Synergistic interactions between the emerging contaminant ivermectin and the ubiquitous pesticide glyphosate at an environmentally relevant ratio on Rhinella arenarum larvae

Glyphosate (GLY) is a widely used broad-spectrum herbicide, and ivermectin (IVM) is a commonly used antiparasitic in livestock farming. Both substances can be found in water bodies from agricultural areas and can have negative impacts on ecosystems. The aim of this study was to evaluate the lethal and sublethal toxicity individually and in combination of a glyphosate-based herbicide (GBH) and an ivermectin commercial formulation (ICF). Groups of 10 larvae were exposed for 504 h, in triplicate to a concentration gradient of the commercial formulation of glyphosate and ivermectin, individually, and to a series of dilutions of a non-equitoxic mixture of both compounds based on environmental concentrations. Additionally, biomarkers of oxidative stress (catalase, glutathione S-transferase, and reduced glutathione) and neurotoxicity (acetylcholinesterase and butyrylcholinesterase) were evaluated at sublethal and environmental concentrations of ivermectin (0.00125 mg/L) and glyphosate (0.7 mg/L) individually and in mixture. The ICF (LC50-504h: 0.047 mg ai IVM/L) was more toxic to larvae than the GBH (LC50-504h: 24.73 mg ae GLY/L). In terms of lethality, exposure to the mixture was synergistic at all exposure times. Both compounds separately caused alterations in the biomarkers of oxidative stress and neurotoxicity. Regarding sublethal effects in organisms exposed to the mixture, potentiation was observed in acetylcholinesterase. The simultaneous exposure to both substances in water bodies can have synergistic and negative effects on aquatic organisms.