Journal of Literature Pharmacy Sciences

Antidepresanların Biyoakümülasyonuna Bağlı Ekotoksisite Riski: Sistematik Derleme
Risk of Ecotoxicity Due to Bioaccumulation of Antidepressants: Systematic Review
Hande YÜCEa, Songül ÜNÜVARa
aİnönü Üniversitesi Eczacılık Fakültesi, Farmasötik Toksikoloji ABD, Malatya, Türkiye
J Lit Pharm Sci. 2022;11(2):152-8
doi: 10.5336/pharmsci.2021-87716
Article Language: TR
Full Text
ÖZET
 İlaçlar, önemli çevresel kirleticiler arasında yer almaktadırlar. Antidepresan ilaçlar, hem yer altı hem de yer üstü sularında sıklıkla rastlanan kontaminantlardır. Antidepresan ilaçların su canlılarında tespit edilmesinin 2 nedeni vardır. Birincisi dünya genelinde yaygın kullanımları, ikincisi ise su canlılarının farklı dokularında birikmeleridir. Bazı balıklar ve yumuşakçalar gibi endemik su hayvanları, dokularında biyolojik olarak farklı antidepresanları biriktirmektedirler. Bu nedenle hedef olmayan birçok organizmayı etkileme potansiyeline sahiptirler. Antidepresanlar, dopamin, norepinefrin ve serotonin gibi nörotransmitterlerle etkileşime girerek santral sinir sistemini doğrudan etkileyen ilaçlardır. Su canlılarında, bu etkilerinin dışında da etkileri gözlenmektedir. Bu ilaçların dünya çapında artan kullanımına bağlı olarak, kentsel sularda, yer altı sularında, nehirlerlerde ve okyanuslarda yaygın tespit edilmektedirler. Ayrıca şu anda mevcut olan atık su arıtma tesisleri, ilaç kalıntılarını uzaklaştıracak şekilde dizayn edilmemiştir. Sulardaki ilaç kontaminasyonu, önümüzdeki yıllarda artacak gibi görünmektedir. Çünkü mevcut koronavirüs hastalığı-2019 pandemisi, dünya çapında genel depresyon ve anksiyeteyi tetikleyerek, antidepresan kullanımını ve dolayısıyla çevrede tespit edilen konsantrasyonlarını artırmıştır. Çevresel ilaç kontaminasyonu, bilimsel belirsizliklerin eşlik ettiği yaygın bir sorundur. Olası çözümler arasında, ilaçları akılcı kullanmak, çevre dostu ilaçlar reçete etmek, biyolojik olarak daha kolay parçalanan farmasötikler tasarlamak, çevre ve sağlık bilimleri arasındaki koordinasyonu ve iş birliğini geliştirmek sayılabilir. Bu derlemede, bazı antidepresanların yer altı ve yer üstü sulardaki kontaminasyonuna bağlı su canlıları üzerindeki biyoakümülasyonundan ve ekotoksikolojik etkilerinden bahsedilmektedir.

Anahtar Kelimeler: Antidepresanlar; çevre kirleticileri; ilaç kontaminasyonu; biyoakümülasyon
ABSTRACT
 Drugs are among the important environmental pollutants. Antidepressant drugs are frequently found contaminants in both ground and surface waters. There are 2 reasons why antidepressant drugs are detected in aquatic organisms. The first is their widespread use throughout the world, and the second is their accumulation in different tissues of aquatic organisms. Endemic aquatic animals, such as some fish and mollusks, accumulate biologically different antidepressants in their tissues. Therefore, they have the potential to affect many non-target organisms. Antidepressants are drugs that directly affect the central nervous system by interacting with neurotransmitters such as dopamine, norepinephrine, and serotonin. Apart from these effects, effects are also observed in aquatic organisms. Due to the increasing use of these drugs worldwide, they are widely detected in urban waters, groundwater, rivers and oceans. In addition, currently existing wastewater treatment plants are not designed to remove drug residues. Drug contamination in waters is likely to increase in the coming years. Because the current coronavirus disease-2019 pandemic has triggered general depression and anxiety worldwide, increasing the use of antidepressants and thus their concentrations detected in the environment. Environmental drug contamination is a common problem accompanied by scientific uncertainties. Possible solutions include using drugs rationally, prescribing environmentally friendly drugs, designing more biodegradable pharmaceuticals, and improving coordination and collaboration between environmental and health sciences. In this review, the bioaccumulation and ecotoxicological effects of some antidepressants on aquatic organisms due to the contamination of underground and surface waters are mentioned.

Keywords: Antidepressants; environmental pollutants; drug contamination; bioaccumulation
REFERENCES:
  1. Grabicova K, Grabic R, Fedorova G, Fick J, Cerveny D, Kolarova J, et al. Bioaccumulation of psychoactive pharmaceuticals in fish in an effluent dominated stream. Water Res. 2017;124:654-62. [Crossref]  [PubMed] 
  2. Miller TH, Bury NR, Owen SF, MacRae JI, Barron LP. A review of the pharmaceutical exposome in aquatic fauna. Environ Pollut. 2018;239:129-46. [Crossref]  [PubMed]  [PMC] 
  3. Fatta-Kassinos D, Meric S, Nikolaou A. Pharmaceutical residues in environmental waters and wastewater: current state of knowledge and future research. Anal Bioanal Chem. 2011;399(1):251-75. [Crossref]  [PubMed] 
  4. Rossi A, Barraco A, Donda P. Fluoxetine: a review on evidence based medicine. Ann Gen Hosp Psychiatry. 2004;3(1):2. [Crossref]  [PubMed]  [PMC] 
  5. EU (2020). Commission Implementing Decision (EU) 2020/1161 of 4 August 2020 establishing a watch list of substances for union-wide monitoring in the field of water policy pursuant to Directive 2008/105/EC of the European Parliament and of the Council. Off J Eur Union L, 257/32. 2020. [Link] 
  6. Silva VH, Dos Santos Batista AP, Silva Costa Teixeira AC, Borrely SI. Degradation and acute toxicity removal of the antidepressant Fluoxetine (Prozac(®)) in aqueous systems by electron beam irradiation. Environ Sci Pollut Res Int. 2016;23(12):11927-36. [Crossref]  [PubMed] 
  7. Lajeunesse A, Smyth SA, Barclay K, Sauvé S, Gagnon C. Distribution of antidepressant residues in wastewater and biosolids following different treatment processes by municipal wastewater treatment plants in Canada. Water Res. 2012;46(17):5600-12. [Crossref]  [PubMed] 
  8. Kostich MS, Batt AL, Lazorchak JM. Concentrations of prioritized pharmaceuticals in effluents from 50 large wastewater treatment plants in the US and implications for risk estimation. Environ Pollut. 2014;184:354-9. [Crossref]  [PubMed] 
  9. González Alonso S, Catalá M, Maroto RR, Gil JL, de Miguel AG, Valcárcel Y. Pollution by psychoactive pharmaceuticals in the Rivers of Madrid metropolitan area (Spain). Environ Int. 2010;36(2):195-201. [Crossref]  [PubMed] 
  10. Oakes KD, Coors A, Escher BI, Fenner K, Garric J, Gust M, et al. Environmental risk assessment for the serotonin re-uptake inhibitor fluoxetine: Case study using the European risk assessment framework. Integr Environ Assess Manag. 2010;6 Suppl:524-39. [Crossref]  [PubMed] 
  11. Grzesiuk M, Pawelec A. Fluoxetine results in misleading conclusions on fish behavior. Ecol Evol. 2021;11(14):9707-14. [Crossref]  [PubMed]  [PMC] 
  12. Ansai S, Hosokawa H, Maegawa S, Kinoshita M. Chronic fluoxetine treatment induces anxiolytic responses and altered social behaviors in medaka, Oryzias latipes. Behav Brain Res. 2016;303:126-36. [Crossref]  [PubMed] 
  13. Campos B, Rivetti C, Kress T, Barata C, Dircksen H. Depressing antidepressant: fluoxetine affects serotonin neurons causing adverse reproductive responses in daphnia magna. Environ Sci Technol. 2016;50(11):6000-7. [Crossref]  [PubMed] 
  14. Minguez L, Farcy E, Ballandonne C, Lepailleur A, Serpentini A, Lebel JM, et al. Acute toxicity of 8 antidepressants: what are their modes of action? Chemosphere. 2014;108:314-9. [Crossref]  [PubMed] 
  15. Flaherty CM, Dodson SI. Effects of pharmaceuticals on Daphnia survival, growth, and reproduction. Chemosphere. 2005;61(2):200-7. [Crossref]  [PubMed] 
  16. Ding J, Zou H, Liu Q, Zhang S, Mamitiana Razanajatovo R. Bioconcentration of the antidepressant fluoxetine and its effects on the physiological and biochemical status in Daphnia magna. Ecotoxicol Environ Saf. 2017;142:102-9. [Crossref]  [PubMed] 
  17. Meredith-Williams M, Carter LJ, Fussell R, Raffaelli D, Ashauer R, Boxall AB. Uptake and depuration of pharmaceuticals in aquatic invertebrates. Environ Pollut. 2012;165:250-8. [Crossref]  [PubMed] 
  18. Mesquita SR, Guilhermino L, Guimarães L. Biochemical and locomotor responses of Carcinus maenas exposed to the serotonin reup take inhibitor fluoxetine. Chemosphere. 2011;85(6):967-76. [Crossref]  [PubMed] 
  19. Katzman MA, Jacobs L. Venlafaxine in the treatment of panic disorder. Neuropsychiatr Dis Treat. 2007;3(1):59-67. [Crossref]  [PubMed]  [PMC] 
  20. Ziegler M, Eckstein H, Ottmann S, Reinelt L, Stepinski S, Köhler HR. Biochemical and cellular biomarkers in brown trout (Salmo trutta f. fario) in response to the antidepressants citalopram and venlafaxine. Environ Sci Eur. 2020;32(1):1-15. [Crossref] 
  21. Fernández-Rubio J, Rodríguez-Gil JL, Postigo C, Mastroianni N, López de Alda M, Barceló D, et al. Psychoactive pharmaceuticals and illicit drugs in coastal waters of North-Western Spain: Environmental exposure and risk assessment. Chemosphere. 2019;224:379-89. [Crossref]  [PubMed] 
  22. DrugBank [Internet]. [Cited: ]. Venlafaxine. Available from: [Link] 
  23. Lacaze E, Pédelucq J, Fortier M, Brousseau P, Auffret M, Budzinski H, et al. Genotoxic and immunotoxic potential effects of selected psychotropic drugs and antibiotics on blue mussel (Mytilus edulis) hemocytes. Environ Pollut. 2015;202:177-86. [Crossref]  [PubMed] 
  24. Sharbaf Shoar N, Fariba KA, Padhy RK. Citalopram. 2021. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022. [PubMed] 
  25. Schultz MM, Furlong ET, Kolpin DW, Werner SL, Schoenfuss HL, Barber LB, et al. Antidepressant pharmaceuticals in two U.S. effluent-impacted streams: occurrence and fate in water and sediment, and selective uptake in fish neural tissue. Environ Sci Technol. 2010;44(6):1918-25. [Crossref]  [PubMed] 
  26. Silva LJ, Pereira AM, Meisel LM, Lino CM, Pena A. A one-year follow-up analysis of antidepressants in Portuguese wastewaters: occurrence and fate, seasonal influence, and risk assessment. Sci Total Environ. 2014;490:279-87. [Crossref]  [PubMed] 
  27. Fick J, Söderström H, Lindberg RH, Phan C, Tysklind M, Larsson DG. Contamination of surface, ground, and drinking water from pharmaceutical production. Environ Toxicol Chem. 2009;28(12):2522-7. [Crossref]  [PubMed] 
  28. Martin JM, Saaristo M, Bertram MG, Lewis PJ, Coggan TL, Clarke BO, et al. The psychoactive pollutant fluoxetine compromises antipredator behaviour in fish. Environ Pollut. 2017;222:592-9. [Crossref]  [PubMed] 
  29. Kellner M, Porseryd T, Porsch-Hällström I, Borg B, Roufidou C, Olsén KH. Developmental exposure to the SSRI citalopram causes long-lasting behavioural effects in the three-spined stickleback (Gasterosteus aculeatus). Ecotoxicology. 2018;27(1):12-22. [Crossref]  [PubMed]  [PMC] 
  30. Ziegler M, Knoll S, Köhler HR, Tisler S, Huhn C, Zwiener C, et al. Impact of the antidepressant citalopram on the behaviour of two different life stages of brown trout. PeerJ. 2020;8:e8765. [Crossref]  [PubMed]  [PMC] 
  31. Ma LD, Li J, Li JJ, Liu M, Yan DZ, Shi WY, et al. Occurrence and source analysis of selected antidepressants and their metabolites in municipal wastewater and receiving surface water. Environ Sci Process Impacts. 2018;20(7):1020-9. [Crossref]  [PubMed] 
  32. Ziarrusta H, Mijangos L, Izagirre U, Plassmann MM, Benskin JP, Anakabe E, et al. Bioconcentration and Biotransformation of Amitriptyline in Gilt-Head Bream. Environ Sci Technol. 2017;51(4):2464-71. [Crossref]  [PubMed] 
  33. Zenker A, Cicero MR, Prestinaci F, Bottoni P, Carere M. Bioaccumulation and biomagnification potential of pharmaceuticals with a focus to the aquatic environment. J Environ Manage. 2014;133:378-87. [Crossref]  [PubMed] 
  34. Lajeunesse A, Gagnon C, Gagné F, Louis S, Cejka P, Sauvé S. Distribution of antidepressants and their metabolites in brook trout exposed to municipal wastewaters before and after ozone treatment--evidence of biological effects. Chemosphere. 2011;83(4):564-71. [Crossref]  [PubMed] 
  35. Uhr M, Grauer MT, Yassouridis A, Ebinger M. Blood-brain barrier penetration and pharmacokinetics of amitriptyline and its metabolites in p-glycoprotein (abcb1ab) knock-out mice and controls. J Psychiatr Res. 2007;41(1-2):179-88. [Crossref]  [PubMed] 
  36. Guo W, Hossain MS, Kubec J, Grabicová K, Randák T, Buřič M, et al. Psychoactive compounds at environmental concentration alter burrowing behavior in the freshwater crayfish. Sci Total Environ. 2020;711:135138. [Crossref]  [PubMed] 
  37. Chen H, Liang X, Gu X, Zeng Q, Mao Z, Martyniuk CJ. Environmentally relevant concentrations of sertraline disrupts behavior and the brain and liver transcriptome of juvenile yellow catfish (Tachysurus fulvidraco): Implications for the feeding and growth axis. J Hazard Mater. 2021;409:124974. [Crossref]  [PubMed] 
  38. Mole RA, Brooks BW. Global scanning of selective serotonin reuptake inhibitors: occurrence, wastewater treatment and hazards in aquatic systems. Environ Pollut. 2019;250:1019-31. [Crossref]  [PubMed] 
  39. Styrishave B, Halling-Sørensen B, Ingerslev F. Environmental risk assessment of three selective serotonin reuptake inhibitors in the aquatic environment: a case study including a cocktail scenario. Environ Toxicol Chem. 2011;30(1):254-61. [Crossref]  [PubMed] 
  40. Valenti TW, Gould GG, Berninger JP, Connors KA, Keele NB, Prosser KN, et al. Human therapeutic plasma levels of the selective serotonin reuptake inhibitor (SSRI) sertraline decrease serotonin reuptake transporter binding and shelter-seeking behavior in adult male fathead minnows. Environ Sci Technol. 2012;46(4):2427-35. [Crossref]  [PubMed]  [PMC] 
  41. Bossus MC, Guler YZ, Short SJ, Morrison ER, Ford AT. Behavioural and transcriptional changes in the amphipod Echinogammarus marinus exposed to two antidepressants, fluoxetine and sertraline. Aquat Toxicol. 2014;151:46-56. [Crossref]  [PubMed] 
  42. Dorelle LS, Da Cu-a RH, Sganga DE, Rey Vázquez G, López Greco L, Lo Nostro FL. Fluoxetine exposure disrupts food intake and energy storage in the cichlid fish Cichlasoma dimerus (Teleostei, Cichliformes). Chemosphere. 2020;238:124609. [Crossref]  [PubMed] 
  43. Miotto K, Cho AK, Khalil MA, Blanco K, Sasaki JD, Rawson R. Trends in tramadol: pharmacology, metabolism, and misuse. Anesth Analg. 2017;124(1):44-51. [Crossref]  [PubMed] 
  44. Bigal LM, Bibeau K, Dunbar S. Tramadol prescription over a 4-year period in the USA. Curr Pain Headache Rep. 2019;23(10):76. [Crossref]  [PubMed] 
  45. Grabicová K, Grabic R, Fedorova G, Vojs Staňová A, Bláha M, Randák T, et al. Water reuse and aquaculture: Pharmaceutical bioaccumulation by fish during tertiary treatment in a wastewater stabilization pond. Environ Pollut. 2020;267:115593. [Crossref]  [PubMed] 
  46. Bláha M, Grabicova K, Shaliutina O, Kubec J, Randák T, Zlabek V, et al. Foraging behaviour of top predators mediated by pollution of psychoactive pharmaceuticals and effects on ecosystem stability. Sci Total Environ. 2019;662:655-61. [Crossref]  [PubMed] 
  47. Douda K, Zhao S, Vodáková B, Horký P, Grabicová K, Božková K, et al. Host-parasite interaction as a toxicity test endpoint using asymmetrical exposures. Aquat Toxicol. 2019;211:173-80. [Crossref]  [PubMed] 
  48. Sehonova P, Plhalova L, Blahova J, Doubkova V, Prokes M, Tichy F, et al. Toxicity of naproxen sodium and its mixture with tramadol hydrochloride on fish early life stages. Chemosphere. 2017;188:414-23. [Crossref]  [PubMed] 
  49. Santos MES, Horký P, Grabicová K, Hubená P, Slavík O, Grabic R, et al. Traces of tramadol in water impact behaviour in a native European fish. Ecotoxicol Environ Saf. 2021;212:111999. [Crossref]  [PubMed] 
  50. Wawryniuk M, Pietrzak A, Nałęcz-Jawecki G. Evaluation of direct and indirect photodegradation of mianserin with high-performance liquid chromatography and short-term bioassays. Ecotoxicol Environ Saf. 2015;115:144-51. [Crossref]  [PubMed] 
  51. Nałęcz-Jawecki G, Wawryniuk M, Giebułtowicz J, Olkowski A, Drobniewska A. Influence of Selected Antidepressants on the Ciliated Protozoan Spirostomum ambiguum: Toxicity, Bioaccumulation, and Biotransformation Products. Molecules. 2020;25(7):1476. [Crossref]  [PubMed]  [PMC] 

.: Up To Date

.: Process List

Login

 Forgot your password?

 New Registration  

Contact

Ortadoğu Reklam Tanıtım Yayıncılık Turizm Eğitim İnşaat Sanayi ve Ticaret A.Ş.

.: Address

Turkocagi Caddesi No:30 06520 Balgat / ANKARA
Phone: +90 312 286 56 56
Fax: +90 312 220 04 70
E-mail: info@turkiyeklinikleri.com

.: Manuscript Editing Department

Phone: +90 312 286 56 56/ 2
E-mail: yaziisleri@turkiyeklinikleri.com

.: English Language Redaction

Phone: +90 312 286 56 56/ 145
E-mail: tkyayindestek@turkiyeklinikleri.com

.: Marketing Sales-Project Department

Phone: +90 312 286 56 56/ 142
E-mail: reklam@turkiyeklinikleri.com

.: Subscription and Public Relations Department

Phone: +90 312 286 56 56/ 118
E-mail: abone@turkiyeklinikleri.com

.: Customer Services

Phone: +90 312 286 56 56/ 118
E-mail: satisdestek@turkiyeklinikleri.com

1. TERMS OF USE

1.1. To use the web pages with http://www.turkiyeklinikleri.com domain name or the websites reached through the sub domain names attached to the domain name (They will be collectively referred as "SITE"), please read the conditions below. If you do not accept these terms, please cease to use the "SITE." "SITE" owner reserves the right to change the information on the website, forms, contents, the "SITE," "SITE" terms of use anytime they want.

1.2. The owner of the "SITE" is Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. (From now on it is going to be referred as "Turkiye Klinikleri", shortly) and it resides at Turkocagi cad. No:30, 06520 Balgat Ankara. The services in the "SITE" are provided by "Turkiye Klinikleri."

1.3. Anyone accessing the "SITE" with or without a fee whether they are a natural person or a legal identity is considered to agree these terms of use. In this contract hereby, "Turkiye Klinikleri" may change the stated terms anytime. These changes will be published in the "SITE" periodically and they will be valid when they are published. Any natural person or legal identity benefiting from and reaching to the "SITE" are considered to be agreed to any change on hereby contract terms done by "Turkiye Klinikleri."

1.4. The "Terms of Use" hereby is published in the website with the last change on March 30th 2014 and the "SITE" is activated by enabling the access to everyone. The "Terms of Use" hereby is also a part of the any "USER Contract" was and/or will be done with the users using "Turkiye Klinikleri" services with or without a fee an inseparable.

2. DEFINITIONS

2.1. "SITE": A website offering different kind of services and context with a certain frame determined by "Turkiye Klinikleri" and it is accessible on-line on http://www.turkiyeklinikleri.com domain name and/or subdomains connected to the domain name.

2.2. USER: A natural person or a legal identity accessing to the "SITE" through online settings.

2.3. LINK: A link enabling to access to another website through the "SITE", the files, the context or through another website to the "SITE", the files and the context.

2.4. CONTEXT: Any visual, literary and auditory images published in the "Turkiye Klinikleri", "SITE" and/or any website or any accessible information, file, picture, number/figures, price, etc.

2.5. "USER CONTRACT": An electronically signed contract between a natural or a legal identity benefiting from special services "Turkiye Klinikleri" will provide and "Turkiye Klinikleri".

3. SCOPE OF THE SERVICES

3.1. "Turkiye Klinikleri" is completely free to determine the scope and quality of the services via the "SITE".

3.2. To benefit the services of "Turkiye Klinikleri" "SITE", the "USER" must deliver the features that will be specified by "Turkiye Klinikleri". "Turkiye Klinikleri" may change this necessity any time single-sided.

3.3. Not for a limited number, the services "Turkiye Klinikleri" will provide through the "SITE" for a certain price or for free are;

- Providing scientific articles, books and informative publications for health industry.

- Providing structural, statistical and editorial support to article preparation stage for scientific journals.

4. GENERAL PROVISIONS

4.1. "Turkiye Klinikleri" is completely free to determine which of the services and contents provided in the "SITE" will be charged.

4.2. People benefiting from the services provided by "Turkiye Klinikleri" and using the website can use the "SITE" only according to the law and only for personal reasons. Users have the criminal and civil liability for every process and action they take in the "SITE". Every USER agrees, declares and undertakes that they will not proceed by any function or action infringement of rights of "Turkiye Klinikleri"s and/or other third parties', they are the exclusive right holder on usage, processing, storage, made public and revealing any written, visual or auditory information reported to Turkiye Klinikleri" and/or "SITE" to the third parties. "USER" agrees and undertakes that s/he will not duplicate, copy, distribute, process, the pictures, text, visual and auditory images, video clips, files, databases, catalogs and lists within the "SITE", s/he will not be using these actions or with other ways to compete with "Turkiye Klinikleri", directly or indirectly.

4.3. The services provided and the context published within the "SITE" by third parties is not under the responsibility of "Turkiye Klinikleri", institutions collaborated with "Turkiye Klinikleri", "Turkiye Klinikleri" employee and directors, "Turkiye Klinikleri" authorized salespeople. Commitment to accuracy and legality of the published information, context, visual and auditory images provided by any third party are under the full responsibility of the third party. "Turkiye Klinikleri" does not promise and guarantee the safety, accuracy and legality of the services and context provided by a third party.

4.4. "USER"s cannot act against "Turkiye Klinikleri", other "USER"s and third parties by using the "SITE". "Turkiye Klinikleri" has no direct and/or indirect responsibility for any damage a third party suffered or will suffer regarding "USER"s actions on the "SITE" against the rules of the hereby "Terms of Use" and the law.

4.5. "USER"s accept and undertake that the information and context they provided to the "SITE" are accurate and legal. "Turkiye Klinikleri" is not liable and responsible for promising and guaranteeing the verification of the information and context transmitted to "Turkiye Klinikleri" by the "USER"s, or uploaded, changed and provided through the "SITE" by them and whether these information are safe, accurate and legal.

4.6. "USER"s agree and undertake that they will not perform any action leading to unfair competition, weakening the personal and commercial credit of "Turkiye Klinikleri" and a third party,  encroaching and attacking on personal rights within the "SITE" in accordance with the Turkish Commercial Code Law.

4.7. "Turkiye Klinikleri" reserves the right to change the services and the context within the "SITE"  anytime. "Turkiye Klinikleri" may use this right without any notification and timelessly. "USER"s have to make the changes and/or corrections "Turkiye Klinikleri" required immediately. Any changes and/or corrections that are required by "Turkiye Klinikleri", may be made by "Turkiye Klinikleri" when needed. Any harm, criminal and civil liability resulted or will result from changes and/or corrections required by "Turkiye Klinikleri" and were not made on time by the "USER"s belongs completely to the users.

4.8. "Turkiye Klinikleri" may give links through the "SITE" to other websites and/or "CONTEXT"s and/or folders that are outside of their control and owned and run by third parties. These links are provided for ease of reference only and do not hold qualification for support the respective web SITE or the admin or declaration or guarantee for the information inside. "Turkiye Klinikleri" does not hold any responsibility over the web-sites connected through the links on the "SITE", folders and context, the services or products on the websites provided through these links or their context.

4.9. "Turkiye Klinikleri" may use the information provided to them by the "USERS" through the "SITE" in line with the terms of the "PRIVACY POLICY" and "USER CONTRACT". It may process the information or classify and save them on a database. "Turkiye Klinikleri" may also use the USER's or visitor's identity, address, e-mail address, phone number, IP number, which sections of the "SITE" they visited, domain type, browser type, date and time information to provide statistical evaluation and customized services.

5. PROPRIETARY RIGHTS

5.1. The information accessed through this "SITE" or provided by the users legally and all the elements (including but not limited to design, text, image, html code and other codes) of the "SITE" (all of them will be called as studies tied to "Turkiye Klinikleri"s copyrights) belongs to "Turkiye Klinikleri". Users do not have the right to resell, process, share, distribute, display or give someone permission to access or to use the "Turkiye Klinikleri" services, "Turkiye Klinikleri" information and the products under copyright protection by "Turkiye Klinikleri". Within hereby "Terms of Use" unless explicitly permitted by "Turkiye Klinikleri" nobody can reproduce, process, distribute or produce or prepare any study from those under "Turkiye Klinikleri" copyright protection.

5.2. Within hereby "Terms of Use", "Turkiye Klinikleri" reserves the rights for "Turkiye Klinikleri" services, "Turkiye Klinikleri" information, the products associated with "Turkiye Klinikleri" copyrights, "Turkiye Klinikleri" trademarks, "Turkiye Klinikleri" trade looks or its all rights for other entity and information it has through this website unless it is explicitly authorized by "Turkiye Klinikleri".

6. CHANGES IN THE TERMS OF USE

"Turkiye Klinikleri" in its sole discretion may change the hereby "Terms of Use" anytime announcing within the "SITE". The changed terms of the hereby "Terms of Use" will become valid when they are announced. Hereby "Terms of Use" cannot be changed by unilateral declarations of users.

7. FORCE MAJEURE

"Turkiye Klinikleri" is not responsible for executing late or never of this hereby "Terms of Use", privacy policy and "USER Contract" in any situation legally taken into account as force majeure. Being late or failure of performance or non-defaulting of this and similar cases like this will not be the case from the viewpoint of "Turkiye Klinikleri", and "Turkiye Klinikleri" will not have any damage liability for these situations. "Force majeure" term will be regarded as outside of the concerned party's reasonable control and any situation that "Turkiye Klinikleri" cannot prevent even though it shows due diligence. Also, force majeure situations include but not limited to natural disasters, rebellion, war, strike, communication problems, infrastructure and internet failure, power cut and bad weather conditions.

8. LAW AND AUTHORISATION TO FOLLOW

Turkish Law will be applied in practicing, interpreting the hereby "Terms of Use" and managing the emerging legal relationships within this "Terms of Use" in case of finding element of foreignness, except for the rules of Turkish conflict of laws. Ankara Courts and Enforcement Offices are entitled in any controversy happened or may happen due to hereby contract.

9. CLOSING AND AGREEMENT

Hereby "Terms of Use" come into force when announced in the "SITE" by "Turkiye Klinikleri". The users are regarded to agree to hereby contract terms by using the "SITE". "Turkiye Klinikleri" may change the contract terms and the changes will be come into force by specifying the version number and the date of change on time it is published in the "SITE".

 

30.03.2014

Privacy Policy

We recommend you to read the terms of use below before you visit our website. In case you agree these terms, following our rules will be to your favor. Please read our Terms of Use thoroughly.

www.turkiyeklinikleri.com website belongs to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. and is designed in order to inform physicians in the field of health

www.turkiyeklinikleri.com cannot reach to user’s identity, address, service providers or other information. The users may send this information to the website through forms if they would like to. However, www.turkiyeklinikleri.com may collect your hardware and software information. The information consists of your IP address, browser type, operating system, domain name, access time, and related websites. www.turkiyeklinikleri.com cannot sell the provided user information (your name, e-mail address, home and work address, phone number) to the third parties, publish it publicly, or keep it in the website. Gathered information has a directing feature to be a source for the website’s visitor profile, reporting and promotion of the services.

www.turkiyeklinikleri.com uses the taken information:

-To enhance, improve and maintain the quality of the website

-To generate visitor’s profile and statistical data

-To determine the tendency of the visitors on using our website

-To send print publications/correspondences

-To send press releases or notifications through e-mail

-To generate a list for an event or competition

By using www.turkiyeklinikleri.com you are considered to agree that;

-Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. cannot be hold responsible for any user’s illegal and immoral behavior,

-Terms of use may change from time to time,

-It is not responsible for other websites’ contents it cannot control or the harms they may cause although it uses the connection they provided.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

-Information with wrong, incomplete, deceiving or immoral expressions is recorded to the website,

-Proclamation, advertisement, announcement, libelous expressions are used against natural person or legal identity,

-During various attacks to the website,

-Disruption of the website because of a virus.

Written, visual and audible materials of the website, including the code and the software are under protection by legal legislation.

Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

All rights of the software and the design of the website belong to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. will be pleased to hear your comments about our terms of use. Please share the subjects you think may enrich our website or if there is any problem regarding our website.

info@turkiyeklinikleri.com