Risks of caffeine residues in the environment: Necessity for a targeted ecopharmacovigilance program.

Due to the huge consumption of caffeinated food, beverages and medicines around the world, caffeine has been considered as a most representative pharmaceutically active compound (PhAC) pollutant based on its high abundance in environment and its indicator property for anthropogenic inputs of PhACs to water bodies. This review analyzed the existing literature about the bioaccumulation and environmental risks of caffeine residues in non-target organisms. There are 6 studies which were published in the last 5 years have reported the distribution of caffeine in tissues of aquatic organisms including fishes, clams, macroalgae and other aquatic plants, suggesting bioaccumulation of caffeine in organisms. The maximum detected levels of caffeine residues in tissues ranged from 1.55 to 344.9 ng/g. Importantly, definitive evidences have been provided that environmentally relevant caffeine concentrations exert adverse impacts on aquatic species and terrestrial insects, which included lethality, decreasing general stress, inducing oxidative stress and lipid peroxidation, affecting energy reserves and metabolic activity, neurotoxic effects, affecting reproduction and development, etc. In view of the severity and potential adverse impacts of caffeine pollution in the environment, we proposed that caffeine should be considered as a high-priority environmentally hazardous PhAC pollutant, and it is necessary to implement an ecopharmacovigilance (EPV) program targeting caffeine to minimize its environmental load from a pharmacy perspective.