CRUCIAL PAPER 5:
Roundup residues interfere with multiple metabolic
pathways
Citation: M Malatesta, F Perdoni, G Santin, S Battistelli, S Muller, M
Biggiogera (2008).
Hepatoma tissue culture (HTC) cells as a model for
investigating the effects of low concentrations of herbicide on cell
structure and function.
Toxicol In Vitro. 2008 Sep 18; : 18835430
(P,S,G,E,B,D)
Abstract
Previous studies on mice fed genetically modified (GM) soybean demonstrated modifications of the mitochondrial functions and of the transcription/splicing pathways in hepatocytes. The cause(s) of these alterations could not be conclusively established but, since the GM soybean used is tolerant to glyphosate and was treated with the glyphosate-containing herbicide Roundup(trade mark), the possibility exists that the effects observed may be due to herbicide residues. In order to verify this hypothesis, we treated HTC cells with 1-10mM Roundup and analysed cellular features by flow cytometry, fluorescence and electron microscopy. Under these experimental conditions, the death rate and the general morphology of HTC cells were not affected, as well as most of the cytoplasmic organelles. However, in HTC-treated cells, lysosome density increased and mitochondrial membranes modified indicating a decline in the respiratory activity. Moreover, nuclei underwent morpho-functional modifications suggestive of a decreased transcriptional/splicing activity. Although we cannot exclude that other factors than the presence of the herbicide residues could be responsible for the cellular modifications described in GM-fed mice, the concordance of the effects induced by low concentrations of Roundup on HTC cells suggests that the presence of Roundup residues could be one of the factors interfering with multiple metabolic pathways.
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Comment
This paper follows others examining the effects of GM soy on animals in feeding experiments, and specifically looks into the "indirect" effects of the use of Roundup. Since all RR varieties have to be used with Roundup herbicide, the indirect effects associated with its use as prescribed by the manufacturer MUST be considered by the regulators, as required by law. The EU Directives relating to the planting and use of GM crops are quite clear on this point. The following is one of the "Top 25 Censored Stories for 2007" ---
New Evidence Establishes Dangers of Roundup
Sources:
Third World Resurgence, No. 176, April 2005 Title: “New Evidence of Dangers of Roundup Weedkiller” Author: Chee Yoke Heong http://www.projectcensored.org/top-stories/articles/13-new-evidence- establishes-dangers-of-roundup/
New studies from both sides of the Atlantic reveal that Roundup, the most widely used weedkiller in the world, poses serious human health threats. More than 75 percent of genetically modified (GM) crops are engineered to tolerate the absorption of Roundup—it eliminates all plants that are not GM. Monsanto Inc., the major engineer of GM crops, is also the producer of Roundup. Thus, while Roundup was formulated as a weapon against weeds, it has become a prevalent ingredient in most of our food crops.
Three recent studies show that Roundup, which is used by farmers and home gardeners, is not the safe product we have been led to trust.
A group of scientists led by biochemist Professor Gilles-Eric Seralini from the University of Caen in France found that human placental cells are very sensitive to Roundup at concentrations lower than those currently used in agricultural application.
An epidemiological study of Ontario farming populations showed that exposure to glyphosate, the key ingredient in Roundup, nearly doubled the risk of late miscarriages. Seralini and his team decided to research the effects of the herbicide on human placenta cells. Their study confirmed the toxicity of glyphosate, as after eighteen hours of exposure at low concentrations, large proportions of human placenta began to die. Seralini suggests that this may explain the high levels of premature births and miscarriages observed among female farmers using glyphosate.
Seralini’s team further compared the toxic effects of the Roundup formula (the most common commercial formulation of glyphosate and chemical additives) to the isolated active ingredient, glyphosate. They found that the toxic effect increases in the presence of Roundup ‘adjuvants’ or additives. These additives thus have a facilitating role, rendering Roundup twice as toxic as its isolated active ingredient, glyphosate.
Another study, released in April 2005 by the University of Pittsburgh, suggests that Roundup is a danger to other life-forms and non-target organisms. Biologist Rick Relyea found that Roundup is extremely lethal to amphibians. In what is considered one of the most extensive studies on the effects of pesticides on nontarget organisms in a natural setting, Relyea found that Roundup caused a 70 percent decline in amphibian biodiversity and an 86 percent decline in the total mass of tadpoles. Leopard frog tadpoles and gray tree frog tadpoles were nearly eliminated.
In 2002, a scientific team led by Robert Belle of the National Center for Scientific Research (CNRS) biological station in Roscoff, France showed that Roundup activates one of the key stages of cellular division that can potentially lead to cancer.
Belle and his team have been studying the impact of glyphosate formulations on sea urchin cells for several years. The team has recently demonstrated in Toxicological Science (December 2004) that a “control point” for DNA damage was affected by Roundup, while glyphosate alone had no effect. “We have shown that it’s a definite risk factor, but we have not evaluated the number of cancers potentially induced, nor the time frame within which they would declare themselves,” Belle acknowledges.
There is, indeed, direct evidence that glyphosate inhibits an important process called RNA transcription in animals, at a concentration well below the level that is recommended for commercial spray application.
There is also new research that shows that brief exposure to commercial glyphosate causes liver damage in rats, as indicated by the leakage of intracellular liver enzymes. The research indicates that glyphosate and its surfactant in Roundup were found to act in synergy to increase damage to the liver.
UPDATE BY CHEE YOKE HEONG
Roundup Ready weedkiller is one of the most widely used weedkillers in the world for crops and backyard gardens. Roundup, with its active ingredient glyphosate, has long been promoted as safe for humans and the environment while effective in killing weeds. It is therefore significant when recent studies show that Roundup is not as safe as its promoters claim.
This has major consequences as the bulk of commercially planted genetically modified crops are designed to tolerate glyphosate (and especially Roundup), and independent field data already shows a trend of increasing use of the herbicide. This goes against industry claims that herbicide use will drop and that these plants will thus be more “environment-friendly.” Now it has been found that there are serious health effects, too. My story therefore aimed to highlight these new findings and their implications to health and the environment.
Not surprisingly, Monsanto came out refuting some of the findings of the studies mentioned in the article. What ensued was an open exchange between Dr. Rick Relyea and Monsanto, whereby the former stood his grounds. Otherwise, to my knowledge, no studies have since emerged on Roundup.
For more information look to the following sources: Professor Gilles-Eric, criigen@ibfa.unicaen.fr Biosafety Information Center, http://www.biosafety-info.net Institute of Science in Society, http://www.i-sis.org.uk
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Reference: Sophie Richard, Safa Moslemi, Herbert Sipahutar, Nora Benachour, and Gilles-Eric Seralini (2005) Differential Effects of Glyphosate and Roundup on Human Placental Cells and Aromatase. Environmental Health Perspectives Volume 113, Number 6, June 2005
Abstract Roundup is a glyphosate-based herbicide used worldwide, including on most genetically modified plants that have been designed to tolerate it. Its residues may thus enter the food chain, and glyphosate is found as a contaminant in rivers. Some agricultural workers using glyphosate have pregnancy problems, but its mechanism of action in mammals is questioned. Here we show that glyphosate is toxic to human placental JEG3 cells within 18 hr with concentrations lower than those found with agricultural use, and this effect increases with concentration and time or in the presence of Roundup adjuvants. Surprisingly, Roundup is always more toxic than its active ingredient. We tested the effects of glyphosate and Roundup at lower nontoxic concentrations on aromatase, the enzyme responsible for estrogen synthesis. The glyphosate-based herbicide disrupts aromatase activity and mRNA levels and interacts with the active site of the purified enzyme, but the effects of glyphosate are facilitated by the Roundup formulation in microsomes or in cell culture. We conclude that endocrine and toxic effects of Roundup, not just glyphosate, can be observed in mammals. We suggest that the presence of Roundup adjuvants enhances glyphosate bioavailability and/or bioaccumulation.
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N. Benachour, H. Sipahutar, S. Moslemi, C. Gasnier, C. Travert and G. E. Seralini (2007). Time- and Dose-Dependent Effects of Roundup on Human Embryonic and Placental Cells. Archives of Environmental Contamination and Toxicology LLC 2007, 10.1007/s00244-006-0154-8 http://www.springerlink.com/content/d13171q7k863l446/fulltext.html
Abstract
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 (LD50) 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 μM 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.