Moderate levels of glyphosate and its formulations vary in their cytotoxicity and genotoxicity in a whole blood model and in human cell lines with different estrogen receptor status

In vitro studies were conducted to determine the short-term cytotoxic and genotoxic effects of pure glyphosate and two glyphosate formulations (Roundup (R) and Wipeout (R) ) at concentrations relevant to human exposure using whole blood (cytotoxicity) and various cancer cell lines (cytotoxicity and genotoxicity). Pure glyphosate (pure glyph) and Roundup (R) (Ro) showed similar non-monotonic toxicological profiles at low dose exposure (from 10 mu g/ml), whereas Wipeout (R) (Wo) demonstrated a monotonic reduction in cell viability from a threshold concentration of 50 mu g/ml, when tested in whole blood. We evaluated whether using various cancer cells (the estrogen-E2-responsive HEC1A, MCF7 and the estrogen-insensitive MDA-MB-231) exposed to moderate doses (75-500 mu g/ml) would indicate varied toxicity and results indicated significant effects in the HEC1A cancer cells. A non-monotonic reduction in cell viability was observed in HEC1A exposed to pure glyph (75-500 mu g/ml) and proliferative effects were observed after exposure to Wo (75, 125 and 250 mu g/ml). Genotoxicity assessment (test concentration 500 mu g/ml) demonstrated DNA damage in the HEC1A and MDA-MB-231 cells. Adjuvants and/or glyphosate impurities were potential contributing factors of toxicity based on the differential toxicities displayed by Ro and Wo in human whole blood and the HEC1A cells. This study contributes to the existing knowledge about in vitro exposure to moderate concentrations of glyphosate or glyphosate formulations at cytotoxic and genotoxic levels. In addition, a suggestion on the relevance of the estrogen receptor status of the cell lines used is provided, leading to the need to further investigate a potential endocrine disruptive role.