The use of human and veterinary drugs has led to the accumulation of pharmaceuticals in various aquatic environments at progressively increasing levels, exhibiting strong ecological risks. Metformin is widely used as a first-line prescription drug for the treatment of type 2 diabetes mellitus as well as a livestock drug. Unlike other drugs, metformin is not metabolized in the body, and almost all of its intake is excreted and released into the aquatic environment via urine and feces, causing adverse effects on aquatic ecosystems. This review provides an overview of the occurrence and detection of metformin in the aquatic environment and its toxic effects on different aquatic organisms (fish, daphnia, rotifers, chlorella). Metformin has been documented in a variety of aqueous environments such as wastewater, surface water, and groundwater as well as drinking water. The wide distribution of metformin in the aqueous environment calls for the development of more accurate detection methods. This paper reviews detection methods for metformin in the aqueous environment and evaluates their advantages and disadvantages. Toxicity studies have shown that metformin can cause adverse reactions in fish, such as oxidative stress, genotoxicity, disruption of intestinal flora, and morphological alterations; it also affects the growth and reproduction of small aquatic organisms. Knowledge gaps in the field of metformin research were assessed, and future research priorities were identified.

Polybrominated biphenyls (PBBs) are metabolically transformed into monohydroxylated PBBs (OH-PBBs) in the environment and living organisms. Although OH-PBBs pose a significant health threat to organisms, little is known about the immunotoxicity of OH-PBBs. Therefore, the objectives of this study were to validate BB-80 and OH-BB-80 induced immunotoxicity and to explore the associated pathway mechanisms. Early development of zebrafish (Danio rerio) larvae was inhibited by 10 μg/L BB-80 and OH-BB-80, as indicated by negative changes in developmental indices. BB-80 and OH-BB-80 induced oxidative stress, significantly up-regulated reactive oxygen species (ROS) and reactive nitrogen species (RNS), and activated the antioxidant enzyme system at 10 μg/L. The mRNA expression levels of inflammatory cytokines and inflammatory chemokines were up-regulated, indicative of the onset of inflammation in zebrafish after BB-80 and OH-BB-80 exposure. In addition, downregulation of toll-like receptor 4 (TLR4), MyD88, and NF-κB pathway-related genes was observed, suggesting that BB-80 and OH-BB-80 target the TLR/NF-κB signaling pathway. Molecular docking data showed that BB-80 and OH-BB-80 bound stably to TLR4. Taken together, BB-80 and OH-BB-80 mediate immunotoxicity and early developmental suppression associated with the TLR4/NF-κB signaling pathway. Our results further the understanding of BB-80- and OH-BB-80-induced immunotoxicity, highlighting the need for toxicological studies to examine the toxic effects of the transformation products of PBBs.