Pharmaceuticals in the Sea of Marmara, Türki̇ye
Nagihan Ersoy Korkmaz, Nuray Çağlar Balkıs, Abdullah Aksu, Başak Savun Hekimoğlu, Güldehan DeryalPharmaceuticals are a particular class of emerging contaminants, and their significance is becoming increasingly understood due to their physiological impacts on humans, even at low doses. According to the literature, different pharmaceutical compounds are frequently found in varied water, soil, and biota samples. In this study, eleven commonly used pharmaceutical compounds were reviewed in seawater, sediment, and biota in the Sea of Marmara. The studied compounds consist of four groups which are anti-inflammatory (naproxen, diclofenac, ibuprofen, ketoprofen, fenoprofen), hormones (estrone, 17β-estradiol, 17α-ethynylestradiol), antiepileptic (carbamazepine), lipid regulators (gemfibrozil and clofibric acid). Gemfibrozil, ibuprofen, and 17-ethynylestradiol were among the pharmaceutical substances that were frequently found in the Sea of Marmara. Gemfibrozil was detected in concentrations ranging from <0.054 to 9.71 µg/L for seawater, 124 ng/g for sediment, and <3.2 to 9135 ng/g for biota. Ibuprofen was detected in the range of <0.015 – 2.46 µg/L, 215 ng/g, and <3 – 5098 ng/g in seawater, sediment and biota, respectively. 17α-ethynylestradiol was found in concentrations ranging from <0.010 – 3.55 µg/L for seawater, 319 ng/g for sediment, <2 – 1258 ng/g for biota. The negative impacts that these substances may have on both human health and the ecosystems in which they are found are thus of utmost significance. Furthermore, research on the trophic transfer of pharmaceuticals is relatively few and remains a gap in the literature despite the potential bioaccumulation of these substances. The present study reviews the current knowledge on the sources, transport, and degradation of pharmaceuticals in the seawater environment and assesses the environmental risk they pose in light of the criteria of permanence, bioaccumulation, and toxicity. Environmental risk evaluations and the identification of various pharmaceutical residues in water, sediment, and biota samples collected from the Sea of Marmara were thoroughly examined. 17-estradiol, gemfibrozil, and 17-ethynylestradiol pose a significant risk to aquatic life in the Sea of Marmara based on the risk quotient. Due to their extensive usage, the study focused on anti inflammatory medications, steroid hormones, antiepileptic medicines, and lipid regulators. Finally, future perspectives are discussed while considering the research gaps found in the context of the available information.
References
- Adeel, M, Song, X, Wang, Y, Francis, D, Yang, Y, 2017. Environmental impact of estrogens on human, animal and plant life: A critical review. Environ Int 99:107-119. google scholar
- Ahmed, M K, Baki, M A, Islam, M S, Kundu, G K, Habibullah-Al-Mamun, M, Sarkar, S K, Hossain, M M, 2015. Human health risk assessment of heavy metals in tropical fish and shellfish collected from the river Buriganga, Bangladesh. Environmental Science and Pollution Research 22:15880-15890. google scholar
- Aksu, A, Balkis, N, Taskin, O, Ersan, M, 2011. Toxic metal (Pb, Cd, As and Hg) and organochlorine residue levels in hake (Merluccius merluccius) from the Sea of Marmara, Turkey. Environmental monitoring and assessment 182:509-521. google scholar
- Algan, O, Balkıs, N, Çağatay, M N, Sarı, E, 2004. The sources of metal contents in the shelf sediments from the Sea of Marmara, Turkey. Environmental Geology 46:932-950. google scholar
- Ali, A M, R0nning, H T, Sydnes, L K, Alarif, W M, Kallenborn, R, Al-Lihaibi, S S, 2018. Detection of PPCPs in marine organisms from contaminated coastal waters of the Saudi Red Sea. The Science of the total en-vironment 621:654-662. google scholar
- Alpar, B, Hüseyin, Y, Türker, A, 2003. Water exchange in the Golden Horn Estuary. Journal of The Black Sea/ Mediterranean Environment 9. google scholar
- Âlvarez-Munoz, D, Rodriguez-Mozaz, S, Maulvault, A L, Tediosi, A, Fernandez-Tejedor, M, Van den Heuvel, F, Kotterman, M, Marques, A, Barcelo, D, 2015. Occurrence of pharmaceuticals and endocrine disrupting com-pounds in macroalgaes, bivalves, and fish from coastal areas in Europe. Environmental research 143:56-64. google scholar
- Alygizakis, N A, Gago-Ferrero, P, Borova, V L, Pavlidou, A, Hatzianestis, I, Thomaidis, N S, 2016. Occurrence and spatial distribution of 158 pharmaceuticals, drugs of abuse and related metabolites in offshore seawater. Science of The Total Environment 541:1097-1105. google scholar
- Andersson, C, Katsiadaki, I, Lundstedt-Enkel, K, Orberg, J, 2007. Effects of 17alpha-ethynylestradiol on EROD activity, spiggin and vitellogenin in three-spined stickleback (Gasterosteus aculeatus). Aquatic toxicology (Amsterdam, Netherlands) 83:33-42. google scholar
- Andreozzi, R, Raffaele, M, Nicklas, P, 2003. Pharmaceuticals in STP effluents and their solar photodegradation in aquatic environment. Chemosphere 50:1319-1330. google scholar
- Anim, A K, Thompson, K, Duodu, G O, Tscharke, B, Birch, G, Goonetilleke, A, Ayoko, G A, Mueller, J F, 2020. Pharmaceuticals, personal care products, food additive and pesticides in surface waters from three Australian east coast estuaries (Sydney, Yarra and Brisbane). Mar Pollut Bull 153:111014. google scholar
- Araujo, L, Villa, N, Camargo, N, Bustos, M, Garda, T, Prieto, A d J, 2011. Persistence of gemfibrozil, naproxen and mefenamic acid in natural waters. Environmental Chemistry Letters 9:13-18. google scholar
- Aris, A Z, Shamsuddin, A S, Praveena, S M, 2014. Occurrence of 17a-ethynylestradiol (EE2) in the environment and effect on exposed biota: a review. Environ Int 69:104-119. google scholar
- Arukwe, A, Goks0yr, A, 1997. Changes in three hepatic cytochrome P450 subfamilies during a reproductive cycle in turbot (Scophthalmus maximus L.). Journal of Experimental Zoology 277:313-325. google scholar
- Aslan, E, Aksu, A, Korkmaz, N E, Taskin, O S, Caglar, N B, 2019. Monitoring the antioxidant activities by extracting the polyphenolic contents of algae collected from the Bosphorus. Marine Pollution Bulletin 141:313-317. google scholar
- Aydin, E, Talinli, I, 2013. Analysis, occurrence and fate of commonly used pharmaceuticals and hormones in the Buyukcekmece Watershed, Turkey. Chemosphere 90:2004-2012. google scholar
- Baena-Nogueras, R M, Gonzalez-Mazo, E, Lara-Martm, P A, 2017. Degradation kinetics of pharmaceuticals and personal care products in surface waters: photolysis vs biodegradation. Science of The Total Environment 590-591:643-654. google scholar
- Balkıs, N, Şenol, E, Aksu, A, 2007. Trace Metal Distributions in Water Column And Surface Sediments of Izmit Bay (Turkey) After Marmara (Izmit) Earthquake Fresenius Environmental Bulletin 16:910-916. google scholar
- Balkis, N, Müftüoğlu, E, Aksu, A, Sur, H I, Apak, R, 2010. The chemical oceanographic consequences of environmental restoration projects in the Golden Horn estuary (Sea of Marmara, Turkey). Environ Monit Assess 164:67-79. google scholar
- Barreto, A, Luis, L G, Pa^ga, P, Santos, L H M L M, Delerue-Matos, C, Soares, A M V M, Hylland, K, Loureiro, S, Oliveira, M, 2018. A multibiomarker approach highlights effects induced by the human pharmaceutical gemfibrozil to gilthead seabream Sparus aurata. Aquatic Toxicology 200:266-274. google scholar
- Barsiene, J, Lehtonen, K K, Koehler, A, Broeg, K, Vuorinen, P J, Lang, T, Pempkowiak, J, Syvokiene, J, De-donyte, V, Rybakovas, A, Repecka, R, Vuontisjârvi, H, Kopecka, J, 2006. Biomarker responses in flounder (Platichthys flesus) and mussel (Mytilus edulis) in the Klaipeda-Bütinge area (Baltic Sea). Marine Pollution Bulletin 53:422-436. google scholar
- Bayen, S, Zhang, H, Desai, M M, Ooi, S K, Kelly, B C, 2013. Occurrence and distribution of pharmaceutically active and endocrine disrupting compounds in Singapore’s marine environment: Influence of hydrodynamics and physical-chemical properties. Environmental Pollution 182:1-8. google scholar
- Bayram, D, Vızdıklar, C, Aydin, V, İşli, F, Akici, A, 2020. Investigation of prescribing trends and prescriptions for common diagnoses in primary care: Nationwide data of Turkey.695-708. google scholar
- Belkaya, H, Ozmen, I, Karamut, I, 2008. The Marmaray project: Managing a large scale project with various stake holders, Proceedings of the World Congress on Engineering 2008. google scholar
- Beşiktepe, Ş T, Sur, H İ, Özsoy, E, Latif, M A, Oğuz, T, Ünlüata, Ü, 1994. The circulation and hydrography of the Sea of Marmara. Progress in Oceanography 34:285-334. google scholar
- Bizarro, C, Ros, O, Vallejo, A, Prieto, A, Etxebarria, N, Cajaraville, M P, Ortiz-Zarragoitia, M, 2014. Intersex condition and molecular markers of endocrine disruption in relation with burdens of emerging pollutants in thicklip grey mullets (Chelon labrosus) from Basque estuaries (South-East Bay of Biscay). Marine en-vironmental research 96:19-28. google scholar
- Bousse, L, Mostarshed, S, Van Der Shoot, B, de Rooij, N F, Gimmel, P, Göpel, W, 1991. Zeta potential measu-rements of Ta2O5 and SiO2 thin films. Journal of Colloid and Interface Science 147:22-32. google scholar
- Box, A, Sureda, A, Galgani, F, Pons, A, Deudero, S, 2007. Assessment of environmental pollution at Balearic Islands applying oxidative stress biomarkers in the mussel Mytilus galloprovincialis. Comparative bioche-mistry and physiology. Toxicology & pharmacology : CBP 146:531-539. google scholar
- Bringolf, R B, Heltsley, R M, Newton, T J, Eads, C B, Fraley, S J, Shea, D, Cope, W G, 2010. Environmental occurrence and reproductive effects of the pharmaceutical fluoxetine in native freshwater mussels. Envi-ronmental toxicology and chemistry 29:1311-1318. google scholar
- Caban, M, Szaniawska, A, Stepnowski, P, 2016. Screening of 17a-ethynylestradiol and non-steroidal anti-inflam-matory pharmaceuticals accumulation in (Gould, 1890) collected from the Gulf of Gdansk. Oceanological and Hydrobiological Studies 45:605-614. google scholar
- Camacho-Munoz, D, Martin, J, Santos, J L, Aparicio, I, Alonso, E, 2009. An affordable method for the simul-taneous determination of the most studied pharmaceutical compounds as wastewater and surface water pollutants. Journal of separation science 32:3064-3073. google scholar
- Chiu, J M Y, Po, B H K, Degger, N, Tse, A, Liu, W, Zheng, G, Zhao, D M, Xu, D, Richardson, B, Wu, R S S, 2018. Contamination and risk implications of endocrine disrupting chemicals along the coastline of China: A systematic study using mussels and semipermeable membrane devices. The Science of the total environ-ment 624:1298-1307. google scholar
- Cleuvers, M, 2004. Mixture toxicity of the anti-inflammatory drugs diclofenac, ibuprofen, naproxen, and acety-lsalicylic acid. Ecotoxicology and environmental safety 59:309-315. google scholar
- Coleman, H M, Kanat, G, Aydinol Turkdogan, F I, 2009. Restoration of the Golden Horn Estuary (Halic). Water Research 43:4989-5003. google scholar
- Cui, Y, Wang, Y, Pan, C, Li, R, Xue, R, Guo, J, Zhang, R, 2019. Spatiotemporal distributions, source apportion-ment and potential risks of 15 pharmaceuticals and personal care products (PPCPs) in Qinzhou Bay, South China. Marine Pollution Bulletin 141:104-111. google scholar
- Cunha, S C, Pena, A, Fernandes, J O, 2017. Mussels as bioindicators of diclofenac contamination in coastal environments. Environmental Pollution 225:354-360. google scholar
- Çağatay, M N, Algan, O, Sakınç, M, E., C J, Egesel, L, Balkis, N, Ongan, D, Caner, H, 1999. A mid-late Holoce-ne sapropelic sediment unit from the southern Sea of Marmara shelf and its palaeoceanographic significance. Quaternary Science Reviews 18:531-540. google scholar
- Çolpan Polat, S, Tugrul, S, 1995. Nutrient and organic carbon exchanges between the Black and Sea of Marmaras through the Bosphorus Strait. Continental Shelf Research 15:1115-1132. google scholar
- Daughton, C G, 2002. Environmental stewardship and drugs as pollutants. Lancet (London, England) 360:1035-1036. google scholar
- David, A, Dagnino, S, Pichot, Y, Munaron, D, Escande, A, Casellas, C, Fenet, H, Gomez, E, 2008. Temporal study of estrogenic responses of mussel (Mytilus galloprovinciallis) extracts applied to reporter cell lines. Marine environmental research 66:105-107. google scholar
- Del Rosario, K L, Mitra, S, Humphrey, C P, Jr., O’Driscoll, M A, 2014. Detection of pharmaceuticals and other personal care products in groundwater beneath and adjacent to onsite wastewater treatment systems in a coastal plain shallow aquifer. The Science of the total environment 487:216-223. google scholar
- Doğan, M, 2013. Industrialization Process in Istanbul and Its Development in the Last 10 Years from Past to Present. Marmara Journal of Geography:511-550. google scholar
- EMA, 2006. European medicine agency guideline on the environmental risk assessment of medicinal products for human use (EMEA/CHMP/SWP/4447/00). google scholar
- Erdik, T, Şen, O, Öztürk, İ, 2019. Testing various scenarios to improve circulation in Golden Horn Estuary: A case study. Marine Pollution Bulletin 146:598-607. google scholar
- Ergin, M, Ediger, V, Bodur, M, Okyar, M, 1990. A review of modern sedimentation in the Golden Horn Estuary (Sea of Marmara), Turkey. Bollettino di Oceanologia Teorica ed Applicata 8:135-151. google scholar
- 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. Mar Pollut Bull 64:1435-1444. google scholar
- Fein, J B, 2002. The effects of ternary surface complexes on the adsorption of metal cations and organic acids onto mineral surfaces, in: Hellmann R, Wood S.A. (Ed.), Water-Rock Interactions, Ore Deposits, and En-vironmental Geochemistry A tribute to David A. Crerar. The Geochemical Society, Special Publication No 7: Washington, ABD, pp. 365-378. google scholar
- Fent, K, Weston, A A, Caminada, D, 2006. Ecotoxicology of human pharmaceuticals. Aquatic Toxicology 76:122-159. google scholar
- Friberg, N, Bonada, N, Bradley, D C, Dunbar, M J, Edwards, F K, Grey, J, Hayes, R B, Hildrew, A G, Lamouroux, N, Trimmer, M, Woodward, G, 2011. Biomonitoring of Human Impacts in Freshwater Ecosystems: The Good, the Bad and the Ugly, in: Woodward G (Ed.), Advances in Ecological Research. Academic Press, pp. 1-68. google scholar
- Gonzalez-Rey, M, Tapie, N, Le Menach, K, Devier, M-H, Budzinski, H, Bebianno, M J, 2015. Occurrence of pharmaceutical compounds and pesticides in aquatic systems. Marine Pollution Bulletin 96:384-400. google scholar
- Grenni, P, Patrolecco, L, Ademollo, N, Di Lenola, M, Barra Caracciolo, A, 2014. Capability of the natural microbial community in a river water ecosystem to degrade the drug naproxen. Environmental science and pollution research international 21:13470-13479. google scholar
- Hallmann, A, Smolarz, K, Konieczna, L, Zabrzanska, S, Belka, M, B^czek, T, 2016. LC-MS measurment of free steroids in mussels (Mytilus trossulus) from the southern Baltic Sea. Journal of Pharmaceutical and Biomedical Analysis 117:311-315. google scholar
- 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 75:53-64. google scholar
- Huber, M M, GÖbel, A, Joss, A, Hermann, N, LÖffler, D, McArdell, C S, Ried, A, Siegrist, H, Ternes, T A, von Gunten, U, 2005a. Oxidation of Pharmaceuticals during Ozonation of Municipal Wastewater Effluents: A Pilot Study. Environmental Science & Technology 39:4290-4299. google scholar
- Huber, M M, Korhonen, S, Ternes, T A, von Gunten, U, 2005b. Oxidation of pharmaceuticals during water treatment with chlorine dioxide. Water Research 39:3607-3617. google scholar
- Hunter, S, Khan, M Z, Shieh, B H, Doerr, B, Ali, S, Law, F C, 2012. Assessing estrogenic chemicals in anchovy and mussel samples from Karachi, Pakistan with the yeast estrogen screen bioassay. Bulletin of environ-mental contamination and toxicology 89:990-994. google scholar
- Ikkere, L E, Perkons, I, Sire, J, Pugajeva, I, Bartkevics, V, 2018. Occurrence of polybrominated diphenyl ethers, perfluorinated compounds, and nonsteroidal anti-inflammatory drugs in freshwater mussels from Latvia. Chemosphere 213:507-516. google scholar
- ISKI (Istanbul Water And Sewage Administration), (2006). Flow and effluent analysis reports of wastewater treatment plants. google scholar
- Jia, Y, Kong, Q, Yang, Z, Wang, L, 2016. Accumulation behavior and risk assessment of heavy metals and arsenic in tissues of white bream (Parabramis pekinensis) from the Xiang River, southern China. Environmental Science and Pollution Research 23:25056-25064. google scholar
- Jia, Y, Wang, L, Qu, Z, Wang, C, Yang, Z, 2017. Effects on heavy metal accumulation in freshwater fishes: species, tissues, and sizes. Environmental Science and Pollution Research 24:9379-9386. google scholar
- Jones, O A H, Voulvoulis, N, Lester, J N, 2005. Human Pharmaceuticals in Wastewater Treatment Processes. Critical Reviews in Environmental Science and Technology 35:401-427. google scholar
- Jürgens, M D, Holthaus, K I, Johnson, A C, Smith, J L, Hetheridge, M, Williams, R J, 2002. The potential for estradiol and ethinylestradiol degradation in English rivers. Environmental toxicology and chemistry 21:480-488. google scholar
- Karakaş, K. (2011). Statistical Evaluation of Golden Horn Estuary Improvement Project Study Results. Yıldız Technical University, Environmental engineering Department. Master’s Thesis. google scholar
- Khetan, S K, Collins, T J, 2007. Human Pharmaceuticals in the Aquatic Environment: A Challenge to Green Chemistry. Chemical Reviews 107:2319-2364. google scholar
- Kim, H-Y, Lee, I-S, Oh, J-E, 2017. Human and veterinary pharmaceuticals in the marine environment including fish farms in Korea. Science of The Total Environment 579:940-949. google scholar
- Klosterhaus, S L, Grace, R, Hamilton, M C, Yee, D, 2013. Method validation and reconnaissance of pharma-ceuticals, personal care products, and alkylphenols in surface waters, sediments, and mussels in an urban estuary. Environment International 54:92-99. google scholar
- Korkmaz, N E, Caglar, N B, Aksu, A, 2021. Determination of Some Selected Pharmaceuticals In Marine Biota: A Case Study In The Istanbul Metropolitan Area, Turkey. Fresenius Envıronmental Bulletin 30:10825-10835. google scholar
- Korkmaz, N E, Caglar, N B, Aksu, A, 2022a. Presence and distribution of selected pharmaceutical compounds in water and surface sediment of the Golden Horn Estuary, Sea of Marmara, Turkey. Regional Studies in Marine Science 51:102221. google scholar
- Korkmaz, N E, Caglar, N B, Aksu, A, Unsal, T, Balcıoglu, E B, Cavus Arslan, H, Demirel, N, 2023. Occurren-ce, bioconcentration, and human health risks of pharmaceuticals in biota in the Sea of Marmara, Türkiye. Chemosphere:138296. google scholar
- Korkmaz, N E, Savun-Hekimoğlu, B, Aksu, A, Burak, S, Caglar, N B, 2022b. Occurrence, sources and environ-mental risk assessment of pharmaceuticals in the Sea of Marmara, Turkey. Science of The Total Environment 819:152996. google scholar
- Kramer, R D, Filippe, T C, Prado, M R, de Azevedo, J C R, 2018. The influence of solid-liquid coefficient in the fate of pharmaceuticals and personal care products in aerobic wastewater treatment. Environmental science and pollution research international 25:25515-25525. google scholar
- Kwon, J W, Armbrust, K L, 2008. Aqueous solubility, n-octanol-water partition coefficient, and sorption of five selective serotonin reuptake inhibitors to sediments and soils. Bulletin of environmental contamination and toxicology 81:128-135. google scholar
- Lam, M W, Young, C J, Brain, R A, Johnson, D J, Hanson, M A, Wilson, C J, Richards, S M, Solomon, K R, Mabury, S A, 2004. Aquatic persistence of eight pharmaceuticals in a microcosm study. Environmental toxicology and chemistry 23:1431-1440. google scholar
- Letsinger, S, Kay, P, Rodriguez-Mozaz, S, Villagrassa, M, Barcelo, D, Rotchell, J M, 2019. Spatial and temporal occurrence of pharmaceuticals in UK estuaries. Science of The Total Environment 678:74-84. google scholar
- Li, W C, 2014. Occurrence, sources, and fate of pharmaceuticals in aquatic environment and soil. Environmental Pollution 187:193-201. google scholar
- Lindholm-Lehto, P C, Ahkola, H S, Knuutinen, J S, Herve, S H, 2016. Widespread occurrence and seasonal variation of pharmaceuticals in surface waters and municipal wastewater treatment plants in central Finland. Environmental science and pollution research international 23:7985-7997. google scholar
- Lowe, B M, Skylaris, C-K, Green, N G, 2015. Acid-base dissociation mechanisms and energetics at the silica-water interface: An activationless process. Journal of Colloid and Interface Science 451:231-244. google scholar
- Martmez Bueno, M J, Boillot, C, Fenet, H, Chiron, S, Casellas, C, Gomez, E, 2013. Fast and easy extraction combined with high resolution-mass spectrometry for residue analysis of two anticonvulsants and their transformation products in marine mussels. Journal of Chromatography A 1305:27-34. google scholar
- Mathewson, J H, 2003. Oceanography, Chemical, in: Meyers R A (Ed.), Encyclopedia of Physical Science and Technology (Third Edition). Academic Press: New York, pp. 99-115. google scholar
- Matozzo, V, Gagne, F, Marin, M G, Ricciardi, F, Blaise, C, 2008. Vitellogenin as a biomarker of exposure to estrogenic compounds in aquatic invertebrates: A review. Environment International 34:531-545. google scholar
- McEneff, G, Barron, L, Kelleher, B, Paull, B, Quinn, B, 2014. A year-long study of the spatial occurrence and relative distribution of pharmaceutical residues in sewage effluent, receiving marine waters and marine bivalves. The Science of the total environment 476-477:317-326. google scholar
- Mezzelani, M, Gorbi, S, Da Ros, Z, Fattorini, D, d’Errico, G, Milan, M, Bargelloni, L, Regoli, F, 2016a. Ecotoxi-cological potential of non-steroidal anti-inflammatory drugs (NSAIDs) in marine organisms: Bioavailability, biomarkers and natural occurrence in Mytilus galloprovincialis. Marine environmental research 121:31-39. google scholar
- Mezzelani, M, Gorbi, S, Fattorini, D, d’Errico, G, Benedetti, M, Milan, M, Bargelloni, L, Regoli, F, 2016b. Transcriptional and cellular effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in experimentally exposed mussels, Mytilus galloprovincialis. Aquatic toxicology (Amsterdam, Netherlands) 180:306-319. google scholar
- Mijangos, L, Ziarrusta, H, Ros, O, Kortazar, L, Fernandez, L A, Olivares, M, Zuloaga, O, Prieto, A, Etxebarria, N, 2018. Occurrence of emerging pollutants in estuaries of the Basque Country: Analysis of sources and distribution, and assessment of the environmental risk. Water Research 147:152-163. google scholar
- Mompelat, S, Le Bot, B, Thomas, O, 2009. Occurrence and fate of pharmaceutical products and by-products, from resource to drinking water. Environment International 35:803-814. google scholar
- Moore, M N, Lowe, D M, Fieth, P E, 1978. Responses of lysosomes in the digestive cells of the common mussel, Mytilus edulis, to sex steroids and cortisol. Cell and tissue research 188:1-9. google scholar
- Moreno-Gonzalez, R, Rodriguez-Mozaz, S, Gros, M, Perez-Canovas, E, Barcelo, D, Leon, V M, 2014. Input of pharmaceuticals through coastal surface watercourses into a Mediterranean lagoon (Mar Menor, SE Spain): Sources and seasonal variations. Science of The Total Environment 490:59-72. google scholar
- Müftüoğlu, A E, 2008. Hydrodynamic structure of the bays and the estuary of the Sea of Marmara, Institute of Marine Sciences and Management. Istanbul University, Istanbul, Turkey, p. 176. google scholar
- Norling, P, Kautsky, N, 2008. Patches of the mussel Mytilus sp. Are islands of high biodiversity in subtidal sediment habitats in the Baltic Sea. Aquatic Biology 4. google scholar
- O’Flynn, D, Lawler, J, Yusuf, A, Parle-McDermott, A, Harold, D, Mc Cloughlin, T, Holland, L, Regan, F, White, B, 2021. A review of pharmaceutical occurrence and pathways in the aquatic environment in the context of a changing climate and the COVID-19 pandemic. Analytical Methods 13:575-594. google scholar
- Okus, E, Ozturk, I, Sur, H I, Yuksek, A, Tas, S, Aslan-Yilmaz, A, Altiok, H, Balkis, N, Dogan, E, Ovez, S, Aydin, A F, 2008. Critical evaluation of wastewater treatment and disposal strategies for Istanbul with regards to water quality monitoring study results. Desalination 226:231-248. google scholar
- Oliver, L M, Fisher, W S, Winstead, J T, Hemmer, B L, Long, E R, 2001. Relationships between tissue contami-nants and defense-related characteristics of oysters (Crassostrea virginica) from five Florida bays. Aquatic toxicology (Amsterdam, Netherlands) 55:203-222. google scholar
- Pa^ga, P, Lolic, A, Hellebuyck, F, Santos, L H M L M, Correia, M, Delerue-Matos, C, 2015. Development of a SPE-UHPLC-MS/MS methodology for the determination of non-steroidal anti-inflammatory and analgesic pharmaceuticals in seawater. Journal of Pharmaceutical and Biomedical Analysis 106:61-70. google scholar
- Pal, A, Gin, K Y-H, Lin, A Y-C, Reinhard, M, 2010. Impacts of emerging organic contaminants on freshwa-ter resources: Review of recent occurrences, sources, fate and effects. Science of The Total Environment 408:6062-6069. google scholar
- Papagiannaki, D, Morgillo, S, Bocina, G, Calza, P, Binetti, R, 2021. Occurrence and Human Health Risk As-sessment of Pharmaceuticals and Hormones in Drinking Water Sources in the Metropolitan Area of Turin in Italy. Toxics 9. google scholar
- Patrolecco, L, Capri, S, Ademollo, N, 2015. Occurrence of selected pharmaceuticals in the principal sewage treatment plants in Rome (Italy) and in the receiving surface waters. Environmental science and pollution research international 22:5864-5876. google scholar
- Peker, F. (2007). Pollutant sources causing marine pollution in the Bosphorus and changes in water quality. google scholar
- Pemberthy M, D, Padilla, Y, Echeverri, A, Penuela, G A, 2020. Monitoring pharmaceuticals and personal care products in water and fish from the Gulf of Uraba, Colombia. Heliyon 6:e04215. google scholar
- Pereira, C D S, Maranho, L A, Cortez, F S, Pusceddu, F H, Santos, A R, Ribeiro, D A, Cesar, A, Guimarâes, L L, 2016. Occurrence of pharmaceuticals and cocaine in a Brazilian coastal zone. The Science of the total environment 548-549:148-154. google scholar
- Phillips, D J H, Rainbow, P S, 2012. Biomonitoring of Trace Aquatic Contaminants. google scholar
- Pignotti, E, Dinelli, E, 2018. Distribution and partition of endocrine disrupting compounds in water and se-diment: Case study of the Romagna area (North Italy). Journal of Geochemical Exploration 195:66-77., google scholar
- Poirier Larabie, S, Houde, M, Gagnon, C, 2017. Determination of the bioavailability of selected pharmaceutical residues in fish plasma using liquid chromatography coupled to tandem mass spectrometry. Journal of Chromatography A 1522:48-55. google scholar
- Pojana, G, Gomiero, A, Jonkers, N, Marcomini, A, 2007. Natural and synthetic endocrine disrupting compounds (EDCs) in water, sediment and biota of a coastal lagoon. Environ Int 33:929-936. google scholar
- Prindiville, J S, Mennigen, J A, Zamora, J M, Moon, T W, Weber, J M, 2011. The fibrate drug gemfibrozil dis-rupts lipoprotein metabolism in rainbow trout. Toxicology and applied pharmacology 251:201-208. google scholar
- Reis-Santos, P, Pais, M, Duarte, B, Caçador, I, Freitas, A, Vila Pouca, A S, Barbosa, J, Leston, S, Rosa, J, Ramos, F, Cabral, H N, Gillanders, B M, Fonseca, V F, 2018. Screening of human and veterinary pharmaceuticals in estuarine waters: A baseline assessment for the Tejo estuary. Marine Pollution Bulletin 135:1079-1084. google scholar
- Rzymski, P, Drewek, A, Klimaszyk, P, 2017. Pharmaceutical pollution of aquatic environment: an emerging and enormous challenge. Limnological Review 17:97-107. google scholar
- Saravanabhavan, G, Helleur, R, Hellou, J, 2009. GC-MS/MS measurement of natural and synthetic estrogens in receiving waters and mussels close to a raw sewage ocean outfall. Chemosphere 76:1156-1162. google scholar
- Schwarz, T I, Katsiadaki, I, Maskrey, B H, Scott, A P, 2017. Mussels (Mytilus spp.) display an ability for rapid and high capacity uptake of the vertebrate steroid, estradiol-17p from water. The Journal of steroid bioche-mistry and molecular biology 165:407-420. google scholar
- Sharma, B M, Becanova, J, Scheringer, M, Sharma, A, Bharat, G K, Whitehead, P G, Klanova, J, Nizzetto, L, 2019. Health and ecological risk assessment of emerging contaminants (pharmaceuticals, personal care products, and artificial sweeteners) in surface and groundwater (drinking water) in the Ganges River Basin, India. The Science of the total environment 646:1459-1467. google scholar
- Silva, B F d, Jelic, A, Lopez-Serna, R, Mozeto, A A, Petrovic, M, Barcelo, D, 2011. Occurrence and distribution of pharmaceuticals in surface water, suspended solids and sediments of the Ebro river basin, Spain. Che-mosphere 85:1331-1339. google scholar
- Sun, Q, Li, Y, Li, M, Ashfaq, M, Lv, M, Wang, H, Hu, A, Yu, C-P, 2016. PPCPs in Jiulong River estuary (Chi-na): Spatiotemporal distributions, fate, and their use as chemical markers of wastewater. Chemosphere 150:596-604. google scholar
- Taşkın, Ö S, Aksu, A, Balkıs, N, 2011. Metal (Al, Fe, Mn and Cu) distributions and origins of polycyclic aromatic hydrocarbons (PAHs) in the surface sediments of the Sea of Marmara and the coast of Istanbul, Turkey. Marine Pollution Bulletin 62:2568-2570. google scholar
- Thomas, K V, Hilton, M J, 2004. The occurrence of selected human pharmaceutical compounds in UK estuaries. Marine Pollution Bulletin 49:436-444. google scholar
- Tixier, C, Singer, H P, Oellers, S, Müller, S R, 2003. Occurrence and Fate of Carbamazepine, Clofibric Acid, Diclofenac, Ibuprofen, Ketoprofen, and Naproxen in Surface Waters. Environmental Science & Technology 37:1061-1068. google scholar
- Togola, A, Budzinski, H, 2008. Multi-residue analysis of pharmaceutical compounds in aqueous samples. Journal of chromatography. A 1177:150-158. google scholar
- Tolls, J, 2001. Sorption of Veterinary Pharmaceuticals in Soils: A Review. Environmental Science & Technology 35:3397-3406. google scholar
- Torres, M A, Barros, M P, Campos, S C G, Pinto, E, Rajamani, S, Sayre, R T, Colepicolo, P, 2008. Biochemical biomarkers in algae and marine pollution: A review. Ecotoxicology and environmental safety 71:1-15. google scholar
- TUIK (2022). Turkish Statistical Institute. https://biruni.tuik.gov.tr/medas/?locale=tr google scholar
- Ünlülata, Ü, Oğuz, T, Latif, M A, Özsoy, E, 1990. On the Physical Oceanography of the Turkish Straits, in: Pratt L J (Ed.), The Physical Oceanography of Sea Straits. Springer Netherlands: Dordrecht, pp. 25-60. google scholar
- Vieno, N, Sillanpââ, M, 2014. Fate of diclofenac in municipal wastewater treatment plant — A review. Envi-ronment International 69:28-39. google scholar
- Weigel, S, Kuhlmann, J, Hühnerfuss, H, 2002. Drugs and personal care products as ubiquitous pollutants: occurrence and distribution of clofibric acid, caffeine and DEET in the North Sea. Science of The Total Environment 295:131-141. google scholar
- Wilkinson, J, Hooda, P S, Barker, J, Barton, S, Swinden, J, 2017. Occurrence, fate and transformation of emer-ging contaminants in water: An overarching review of the field. Environmental Pollution 231:954-970. google scholar
- Wille, K, Kiebooms, J A, Claessens, M, Rappe, K, Vanden Bussche, J, Noppe, H, Van Praet, N, De Wulf, E, Van Caeter, P, Janssen, C R, De Brabander, H F, Vanhaecke, L, 2011. Development of analytical strategies using U-HPLC-MS/MS and LC-ToF-MS for the quantification of micropollutants in marine organisms. Analytical and bioanalytical chemistry 400:1459-1472. google scholar
- Wolecki, D, Caban, M, Pazdro, K, Mulkiewicz, E, Stepnowski, P, Kumirska, J, 2019. Simultaneous determina-tion of non-steroidal anti-inflammatory drugs and natural estrogens in the mussels Mytilus edulis trossulus. Talanta 200:316-323. google scholar
- Wu, M, Xiang, J, Que, C, Chen, F, Xu, G, 2015. Occurrence and fate of psychiatric pharmaceuticals in the urban water system of Shanghai, China. Chemosphere 138:486-493. google scholar
- Xie, H, Hao, H, Xu, N, Liang, X, Gao, D, Xu, Y, Gao, Y, Tao, H, Wong, M, 2019. Pharmaceuticals and personal care products in water, sediments, aquatic organisms, and fish feeds in the Pearl River Delta: Occurrence, distribution, potential sources, and health risk assessment. Science of The Total Environment 659:230-239. google scholar
- Xie, Z, Lu, G, Liu, J, Yan, Z, Ma, B, Zhang, Z, Chen, W, 2015. Occurrence, bioaccumulation, and trophic magnification of pharmaceutically active compounds in Taihu Lake, China. Chemosphere 138:140-147. google scholar
- Xie, Z, Lu, G, Yan, Z, Liu, J, Wang, P, Wang, Y, 2017. Bioaccumulation and trophic transfer of pharmaceuticals in food webs from a large freshwater lake. Environmental Pollution 222:356-366. google scholar
- Xu, E G, Ho, P W-L, Tse, Z, Ho, S-L, Leung, K M Y, 2016. Revealing ecological risks of priority endocrine disrupting chemicals in four marine protected areas in Hong Kong through an integrative approach. Envi-ronmental Pollution 215:103-112. google scholar
- Yamamoto, H, Nakamura, Y, Moriguchi, S, Nakamura, Y, Honda, Y, Tamura, I, Hirata, Y, Hayashi, A, Sekizawa, J, 2009. Persistence and partitioning of eight selected pharmaceuticals in the aquatic environment: Labora-tory photolysis, biodegradation, and sorption experiments. Water Research 43:351-362. google scholar
- Yang, J, Li, H, Ran, Y, Chan, K, 2014. Distribution and bioconcentration of endocrine disrupting chemicals in surface water and fish bile of the Pearl River Delta, South China. Chemosphere 107:439-446. google scholar
- Yılmaz, A, Tolun, L G, Okay, O S, 2019. Pollution and toxicity of sediment in potential dredging sites of the Sea of Marmara, Turkey. Journal of Environmental Science and Health, Part A 54:1206-1218. google scholar
- Ying, G-G, Kookana, R S, Dillon, P, 2003. Sorption and degradation of selected five endocrine disrupting che-micals in aquifer material. Water Research 37:3785-3791. google scholar
- Yücesoy Eryılmaz, F, Ergin, M, 1992. Heavy-metal geochemistry of surface sediments from the southern The Black Sea shelf and upper slope. Chemical Geology 99:265-287. google scholar
- Zhang, A, Li, Y, Chen, L, 2014. Distribution and seasonal variation of estrogenic endocrine disrupting compoun-ds, N-nitrosodimethylamine, and N-nitrosodimethylamine formation potential in the Huangpu River, China. Journal of environmental sciences (China) 26:1023-1033. google scholar
- Zhou, X, Yang, Z, Luo, Z, Li, H, Chen, G, 2019a. Endocrine disrupting chemicals in wild freshwater fishes: Species, tissues, sizes and human health risks. Environmental Pollution 244:462-468. google scholar
- Zhou, X, Yang, Z, Luo, Z, Li, H, Chen, G, 2019b. Endocrine disrupting chemicals in wild freshwater fishes: Spe cies, tissues, sizes and human health risks. Environmental pollution (Barking, Essex : 1987) 244:462-468. google scholar
- Zuo, Y, Zhang, K, Deng, Y, 2006. Occurrence and photochemical degradation of 17alpha-ethinylestradiol in Acushnet River Estuary. Chemosphere 63:1583-1590. google scholar