Cytotoxicity mechanisms and composition of the glyphosate formulated herbicide RangerPro

Understanding the nature of co-formulants and toxic effects of major glyphosate-based herbicide (GBH) formulations is considered a research priority. Indeed, the toxicity of the co-formulants present in GBHs have been widely discussed and the European Union recently banned the co-formulant polyoxyethylene tallow amine (POEA). We provide a foundation for the development of new environmental epidemiological studies by reporting the presence of the most commonly used POEA, known as POE-15 tallow amine, in the widely used US GBH RangerPro. In order to understand if POE-15 tallow amine is present in RangerPro at a concentration at which it can exert toxic effects, we also tested the cytotoxicity of this GBH compared to glyphosate and POE-15 tallow amine in the human epithelial cell line Caco-2, a representative of the human intestinal epithelium, and the first to be exposed from the human diet to glyphosate herbicides. The lethal concentration 50 for each of these substances was 125 μg/ml, 17200 μg/ml, and 5.7 μg/ml, for RangerPro, glyphosate and POE-15, respectively. The Caco-2 cell cytotoxicity assay indicated that RangerPro is more cytotoxic than glyphosate, suggesting that its toxicity can be due to the presence of the POE-15 surfactant. RangerPro and POE-15 tallow amine but not glyphosate exerted cell necrotic effects, but did not induce oxidative stress. We show that RangerPro contains POE-15 tallow amine at a concentration at which it could exert toxic effects, which offers a starting point for conducting surveys of co-formulant exposure in human populations.