{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T05:58:33Z","timestamp":1785909513381,"version":"3.56.0"},"reference-count":63,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,13]],"date-time":"2025-07-13T00:00:00Z","timestamp":1752364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Pharmaceuticals such as fluoxetine, paroxetine, sertraline, and mianserin occur in aquatic environments at low yet persistent concentrations due to their incomplete removal in wastewater treatment plants. Although frequently detected, these neuroactive compounds remain underrepresented in ecotoxicological assessments. Given their pharmacodynamic potency, environmentally relevant concentrations may induce sublethal effects in non-target organisms. In this study, we applied untargeted LC-MS-based metabolomics to investigate the sublethal effects of four widely used antidepressants\u2014paroxetine, sertraline, fluoxetine (SSRIs), and mianserin (TeCA)\u2014on two ecologically relevant freshwater invertebrates: S. ambiguum and D. magna. Organisms were individually exposed to each compound for 48 h at a concentration of 100 \u00b5g\/L and 25 \u00b5g\/L, respectively. Untargeted metabolomics captured the sublethal biochemical effects of these antidepressants, revealing both shared disruptions\u2014e.g., in glycerophospholipid metabolism and cysteine and methionine metabolism\u2014and species-specific responses. More pronounced pathway changes observed in D. magna suggest interspecies differences in metabolic capacity or xenobiotic processing mechanisms between taxa. Among the four antidepressants tested, sertraline in D. magna and fluoxetine in S. ambiguum exerted the most extensive metabolomic perturbations, as evidenced by the highest number and pathway impact scores. In D. magna, fluoxetine and mianserin produced similar metabolic profiles, largely overlapping with those of sertraline, whereas paroxetine affected only a single pathway, indicating minimal impact. In S. ambiguum, paroxetine and mianserin elicited comparable responses, also overlapping with those of fluoxetine, while sertraline triggered the fewest changes. These results suggest both compound-specific effects and a conserved metabolic response pattern among the antidepressants used. They also underscore the considerable potential of metabolomics as a powerful and sensitive tool for ecotoxicological risk assessments, particularly when applied across multiple model organisms to capture interspecies variations. However, further research is essential to identify which specific pathway disruptions are most predictive of adverse effects on organismal health.<\/jats:p>","DOI":"10.3390\/molecules30142952","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T09:56:54Z","timestamp":1752487014000},"page":"2952","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Environmental Antidepressants Disrupt Metabolic Pathways in Spirostomum ambiguum and Daphnia magna: Insights from LC-MS-Based Metabolomics"],"prefix":"10.3390","volume":"30","author":[{"given":"Artur","family":"J\u0119dreas","sequence":"first","affiliation":[{"name":"Department of Drug Chemistry, Pharmaceutical and Biomedical Analysis, Medical University of Warsaw, 02-091 Warszawa, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7079-7527","authenticated-orcid":false,"given":"Sylwia","family":"Michorowska","sequence":"additional","affiliation":[{"name":"Department of Drug Chemistry, Pharmaceutical and Biomedical Analysis, Medical University of Warsaw, 02-091 Warszawa, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8320-1200","authenticated-orcid":false,"given":"Agata","family":"Drobniewska","sequence":"additional","affiliation":[{"name":"Department of Toxicology and Food Science, Medical University of Warsaw, 02-091 Warszawa, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2567-4453","authenticated-orcid":false,"given":"Joanna","family":"Giebu\u0142towicz","sequence":"additional","affiliation":[{"name":"Department of Drug Chemistry, Pharmaceutical and Biomedical Analysis, Medical University of Warsaw, 02-091 Warszawa, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107560","DOI":"10.1016\/j.jece.2022.107560","article-title":"Emerging organic contaminants in global community drinking water sources and supply: A review of occurrence, processes and remediation","volume":"10","author":"Mukhopadhyay","year":"2022","journal-title":"J. Environ. Chem. Eng."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.envpol.2018.04.012","article-title":"A review of the pharmaceutical exposome in aquatic fauna","volume":"239","author":"Miller","year":"2018","journal-title":"Environ. Pollut."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1111\/1365-2656.14152","article-title":"Long-term effects of widespread pharmaceutical pollution on trade-offs between behavioural, life-history and reproductive traits in fish","volume":"94","author":"Aich","year":"2025","journal-title":"J. Anim. Ecol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.scitotenv.2015.06.143","article-title":"Concentration and risk of pharmaceuticals in freshwater systems are related to the population density and the livestock units in Iberian Rivers","volume":"540","author":"Osorio","year":"2016","journal-title":"Sci. Total Environ."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Sumpter, J.P., and Margiotta-Casaluci, L. (2022). Environmental Occurrence and Predicted Pharmacological Risk to Freshwater Fish of over 200 Neuroactive Pharmaceuticals in Widespread Use. Toxics, 10.","DOI":"10.3390\/toxics10050233"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.chroma.2012.05.084","article-title":"Fast and comprehensive multi-residue analysis of a broad range of human and veterinary pharmaceuticals and some of their metabolites in surface and treated waters by ultra-high-performance liquid chromatography coupled to quadrupole-linear ion trap tandem mass spectrometry","volume":"1248","author":"Gros","year":"2012","journal-title":"J. Chromatogr. A"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.envpol.2012.11.022","article-title":"Occurrence of 95 pharmaceuticals and transformation products in urban groundwaters underlying the metropolis of Barcelona, Spain","volume":"174","author":"Jurado","year":"2013","journal-title":"Environ. Pollut."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.ecoenv.2014.02.020","article-title":"Occurrence of antidepressant residues in the sewage-impacted Vistula and Utrata rivers and in tap water in Warsaw (Poland)","volume":"104","author":"Giebultowicz","year":"2014","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"10652","DOI":"10.1021\/acs.est.7b02912","article-title":"Selective Uptake and Bioaccumulation of Antidepressants in Fish from Effluent-Impacted Niagara River","volume":"51","author":"Arnnok","year":"2017","journal-title":"Environ. Sci. Technol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1021\/ac702154e","article-title":"Trace analysis of antidepressant pharmaceuticals and their select degradates in aquatic matrixes by LC\/ESI\/MS\/MS","volume":"80","author":"Schultz","year":"2008","journal-title":"Anal. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.scitotenv.2018.07.240","article-title":"Environmental loadings of Active Pharmaceutical Ingredients from manufacturing facilities in Canada","volume":"646","author":"Kleywegt","year":"2019","journal-title":"Sci. Total Environ."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1016\/j.envpol.2011.07.004","article-title":"Assessing the diurnal variability of pharmaceutical and personal care products in a full-scale activated sludge plant","volume":"159","author":"Salgado","year":"2011","journal-title":"Environ. Pollut."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.envpol.2013.09.013","article-title":"Concentrations of prioritized pharmaceuticals in effluents from 50 large wastewater treatment plants in the US and implications for risk estimation","volume":"184","author":"Kostich","year":"2014","journal-title":"Environ. Pollut."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5600","DOI":"10.1016\/j.watres.2012.07.042","article-title":"Distribution of antidepressant residues in wastewater and biosolids following different treatment processes by municipal wastewater treatment plants in Canada","volume":"46","author":"Lajeunesse","year":"2012","journal-title":"Water Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1016\/j.chemosphere.2012.10.089","article-title":"Detection, occurrence and fate of 22 psychiatric pharmaceuticals in psychiatric hospital and municipal wastewater treatment plants in Beijing, China","volume":"90","author":"Yuan","year":"2013","journal-title":"Chemosphere"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Nowakowska, K., Giebultowicz, J., Kamaszewski, M., Adamski, A., Szudrowicz, H., Ostaszewska, T., Solarska-Dzieciolowska, U., Nalecz-Jawecki, G., Wroczynski, P., and Drobniewska, A. (2020). Acute exposure of zebrafish (Danio rerio) larvae to environmental concentrations of selected antidepressants: Bioaccumulation, physiological and histological changes. Comp. Biochem. Physiol. C Toxicol. Pharmacol., 229.","DOI":"10.1016\/j.cbpc.2019.108670"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Dumas, T., Courant, F., Fenet, H., and Gomez, E. (2022). Environmental Metabolomics Promises and Achievements in the Field of Aquatic Ecotoxicology: Viewed through the Pharmaceutical Lens. Metabolites, 12.","DOI":"10.3390\/metabo12020186"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"107117","DOI":"10.1016\/j.aquatox.2024.107117","article-title":"Ecotoxicological and metabolomic investigation of chronic exposure of Daphnia magna (Straus, 1820) to yttrium environmental concentrations","volume":"276","author":"Salvatore","year":"2024","journal-title":"Aquat. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"104157","DOI":"10.1016\/j.etap.2023.104157","article-title":"The impact of pharmaceutical pollutants on daphnids\u2014A metabolomic approach","volume":"100","author":"Virgiliou","year":"2023","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"174036","DOI":"10.1016\/j.scitotenv.2024.174036","article-title":"Metabolomic study on ostracods exposed to environmentally relevant concentrations of five pharmaceuticals selected via a novel approach","volume":"946","author":"Michorowska","year":"2024","journal-title":"Sci. Total Environ."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"133065","DOI":"10.1016\/j.chemosphere.2021.133065","article-title":"Long-term exposure to environmental diclofenac concentrations impairs growth and induces molecular changes in Lymnaea stagnalis freshwater snails","volume":"291","author":"Bouly","year":"2022","journal-title":"Chemosphere"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"109501","DOI":"10.1016\/j.ecoenv.2019.109501","article-title":"Responses in the crucian carp (Carassius auratus) exposed to environmentally relevant concentration of 17alpha-Ethinylestradiol based on metabolomics","volume":"183","author":"Zhou","year":"2019","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.ecoenv.2017.05.031","article-title":"Sex steroids and metabolic responses in mussels Mytilus galloprovincialis exposed to drospirenone","volume":"143","author":"Cappello","year":"2017","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.chemosphere.2017.08.149","article-title":"Assessing biological effects of fluoxetine in developing zebrafish embryos using gas chromatography-mass spectrometry based metabolomics","volume":"188","author":"Mishra","year":"2017","journal-title":"Chemosphere"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"175993","DOI":"10.1016\/j.scitotenv.2024.175993","article-title":"Antidepressants and COVID-19: Increased use, occurrence in water and effects and consequences on aquatic environment. A review","volume":"953","author":"Puga","year":"2024","journal-title":"Sci. Total Environ."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.ecoenv.2015.02.014","article-title":"Evaluation of direct and indirect photodegradation of mianserin with high-performance liquid chromatography and short-term bioassays","volume":"115","author":"Wawryniuk","year":"2015","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"131904","DOI":"10.1016\/j.jhazmat.2023.131904","article-title":"Combined exposure of the bivalve Mytilus galloprovincialis to polyethylene microplastics and two pharmaceuticals (citalopram and bezafibrate): Bioaccumulation and metabolomic studies","volume":"458","author":"Courant","year":"2023","journal-title":"J. Hazard. Mater."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"105581","DOI":"10.1016\/j.aquatox.2020.105581","article-title":"Influence of dissolved organic matter on the accumulation, metabolite production and multi-biological effects of environmentally relevant fluoxetine in crucian carp (Carassius auratus)","volume":"226","author":"Yan","year":"2020","journal-title":"Aquat. Toxicol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1002\/tox.20023","article-title":"Spirotox-Spirostomum ambiguum acute toxicity test-10 years of experience","volume":"19","year":"2004","journal-title":"Environ. Toxicol."},{"key":"ref_30","unstructured":"OECD (2004). OECD Guidelines for the testing of chemicals, section 2: Effects on biotic systems. OECD Library, The Organisation for Economic Co-operation and Development."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Zhukov, A., and Popov, V. (2023). Eukaryotic Cell Membranes: Structure, Composition, Research Methods and Computational Modelling. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241311226"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.chemosphere.2014.01.057","article-title":"Acute toxicity of 8 antidepressants: What are their modes of action?","volume":"108","author":"Minguez","year":"2014","journal-title":"Chemosphere"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Nalecz-Jawecki, G., Wawryniuk, M., Giebultowicz, J., Olkowski, A., and Drobniewska, A. (2020). Influence of Selected Antidepressants on the Ciliated Protozoan Spirostomum ambiguum: Toxicity, Bioaccumulation, and Biotransformation Products. Molecules, 25.","DOI":"10.3390\/molecules25071476"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"27988","DOI":"10.1007\/s11356-024-32846-5","article-title":"Binary effects of fluoxetine and zinc on the biomarker responses of the non-target model organism Daphnia magna","volume":"31","author":"Atli","year":"2024","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_35","first-page":"127","article-title":"Compounds altering fat storage in Daphnia magna","volume":"545\u2013546","author":"Garreta","year":"2016","journal-title":"Sci. Total Environ."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"127814","DOI":"10.1016\/j.chemosphere.2020.127814","article-title":"Characterization of neurotransmitters and related metabolites in Daphnia magna juveniles deficient in serotonin and exposed to neuroactive chemicals that affect its behavior: A targeted LC-MS\/MS method","volume":"263","author":"Fuertes","year":"2021","journal-title":"Chemosphere"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"107161","DOI":"10.1016\/j.aquatox.2024.107161","article-title":"Maternal Daphnia magna exposure to the antidepressant sertraline causes molting disorder, multi-generational reproductive and serotonergic dysfunction","volume":"278","author":"Dong","year":"2025","journal-title":"Aquat. Toxicol."},{"key":"ref_38","first-page":"35","article-title":"Genomic analyses of aminergic signaling systems (dopamine, octopamine and serotonin) in Daphnia pulex","volume":"7","author":"McCoole","year":"2012","journal-title":"Comp. Biochem. Physiol. Part. D Genom. Proteom."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6000","DOI":"10.1021\/acs.est.6b00826","article-title":"Depressing Antidepressant: Fluoxetine Affects Serotonin Neurons Causing Adverse Reproductive Responses in Daphnia magna","volume":"50","author":"Campos","year":"2016","journal-title":"Environ. Sci. Technol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.ecoenv.2017.03.042","article-title":"Bioconcentration of the antidepressant fluoxetine and its effects on the physiological and biochemical status in Daphnia magna","volume":"142","author":"Ding","year":"2017","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_41","first-page":"211","article-title":"Oxidative and apoptotic effects of fluoxetine and its metabolite norfluoxetine in Daphnia magna","volume":"71","author":"Taskin","year":"2020","journal-title":"Arh. Hig. Rada Toksikol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1021\/es203157f","article-title":"Mechanisms of Action of Selective Serotonin Reuptake Inhibitors in Daphnia magna","volume":"46","author":"Campos","year":"2012","journal-title":"Environ. Sci. Technol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9434","DOI":"10.1021\/es4012299","article-title":"Identification of Metabolic Pathways in Daphnia magna Explaining Hormetic Effects of Selective Serotonin Reuptake Inhibitors and 4-Nonylphenol Using Transcriptomic and Phenotypic Responses","volume":"47","author":"Campos","year":"2013","journal-title":"Environ. Sci. Technol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.toxlet.2016.07.001","article-title":"Fluoxetine and the mitochondria: A review of the toxicological aspects","volume":"258","year":"2016","journal-title":"Toxicol. Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1021\/acs.chemrestox.3c00017","article-title":"Cystine\/Glutamate Xc(-) Antiporter Induction Compensates for Transsulfuration Pathway Repression by 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) to Ensure Cysteine for Hepatic Glutathione Biosynthesis","volume":"36","author":"Orlowska","year":"2023","journal-title":"Chem. Res. Toxicol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1289\/ehp.1409163","article-title":"Obesogens beyond Vertebrates: Lipid Perturbation by Tributyltin in the Crustacean Daphnia magna","volume":"123","author":"Casas","year":"2015","journal-title":"Environ. Health Perspect."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"139029","DOI":"10.1016\/j.scitotenv.2020.139029","article-title":"Changes in lipid profiles in Daphnia magna individuals exposed to low environmental levels of neuroactive pharmaceuticals","volume":"733","author":"Fuertes","year":"2020","journal-title":"Sci. Total Environ."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1016\/j.scitotenv.2018.06.333","article-title":"Effect of psychiatric drugs on Daphnia magna oxylipin profiles","volume":"644","author":"Checa","year":"2018","journal-title":"Sci. Total Environ."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Yang, H., Xing, H., Chen, Z., Kong, L., Jiang, H., and Zhu, T. (2025). Comparative Toxicokinetics and Biomarker Responses of Typical Psychiatric Pharmaceuticals in Daphnia magna. Toxics, 13.","DOI":"10.3390\/toxics13060481"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Chojnacka, J., Drobniewska, A., Lenga, W., Misztal, J., Wawryniuk, M., and Na\u0142\u0119cz-Jawecki, G. (2023). The Mutual Effect of Microparticles and Antidepressants on the Protozoan Spirostomum ambiguum (M\u00fcller, 1786) Ehrenberg, 1835. Water, 15.","DOI":"10.3390\/w15030552"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1006\/eesa.1998.1698","article-title":"A New Low-Cost Microbiotest with the ProtozoanSpirostomum teres: Culture Conditions and Assessment of Sensitivity of the Ciliate to 14 Pure Chemicals","volume":"41","author":"Twagilimana","year":"1998","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/0300-9629(91)90181-B","article-title":"Hormones and signal transduction in protozoa","volume":"100","author":"Renaud","year":"1991","journal-title":"Comp. Biochem. Physiol. A Comp. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s00441-005-0052-9","article-title":"How does the unicellular Tetrahymena utilise the hormones that it produces? Paying a visit to the realm of atto-and zeptomolar concentrations","volume":"327","author":"Csaba","year":"2007","journal-title":"Cell Tissue Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s40409-018-0165-8","article-title":"Efficacy of sertraline against Trypanosoma cruzi: An in vitro and in silico study","volume":"24","author":"Ferreira","year":"2018","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_55","first-page":"170","article-title":"Aquatic toxicity of various pharmaceuticals on some isolated plankton species","volume":"3","author":"Touliabah","year":"2012","journal-title":"Int. J. Med. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/j.bbagen.2018.01.015","article-title":"Ophthalmic acid is a marker of oxidative stress in plants as in animals","volume":"1862","author":"Servillo","year":"2018","journal-title":"Biochim. Biophys. Acta (BBA)\u2014General. Subj."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.exppara.2014.06.004","article-title":"Mianserin, an antidepressant kills Leishmania donovani by depleting ergosterol levels","volume":"144","author":"Dinesh","year":"2014","journal-title":"Exp. Parasitol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"113029","DOI":"10.1016\/j.envpol.2019.113029","article-title":"Analysis of neurotransmitters in Daphnia magna affected by neuroactive pharmaceuticals using liquid chromatography-high resolution mass spectrometry","volume":"254","author":"Barata","year":"2019","journal-title":"Environ. Pollut."},{"key":"ref_59","unstructured":"Daphtoxkit, F. (2025, April 15). Daphnia magna. Crustacean Toxicity Screening Test for Freshwater. Standard Operational Procedure. Creasel: Deinze, Belgium. Available online: http:\/\/www.microbiotests.be\/SOPs\/Daphtoxkit%20magna%20F%20SOP%20-%20A5.pdf."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.envpol.2019.04.118","article-title":"Global scanning of selective serotonin reuptake inhibitors: Occurrence, wastewater treatment and hazards in aquatic systems","volume":"250","author":"Mole","year":"2019","journal-title":"Environ. Pollut."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.aquatox.2017.01.001","article-title":"Metabolomics for informing adverse outcome pathways: Androgen receptor activation and the pharmaceutical spironolactone","volume":"184","author":"Davis","year":"2017","journal-title":"Aquat. Toxicol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e00161","DOI":"10.1016\/j.teac.2022.e00161","article-title":"Metabolomics in environmental toxicology: Applications and challenges","volume":"34","author":"Bedia","year":"2022","journal-title":"Trends Environ. Anal. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.1039\/D0AN02212H","article-title":"Approaches in metabolomics for regulatory toxicology applications","volume":"146","author":"Olesti","year":"2021","journal-title":"Analyst"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/14\/2952\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:09:13Z","timestamp":1760033353000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/14\/2952"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,13]]},"references-count":63,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["molecules30142952"],"URL":"https:\/\/doi.org\/10.3390\/molecules30142952","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,13]]}}}