Cytotoxicity on human cells of Cry1Ab and Cry1Ac Bt insecticidal toxins alone or with a glyphosate-based herbicide
Mesnage R., Clair E., Gress S., Then C., Székács A., Séralini G.-E Article first published online: 15 FEB 2012, Journal of Applied Toxicology
The study of combined effects of pesticides represents a challenge for toxicology. In the case of the new growing generation of genetically modified (GM) plants with stacked traits, glyphosate-based herbicides (like Roundup) residues are present in the Roundup-tolerant edible plants (especially corns) and mixed with modified Bt insecticidal toxins that are produced by the GM plants themselves. The potential side effects of these combined pesticides on human cells are investigated in this work. Here we have tested for the very first time Cry1Ab and Cry1Ac Bt toxins (10 ppb to 100 ppm) on the human embryonic kidney cell line 293, as well as their combined actions with Roundup, within 24 h, on three biomarkers of cell death: measurements of mitochondrial succinate dehydrogenase, adenylate kinase release by membrane alterations and caspase 3/7 inductions. Cry1Ab caused cell death from 100 ppm. For Cry1Ac, under such conditions, no effects were detected. The Roundup tested alone from 1 to 20 000 ppm is necrotic and apoptotic from 50 ppm, far below agricultural dilutions (50% lethal concentration 57.5 ppm). The only measured significant combined effect was that Cry1Ab and Cry1Ac reduced caspases 3/7 activations induced by Roundup; this could delay the activation of apoptosis. There was the same tendency for the other markers. In these results, we argue that modified Bt toxins are not inert on nontarget human cells, and that they can present combined side-effects with other residues of pesticides specific to GM plants. Copyright © 2012 John Wiley & Sons, Ltd.
Insecticidal Bt toxins such as those produced in genetically engineered plants can be detrimental to human cells. This is a result of recent research led by researchers at the University of Caen (France). Their experiments showed that toxins produced in, for example, the genetically engineered maize MON810, can significantly impact the viability of human cells. The effects were observed with relatively high concentrations of the toxins, nevertheless there is cause for concern. According to companies like Monsanto, which produces genetically engineered maize with these toxins, the toxins are supposed to be active only against particular insects and should have no effect on mammals and humans at all. For the first time, experiments have now shown that they can have an effect on human cells. These kinds of investigations are not a requirement for risk assessment in Europe or in any other region.
Another finding of the researchers concerns a herbicide formulation sold under the brand name Roundup. Massive amounts of this herbicide are sprayed on genetically engineered soybean crops and its residues can be found in food and feed. According to the new publication, even extremely low dosages of Roundup (glyphosate formulations) can damage human cells. These findings are in accordance with several other investigations highlighting unexpected health risks associated with glyphosate preparations.
“We were very much surprised by our findings. Until now, it has been thought almost impossible for Bt proteins to be toxic to human cells. Now further investigations have to be conducted to find out how these toxins impact the cells and if combinatorial effects with other compounds in the food and feed chain have to be taken into account,” says Gilles-Eric Séralini from the University of Caen, who supervised the experiments. “In conclusion, these experiments show that the risks of Bt toxins and of Roundup have been underestimated.”
Bt toxins and tolerance to herbicides are broadly used in genetically engineered plants. Bt proteins only naturally occur in soil bacteria. By introducing the modified toxin gene into the plants, the structure of the toxins is modified and may thereby cause selectivity to be changed. The content of the proteins within the plants is highly variable. Many genetically engineered plants contain several Bt toxins at the same time. For example, SmartStax produces six different Bt toxins and therefore has a higher overall content of the proteins. In addition, it was made tolerant to herbicides. So far, there has been no investigation of the combinatorial effects of these toxins and residues from spraying, or their potential risks for human health, which was considered unlikely. The researchers have now shown that interactivity does occur. Under the specific conditions of their experiment, the modified Bt toxin lowered the toxicity of Roundup. Further investigations are necessary to examine other potential combinatorial effects under varying conditions.
“These results are pretty worrying. Risk assessment requirements for genetically engineered plants and pesticides need to be rigidly enforced. In the light of these findings, we think that the commercialization of these plants is not in accordance with EU regulations”, says Christoph Then at Testbiotech. Testbiotech is closely following risk assessment at the European Food Safety Authority EFSA and has repeatedly brought attention to gaps in risk assessment.
The research was supported by GEKKO foundation (Germany). CRIIGEN Association (France) and Testbiotech (Germany) were involved in planning the experiments and the discussion of results.
Findings were published after peer review process. Mesnage R., Clair E., Gress S., Then C., Székács A., Séralini G.-E., 2012, Cytotoxicity on human cells of Cry1Ab and Cry1Ac Bt insecticidal toxins alone or with a glyphosate-based herbicide, Journal of Applied Toxicologyhttp://onlinelibrary.wiley.com/doi/10.1002/jat.2712/abstract
Contacts: Professor Gilles-Eric Séralini, France: email@example.com www.criigen.org Christoph Then, Testbiotech, Germany: +49.15154638040, firstname.lastname@example.org, www.testbiotech.org