), 591-598.
Li, L. (2021). Toxicity evaluation and by-products identification of triclosan ozonation and chlorination. Chemosphere, 263, 128223.
Liu, Q., Feng, X., Chen, N., Shen, F., Zhang, H., Wang, S., Sheng, Z., & Li, J. (2022). Occurrence and risk assessment of typical PPCPs and biodegradation pathway of ribavirin in wastewater treatment plants. Environmental Science and Ecotechnology, 11, 100184.
Liu, Y.-Y., Wang, Y., Walsh, T. R., Yi, L.-X., Zhang, R., Spencer, J., Doi, Y., Tian, G., Dong, B., & Huang, X. (2016). Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. The Lancet Infectious Diseases, 16(2), 161-168.
Losacco, G. L., Veuthey, J.-L., & Guillarme, D. (2019). Supercritical fluid chromatography–Mass spectrometry: Recent evolution and current trends. TrAC Trends in Analytical Chemistry, 118, 731-738.
Mahajan, D. K., & London, S. N. (1997). Mifepristone (RU486): a review. Fertility and Sterility, 68(6), 967-976.
Mamiş, M. S., Uyar, N., Eren, M. A., & Sabuncu, T. (2022). The treatment of hyperthyroidism with methimazole in a pregnant who developed agranulocytosis due to propylthiouracil. Journal of Clinical Trials and Experimental Investigations, 1(2), 56-59.
Martínez-Alcalá, I., Guillén-Navarro, J. M., & Lahora, A. (2021). Occurrence and fate of pharmaceuticals in a wastewater treatment plant from southeast of Spain and risk assessment. Journal of Environmental Management, 279, 111565.
McClellan, K. J., & Markham, A. (1998). Telmisartan. Drugs, 56(6), 1039-1044; discussion 1045.
Musee, N. (2018). Environmental risk assessment of triclosan and triclocarban from personal care products in South Africa. Environmental Pollution, 242, 827-838.
Ofrydopoulou, A., Nannou, C., Evgenidou, E., Christodoulou, A., & Lambropoulou, D. (2022). Assessment of a wide array of organic micropollutants of emerging concern in wastewater treatment plants in Greece: Occurrence, removals, mass loading and potential risks. Science of the Total Environment, 802, 149860.
Palma, P., Köck-Schulmeyer, M., Alvarenga, P., Ledo, L., Barbosa, I., De Alda, M. L., & Barceló, D. (2014). Risk assessment of pesticides detected in surface water of the Alqueva reservoir (Guadiana basin, southern of Portugal). Science of the Total Environment, 488, 208-219.
Papageorgiou, M., Kosma, C., & Lambropoulou, D. (2016). Seasonal occurrence, removal, mass loading and environmental risk assessment of 55 pharmaceuticals and personal care products in a municipal wastewater treatment plant in Central Greece. Science of the Total Environment, 543, 547-569.
Pitchai, A., Rajaretinam, R. K., & Freeman, J. L. (2019). Zebrafish as an emerging model for bioassay-guided natural product drug discovery for neurological disorders. Medicines, 6(2), 61.
Prescott, L. (1980). Kinetics and metabolism of paracetamol and phenacetin. British Journal of Clinical Pharmacology, 10(S2), 291S-298S.
Pugajeva, I., Rusko, J., Perkons, I., Lundanes, E., & Bartkevics, V. (2017). Determination of pharmaceutical residues in wastewater using high performance liquid chromatography coupled to quadrupole-Orbitrap mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis, 133, 64-74.
Rivera-Jaimes, J. A., Postigo, C., Melgoza-Alemán, R. M., Aceña, J., Barceló, D., & de Alda, M. L. (2018). Study of pharmaceuticals in surface and wastewater from Cuernavaca, Morelos, Mexico: Occurrence and environmental risk assessment. Science of the Total Environment, 613, 1263-1274.
Roberts, J., Kumar, A., Du, J., Hepplewhite, C., Ellis, D. J., Christy, A. G., & Beavis, S. G. (2016). Pharmaceuticals and personal care products (PPCPs) in Australia's largest inland sewage treatment plant, and its contribution to a major Australian river during high and low flow. Science of the Total Environment, 541, 1625-1637.
Rocha, M. J., Cruzeiro, C., & Rocha, E. (2013). Quantification of 17 endocrine disruptor compounds and their spatial and seasonal distribution in the Iberian Ave River and its coastline. Toxicological & Environmental Chemistry, 95(3), 386-399.
Rogers, H. R. (1996). Sources, behaviour and fate of organic contaminants during sewage treatment and in sewage sludges. Science of the Total Environment, 185(1-3), 3-26.
Routledge, E. J., & Sumpter, J. P. (1996). Estrogenic activity of surfactants and some of their degradation products assessed using a recombinant yeast screen. Environmental Toxicology and Chemistry: An International Journal, 15(3), 241-248.
Santos, L. H., Araújo, A. N., Fachini, A., Pena, A., Delerue-Matos, C., & Montenegro, M. (2010). Ecotoxicological aspects related to the presence of pharmaceuticals in the aquatic environment. Journal of Hazardous Materials, 175(1-3), 45-95.
Sari, S., Ozdemir, G., Yangin-Gomec, C., Zengin, G. E., Topuz, E., Aydin, E., Pehlivanoglu-Mantas, E., & Tas, D. O. (2014). Seasonal variation of diclofenac concentration and its relation with wastewater characteristics at two municipal wastewater treatment plants in Turkey. Journal of Hazardous Materials, 272, 155-164.
Schrier, R. W., Masoumi, A., & Elhassan, E. (2010). Aldosterone: role in edematous disorders, hypertension, chronic renal failure, and metabolic syndrome. Clinical Journal of the American Society of Nephrology, 5(6), 1132-1140.
Sheng, Z.-G., Tang, Y., Liu, Y.-X., Yuan, Y., Zhao, B.-Q., Chao, X.-J., & Zhu, B.-Z. (2012). Low concentrations of bisphenol a suppress thyroid hormone receptor transcription through a nongenomic mechanism. Toxicology and Applied Pharmacology, 259(1), 133-142.
Shields, G. S., Sazma, M. A., & Yonelinas, A. P. (2016). The effects of acute stress on core executive functions: A meta-analysis and comparison with cortisol. Neuroscience & Biobehavioral Reviews, 68, 651-668.
Shiizaki, K., Asai, S., Ebata, S., Kawanishi, M., & Yagi, T. (2010). Establishment of yeast reporter assay systems to detect ligands of thyroid hormone receptors α and β. Toxicology in Vitro, 24(2), 638-644.
Sica, D. A. (2015). Mineralocorticoid receptor antagonists for treatment of hypertension and heart failure. Methodist DeBakey Cardiovascular Journal, 11(4), 235.
Soares, A., Guieysse, B., Jefferson, B., Cartmell, E., & Lester, J. (2008). Nonylphenol in the environment: a critical review on occurrence, fate, toxicity and treatment in wastewaters. Environment International, 34(7), 1033-1049.
Steinauer, J., Pritts, E. A., Jackson, R., & Jacoby, A. F. (2004). Systematic review of mifepristone for the treatment of uterine leiomyomata. Obstetrics & Gynecology, 103(6), 1331-1336.
Stokkermans, T. J., Goyal, A., Bansal, P., & Trichonas, G. (2019). Chloroquine and hydroxychloroquine toxicity.
Stuer-Lauridsen, F., Birkved, M., Hansen, L., Lützhøft, H.-C. H., & Halling-Sørensen, B. (2000). Environmental risk assessment of human pharmaceuticals in Denmark after normal therapeutic use. Chemosphere, 40(7), 783-793.
Su, C., Cui, Y., Liu, D., Zhang, H., & Baninla, Y. (2020). Endocrine disrupting compounds, pharmaceuticals and personal care products in the aquatic environment of China: which chemicals are the prioritized ones? Science of the Total Environment, 720, 137652.
Svanfelt, J., Eriksson, J., & Kronberg, L. (2010). Analysis of thyroid hormones in raw and treated waste water. Journal of Chromatography A, 1217(42), 6469-6474.
Suksomboon, N., Poolsup, N., & Prasit, T. (2012). Systematic review of the effect of telmisartan on insulin sensitivity in hypertensive patients with insulin resistance or diabetes. Journal of Clinical Pharmacy and Therapeutics, 37(3), 319-327.
Svobodová, K., & Cajthaml, T. (2010). New in vitro reporter gene bioassays for screening of hormonal active compounds in the environment. Applied Microbiology and Biotechnology, 88, 839-847.
Tamura, I., Yasuda, Y., Kagota, K.-i., Yoneda, S., Nakada, N., Kumar, V., Kameda, Y., Kimura, K., Tatarazako, N., & Yamamoto, H. (2017). Contribution of pharmaceuticals and personal care products (PPCPs) to whole toxicity of water samples collected in effluent-dominated urban streams. Ecotoxicology and Environmental Safety, 144, 338-350.
Tang, Z., Liu, Z.-h., Wang, H., Dang, Z., Yin, H., Zhou, Y., & Liu, Y. (2020). Trace determination of eleven natural estrogens and insights from their occurrence in a municipal wastewater treatment plant and river water. Water Research, 182, 115976.
ten Oever, J., & Gyssens, I. C. (2022). General Principles of Antimicrobial Therapy. In A Rational Approach to Clinical Infectious Diseases (pp. 48-62). Elsevier.
Thiebault, T., Boussafir, M., & Le Milbeau, C. (2017). Occurrence and removal efficiency of pharmaceuticals in an urban wastewater treatment plant: mass balance, fate and consumption assessment. Journal of Environmental Chemical Engineering, 5(3), 2894-2902.
Timmermans, S., Souffriau, J., & Libert, C. (2019). A general introduction to glucocorticoid biology. Frontiers in Immunology, 10, 1545.
Tran, D. Q., Klotz, D. M., Ladlie, B. L., Ide, C. F., Mclachlan, J. A., & Arnold, S. F. (1996). Inhibition of progesterone receptor activity in yeast by synthetic chemicals. Biochemical and Biophysical Research Communications, 229(2), 518-523.
Tran, N. H., & Gin, K. Y.-H. (2017). Occurrence and removal of pharmaceuticals, hormones, personal care products, and endocrine disrupters in a full-scale water reclamation plant. Science of the Total Environment, 599, 1503-1516.
Tran, N. H., Reinhard, M., & Gin, K. Y.-H. (2018). Occurrence and fate of emerging contaminants in municipal wastewater treatment plants from different geographical regions-a review. Water Research, 133, 182-207.
Veldhoen, N., Skirrow, R. C., Brown, L. L., van Aggelen, G., & Helbing, C. C. (2014). Effects of acute exposure to the non-steroidal anti-inflammatory drug ibuprofen on the developing North American bullfrog (Rana catesbeiana) tadpole. Environmental Science & Technology, 48(17), 10439-10447.
Verlicchi, P., Al Aukidy, M., Jelic, A., Petrović, M., & Barceló, D. (2014). Comparison of measured and predicted concentrations of selected pharmaceuticals in wastewater and surface water: a case study of a catchment area in the Po Valley (Italy). Science of the Total Environment, 470, 844-854.
Verlicchi, P., Al Aukidy, M., & Zambello, E. (2012). Occurrence of pharmaceutical compounds in urban wastewater: removal, mass load and environmental risk after a secondary treatment—a review. Science of The Total Environment, 429, 123-155.
Vieno, N., & Sillanpää, M. (2014). Fate of diclofenac in municipal wastewater treatment plant—A review. Environment International, 69, 28-39.
Vilca, F. Z., Galarza, N. C., Tejedo, J. R., Cuba, W. A. Z., Quiróz, C. N. C., & Tornisielo, V. L. (2021). Occurrence of residues of veterinary antibiotics in water, sediment and trout tissue (Oncorhynchus mykiss) in the southern area of Lake Titicaca, Peru. Journal of Great Lakes Research, 47(4), 1219-1227.
Wang, Y., Li, Y., Hu, A., Rashid, A., Ashfaq, M., Wang, Y., Wang, H., Luo, H., Yu, C.-P., & Sun, Q. (2018). Monitoring, mass balance and fate of pharmaceuticals and personal care products in seven wastewater treatment plants in Xiamen City, China. Journal of Hazardous Materials, 354, 81-90.
Witorsch, R. J., & Thomas, J. A. (2010). Personal care products and endocrine disruption: a critical review of the literature. Critical Reviews in Toxicology, 40(sup3), 1-30.
Yan, Q., Gao, X., Huang, L., Gan, X.-M., Zhang, Y.-X., Chen, Y.-P., Peng, X.-Y., & Guo, J.-S. (2014). Occurrence and fate of pharmaceutically active compounds in the largest municipal wastewater treatment plant in Southwest China: mass balance analysis and consumption back-calculated model. Chemosphere, 99, 160-170.
Yao, L., Chen, Z.-Y., Dou, W.-Y., Yao, Z.-K., Duan, X.-C., Chen, Z.-F., Zhang, L.-J., Nong, Y.-J., Zhao, J.-L., & Ying, G.-G. (2021). Occurrence, removal and mass loads of antiviral drugs in seven wastewater treatment plants with various treatment processes. Water Research, 207, 117803.
Yao, X., Ye, F., Zhang, M., Cui, C., Huang, B., Niu, P., Liu, X., Zhao, L., Dong, E., & Song, C. (2020). In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical Infectious Diseases, 71(15), 732-739.
Ye, D., Bao, Z., Yu, Y., Han, Z., Yu, Y., Xu, Z., Ma, W., Yuan, Y., Zhang, L., & Xu, Y. (2020). Inhibition of cardiomyocyte differentiation of human induced pluripotent stem cells by Ribavirin: Implication for its cardiac developmental toxicity. Toxicology, 435, 152422.
Zhang, X., Zhao, H., Du, J., Qu, Y., Shen, C., Tan, F., Chen, J., & Quan, X. (2017). Occurrence, removal, and risk assessment of antibiotics in 12 wastewater treatment plants from Dalian, China. Environmental Science and Pollution Research, 24, 16478-16487.
Zhang, Z., Zhou, Y., Han, L., Guo, X., Wu, Z., Fang, J., Hou, B., Cai, Y., Jiang, J., & Yang, Z. (2022). Impacts of COVID-19 pandemic on the aquatic environment associated with disinfection byproducts and pharmaceuticals. Science of the Total Environment, 811, 151409.
Zloh, M., Perez-Diaz, N., Tang, L., Patel, P., & Mackenzie, L. S. (2016). Evidence that diclofenac and celecoxib are thyroid hormone receptor beta antagonists. Life Sciences, 146, 66-72.
陳柏均. (2018), 污水廠中內分泌干擾活性及藥物之檢測和藥物綠化衍生物之活性變化, 成功大學環境工程學系碩士學位論文, 1-125.
李哲宏. (2019), 藥物於污水處理廠水相和固相樣本中之分布及其內分泌干擾活性探討, 成功大學環境工程學系碩士學位論文, 1-139.
余致廣. (2020), 污水處理廠中內分泌干擾活性及個人保健用品之濃度變化和二苯甲酮類氯化衍生物之活性探討, 成功大學環境工程學系碩士學位論文, 1-134.