Effects of glyphosate and glyphosate-based herbicides on amphibian development from early cleavage to metamorphosis: A systematic review of laboratory evidence

Glyphosate (GLY) and glyphosate-based herbicides (GBHs) are among the most widely applied herbicides worldwide and are frequently detected in surface waters where amphibians breed and develop, a taxon currently undergoing pronounced global declines. Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we systematically reviewed the effects of GLY and GBHs on amphibian development from early cleavage to metamorphosis and identified 70 eligible peer-reviewed studies in PubMed and Web of Science. Overall, lethal toxicity spanned several orders of magnitude (LC50 (96h) from 0.8 to 5257 mg/L), however, GBHs were generally more toxic than pure GLY. Lethal sensitivity varied widely across exposure characteristics, specific formulation products and amphibian developmental stages, with early larval stages being most susceptible. Sublethal effects were demonstrated across a wide range of concentrations from 0.0007 to 440 mg/L and spanned multiple biological levels, including gene-related defects and molecular levels up to histopathological changes affecting various organ systems in developing amphibians. Notably, many sublethal and some lethal endpoints occurred at, or below, concentrations measured in surface waters (∼0.1-2.8 mg/L with peaks up to 105 mg/L), including levels within legally permitted freshwater limits (0.0001-0.80 mg/L). Environmentally realistic exposures can disrupt amphibian development and reduce metamorphic success and juvenile fitness, potentially contributing to ongoing population declines. Despite this sensitivity, amphibians remain underrepresented in regulatory risk-assessment frameworks. Knowledge gaps in taxonomic coverage, formulation transparency, reported endpoints and mechanistic understanding further hinder robust risk assessment.