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They may negatively affect nontarget organisms even at low environmental concentrations. To make an accurate risk evaluation, the (eco)toxicity of both enantiomers needs to be assessed. Promethazine (PMZ) is a chiral antihistamine that has been detected in aquatic ecosystems owing to its high consumption. Promethazine undergoes metabolism in the liver, producing chiral metabolites such as promethazine sulfoxide (PMZSO) and N-desmethylpromethazine (DMPMZ) that reach water bodies. However, knowledge regarding the enantioselective toxicity of PMZ and its metabolites on aquatic organisms is missing. This study aimed to explore the potential enantioselective toxicity of PMZ and its metabolites on two relevant freshwater organisms, daphniid and fish, representing different trophic levels. The half maximal effect concentrations (EC50s) in Daphnia magna of PMZ, DMPMZ, and PMZSO were 2.33, 2.31, &amp;gt;\u20094\u2009mg L\u22121, respectively, &amp;gt; 4 and 2.50\u2009mg L\u22121 for (R) and (S)-PMZ, respectively, and &amp;gt; 4\u2009mg L\u22121 for the enantiomers of DMPMZ and PMZSO. In studies involving zebrafish, Danio rerio, (R, S)-PMZ showed a median lethal concentration (LC50) of .72\u2009mg L\u22121, and specific assays revealed that (R)-PMZ exhibited more pronounced adverse effects on larvae at the embryonic, morphological, and biochemical level than the racemate and (S)-PMZ. Toxicity and potential bioaccumulation of these compounds in daphniids and fish were also conducted using in silico tests through proprietary software. The results revealed a concordance between the experimental and predicted EC50 and LC50 values in both species.<\/jats:p>","DOI":"10.1093\/etojnl\/vgae028","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T04:22:25Z","timestamp":1736137345000},"page":"184-196","source":"Crossref","is-referenced-by-count":2,"title":["Enantioselective ecotoxicity of promethazine in two freshwater organisms: daphnia\n                    <i>(Daphnia magna)<\/i>\n                    and zebrafish (\n                    <i>Danio rerio<\/i>\n                    )"],"prefix":"10.1093","volume":"44","author":[{"given":"Maria Miguel","family":"Coelho","sequence":"first","affiliation":[{"name":"Laboratory of Organic Chemistry and Pharmaceuticals, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto , Porto,","place":["Portugal"]},{"name":"CIIMAR-Interdisciplinary Center of Marine and Environmental Research University of Porto , Matosinhos,","place":["Portugal"]},{"name":"UCIBIO-Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto , Porto,","place":["Portugal"]}]},{"given":"Ondina","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Inov4Agro, Institute for Innovation, Capacity Building and Sustainability of Agri-food Production, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD) , Vila Real,","place":["Portugal"]},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU) , Gandra,","place":["Portugal"]}]},{"given":"Ana Rita","family":"Carvalho","sequence":"additional","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU) , Gandra,","place":["Portugal"]},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, University Institute of Health Sciences\u2014CESPU , Gandra,","place":["Portugal"]}]},{"given":"Ariana","family":"P\u00e9rez-Pereira","sequence":"additional","affiliation":[{"name":"Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Inov4Agro, Institute for Innovation, Capacity Building and Sustainability of Agri-food Production, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD) , Vila Real,","place":["Portugal"]},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU) , Gandra,","place":["Portugal"]},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, University Institute of Health Sciences\u2014CESPU , Gandra,","place":["Portugal"]}]},{"given":"Cl\u00e1udia","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU) , Gandra,","place":["Portugal"]},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, University Institute of Health Sciences\u2014CESPU , Gandra,","place":["Portugal"]}]},{"given":"Carla","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Laboratory of Organic Chemistry and Pharmaceuticals, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto , Porto,","place":["Portugal"]},{"name":"CIIMAR-Interdisciplinary Center of Marine and Environmental Research University of Porto , Matosinhos,","place":["Portugal"]}]},{"given":"Fernando","family":"Remi\u00e3o","sequence":"additional","affiliation":[{"name":"UCIBIO-Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto , Porto,","place":["Portugal"]},{"name":"Associate Laboratory i4HB-Insitute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto , Porto,","place":["Portugal"]}]},{"given":"Jo\u00e3o Soares","family":"Carrola","sequence":"additional","affiliation":[{"name":"Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Inov4Agro, Institute for Innovation, Capacity Building and Sustainability of Agri-food Production, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD) , Vila Real,","place":["Portugal"]}]},{"given":"Maria Elizabeth","family":"Tiritan","sequence":"additional","affiliation":[{"name":"Laboratory of Organic Chemistry and Pharmaceuticals, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto , Porto,","place":["Portugal"]},{"name":"CIIMAR-Interdisciplinary Center of Marine and Environmental Research 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