Toxicity Risks Associated With the Beta-Blocker Metoprolol in Marine and Freshwater Organisms: A Review

The detection of pharmaceuticals in aquatic ecosystems has generated concern for wildlife and human health over the past several decades. β-adrenergic blocking agents are a class of drugs designed to treat cardiovascular diseases and high blood pressure. Metoprolol is a second-generation β1-adrenergic receptor inhibitor detected in effluent derived from sewage treatment plants. Our review presents an updated survey of the current state of knowledge regarding the sources, occurrence, and toxicity of metoprolol in aquatic ecosystems. We further aimed to summarize the current literature on the presence of metoprolol in various classes of aquatic species and to consider the trophic transfer of these contaminants in marine mammals. The biological impacts of metoprolol have been reported in 20 aquatic organisms, with a primary focus on cardiac function and oxidative stress. Our review reveals that concentrations of metoprolol that cause toxicity in aquatic species are above levels that are typical of marine and freshwater environments. Future studies should investigate the effects of metoprolol at lower concentrations in aquatic organisms. Other recommendations include (1) a further focus on noncardiac endpoints, because computational assessments of currently available molecular data identify gonadotropins, vitellogenin, collagen, and cytokines as potential targets of modulation, and (2) development of adverse outcome pathways for cardiac dysfunction in aquatic species to improve our understanding of molecular interactions and outcomes following exposure. As the next generation of β-blockers is developed, continued diligence is needed for assessing environmental impacts in aquatic ecosystems to determine their potential accumulation and long-term effects on wildlife and humans. Environ Toxicol Chem 2024;43:2530-2544. © 2024 SETAC.