Developmental toxicity of glyphosate, its formulations and AMPA in non-target organisms: Insights from zebrafish embryos and larvae

This review comprehensively examines the developmental toxicity of glyphosate (GLY), its commercial formulations, and its major metabolite, aminomethylphosphonic acid (AMPA), specifically focusing on their effects in non-target organisms, with zebrafish embryos and larvae as model system. GLY-based herbicides are widely used to control weeds in agricultural and non-agricultural areas, leading to concerns about their environmental impact and potential risks to human. We summarize the observed adverse developmental effects, which include disruptions in brain development, cardiovascular abnormalities, altered immune responses, impaired energy metabolism, craniofacial dysostosis, skeletal malformations and endocrine interference. These findings are critical as they indicate that exposure to GLY and its derivatives during early developmental stages can lead to significant and potentially irreversible developmental disruptions. Despite these observations, the precise biochemical and molecular mechanisms driving these toxic effects remain largely unclear. Key areas under investigation include the role of oxidative stress, endoplasmic reticulum stress, and mitochondrial dysfunction in mediating these adverse developmental outcomes. There is a pressing need for further studies to elucidate these mechanisms and to understand the long-term effects of chronic, low-dose exposure. Moreover, the potential for bioaccumulation of GLY and AMPA raises additional concerns about the implications for both ecosystem health and human health through the food chain. This review highlights the importance of advancing research in this area to better inform regulatory decisions and to develop strategies for mitigating the risks associated with glyphosate use.