Ethoxylated adjuvants of glyphosate-based herbicides are active principles of human cell toxicity

Re-registration Challenges of Glyphosate in the European Union

“…Three glyphosate-based formulations, Roundup Express R , Roundup Bioforce R , Roundup GT R and Roundup GT Plus R at 5% dilutions corresponding to 0.04-2.3 mg/ml concentrations of glyphosate showed 22-97% inhibition of the mitochondial activity and activation of caspase 3/7 enzymes of HepG2 cells, while such levels of inhibition with glyphosate alone could be achieved only at or above 20 mg/ml concentration (Benachour et al, 2007;Benachour and Séralini, 2009;Gasnier et al, 2009;Mesnage et al, 2013a). Effects were similar, but even somewhat stronger on the more sensitive human Hep3G hepatic cell line (Gasnier et al, 2010).…”

“…In general, the most sensitive cell lines appeared to be the human hematopoietic Epstein-Barr virus transformed lymphocyte Raji cells (Townsend et al, 2017), regenerative fin cell lines of fish origin , human epithelial HaCaT keratinocyte cells (ElieCaille et al, 2010;Heu et al, 2012a,b;Qin et al, 2017) and a murine neuroectodermal stem cell-like line, NE-4C . In contrast, cell types with the lowest apparent sensitivity were human choriocarcinoma cells (JEG3) (Benachour et al, 2007;Benachour and Séralini, 2009;Gasnier et al, 2009;Romano et al, 2010;Mesnage et al, 2013a), human chorioplacental cells (JAr) (Young et al, 2015), human hepatoma cells (HepG2) (Benachour et al, 2007;Benachour and Séralini, 2009;Gasnier et al, 2009Gasnier et al, , 2010, murine osteoblast precursor cells (MC3T3-E1) (Farkas et al, 2018), human embryonic kidney cells (HEK293) (Benachour et al, 2007;Benachour and Séralini, 2009;Gasnier et al, 2009;Mesnage et al, 2013a), and human primary neonate umbilical vein endothelial cells (HUVEC) (Benachour et al, 2007;Benachour and Séralini, 2009;Gasnier et al, 2009). Cytotoxicity has also been detected by other biochemical markers e.g., mitochondrial functions, release of lactate dehydrogenase, cell proliferation determined by the use of sulforhodamine B, or membrane integrity and lysosomal activities indicated by the uptake of neutral red dye (Koller et al, 2012;Defarge et al, 2016).…”

“…Roundup Transorb R exerted cytotoxicity on a zebrafish (Danio rerio) hepatocyte cell line ZF-L at concentrations as low as 0.068-0.27 µg/ml (corresponding to glyphosate concentrations of 0.033-0.13 µg/ml), due mostly to lysosomal instability and inhibition of mitochondrial function, and slightly to impaired cell membrane integrity. Synergistic detrimental effects were observed when Roundup Transorb R was applied with an insecticide formulation (Furadan 350 FIGURE 3 | In vitro cytotoxicity of glyphosate (light columns) and its formulated preparation Roundup ® (dark columns) on various cell lines Raji: human hematopoietic Raji (Epstein-Barr virus transformed human lymphocyte) cells (Townsend et al, 2017), DIMF, diploid fin cell line from the Oriental weather loach Misgurnus anguillicaudatus ; HaCaT, human epithelial keratinocyte cells (Elie-Caille et al, 2010); NE-4C, murine stem cell-like neuroectodermal cells ; Hep-2, human epithelial type 2 (HeLa contaminant) cells (Mañas et al, 2009); GM38, human fibroblast cells (Monroy et al, 2005); HT1080, human fibrosarcoma cells (Monroy et al, 2005); HUVEC, primary neonate human umbilical vein endothelial cells (Benachour et al, 2007;Benachour and Séralini, 2009;Gasnier et al, 2009); HEK293, embryonic kidney cells (Benachour et al, 2007;Benachour and Séralini, 2009;Gasnier et al, 2009;Mesnage et al, 2013a); MC3T3-E1, murine osteoblast precursor cells (Farkas et al, 2018); HepG2, human hepatoma cells (Benachour et al, 2007;Benachour and Séralini, 2009;Gasnier et al, 2009); JAr, human chorioplacental cells (Young et al, 2015); JEG3, human choriocarcinoma cells (Benachour et al, 2007;Benachour and Séralini, 2009;Gasnier et al, 2009;Mesnage et al, 2013aMesnage et al, , 2017a. Plain and grid column patterns indicate cytotoxicity detected by MTT test and mutagenicity tests, respectively.…”

“…Less ethoxylated POEA products are used for emulsifying mineral oils, and as dispersants, stabilizers, sanitizers, and defoaming agents, industrial detergents, metal cleaners, textile dye-leveling agents, paper de-inking reagents, and drilling lubricants. Among a number of surfactants used in the formulation of PPPs (Table 1), POEA appears to be associated with highest toxicity concerns, particularly in of formulated glyphosate-based PPPs (Romano et al, 2010;Mesnage et al, 2013a;Székács et al, 2014;Farkas et al, 2018). Considering this unfavorable toxicity profile, particularly as related to aquatic toxicity (Prosser et al, 2017;Rodriguez-Gil et al, 2017a,b), cytotoxicity and also the assessment by EFSA (European Food Safety Authority, 2015c), the EC has recommended EU MSs in September, 2016 to exclude POEA as a co-formulant from the use in PPPs containing glyphosate (European Commission, 2016a,b).…”

Are Ready for Market Genetically Modified, Conventional and Organic Soybeans Substantially Equivalent as Food and Feed?

“…Polyoxyethylene amine (POEA) and polyethoxylated tallowamine (POE-15) are commonly used surfactants in Roundup formulations, and have been shown to contribute significantly to the toxicity of Roundup formulations Mesnage et al 2012;Moore et al 2012). However, glyphosate alone has also been shown to interfere with molecular mechanisms that regulate early development in frogs and chicken, with deformities of embryos as a consequence and the retinoic acid signaling pathway as the affected mediator (Paganelli et al 2010).…”