EcologyEcologyЭкология0367-05973034-6142The Russian Academy of Sciences69704810.31857/S0367059725040019ArticlesСтатьиResearch ArticlePharmaceuticals in the environment: Current state of research and overcoming collective problemsФармацевтические препараты в окружающей среде: современное состояние исследований и преодоление коллективных проблемIvshinaI. B.ИвшинаИ. Б.ivshina@iegm.ruPerm Federal Research Center, Ural Branch, Russian Academy of SciencesПермский федеральный исследовательский центр УрО РАН150820254NO4 (2025)№4 (2025)25328026112025Copyright ©; 2025, Russian Academy of SciencesCopyright ©; 2025, Российская академия наук2025Russian Academy of SciencesРоссийская академия наукhttps://transsyst.ru/0367-0597/article/view/697048

Environmental pollution by pharmaceuticals is a new global environmental problem that threatens human health and biota. The active ingredients of drugs are found in trace concentrations in aquatic and terrestrial ecosystems and are considered dangerous emergent pollutants. Their continuous emission into open ecosystems is uncontrolled, and detection has become possible due to the development of highly sensitive analytical methods. The review systematizes data on the occurrence of pharmaceutical micro-pollutants, their ecotoxicity, detoxification strategies, and modern methods of wastewater treatment and pharmaceutical waste disposal. Critical risk assessment requires constant updating of scientific information in order to develop effective measures to reduce the negative effects of pharmaceutical pollution. Specific steps are proposed to solve the problem in practice and minimize environmental damage.

Загрязнение окружающей среды фармацевтическими препаратами является новой глобальной экологической проблемой, угрожающей здоровью человека и биоте. Активные ингредиенты лекарств обнаруживаются в водных и наземных экосистемах в следовых концентрациях и относятся к опасным эмерджентным загрязнителям. Их непрерывное поступление в открытые экосистемы неконтролируемо, а выявление стало возможным благодаря развитию высокочувствительных аналитических методов. В обзоре систематизированы данные о распространенности фармацевтических микрозагрязнителей, их экотоксичности, стратегиях детоксикации и современных методах очистки сточных вод и утилизации фармотходов. Критическая оценка рисков требует постоянного обновления научной информации для выработки эффективных мер по снижению негативных последствий фармацевтического загрязнения. Предлагаются конкретные шаги для практического решения проблемы и минимизации экологического ущерба.

pharmaceutical pollutionenvironmental impactecotoxicitybioremediationRhodococcusфармацевтическое загрязнениевоздействие на окружающую средуэкотоксичностьбиоремедиацияRhodococcusРабота выполнена в рамках государственного задания (тема № 124020500028-4) Министерства науки и высшего образования Российской Федерации.Баренбойм Г.М., Чиганова М.А.Загрязнение природных вод лекарствами. М.: Наука, 2015. 283 с.Тюмина Е.А., Бажутин Г.А., Картагена Гомез А.д.П.и др. Нестероидные противовоспалительные средства как разновидность эмерджентных загрязнителей // Микробиология. 2020. Т. 89. № 2. С. 152–168. https://doi.org/10.31857/S0026365620020135Boxall A.B.A., Rudd M.A., Brooks B.W. et al. Pharmaceuticals and personal care products in the environment: What are the big questions? // Environ. Health Perspect. 2012. V. 120. № 9. P. 1221−1229. https://doi.org/10.1289/ehp.1104477Singh A., Saluja S. Microbial degradation of antibiotics from effluents // Environmental and Microbial Biotechnology. Singapore: Springer, 2021. P. 389–404. https://doi.org/10.1007/978-981-16-0518-5_15González-González R.B., Sharma P., Singh S.P. et al. Persistence, environmental hazards, and mitigation of pharmaceutically active residual contaminants from water matrices // Sci. Total Environ.2022. V. 108. P. 115–121. https://doi.org/10.1016/j.ibiod.2015.12.018Barathe P., Kaur K., Reddy S. et al. Antibiotic pollution and associated antimicrobial resistance in the environment // J. Hazard. Mater. Lett. 2024. V. 5. Art. 100105. https://doi.org/10.1016/j.hazl.2024.100105Blasco J., Trombini C. Ibuprofen and diclofenac in the marine environment – a critical review of their occurrence and potential risk for invertebrate species // Water Emerg. Contam. Nanoplastics. 2023. V. 2. Art. 14. https://doi.org/10.20517/wecn.2023.06Patel M., Kumar R., Kishor K. et al. Pharmaceuticals of emerging concern in aquatic systems: Chemistry, occurrence, effects, and removal methods // Chem. Rev. 2019. V. 119. № 6. P. 3510–3673. https://doi.org/10.1021/acs.chemrev.8b00299Majumder S., Chatterjee S., Basnet P. et al. ZnO based nanomaterials for photocatalytic degradation of aqueous pharmaceutical waste solutions – A contemporary review // Environ. Nanotechnol. Monit. Manag. 2020. V. 14. Art. 100386. https://doi.org/10.1016/j.enmm.2020.100386Wilkinson J.L., Boxall A.B., Kolpin D.W. et al. Pharmaceutical pollution of the world’s rivers // PNAS. 2022. V. 119. Art. e2113947119. https://doi.org/10.1073/pnas.2113947119Sapingi M.S.M., Khasawneh O.F.S., Palaniandy P. et al. Analytical techniques for the detection of pharmaceuticals in the environment // The Treatment of Pharmaceutical Wastewater: Innovative Technologies and the Adaption of Treatment Systems. Eds. Khan A.H., Khan N.A., Naushad Mu., Aziz H.A. Elsevier, 2023. P. 149−177. https://doi.org/10.1016/B978-0-323-99160-5.00003-5Muniandy Y., Mohamad S., Raoov M. Green and efficient magnetic micro-solid phase extraction utilizing tea waste impregnated with magnetic nanoparticles for the analysis of ibuprofen in water samples by using UV-vis spectrophotometry //RSC Adv. 2024. V. 14(17). P. 11977−11985. https://doi.org/10.1039/d4ra00940aWilkinson J.L., Thornhill I., Oldenkamp R. et al. Pharmaceuticals and personal care products in the aquatic environment: How can regions at risk be identified in the future? // Environ. Toxic. Chem. 2024. V. 43. P. 575–588. https://doi.org/10.1002/etc.5763aus der BeekT., Weber F.-A., Bergmann A. et al. Pharmaceuticals in the environment – Global occurrences and perspectives // Environ. Toxicol. Chem. 2016. V. 35. № 4. P. 823–835. https://doi.org/10.1002/etc.3339Branchet P., Arpin-Pont L., Piram A. et al. Pharmaceuticals in the marine environment: What are the present challenges in their monitoring? // Sci. Total Environ. 2021. V. 766. Art. 142644. https://doi.org/10.1016/j.scitotenv.2020.142644Boxall A.B.A., Brooks B.W. Pharmaceuticals and personal care products in the environment: what progress has been made in addressing the big research questions? // Environ. Toxicol. Chem. 2024. V. 43. № 3. P. 481–487. https://doi.org/10.1002/etc.5827Khan H.K., Abdur RehmanM.Y., Malik R.N. Fate and toxicity of pharmaceuticals in water environment: An insight on their occurrence in South Asia // J. Environ. Manage.2020. V. 271. Art. 111030. https://doi.org/10.1016/j.jenvman.2020.111030Kovacs E.D., Kovacs M.H., Barcelo D. et al.Nonsteroidal anti-inflammatory drugs impact the microbial community in three different soil types – a laboratory experiment// Case Stud. Chem. Environ. Eng. 2024. V. 10. Art. 100833. https://doi.org/10.1016/j.cscee.2024.100833Vaduganathan M., van Meijgaard J., Mehra M.R. et al. Prescription fill patterns for commonly used drugs during the COVID-19 pandemic in the United States // J. Am. Med. Assoc. 2020. V. 323(24). P. 2524–2526. https://doi.org/10.1001/jama.2020.9184Ammassari A., Di Filippo A., Trotta M.P. et al. Comparison of demand for drugs used for COVID-19 treatment and other drugs during the early phase of the COVID-19 pandemic in Italy // JAMA Netw. Open.2021. V. 4. № 2.Art. e2037060. https://doi.org/10.1001/jamanetworkopen.2020.37060Argaluza J., Domingo-Echaburu S., Orive G. et al. Environmental pollution with psychiatric drugs // World J. Psychiatr. 2021. V. 11. № 10. P. 791−804. https://doi.org/10.5498/wjp.v11.i10.791Jacob L., Bohlken J., Kostev K. What have we learned in the past year? A study on pharmacy purchases of psychiatric drugs from wholesalers in the days prior to the first and second COVID-19 lockdowns in Germany // J. Psychiatric Res. 2021. V. 140. P. 346−349. https://doi.org/10.1016/j.jpsychires.2021.05.073Stall N.M., Zipursky J.S., Rangrej J. et al. Assessment of psychotropic drug prescribing among nursing home residents in Ontario, Canada, during the COVID-19 pandemic // JAMA Intern. Med. 2021. V.181. № 6. P. 861−863. https://doi.org/10.1001/jamainternmed.2021.0224Martínez S.A.H., Melchor-Martínez E.M., González-González R.B. et al. Environmental concerns and bioaccumulation of psychiatric drugs in water bodies – Conventional versus biocatalytic systems of mitigation //Environ. Res. 2023. V. 229. № 21.Art. 115892. https://doi.org/10.1016/ j.envres.2023.115892Eapen J.V., Thomas S., Antony S. et al. A review of the effects of pharmaceutical pollutants on humans and aquatic ecosystem // Explor. Drug Sci. 2024. V. 2. P. 484–507. https://doi.org/10.37349/eds.2024.00058Caban M., Stepnowski P. How to decrease pharmaceuticals in the environment? A review //Environ. Chem. Lett. 2021. V. 19. № 4. P. 3115−3138. https://doi.org/10.1007/s10311-021-01194-yThe Global Use of Medicines 2024: Outlook to 2028. The IQVIA Institute. 2024. 27 p.Ternes T.A., Bonerz M., Schmidt T. Determination of neutral pharmaceuticals in wastewater and rivers by liquid chromatography-electrospray tandem mass spectrometry // J. Chromatogr. A. 2001. V. 938. № 1−2. P. 175−185. https://doi.org/10.1016/s0021-9673(01)01205-5World Health Organization. Pharmaceuticals in drinking water. Available from:https://www.who.int/water_sanitation_health/publications /2012/pharmaceuticals/en/ [cited 12 June 2025].Onesios-Barry K.M., Berry D., Proescher J.B. et al. Removal of pharmaceuticals and personal care products during water recycling: microbial community structure and effects of substrate concentration // Appl. Environ. Microbiol. 2014. V. 80. № 8. P. 2440−2450. https://doi.org/10.1128/AEM.03693-13Sarmah A.K., Meyer M.T., Boxall A.B.A. A global perspective on the use, sales, exposure pathways, occurrence, fate and effects of veterinary antibiotics (VAs) in the environment // Chemosphere. 2006. V. 65. № 5. P. 725–759. https://doi.org/10.1016/j.chemosphere.2006.03.026Bloomer E., McKee M. Policy options for reducing antibiotics and antibiotic-resistant genes in the environment // J. Public Health Policy. 2018. V. 39. P. 389–406. https://doi.org/10.1057/s41271-018-0144-xVan Boeckel T.P., Brower C., Gilbert M. et al.Global trends in antimicrobial use in food animals // Proc. Natl. Acad. Sci. USA. 2015. V. 112. № 18. Art. 56DOI5654. https://doi.org/10.1073/pnas.1503141112Carter L.J., Harris E., Mike W. et al. Fate and uptake of pharmaceuticals in soil-plant systems // J. Agric. Food. Chem. 2014. V. 62. № 4. P. 816‒825. https://doi.org/10.1021/jf404282yTrapp S., Shi J., Zeng L. Generic model for plant uptake of ionizable pharmaceuticals and personal care products // Environ. Toxicol. Chem. 2023. V. 42. № 4. P. 793‒804. https://doi.org/10.1002/etc.5582Saeed H., Padmest S., Singh A. et al. Impact of veterinary pharmaceuticals on environment and their mitigation through microbial bioremediation // Front. Microbiol. 2024. V. 15. Art. 1396116. https://doi.org/10.3389/fmicb.2024.1396116Wollenberger L., Halling-Sørensen B., Kusk O. Acute and chronic toxicity of veterinary antibiotics toDaphnia magna //Chemosphere. 2000. V. 40. № 7. P. 723–730. https://doi.org/10.1016/s0045-6535(99)00443-9Okocha R.C., Olatoye I.O., Adedeji O.B. Food safety impacts of antimicrobial use and their residues in aquaculture // Public Health Rev.2018. V. 39. Art. 21. https://doi.org/10.1186/s40985-018-0099-2Redondo-Salvo S.,Fernández-López R., Ruiz R. et al. Pathways for horizontal gene transfer in bacteria revealed by a global map of their plasmids // Nat. Commun. 2020. V. 11. № 1. Art. 3602. https://doi.org/10.1038/s41467-020-17278-2Zalewska M., Błażejewska A., Czapko A. et al. Antibiotics and antibiotic resistance genes in animal manure – consequences of its application in agriculture // Front. Microbiol. 2021. V. 12. Art. 610656. https://doi.org/10.3389/fmicb.2021.610656Glassmeyer S.T., Hinchey E.K., Boehme S.E. et al. Disposal practices for unwanted residential medications in the United States // Environ. Intern. 2009. V. 35. P. 566−572. https://doi.org/10.1016/j.envint.2008.10.007Slack R.J.,Gronow J.R., Voulvoulis N. Household hazardous waste in municipal landfills: contaminants in leachate // Sci. Total Environ. 2005. V. 337. № 1‒3. Art. 119137. https://doi.org/10.1016/J.scitotenv.2004.07.002Rogowska J., Zimmermann A. Household pharmaceutical waste disposal as a global problem − a review // Int. J. Environ. Res. Public Health. 2022. V. 19. № 23. Art. 15798. https://doi.org/10.3390/ijerph192315798Santos L.H.M.L.M., Rodríguez-Mozaz S., Barceló D. Microplastics as vectors of pharmaceuticals in aquatic organisms – an overview of their environmental implications // Case Stud. Chem. Environ. Eng. 2021. V. 3. Art. 100079. https://doi.org/10.1016/j.cscee.2021.100079Akerman-Sanchez G., Rojas-Jimenez K. Fungi for the bioremediation of pharmaceutical-derived pollutants: a bioengineering approach to water treatment // Environ. Adv.2021. V. 4. Art. 100071. https://doi.org/10.1016/j.envadv.2021.100071Khasawneh O.F.S., Palaniandy P. Occurrence and removal of pharmaceuticals in wastewater treatment plants //Process Saf. Environ. Protect.2021. V.150. P. 532‒556. https://doi.org/10.1016/j. psep.2021.04.045De Ilurdoz M.S., Sadhwani J.J., Reboso J.V. Antibiotic removal processes from water & amp; wastewater for the protection of the aquatic environment − a review // J. Water Process Eng. 2021. V. 45. Art. 102474. https://doi.org/10.1016/j.jwpe.2021.102474Khumalo S.M., Makhathini T.P., Bwapwa J.K. et al. The occurrence and fate of antibiotics and nonsteroidal anti-inflammatory drugs in water treatment processes: A review // J. Hazard. Mater. Adv. 2023. V. 10. Art. 100330. https://doi.org/10.1016/j.hazadv.2023.100330Gupta A., Kumar S., Bajpai Y. et al. Pharmaceutically active micropollutants: origin, hazards and removal // Front. Microbiol. 2024. V. 15. Art. 1339469. https://doi.org/10.3389/fmicb.2024.1339469Meena V., Swami D., Chandel A. et al. Selected emerging contaminants in water: Global occurrence, existing treatment technologies, regulations and associated risk // J. Hazard. Mater. 2025. V. 483. Art. 136541. https://doi.org/10.1016/j.jhazmat.2024.136541Jan-Roblero J., Cruz-Maya J.A. Ibuprofen: toxicology and biodegradation of an emerging contaminant // Molecules. 2023. V. 28(5). Art. 2097. https://doi.org/10.3390/molecules28052097Cizmas L., Sharma V.K., Gray C.M. et al. Pharmaceuticals and personal care products in waters: occurrence, toxicity, and risk // Environ. Chem. Lett. 2015. V. 13. № 4. P. 381‒394. https://doi.org/10.1007/s10311-015-0524-4Gudmundsson L., Boulange J., Do H.X. et al. Globally observed trends in mean and extreme river flow attributed to climate change // Science. 2021. V. 371(6534). P. 1159–1162. https://doi.org/10.1126/science.aba3996Arpin-Pont L., Bueno M.J.M., Gomez E. et al. Occurrence of PPCPs in the marine environment: a review // Environ. Sci. Pollut. Res. Int. 2016. V. 23. № 6. P. 4978−4991. https://doi.org/10.1007/s11356-014-3617-xRichardson S.D.,Ternes T.A. Water Analysis: Emerging contaminants and current issues // Anal. Chem. 2018. V. 90. P. 398−428. https://doi.org/10.1021/acs.analchem.7b04577Kraemer S.A., Ramachandran A., Perron G.G. Antibiotic pollution in the environment: from microbial ecology to public policy // Microorganisms.2019. V. 7. Art.180. https://doi.org/10.3390/microorganisms7060180Barnette D.A., Schleiff M.A., Datta A. et al. Meloxicam methyl group determines enzyme specificity for thiazole bioactivation compared to sudoxicam // Toxic. Lett. 2020. V. 338. P. 10−20. https://doi.org/10.1016/j.toxlet.2020.11.015Izad P., Izadi P., Salem R. et al. Non-steroidal anti-inflammatory drugs in the environment: Where were we and how far we have come? // Environ. Pollut. 2020. V. 267. P. 269–288. https://doi.org/10.1016/j.envpol.2020.115370Joshua D.I., Praveenkumarreddy Y., Prabhasankar V.P. et al. First report of pharmaceuticals and personal care productsin two tropical rivers of southwestern India // Environ. Monit. Assess. 2020. V. 192. № 8. Art. 529. https://doi.org/10.1007/s10661-020-08480-2Kinney C., Furlong E., Werner S. et al. Presence and distribution of wastewater-derived pharmaceuticals in soil irrigated with reclaimed water // Environ. Toxicol. Chem. 2006. V. 25. № 3. P. 317−326. https://doi.org/10.1897/05-187R.1Durán-Alvarez J., Becerril-Bravo E., Castro V. et al. The analysis of a group of acidic pharmaceuticals, carbamazepine, and potential endocrine disrupting compounds in wastewater irrigated soils by gas chromatography-mass spectrometry // Talanta. 2009. V. 78. P. 1159−166. https://doi.org/10.1016/j.talanta.2009.01.035Vazquez-Roig P., Andreu V., Blasco C. et al. Risk assessment on the presence of pharmaceuticals in sediments, soils and waters of the Pego–Oliva Marshlands (Valencia, eastern Spain)//Sci. Total Environ. 2012. V. 440. P. 24–32. https://doi.org/10.1016/j.scitotenv.2012.08.036Butler E., Whelan M., Sakrabani R., van Egmond R. Fate of triclosan in field soils receiving sewage sludge // Environ. Pollut. 2012. V. 167. P. 101−109. https://doi.org/10.1016/j.envpol.2012.03.036Dalkmann P., Broszat M., Siebe C. et al. Accumulation of pharmaceuticals, Enterococcus, and resistance genes in soils irrigated with wastewater for zero to 100 years in central Mexico // PLoS One. 2012. V. 7. № 9. Art. e45397. https://doi.org/10.1371/journal.pone.0045397Ortúzar M., Esterhuizen M., Olicón-Hernández D.R. et al. Pharmaceutical pollution in aquatic environments: A concise review of environmental impacts and bioremediation systems // Front. Microbiol. 2022. V. 13. Art. 869332. https://doi.org/ 10.3389/fmicb.2022.869332Świacka K., Maculewicz J., Kowalska D. et al. Presence of pharmaceuticals and their metabolites in wild-living aquatic organisms − Current state of knowledge // J.Hazard. Mater. 2022. V. 424. Pt A. Art. 127350. https://doi.org/10.1016/j.jhazmat.2021.127350Esteban S., Moreno-Merino L., Matellanes R. et al. Presence of endocrine disruptors in freshwater in the northern Antarctic Peninsula region // Environ. Res. 2016. V. 47. P. 179−192. https://doi.org/10.1016/j.envres.2016.01.034González-Alonso S., Merino L.M., Esteban S. et al. Occurrence of pharmaceutical, recreational and psychotropic drug residues in surface water on the northern Antarctic Peninsula region // Environ. Pollut. 2017. V. 229. P. 241–254. https://doi.org/10.1016/j.envpol.2017.05.060Kallenborn R., Brorström-Lundén E., Reiersen L.O. et al. Pharmaceuticals and personal care products (PPCPs) in Arctic environments: indicator contaminants for assessing local and remote anthropogenic sources in a pristine ecosystem in change // Environ. Sci. Pollut. Res. 2018. V. 25 (33). P. 33001−33013. https://doi.org/10.1007/s11356-017-9726-6Herzberg D., Sukumaran H., Viscusi E. NSAIDs for analgesia in the era of COVID-19 // Reg. Anesth. Pain Med. 2020. V. 45. P. 677–678. https://doi.org/10.1136/rapm-2020-101584Moore N., Bosco-Lévy P., Thurin N. et al. NSAIDs and COVID-19: a systematic review and meta-analysis // Drug Saf. 2021. V. 44. P. 929–938. https://doi.org/10.1007/ s40264-021-01089-5Nippes R.P., Macruz P.D., da Silva G.N. et al. A critical review on environmental presence of pharmaceutical drugs tested for the covid-19 treatment // Process Saf. Environ. Prot. 2021.V. 152. P. 568–582. https://doi.org/10.1016/j.psep.2021.06.040Hejna M., Kapuścińska D., Aksmann A. Pharmaceuticals in the aquatic environment: A review on eco-toxicology and the remediation potential of algae // Int. J. Environ. Res. Public Health. 2022. V. 19(13). Art. 7717. https://doi.org/10.3390/ijerph19137717Gwenzi W., Selvasembian R., Offiong N.A.O. et al. COVID-19 drugs in aquatic systems: a review // Environ. Chem. Lett. 2022. V. 20. № 2. P. 1275–1294. https://doi.org/10.1007/s10311-021-01356-yLee D., Choi K. Comparison of regulatory frameworks of environmental risk assessments for human pharmaceuticals in EU, USA, and Canada // Sci. Total Environ. 2019. V. 671. № 1. P. 1026–1035. https://doi.org/10.1016/j.scitotenv.2019.03.372Olicón-Hernández D.R., González-López J.,Aranda E. Overview on the biochemical potential of filamentous fungi to degrade pharmaceutical compounds // Front. Microbiol.2017. V. 8. Art. 1792. https://doi.org/10.3389/fmicb.2017.01792Da Costa Araújo A.P., Mesak C., Montalvão M.F. et al. Anti-cancer drugs in aquatic environment can cause cancer: insight about mutagenicity in tadpoles // Sci. Total Environ.2019. V. 650. P. 2284–2293. https://doi.org/10.1016/j.scitotenv.2018.09.373Booth A., Aga D.S., Wester A.L. Retrospective analysis of the global antibiotic residues that exceed the predicted no effect concentration for antimicrobial resistance in various environmental matrices // Environ. Int.2020. V. 141. Art. 105796. https://doi.org/10.1016/j.envint.2020.105796Ashfaq M., Khan K.N., Rehman M.S. et al. Ecological risk assessment of pharmaceuticals in the receiving environment of pharmaceutical wastewater in Pakistan //Ecotoxicol. Environ. Saf. 2017. V. 136. P. 31−39. https://doi.org/10.1016/j.ecoenv.2016.10.029Zhang Y., Wang B., Cagnetta G. et al. Typical pharmaceuticals in major WWTPs in Beijing, China: Occurrence, load pattern and calculation reliability // Wat. Res. 2018. V. 140. P. 291–300. https://doi.org/10.1016/j.watres.2018.04.056Bouju H., Nastold P., BeckB. et al. Elucidation of biotransformation of diclofenac and4’hydroxydiclofenac during biological wastewater treatment // J. Hazar. Mat. 2016. V. 301. P. 443–452. https://doi.org/10.1016/j.jhazmat.2015.08.054Maruya K.A., Dodder N.G., Sengupta A. et al. Multimedia screening of contaminants of emerging concern (CECS) in coastal urban watersheds in southern California (USA) // Environ. Toxicol. Chem. 2016. V. 35. № 8. P. 1986–1994. https://doi.org/10.1002/etc.3348Pereira C.D.S., Maranho L.A., Cortez F.S. et al. Occurrence of pharmaceuticals and cocaine in a Brazilian coastal zone // Sci. Total Environ. 2016. V. 548–549. P. 148–154. https://doi.org/10.1016/j.scitotenv.2016.01.051Botero-Coy A.M., Martínez-PachónD., Boix C. et al. An investigation into the occurrence and removal of pharmaceuticals in Colombian wastewater // Sci. Total Environ. 2018. V. 642. P. 842–853. https://doi.org/10.1016/j.scitotenv.2018.06.088Česen M., Ahel M., Terzić S. et al. The occurrence of contaminants of emerging concern in Slovenian and Croatian wastewaters and receiving Sava river // Sci. Total Environ. 2019. V. 650. P. 2446–2453. https://doi.org/10.1016/j.scitotenv.2018.09.238Moreau M., Hadfield J., Hughey J. et al. A baseline assessment of emerging organic contaminants in New Zealand groundwater // Sci. Total Environ. 2019. V. 686. P. 425–439. https://doi.org/10.1016/j.scitotenv.2019.05.210Ebele A.J., Oluseyi T., Drage D. et al. Occurrence, seasonal variation and human exposure to pharmaceuticals and personal care products in surface water, groundwater and drinking water in Lagos State, Nigeria // Emerg. Contam. 2020. V. 6. P. 124–132. https://doi.org/10.1016/j.emcon.2020.02.004Mathias F.T., Henrique F.D., Rodrigo D.G. et al. Effects of low concentrations of ibuprofen on freshwater fishRhamdia quelen// Environ. Toxicol.Pharmacol. 2018. V. 59. P. 105–113. https://doi.org/10.1016/j.etap.2018.03.008Gao X., Geng J., Du Y. et al. Comparative study of the toxicity between three non-steroidal anti-inflammatory drugs and their UV/Na2S2O8degradation products onCyprinus carpio// Sci. Rep. 2018. V. 8. Art. 13512. https://doi.org/10.1038/s41598-018-29524-1Ajima M.N.O., Ogo O.A., Audu B.S. et al. Chronic diclofenac (DCF) exposure alters both enzymatic and haematological profile of African catfish,Clarias gariepinus //Drug Chem. Toxicol. 2015. V. 38. № 4. P. 383–390. https://doi.org/10.3109/01480545.2014.974108Balbi T., Montagna M., Fabbri R. et al. Diclofenac affects early embryo development in the marine bivalve Mytilus galloprovincialis// Sci. Total Environ. 2018. V. 642. P. 601–609. https://doi.org/10.1016/j.scitotenv.2018.06.125Gonzalez-Rey M.,Bebianno M.J. Effects of non-steroidal anti-inflammatory drug (NSAID) diclofenac exposure in musselMytilus galloprovincialis //Aquat. Toxicol. 2014. V. 148. P. 221–230. https://doi.org/10.1016/j.aquatox.2014.01.011Cuthbert R., Parry-Jones J., Green R.E. et al. NSAIDs and scavenging birds: potential impacts beyond Asia’s critically endangered vultures // Biol. Lett. 2007. V. 3. № 1. P. 90–93. https://doi.org/10.1098/rsbl.2006.0554Selderslaghs I.W.T., Blust R., Witters H.E. Feasibility study of the zebrafish assay as an alternative method to screen for developmental toxicity and embryotoxicity using a training set of 27 compounds // Reprod. Toxicol. 2012. V. 33. № 2. P. 142–154. https://doi.org/10.1016/j.reprotox.2011.08.003Novoa-Luna K.A., Romero-Romero R., Natividad-Rangel R. et al. Oxidative stress induced in Hyalella aztecaby an effluent from a NSAID-manufacturing plant in Mexico // Ecotoxicology. 2016. V. 25. № 7. P. 1288–1304. https://doi.org/10.1007/s10646-016-1682-2Stancova V., Plhalova L., Blahová J. et al. Effects of the pharmaceutical contaminants ibuprofen, diclofenac, and carbamazepine alone, and in combination, on oxidative stress parameters in early life stages of tench (Tinca tinca) // Vet. Med. 2017. V. 62. № 2. P. 90–97. https://doi.org/10.17221/125/2016-VETMEDMcRae N.K., Glover C.N., Burket S.R. et al. Acute exposure to an environmentally relevant concentration of diclofenac elicits oxidative stress in the culturally important galaxiid fishGalaxias maculatus// Environ. Toxicol. Chem. 2018. V. 37. P. 224–235. https://doi.org/10.1002/etc.3948Chopra S., Kumar D. Ibuprofen as an emerging organic contaminant in environment, distribution and remediation // Heliyon. 2020. V. 6. Art. e04087. doi:10.1016/j.heliyon.2020.e04087Luo Y., Guo W., Ngo H.H. et al. A review on the occurrence of micropollutants in the aquatic environment and their fate and removal during wastewater treatment // Sci.Total Environ. 2014. V. 473–474. P. 619–641. https://doi.org/10.1016/j.scitotenv.2013.12.065Matongo S., Birungi G., Moodley B. et al. Pharmaceutical residues in water and sediment of Msunduzi river, KwaZulu-natal, South Africa // Chemosphere. 2015. V. 134. P. 133–140. https://doi.org/10.1016/j.chemosphere.2015.03.093Vergeynst L., Haeck A., De Wispelaere P. et al. Multi-residue analysis of pharmaceuticals in wastewater by liquid chromatography–magnetic sector mass spectrometry: Method quality assessment and application in a Belgian case study // Chemosphere.2015. V. 119. P. S2–S8. https://doi.org/10.1016/j.chemosphere.2014.03.069Wiest L., Chonova T., Bergé A. et al. Two-year survey of specific hospital wastewater treatment and its impact on pharmaceutical discharges // Environ. Sci. Pollut. Res. 2018. V. 25. P. 9207–9218. https://doi.org/10.1007/S11356-017-9662-5Chaves M.D.J.S., Barbosa S.C., Primel E.G. Emerging contaminants in Brazilian aquatic environment: identifying targets of potential concern based on occurrence and ecological risk // Environ. Sci. Pollut. Res. 2021. V. 28. P. 67528–67543. https://doi.org/10.1007/ S11356-021-15245-YPapagiannaki D., Morgillo S., Bocina G. et al. Occurrence and human health risk assessment of pharmaceuticals and hormones in drinking water sources in the metropolitan area of Turin in Italy // Toxics. 2021. V. 9. Art. 88. https://doi.org/10.3390/toxics9040088Petrie B., Camacho-Muñoz D. Analysis, fate and toxicity of chiral non steroidal anti-inflammatory drugs in wastewaters and the environment: a review //Environ. Chem. Lett. 2021. V. 19. P. 43–75. https://doi.org/10.1007/S10311-020-01065-YRico A., de Oliveira R., de Souza Nunes G.S. et al. Pharmaceuticals and other urban contaminants threaten Amazonian freshwater ecosystems // Environ. Int. 2021. V. 155. Art. 106702. https://doi.org/10.1016/j.envint.2021.106702Szopińska M., Potapowicz J., Jankowska K. et al. Pharmaceuticals and other contaminants of emerging concern in Admiralty Bay as a result of untreated wastewater discharge: status and possible environmental consequences // Sci. Total Environ. 2022. V. 835. Art. 155400. https://doi.org/10.1016/j.scitotenv.2022.155400Mohd Hanafiah Z., Wan Mohtar W.H.M., Abd Manan T.S. et al. Determination and risk assessment of pharmaceutical residues in the urban water cycle in Selangor Darul Ehsan, Malaysia // PeerJ. 2023. V. 11. Art. e14719. https://doi.org/10.7717/peerj.14719Parolini M., Binelli A., Provini A. Chronic effects induced by ibuprofen on the freshwater bivalveDreissena polymorpha// Ecotoxic. Environ. Saf. 2011. V. 74. № 6. P. 1586–1594. https://doi.org/10.1016/j.ecoenv.2011.04.025Wang H., Jin M., Mao W. et al. Photosynthetic toxicity of non-steroidal anti-inflammatory drugs (NSAIDs) on green algaeScenedesmus obliquus// Sci. Total Environ. 2020. V. 707. Art. 136176. https://doi.org/10.1016/j.scitotenv.2019.136176González-Naranjo V., Boltes K. Toxicity of ibuprofen and perfluorooctanoic acid for risk assessment of mixtures in aquatic and terrestrial environments // Int. J. Environ. Sci. Technol. 2014. V. 11. P. 1743–1750. https://doi.org/10.1007/s13762-013-0379-9Ortiz de García S.A., Pinto Pinto G.,García-Encina P.A. et al. Ecotoxicity and environmental risk assessment of pharmaceuticals and personal care products in aquatic environments and wastewater treatment plants // Ecotoxicology. 2014. V. 23. P. 1517–1533. https://doi.org/10.1007/s10646-014-1293-8Żur J., Piński A., Marchlewicz A. et al. Organic micropollutants paracetamol and ibuprofen – toxicity, biodegradation, and genetic background of their utilization by bacteria // Environ. Sci. Pollut. Res. 2018. V. 25. P. 21498–21524. doi:10.1007/s11356-018-2517-xRangasamy B., Hemalatha D., Shobana C. et al. Developmental toxicity and biological responses of zebrafish (Danio rerio) exposed to anti-inflammatory drug ketoprofen // Chemosphere. 2018. V. 213. P. 423–433. https://doi.org/10.1016/j.chemosphere.2018.09.013Zbikowska E., Lombardo P., Zbikowski J. et al. Ketoprofen-induced inhibition of symptoms of behavioural fever observed in winteringPlanorbarius corneus(L.) (Gastropoda: Planorbidae) // J. Mollusc. Stud. 2017. V. 83. P. 434–439. https://doi.org/10.1093/mollus/eyx026Mennillo E., Pretti C., Cappelli F. et al.Novel organ-specific effects of ketoprofen and its enantiomer, dexketoprofen on toxicological response transcripts and their functional products in salmon // Aquat. Toxicol. 2020. V. 229. Art. 105677. https://doi.org/10.1016/j.aquatox.2020.105677Wu J., Qian X., Yang Z. et al. Study on the matrix effect in the determination of selected pharmaceutical residues in seawater by solid-phase extraction and ultra-high-performance liquid chromatography electrospray ionization low-energy collision-induced dissociation tandem mass spectrometry // J. Chromatogr.A. 2010. V. 1217. P. 1471–1475. https://doi.org/10.1016/j.chroma.2009.12.074Vidal-Dorsch D.E., Bay S.M., Maruya K. et al. Contaminants of emerging concern in municipal wastewater effluents and marine receiving water // Environ. Toxicol. Chem. 2012. V. 31. P. 2674–2682. https://doi.org/10.1002/etc.2004Tran N.H., Urase T., Ta T.T. A preliminary study on the occurrence of pharmaceutically active compounds in hospital wastewater and surface water in Hanoi, Vietnam // Clean Soil Air Water. 2014. V. 42. P. 267–275. https://doi.org/10.1002/clen. 201300021Rivera-Jaimes J.A., Postigo C., Melgoza-Alemán R.M. et al. Study of pharmaceuticals in surface and wastewater from Cuernavaca, Morelos, Mexico: occurrence and environmental risk assessment // Sci. Total Environ. 2018. V. 613–614. P. 1263–1274. https://doi.org/10.1016/j. scitotenv.2017.09.134Thibaut R., Schnell S., Porte C. The interference of pharmaceuticals with endogenous and xenobiotic metabolizing enzymes in carp liver: anin vitrostudy // Environ. Sci. Technol. 2006. V. 40. P. 5154–5160. https://doi.org/10.1021/es0607483Arnold K.E., Boxall A., Brown R. et al. Assessing the exposure risk and impacts of pharmaceuticals in the environment on individuals and ecosystems //Biol. Lett.2013. V. 9. № 4. Art. 20130492. https://doi.org/10.1098/rsbl.2013.0492Overturf M.D., Anderson J.C., Pandelides Z. et al. Pharmaceuticals and personal care products: a critical review of the impacts on fish reproduction // Crit. Rev. Toxicol. 2015. V. 45. № 6. P. 469–491. https://doi.org/10.3109/10408444.2015.1038499Xu C., Niu L., Guo H. et al. Long-term exposure to the non-steroidal anti-inflammatory drug (NSAID) naproxen causes thyroid disruption in zebrafish at environmentally relevant concentrations // Sci. Total Environ. 2019. V. 676. P. 387−395. https://doi.org/10.1016/j.scitotenv.2019.04.323Wang H., Xi H., Xu L. et al. Ecotoxicological effects, environmental fate and risks of pharmaceutical and personal care products in the water environment: A review // Sci. Total Environ. 2021. V. 788. Art. 147819. https://doi.org/10.1016/j.scitotenv.2021.147819OECD. Pharmaceutical Residues in Freshwater: Hazards and Policy Responses, OECD Studies on Water, Paris: OECD Publishing, 2019. https://doi.org/10.1787/c936f42d-enŚwiacka K., Michnowska A., Maculewicz J. et al. Toxic effects of NSAIDs in non-target species: a review from the perspective of the aquatic environment // Environ. Pollut.2020. V. 273. Art. 115891. https://doi.org/10.1016/j.envpol.2020.115891Jørgensen S.E., Halling-Sørensen B. Drug in the environment // Chemosphere. 2000. V. 40. № 7. P. 691−699. https://doi.org/10.1016/s0045-6535(99)00438-5Monteiro S.C., Boxall A.B.A. Factors affecting the degradation of pharmaceuticals in agricultural soils // Environ. Toxicol. Chem. 2009. V. 28. № 12. P. 2546–2554. https://doi.org/10.1897/08-657.1Moghaddam A., Khayatan D., Barzegar P.E.F. et al. Biodegradation of pharmaceutical compounds in industrial wastewater using biological treatment: a comprehensive overview // Int. J. Environ. Sci. Technol.2023. V. 20. № 5. P. 5659−5696. https://doi.org/10.1007/s13762-023-04880-2Donner E., Kosjek T., Qualmann S. et al. Ecotoxicity of carbamazepine and its UV photolysis transformation products //Sci. Total Environ. 2013. V. 443. P. 870−876. https://doi.org/10.1016/j.scitotenv.2012.11.059Boxall A.B.A., Sinclair C.J., Fenner K. et al. When synthetic chemicals degrade in the environment // Environ. Sci. Technol.2004. V. 38. P. 368A–375A. https://doi.org/10.1021/es040624vXu D., Xiao Y., Pan H. et al. Toxic effects of tetracycline and its degradation products on freshwater green algae //Ecotoxicol. Environ. Saf. 2019. V. 174. P. 43−47. https://doi.org/10.1016/j.jhazmat.2020.123996Klementová Š., Poncarová M. Selected widely prescribed pharmaceuticals: toxicity of the drugs and the products of their photochemical degradation to aquatic organisms // J. Appl. Biomed. 2024. V. 22/1. P. 1‒11. https://doi.org/10.32725/jab.2024.007Thomas C.M., Nielsen K.M. Mechanisms of, and barriers to, horizontal gene transfer between bacteria // Nat. Rev. Microbiol. 2005. V. 3(9). P. 711–721. https://doi.org/10.1038/nrmicro1234Forsberg K., Reyes A., Wang B. et al. The shared antibiotic resistome of soil bacteria and human pathogens // Science. 2012. V. 337. P. 1107‒11110. https://doi.org/10.1126/science.1220761Fent K., Weston A.A., Caminada D. Ecotoxicology of human pharmaceuticals // Aquat. Toxicol. 2006. V. 76. № 2. P. 122‒159. https://doi.org/10.1016/j.aquatox.2005.09.009Santos L.H., Araújo A.N., Fachini A. et al. Ecotoxicological aspects related to the presence of pharmaceuticals in the aquatic environment // J. Hazard. Mater. 2010. V. 175 P. 45‒95. https://doi.org/10.1016/j.jhazmat.2009.10.100Krawczyk B., Zięba N., Kaźmierczak A. et al. Growth inhibition, oxidative stress and characterisation of mortality in green algae under the influence of beta-blockers and non-steroidal anti-inflammatory drugs //Sci. Total Environ. 2023. V.896. Art. 165019. https://doi.org/10.1016/j.scitotenv.2023.165019.Tyumina E., Bazhutin G., Kostrikina N. et al. Phenotypic and metabolic adaptations ofRhodococcus cerastiistrain IEGM 1243 to separate and combined effects of diclofenac and ibuprofen // Front. Microbiol. 2023. V.14. Art. 1275553. https://doi.org/10.3389/fmicb.2023.1275553Kataoka C., Kashiwada S. Ecological risks due to immunotoxicological effects on aquatic organisms // Int. J. Mol.Sci. 2021.V. 22. №15. Art. 8305. https://doi.org/10.3390/ijms22158305LakshmiS.D., Geetha B.V., Vibna M. From prescription to pollution: The ecological consequences of NSAIDs in aquatic ecosystems //Toxicol. Rep.2024. V. 13. Art. 101775. https://doi.org/10.1016/j.toxrep.2024.101775Pires P., Pereira A.M.P.T., Pena A. et al. Non-steroidal anti-inflammatory drugs in the aquatic environment and bivalves: The state of the art // Toxics. 2024. V. 12. № 6. Art. 415. https://doi.org/10.3390/toxics12060415Michelini L.A., Reichel R.B., Werner W.C. et al. Sulfadiazine uptake and effects onSalix fragilisL. andZea mays L. plants // Water Air Soil Poll. 2012. V. 223. P. 5243‒5257. https://doi.org/10.1007/s11270-012-1275-5Ayala Cabana L., de Santiago-Martín A., Meffe R. et al. Pharmaceutical and trace metal interaction within the water–soil–plant continuum: Implications for human and soil health // Toxics. 2024. V. 12. № 7. Art. 457. https://doi.org/10.3390/toxics12070457Carter L.J., Armitage J.M., Brooks B.W. et al. Predicting the accumulation of pharmaceuticals and personal care products in aquatic and terrestrial organisms // Environ. Toxicol. Chem. 2024. V. 43. № 3. P. 502‒512. https://doi.org/10.1002/etc.5451Cleuvers M. Aquatic ecotoxicity of pharmaceuticals including the assessment of combination effects // Toxicol. Lett. 2003. V. 142. P. 185−194. https://doi.org/10.1016/S0378-4274(03)00068-7CleuversM. Mixture toxicity of the anti-inflammatory drugs diclofenac, ibuprofen, naproxen, and acetylsalicylic acid //Ecotoxicol. Environ. Saf. 2004. V.59. № 3. P. 309−315. https://doi.org/10.1016/S0147-6513(03)00141-6Gómez-Oliván L.M., Galar-Martínez M.,García-Medina S. et al. Genotoxic response and oxidative stress induced by diclofenac, ibuprofen and naproxen inDaphnia magna// Drug Chem. Toxicol. 2014. V. 37. № 4. P. 391‒399. https://doi.org/10.3109/01480545.2013.870191Parolini M., Magni S., Castiglioni S. et al. Realistic mixture of illicit drugs impaired the oxidative status of the zebra mussel (Dreissena polymorpha) // Chemosphere. 2015. V. 128. P. 96‒102. https://doi.org/10.1016/j.chemosphere.2014.12.092Escher B.I., Fenner K. Recent advances in environmental risk assessment of transformation products // Environ. Sci. Technol. 2011. V. 45. № 9. P. 3835–3847. https://doi.org/10.1021/es1030799Document 02006R1907-20250422. Consolidated text: Regulation (EC) No. 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), establishing a European Chemicals Agency, amending Directive 1999/45/EC and repealing Council Regulation (EEC) No 793/93 and Commission Regulation (EC) No.1488/94 as well as Council Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/EEC, 93/105/EC and 2000/21/EC (Text with EEA relevance). Available from:http://data.europa.eu/eli/reg/2006/1907/2025-04-22[cited 12 June 2025]Thulasisingh A., Murali V., Govindarajan S.et al. Ecotoxicology and health risk assessment due to pharmaceuticals and personal care products in different environmental grids // Development in Wastewater Treatment Research and Processes. Applied Technologies for Clean Up of Environmental Contaminants Ed. Language M.P.S. 2024. https://doi.org/10.1016/B978-0-443-19207-4.00016-1European Commission (2001): Directive 2001/82/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to veterinary medicinal products. [cited 12 June 2025]. Available from:http://ec.europa.eu/health/files/eudralex/vol-5/dir_2001_82/dir_2001_82_en.pdfEuropean Commission (2001): Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use. [cited 12 June 2025]. Available from:http://ec.europa.eu/health/files/eudralex/vol-1/dir_2001_83_consol_2012/dir_2001_83_cons_2012_en.pdfAllen H., Donato J., Wang H. et al. Call of the wild: antibiotic resistance genes in natural environments // Nat. Rev. Microbiol. 2010. V. 8. P. 251‒259. https://doi.org/10.1038/nrmicro2312Marti E., Huerta B., Rodríguez-Mozaz S. et al. Characterization of ciprofloxacin-resistant isolates from a wastewater treatment plant and its receiving river // Water Res. 2014. V. 61. P. 67‒76. https://doi.org/10.1016/j.watres.2014.11.021Carvalho I.T., Santos L. Antibiotics in the aquatic environments: A review of the European scenario // Environ. Int. 2016. V. 94. P. 736–757. https://doi.org/10.1016/j.envint.2016.06.025Chaturvedi P., Shukla P., Giri B.S. et al. Prevalence and hazardous impact of pharmaceutical and personal care products and antibiotics in environment: A review on emerging contaminants // Environ. Res. 2021. V. 194. Art. 110664. https://doi.org/10.1016/j.envres.2020.110664Kusi J., Ojewole C.O., Ojewole A.E. et al. Antimicrobial resistance development pathways in surface waters and publick // Health Implications. Antibiotics – Basel. 2022. V. 11. № 6. Art. 821. https://doi.org/10.3390/antibiotics11060821Wise R. Antimicrobial resistance: priorities for action // J. Antimicrob. Chemother. 2002. V. 49. № 4. P. 585–586. https://doi.org/10.1093/jac/49.4.585Danner M.C., Robertson A., Behrends V. et al. Antibiotic pollution in surface fresh waters: Occurrence and effects // Sci. Total Environ. 2019. V. 664. P. 793–804. https://doi.org/10.1016/j.scitotenv.2019.01.406Founou L.L., Founou R.C., Essack S.Y. Antibiotic resistance in the food chain: A developing country-perspective // Front. Microbiol. 2016. V. 7. Art. 1881. https://doi.org/10.3389/fmicb.2016.01881Barra Caracciolo A., Topp E., Grenni P. Pharmaceuticals in the environment: Biodegradation and effects on natural microbial communities. A review // J. Pharm. Biomed. Anal. 2015. V. 106. P. 25–36. https://doi.org/10.1016/j.jpba.2014.11.040Niu X., de Graaf I.A.M., Langelaar-Makkinje M.et al. Diclofenac toxicity in human intestineex vivois not related to the formation of intestinal metabolites // Arch. Toxicol. 2015. V. 89. № 1. P. 107–119. https://doi.org/10.1007/s00204-014-1242-6Aycan İ.Ö., Elpek Ö., Akkaya B. et al. Diclofenac induced gastrointestinal and renal toxicity is alleviated by thymoquinone treatment // Food Chem. Toxicol. 2018. V. 118. P. 795–804. https://doi.org/10.1016/j.fct.2018.06.038Bessone F. Non-steroidal anti-inflammatory drugs: What is the actual risk of liver damage? // World J. Gastroenterol. 2010. V. 16(45). P. 5651–5661. https://doi.org/10.3748/wjg.v16.i45.5651Sriuttha P., Sirichanchuen B., Permsuwan U. Hepatotoxicity of nonsteroidal anti-inflammatory drugs: A systematic review of randomized controlled trials // Intern. J. Hepatol. 2018. V. 2018. Art. 5253623. https://doi.org/10.1155/2018/5253623Pezzilli R., Morselli-Labate A.M., Corinaldesi R. NSAIDs and acute pancreatitis: A systematic review // Pharmaceuticals. 2010. V. 3(3). P. 558−571. https://doi.org/10.3390/ph3030558Schmidt M., Sørensen H.T., Pedersen L. Diclofenac use and cardiovascular risks: Series of nationwide cohort studies // BMJ Online. 2018. V. 362. Art. k3426. https://doi.org/10.1136/bmj.k3426Oaks J.L., Gilbert M., Virani M.Z. et al. Diclofenac residues as the cause of vulture population decline in Pakistan // Nature. 2004. V. 427(6975). P. 630–633. https://doi.org/10.1038/nature02317Markandya A., Taylor T., Longo A. et al. Counting the cost of vulture decline − An appraisal of the human health and other benefits of vultures in India // Ecol. Econ. 2008. V. 67. № 2. P. 194–204.Herrero-Villar M., Delepoulle É., Suárez-Regalado L.et al. First diclofenac intoxication in a wild avian scavenger in Europe // Sci. Total Environ. 2021. V. 782. Art. 146890. https://doi.org/10.1016/j.scitotenv.2021.146890Peters A., Crane M., Merrington G. et al. Environmental quality standards for diclofenac derived under the European water framework directive: 2. Avian secondary poisoning //Environ. Sci. Eur. 2022. V. 34. Art. 28. https://doi.org/10.1186/s12302-022-00601-7Richards N.L., Cook G., Simpson V. et al. Qualitative detection of the NSAIDs diclofenac and ibuprofen in the hair of Eurasian otters (Lutra lutra) occupying UK waterways with GC-MS // Eur. J. Wildl. Res. 2011. V. 57. № 5. P. 1107–1114. https://doi.org/10.1007/s10344-011-0513-2Alkimin G.D., Daniel D., Frankenbach S. et al. Evaluation of pharmaceutical toxic effects of non-standard endpoints on the macrophyte speciesLemna minorandLemna gibba// Sci. Total Environ. 2019. V. 657. P. 926−937. https://doi.org/10.1016/j.scitotenv.2018.12.002Pi N., Ng J.Z., Kelly B.C. Bioaccumulation of pharmaceutically active compounds and endocrine disrupting chemicals in aquatic macrophytes: Results of hydroponic experiments withEchinodorus horemaniiandEichhornia crassipes// Sci. Total Environ. 2017. V. 601–602. P. 812–820. https://doi.org/10.1016/j.scitotenv.2017.05.137Takara M., Martinefski M., Tripodi V. et al. Effects of non-steroidal anti-inflammatory drugs (ibuprofen and diclofenac) and their mixtures on the growth of three green algae // Ecotoxicol. Environ. Contam. 2024. V. 19. № 1. P. 61‒71. https://doi.org/10.5132/eec.2024.01.07González-González E.D., Gómez-OlivánL. M.,Galar-MartínezM. et al. Metals and nonsteroidal anti-inflammatory pharmaceuticals drugs present in water from Madín Reservoir (Mexico) induce oxidative stress in gill, blood, and muscle of common carp (Cyprinus carpio) // Arch. Environ. Contamin. Toxicol. 2014. V. 67. № 2. P. 281–295. https://doi.org/10.1007/s00244-014-0048-0Sathishkumar P., Meena R.A.A.,Palanisami T. et al. Occurrence, interactive effects and ecological risk of diclofenac in environmental compartments and biota. A review // Sci. Total Environ. 2020. V. 698. Art. 134057. https://doi.org/10.1016/j.scitotenv.2019.134057Mehinto A.C., Hill E.M., Tyler C.R. Uptake and biological effects of environmentally relevant concentrations of the nonsteroidal anti-inflammatory pharmaceutical diclofenac in rainbow trout (Oncorhynchus mykiss) // Environ. Sci. Technol. 2010. V. 44. № 6. P. 2176–2182. https://doi.org/10.1021/es903702mSchwarz S., SchmiegH., Scheurer M. et al. Impact of the NSAID diclofenac on survival, development, behaviour and health of embryonic and juvenile stages of brown trout,Salmo truttaf.fario// Sci. Total Environ. 2017. V. 607–608. P. 1026–1036. https://doi.org/10.1016/j.scitotenv.2017.07.042Näslund J., Asker N., Fick J. et al. Naproxen affects multiple organs in fish but is still an environmentally better alternative to diclofenac // Aquat. Toxicol. 2020. V. 227. Art. 105583. https://doi.org/10.1016/j.aquatox.2020.105583De Felice B., Copia L., Guida M. Gene expression profiling in zebrafish embryos exposed to diclofenac, an environmental toxicant // Mol. Biol. Rep. 2012. V. 39. № 3. P. 2119–2128. https://doi.org/10.1007/s11033-011-0959-zMezzelani M., Gorbi S., Fattorini D. et al. Long-term exposure ofMytilus galloprovincialisto diclofenac, ibuprofen and ketoprofen: Insights into bioavailability, biomarkers and transcriptomic changes // Chemosphere. 2018. V. 198. P. 238–248. https://doi.org/10.1016/j.chemosphere.2018.01.148Yuan N., Ding J., Wu J. et al. A multibiomarker approach to assess the ecotoxicological effects of diclofenac on AsianclamCorbicula fluminea (O.F. Müller, 1774) // Environ. Sci. Pollut. Res. 2023. V. 30(38). P. 88598−88611. https://doi.org/10.1007/s11356-023-28702-7Liu Y., Wang L., Pan B. et al. Toxic effects of diclofenac on life history parameters and the expression of detoxification-related genes in Daphnia magna// Aquat. Toxicol. 2016. V. 183. P. 104–113. https://doi.org/10.1016/j.aquatox.2016.12.020Collard H.J., Ji K., Lee S. et al. Toxicity and endocrine disruption in zebrafish (Danio rerio) and two freshwater invertebrates (Daphnia magnaandMoina macrocopa) after chronic exposure to mefenamic acid // Ecotoxicol. Environ. Saf. 2013. V. 94. P. 80–86. https://doi.org/10.1016/j.ecoenv.2013.04.027Ji K., Liu X., Lee S. et al. Effects of non-steroidal anti-inflammatory drugs on hormones and genes of the hypothalamic-pituitary-gonad axis, and reproduction of zebrafish // J. Hazard. Mater. 2013. V. 254–255. P. 242–251. https://doi.org/10.1016/j.jhazmat.2013.03.036Mohd Zanuri N.B., Bentley M.G., Caldwell G.S. Assessing the impact of diclofenac, ibuprofen and sildenafil citrate (Viagra®) on the fertilisation biology of broadcast spawning marine invertebrates // Mar. Environ. Res. 2017. V. 127. P. 126–136. https://doi.org/10.1016/j.marenvres.2017.04.005Babaniyi G.G., Ajao B.H., Akor U.J. et al. Reproductive endocrinology drug development: Hormones, metabolism, and fertility in female reproductive health // Perspectives of Quorum Quenching in New Drug Development. Eds. Maddela N.R.,Thiriveedi V.,Silviya L.R.Boca Raton. CRC Press, 2024. P. 187‒206. https://doi.org/10.1201/9781003297826Han S., Choi K., Kim J. et al. Endocrine disruption and consequences of chronic exposure to ibuprofen in Japanese medaka (Oryzias latipes) and freshwater cladocerans Daphnia magnaand Moina macrocopa// Aquat.Toxicol. 2010. V. 98. № 3. P. 256–264. https://doi.org/10.1016/j.aquatox.2010.02.013Saravanan M., Hur J.-H., Arul N. et al. Toxicological effects of clofibric acid and diclofenac on plasma thyroid hormones of an Indian major carp,Cirrhinus mrigaladuring short and long-term exposures // Environ. Toxicol. Pharmacol. 2014. V. 38. № 3. P. 948–958. https://doi.org/10.1016/j.etap.2014.10.013Vandenberg L.N., Colborn T., Hayes T.B. et al. Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses // Endocr. Rev. 2012. V. 33. № 3. P. 378−455. https://doi.org/10.1210/er.2011-1050WHO (World Health Organization)/UNEP (United Nations Environment Programme). The State-of-the-Science of Endocrine Disrupting Chemicals-2012. Eds. Bergman Å., Heindel J.J., Jobling S. et al. United Nations Environment Programme/World Health Organization, Geneva, 2013.http://www.who.int/ceh/publications/endocrine/en/index.htmlXie Z., Gan Y., Tang J. et al. Combined effects of environmentally relevant concentrations of diclofenac and cadmium on Chironomus riparius larvae// Ecotoxicol. Environ. Saf. 2020. V. 202. Art. 110906. https://doi.org/10.1016/j.ecoenv.2020.110906.Madesh S., Sudhakaran G., Meenatchi R. et al. Neurobehavioral and bioaccumulative toxicity in adult in-vivo zebrafish model due to prolonged cadmium exposure in the presence of ketoprofen // J. Biochem. Mol. Toxicol. 2024. V. 38. № 11. Art. e70005. https://doi.org/10.1002/jbt.70005Corcoll N., Acuña V., Barceló D. et al. Pollution-induced community tolerance to non-steroidal anti-inflammatory drugs (NSAIDs) in fluvial biofilm communities affected by WWTP effluents // Chemosphere. 2014. V. 112 P. 185–193. https://doi.org/10.1016/j.chemosphere.2014.03.128Kruglova A., Gonzalez-Martinez A., Kråkström M. et al. Bacterial diversity and population shifts driven by spotlight wastewater micropollutants in low-temperature highly nitrifying activated sludge // Sci. Total Environ. 2017. V. 605–606. P. 291–299. https://doi.org/10.1016/j.scitotenv.2017.06.191Nguyen L.N., Nghiem L., Pramanik B.K. et al. Cometabolic biotransformation and impacts of the anti-inflammatory drug diclofenac on activated sludge microbial communities // Sci. Total Environ. 2019. V. 657. P. 739–745. https://doi.org/10.1016/j.scitotenv.2018.12.094Jiang C., Geng J., Hu H. et al. Impact of selected non-steroidal anti-inflammatory pharmaceuticals on microbial community assembly and activity in sequencing batch reactors // PLoS ONE. 2017. V. 12. Art. e0179236. https://doi.org/10.1371/journal.pone.0179236Aguilar-Romero I., Romero E., Wittich R.M. et al. Bacterial ecotoxicity and shifts in bacterial communities associated with the removal of ibuprofen, diclofenac and triclosan in biopurification systems // Sci. Total Environ. 2020. V. 741. Art. 140461. doi:10.1016/j.scitotenv.2020.140461Parolini M. Toxicity of the non-steroidal anti-inflammatory drugs (NSAIDs) acetylsalicylic acid, paracetamol, diclofenac, ibuprofen and naproxen towards freshwater invertebrates: A review // Sci. Total Environ. 2020. V. 40. Art. 140043. https://doi.org/10.1016/j.scitotenv.2020.140043Pino-Otín M.R., Muñiz S., Val J. et al. Effects of 18 pharmaceuticals on the physiological diversity of edaphic microorganisms // Sci. Total Environ. 2017. V. 595. P. 441–450. https://doi.org/10.1016/j.scitotenv.2017.04.002Thai P.N., Ren L., XuW. et al. Chronic diclofenac exposure increases mitochondrial oxidative stress, inflammatory mediators, and cardiac dysfunction // Cardiovasc Drugs Ther. 2023. V. 37. № 1. P. 25–37.https://doi.org/10.1007/s10557-021-07253-4Jia Y., Yu C., Fan J. et al. Alterations in the cell wall ofRhodococcus biphenylivoransunder norfloxacin stress // Front. Microbiol. 2020. V. 11. Art. 54957. https://doi.org/10.3389/fmicb.2020.554957Ivshina I., Bazhutin G., Tyumina E. Rhodococcusstrains as a good biotool for neutralizing pharmaceutical pollutants and obtaining therapeutically valuable products: Through the past into the future // Front. Microbiol. 2022. V. 13. Art. 967127. https://doi.org/10.3389/fmicb.2022.967127Amobonye A., Aruwa C.E., Aransiola S. et al. The potential of fungi in the bioremediation of pharmaceutically active compounds: a comprehensive review // Front. Microbiol. 2023. V. 14. Art. 1207792. https://doi.org/10.3389/fmicb.2023.1207792Chhaya T., Raychoudhury T., Bag R. Insight into the diclofenac and carbamazepine removal by Bacillus subtilis BMT4i immobilizedon different activated carbons: A comparative removal study by activated carbon, bacterial cell, and its composite // Int. J. Environ. Res.2025. V. 19. Art. 28. https://doi.org/10.1007/s41742-024-00687-2Amobonye A., Bhagwat P., Singh S. et al. Plastic biodegradation: frontline microbes and their enzymes // Sci. Total Environ.2021. V.759. P. 143536–143516. https://doi.org/10.1016/j.scitotenv.2020.143536Nazari M.T., Simon V., Machado B.S. et al.Rhodococcus: A promising genus of actinomycetes for the bioremediation of organic and inorganic contaminants //J. Environ. Manag.2022. V.323. Art. 116220. https://doi.org/10.1016/j.jenvman.2022.116220Ivshina I.B., Tyumina E.A., Kuzmina M.V. et al. Features of diclofenac biodegradation byRhodococcus ruberIEGM 346 // Sci. Rep. 2019. V. 9. Art. 9159. https://doi.org/10.1038/s41598-019-45732-9Ivshina I.B.,Tyumina E.A., Bazhutin G.A. et al. Response ofRhodococcus cerastiiIEGM 1278 to toxic effect of ibuprofen // PLoS ONE.2021. V. 16. Art. e0260032. https://doi.org/10.1371/journal.pone.0260032Allocati N., Masulli M., Ilio C.Di.et al. Die for the community: an overview of programmed cell death in bacteria // Cell Death Disease. 2015. V. 6. № 1. Art. e1609. https://doi.org/10.1038/cddis.2014.570Uzoechi S.C., Abu-Lail N.I. The effects of β-lactam antibiotics on urface modifications of multidrug-resistant Escherichia coli: A multiscale approach // Microsc. Microanal. 2019. V. 25. P. 135–150. https://doi.org/10.1017/s1431927618015696Arakha M., Saleem M., Mallick B.C. et al. The effects of interfacial potential on antimicrobial propensity of ZnO nanoparticle //Sci. Rep. 2015. V. 5. Art. 9578. https://doi.org/10.1038/srep09578Halder S., Yadav K.K., Sarkar R. et al. Alteration of Zeta potential and membrane permeability in bacteria: a study with cationic agents // SpringerPlus. 2015. V. 4. Art. 672. https://doi.org/10.1186/s40064-015-1476-7Ivshina I., Kostina L., Krivoruchko A. et al. Removal of polycyclic aromatic hydrocarbons in soil spiked with model mixtures of petroleum hydrocarbons and heterocycles using biosurfactants fromRhodococcusruberIEGM 231 // J. Hazard. Mater. 2016. V. 312. P. 8–17. https://doi.org/10.1016/j.jhazmat.2016.03.007Kuyukina M.S., Ivshina I.B. Production of trehalolipid biosurfactants byRhodococcus// Biology ofRhodococcus. Microbiology Monographs. Ed. Steinbüchel A. Cham: Springer Nature Switzerland, 2019. P. 271‒298. https://doi.org/10.1007/978-3-030-11461-9_10.Ivshina I.B., Kuyukina M.S., Krivoruchko A.V. ExtremotolerantRhodococcusas an important resource for environmental biotechnology //Actinomycetes in Marine and Extreme Environments: Unexhausted Sources for Microbial Biotechnology. Ed. Kurtböke I. Science Publishers, CRC Press: Boca Raton, 2024. P. 209−246. https://doi.org/10.1201/9780429293948Ivshina I.B., Kuyukina M.S., Krivoruchko A.V. Hydrocarbon-oxidizing bacteria and their potential in eco-biotechnology and bioremediation // Microbial Resources: From Functional Existence in Nature to Industrial Applications. Ed. Kurtböke I. London: Elsevier, Academic Press, 2017. P. 121−148. https://doi.org/10.1016/B978-0-12-804765-1.00006-0Guo X., Xie C., Wang L. et al. Biodegradation of persistent environmental pollutants by Arthrobactersp. // Environ. Sci. Pollut. Res. 2019. V. 26. P. 8249–8443. https://doi.org/10.1007/s11356-019-04358-0Bhaskaralingam A., Sharma G., Wang T. et al. Bioremediation of pharmaceuticals waste and pesticides using various microorganisms: A review // Process Saf. Environ. Prot. 2024.V. 194. P. 1116‒1132. https://doi.org/10.1016/j.psep.2024.12.050Efremenko E., Stepanov N., Senko O. et al. Progressive biocatalysts for the treatment of aqueous systems containing pharmaceutical pollutants // Life. 2023. V. 13. Art. 841. https://doi.org/10.3390/life13030841Ivshina I.B., Kuyukina M.S. Specialized microbial resource centers: a driving force of the growing bioeconomy // Microbial Resource Conservation, Soil Biology. Eds.Sharma S.K. and Varma A. Cham: Springer Nature Switzerland AG, 2018. P. 111−140. https://doi.org/10.1007/978-3-319-96971-8_4Sumpter J.P., Johnson A.C., Runnalls T.J. Pharmaceuticals in the aquatic environment: No answers yet to the major questions // Environ. Toxicol. Chem. 2024. V. 43. № 3. P. 589–594. https://doi.org/10. 1002/etc.5421Maack G., Williams M., Backhaus T. et al. Pharmaceuticals in the environment: Just one stressor among others or indicators for the global human influence on ecosystems // Environ. Toxicol. Chem. 2022. V. 41. № 3. P. 541–543. https://doi.org/10.1002/ etc.5256