Enantioselective ecotoxicity of promethazine in two freshwater organisms: daphnia (Daphnia magna) and zebrafish ( Danio rerio )

Journal Article · 05 January 2025 · Environmental Toxicology and Chemistry

DOI: https://doi.org/10.1093/etojnl/vgae028 · OSTI ID:2507498

Coelho, Maria Miguel; Ribeiro, Ondina; Carvalho, Ana Rita; Pérez-Pereira, Ariana; Ribeiro, Cláudia; Fernandes, Carla; Remião, Fernando; Carrola, João Soares; Tiritan, Maria Elizabeth

Abstract Chiral pharmaceuticals, racemic or enantiomerically pure forms and their metabolites, can reach aquatic ecosystems via wastewater effluents (inefficient treatment operations) or by direct human disposal. 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, > 4 mg L−1, respectively, > 4 and 2.50 mg L−1 for (R) and (S)-PMZ, respectively, and > 4 mg L−1 for the enantiomers of DMPMZ and PMZSO. In studies involving zebrafish, Danio rerio, (R, S)-PMZ showed a median lethal concentration (LC50) of .72 mg L−1, 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.

• Sponsoring Organization: USDOE; USDOE Office of Nuclear Energy (NE), Nuclear Fuel Cycle and Supply Chain
• OSTI ID: 2507498
• Journal Information: Environmental Toxicology and Chemistry, Journal Name: Environmental Toxicology and Chemistry Journal Issue: 1 Vol. 44; ISSN 0730-7268
• Publisher: Oxford University PressCopyright Statement
• Country of Publication: United States
• Language: English