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By Dr. Mae-Wan Ho and Brett Cherry
Scientists were able to establish how very low concentrations of the herbicide and other chemicals present in the formulations of the Roundup line cause the death of human cells, thus strengthening the demand for their progressive withdrawal from the market, and an immediate ban on all new release of Roundup tolerant GM crops.
This article was submitted to the US Department of Agriculture (USDA), through the Institute for Science in Society (ISIS). All four formulations of the Roundup line of the herbicide glyphosate, manufactured by Monsanto, are highly toxic to human cells, and at concentrations well below recommended levels for agricultural use.
Researchers from the Institute of Biology in Caen, France, published their latest results in the current issue of the prestigious journal Chemical Research in Toxicology .
Roundup formulations are lethal cocktails. The four formulations in the Roundup line are mixtures of glyphosate with different adjuvants. (An adjuvant is an "auxiliary" substance that is added to increase the effectiveness of the active ingredient).
Roundup formulations are currently and increasingly the world's best-selling non-selective herbicide, with more than 75 percent of genetically modified (GM) crops being Roundup tolerant. Glyphosate and its main metabolite, amino-methyl-phosphonic acid (AMPA), are important pollutants in rivers. Adjuvants, often unmeasured in the environment, are commonly considered "inert" and are protected as a trade secret by the manufacturing industry. Among them, the predominant one is polyoxyethylene amine (POEA).
POEA is used as a surfactant * in Roundup formulations to improve solubility and penetration into plants. The assays were performed on three human cell lines: the HUVEC primary cell line, derived from human umbilical cord epithelium, the human kidney-derived 293 embryonic cell line, and the JEG3 placental cell line. All cells died within 24 hours of exposure to the Roundup formulations. Roundup (R) formulations contain different amounts of the active ingredient glyphosate: Roundup Express, 7.2 g / l (R 7.2); Roundup Bioforce, 360 g / l (R 360); Roundup Grand Travaux, 400 g / l (R 400) and Roundup Grand Travaux Plus, 450 g / l (R 450).
These formulations were compared with glyphosate (G), AMPA, and POEA. All Roundup formulations under study, as well as individual chemical components, were tested at concentrations from 10 ppm (parts per million) to 2 percent (the recommended level for agricultural use), which means that the Roundup formulations were diluted up to 100,000 times or more.
The researchers found that the presence of the other chemicals in Roundup formulations, such as POEA, actually amplified the toxic effects of glyphosate. The toxicity levels of the Roundup formulations were not proportional to the amount of glyphosate they contain, and it is very likely that they are due to the POEA and some other secret ingredient (s) present in all the formulations. POEA alone is much more toxic than Roundup formulations, while AMPA is more toxic than glyphosate.
Multiple targets in toxicity
The researchers tested the effects of the formulations Roundup (Rs), glyphosate (G), AMPA and POEA on three target targets that could lead to cell death: damage to the cell membrane, poisoning of the mitochondria (site of energy metabolism) , and programmed cell death that results in the fragmentation of DNA from the cell nucleus. They measured specific enzyme markers at different concentrations for each damage after 24 h of exposure, and also imaged the cell cultures under a microscope.
All R formulations, as well as G, caused cell death; the results were the same for all human cell types, but at different concentrations. Thus, R 400, the most toxic formulation, killed all cells at 20 ppm, which is equivalent to 8 ppm in G.
However, G alone, in concentrations of 4-10 ppm, is not toxic; its toxicity starts at around 1 percent (10,000 ppm), and it is not connected to the cell membrane. R formulations damage the cell membrane, and they also poison the mitochondria. In contrast, G poisons the mitochondria without damaging the cell membrane.
Contrary to expectations, the R 400 formulation is more toxic than R 450; the latter, on the other hand, is more harmful than R 360, R 7.2 and G. However, the respective toxicities were not proportional to the concentration of G present. The lethal power in R 7.2 cells was almost the same as that of R 360, and these results were consistent across all cell lines.
This suggests that other unknown substances are involved in the toxic effects. Thus, AMPA and POEA also cause cell death by intoxication of the mitochondria and damage to the cell membrane. The surfactant POEA is so potent that it begins to damage the cell membrane in HUVEC and poison the mitochondria at 2 93 and JEG3 at doses of 1 ppm. Roundup formulations are more toxic than G or AMPA. The AMPA metabolite alone destroys the cell membrane, however, G does not do this, although it is 3 to 8 times more toxic to the mitochondria than AMPA. But, as damage to the cell membrane is more serious for the cell, AMPA is more toxic than G, while POEA is the most harmful of all.
What happens when these ingredients are combined? The researchers found that for HUVEC and 293 cells, the combinations of G and POEA, of G and AMPA, of AMPA and POEA were more toxic than the same concentration of the ingredients considered individually. For programmed cell death, the action is faster.
Marker enzymes are activated after 6 hours of exposure, with a maximum of 12 hours in all cases. The HUVEC line is 60-160 times more sensitive than the other cell lines; G and R 360 are effective at exactly the same concentration, starting at 50 ppm. Adjuvants do not appear to be necessary. The individually considered G is 30 percent more powerful here than the Rs; it acted rapidly at concentrations 500-1000 times lower than those for agricultural use.
Roundup-tolerant GM crops ban
These latest studies confirm the abundant evidence accumulated on the toxicity of glyphosate and Roundup formulations  (Glyphosate Toxic & Roundup Worse, "Glyphosate is toxic and Roundup is more", SiS No. 26), and determine the different sites of action, all of which result in cell death. Several previous epidemiological studies have linked glyphosate to spontaneous abortions, non-Hodgkin's lymphoma, and multiple myeloma.
Laboratory studies have shown that glyphosate inhibits transcription in sea urchin eggs and delays development. Brief exposure to glyphosate in rats caused liver damage, and the addition of the surfactant in Roundup had a synergistic effect, causing further liver damage. Roundup was also found to be much more lethal to frogs than to weeds, and that it may have contributed to the worldwide disappearance of amphibians in recent decades  (Roundup kills grogs, SiS No. 26).
We demand a new revision of the regulation on glyphosate and Roundup in 2005 . There are now well-founded reasons for its restriction, if not for a progressive withdrawal of glyphosate and Roundup; in the first instance, by banning the release of Roundup-tolerant GM crops around the world. For the same reason, no new Roundup-tolerant GM crops should be approved for commercial release.
Benachour N. and Séralini G-E. Glyphosate formulations Induce Apoptosis and Necrosis in Human Umbilical, Embryonic, and Placental Cells. Chem. Res. Toxicol., 2009, 22 (1), pp. 97-105
Ho M. W. and Cummins J. Glyphosate toxic and Roundup worse, Science in Society No. 26, 12, 2005. http://www.i-sis.org.uk/GTARW.php
Ho M. Roundup kills grogs, Science in Society No. 26 http://www.i-sis.org.uk/isisnews/sis26.php. 13, 2005.
The English original of this article can be read at: ISIS http://www.i-sis.org.uk/DMPGR.php
* N. of the T .: A surfactant is a substance that reduces the surface tension of the air-liquid interface, facilitating the penetration of a certain product.
Translation: Gladys Guiñez for Action for Biodiversity - http://www.biodiversidadla.org