Benachour N, Sipahutar H, Moslemi S, Gasnier C, Travert C, Séralini G E
Laboratoire Estrogénes et Reproduction, USC-INRA, IBFA, Université de Caen, Caen, France.
Arch Environ Contam Toxicol. 2007 Jul;53(1):126-33. doi: 10.1007/s00244-006-0154-8. Epub 2007 May 4.
Roundup is the major herbicide used worldwide, in particular on genetically modified plants that have been designed to tolerate it. We have tested the toxicity and endocrine disruption potential of Roundup (Bioforce on human embryonic 293 and placental-derived JEG3 cells, but also on normal human placenta and equine testis. The cell lines have proven to be suitable to estimate hormonal activity and toxicity of pollutants. The median lethal dose (LD(50)) of Roundup with embryonic cells is 0.3% within 1 h in serum-free medium, and it decreases to reach 0.06% (containing among other compounds 1.27 mM glyphosate) after 72 h in the presence of serum. In these conditions, the embryonic cells appear to be 2-4 times more sensitive than the placental ones. In all instances, Roundup (generally used in agriculture at 1-2%, i.e., with 21-42 mM glyphosate) is more efficient than its active ingredient, glyphosate, suggesting a synergistic effect provoked by the adjuvants present in Roundup. We demonstrated that serum-free cultures, even on a short-term basis (1 h), reveal the xenobiotic impacts that are visible 1-2 days later in serum. We also document at lower non-overtly toxic doses, from 0.01% (with 210 microM glyphosate) in 24 h, that Roundup is an aromatase disruptor. The direct inhibition is temperature-dependent and is confirmed in different tissues and species (cell lines from placenta or embryonic kidney, equine testicular, or human fresh placental extracts). Furthermore, glyphosate acts directly as a partial inactivator on microsomal aromatase, independently of its acidity, and in a dose-dependent manner. The cytotoxic, and potentially endocrine-disrupting effects of Roundup are thus amplified with time. Taken together, these data suggest that Roundup exposure may affect human reproduction and fetal development in case of contamination. Chemical mixtures in formulations appear to be underestimated regarding their toxic or hormonal impact.
农达是全球使用的主要除草剂，尤其用于那些经设计可耐受它的转基因植物。我们已测试了农达（生物制剂）对人胚胎293细胞和胎盘来源的JEG3细胞的毒性及内分泌干扰潜力，还测试了其对正常人类胎盘和马睾丸的影响。已证明这些细胞系适用于评估污染物的激素活性和毒性。在无血清培养基中，农达对胚胎细胞的半数致死剂量（LD(50)）在1小时内为0.3%，在有血清存在的情况下培养72小时后降至0.06%（含有1.27 mM草甘膦等其他化合物）。在这些条件下，胚胎细胞似乎比胎盘细胞敏感2至4倍。在所有情况下，农达（在农业中通常使用浓度为1 - 2%，即含有21 - 42 mM草甘膦）比其活性成分草甘膦更有效，这表明农达中的助剂引发了协同效应。我们证明，即使是短期（1小时）的无血清培养，也能揭示1 - 2天后在血清中可见的外源性物质影响。我们还记录到在较低的非明显毒性剂量下，即24小时内0.01%（含210 microM草甘膦），农达是一种芳香化酶干扰剂。这种直接抑制作用是温度依赖性的，并在不同组织和物种（胎盘或胚胎肾细胞系、马睾丸细胞系或人类新鲜胎盘提取物）中得到证实。此外，草甘膦直接作为微粒体芳香化酶的部分失活剂，与其酸度无关，且呈剂量依赖性。因此，农达的细胞毒性以及潜在的内分泌干扰作用会随时间增强。综上所述，这些数据表明，在受到污染的情况下，接触农达可能会影响人类生殖和胎儿发育。制剂中的化学混合物在其毒性或激素影响方面似乎被低估了。
