Archives of Environmental Contamination and Toxicology. 53, 126–133 (2007)
N. Benachour, 1 H. Sipahutar, 2 S. Moslemi, 3 C. Gasnier, 1 C. Travert, 1 G. E. Séralini 1
1Laboratoire Estrogènes et Reproduction, USC-INRA, IBFA, UniversitØ de Caen, Caen, France
2Department of Biology, State University of Medan, Medan, Indonesia
3Laboratoire de Biochimie du Tissu Conjonctif, EA3214, CHU Côte de Nacre, Caen, France
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 (BioforceÒ) 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 serumfree 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-termbasis (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 lM 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.
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