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 g/ml, 17200 g/ml, and 5.7 g/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.