Metolachlor exposure induces immune impairment and activates TLR4/NF-κB signaling in zebrafish embryos.

As a herbicide, Metolachlor (MET) has emerged as an 'invisible pollutant' due to its prolonged half-life, high water solubility, and extensive application scope, which pose potential threats to aquatic ecosystems and human health. Nonetheless, systematic evaluations of MET's effects on early growth development and immune mechanisms in vertebrates have been limited. This study is the first to systematically assess the immunotoxic effects of MET on non-target organisms, utilizing zebrafish as a model. The results indicate that exposure to MET reduces embryo hatching rates, slows heart rates, increases mortality, decreases body length, and diminishes immune cell populations. Furthermore, it disrupts the expression of immune response genes and significantly upregulates gene expression levels associated with oxidative stress and apoptosis. Comprehensive analysis reveals that the oxidative stress-TLR4 axis serves as the central regulatory pathway underlying MET-induced embryonic developmental toxicity and immunotoxicity in zebrafish. This study provides critical molecular evidence for the development of environmentally friendly alternatives to herbicides, and its framework can be applied to the ecological risk assessment of other emerging pollutants.