19 research outputs found

    Republished study: long-term toxicity of a Roundup herbicide and a Roundup-tolerantgenetically modified maize

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    The health effects of a Roundup-tolerant NK603 genetically modified (GM) maize (from 11% in the diet), cultivated with or without Roundup application and Roundup alone (from 0.1 ppb of the full pesticide containing glyphosate and adjuvants) in drinking water, were evaluated for 2 years in rats. This study constitutes a follow-up investigation of a 90-day feeding study conducted by Monsanto in order to obtain commercial release of this GMO, employing the same rat strain and analyzing biochemical parameters on the same number of animals per group as our investigation. Our research represents the first chronic study on these substances, in which all observations including tumors are reported chronologically. Thus, it was not designed as a carcinogenicity study. We report the major findings with 34 organs observed and 56 parameters analyzed at 11 time points for most organs

    Co-formulants in glyphosate-based herbicides disrupt aromatase activity in human cells below toxic levels

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    Pesticide formulations contain declared active ingredients and co-formulants presented as inert and confidential compounds. We tested the endocrine disruption of co-formulants in six glyphosate-based herbicides (GBH), the most used pesticides worldwide. All co-formulants and formulations were comparably cytotoxic well below the agricultural dilution of 1% (18-2000 times for co-formulants, 8-141 times for formulations), and not the declared active ingredient glyphosate (G) alone. The endocrine-disrupting effects of all these compounds were measured on aromatase activity, a key enzyme in the balance of sex hormones, below the toxicity threshold. Aromatase activity was decreased both by the co-formulants alone (polyethoxylated tallow amine—POEA and alkyl polyglucoside—APG) and by the formulations, from concentrations 800 times lower than the agricultural dilutions; while G exerted an effect only at 1/3 of the agricultural dilution. It was demonstrated for the first time that endocrine disruption by GBH could not only be due to the declared active ingredient but also to co-formulants. These results could explain numerous in vivo results with GBHs not seen with G alone; moreover, they challenge the relevance of the acceptable daily intake (ADI) value for GBHs exposures, currently calculated from toxicity tests of the declared active ingredient alone.Fil: Defarge, Nicolas. Universite de Caen Basse Normandie; Francia. CRIIGEN; FranciaFil: Takács, Eszter. National Agricultural Research and Innovation Centre; HungríaFil: Lozano, Verónica Laura. Universite de Caen Basse Normandie; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mesnage, Robin. Universite de Caen Basse Normandie; Francia. CRIIGEN; FranciaFil: de Vendômois, Joël Spiroux. CRIIGEN; FranciaFil: Séralini, Gilles Eric. Universite de Caen Basse Normandie; Francia. CRIIGEN; FranciaFil: Székács, András. National Agricultural Research and Innovation Centre; Hungrí

    Sex-dependent impact of Roundup on the rat gut microbiome

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    A growing body of research suggests that dysbiosis of the gut microbiota induced by environmental pollutants, such as pesticides, could have a role in the development of metabolic disorders. We have examined the long-term effects of 3 doses of the Roundup(R) herbicide (made of glyphosate and formulants) on the gut microbiota in male and female Sprague-Dawley rats. A total of 141 bacteria families were identified by a 16S sequencing analysis approach. An OPLS-DA analysis revealed an increased Bacteroidetes family S24-7 and a decreased Lactobacillaceae in 8 out of the 9 females treated with 3 different doses of R (n = 3, for each dose). These effects were confirmed by repetitive sequence-based PCR fingerprinting showing a clustering of treated females. A culture-based method showed that R had a direct effect on rat gut microbiota. Cultivable species showed different sensitivities to R, including the presence of a high tolerant or resistant strain identified as Escherichia coli by 16S rRNA sequencing. The high tolerance of this E. Coli strain was explained by the absence of the EPSPS gene (coding glyphosate target enzyme) as shown by DNA amplification. Overall, these gut microbiome disturbances showed a substantial overlap with those associated with liver dysfunction in other studies. In conclusion, we revealed that an environmental concentration of R (0.1 ppb) and other two concentrations (400 ppm and 5,000 ppm) have a sex-dependent impact on rat gut microbiome composition and thus warrants further investigation.Fil: Lozano, Verónica Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universite de Caen Basse Normandie; FranciaFil: Defarge, Nicolas. Universite de Caen Basse Normandie; Francia. CRIIGEN; FranciaFil: Rocque, Louis-Marie. CRIIGEN; Francia. AdGène Laboratoire; FranciaFil: Mesnage, Robin. AdGène Laboratoire; Francia. Guy's Hospital; Reino UnidoFil: Hennequin, Didier. Universite de Caen Basse Normandie; FranciaFil: Cassier, Renaud. AdGène Laboratoire; FranciaFil: de Vendômois, Joël Spiroux. CRIIGEN; FranciaFil: Panoff, Jean-Michel. CRIIGEN; Francia. Universite de Caen Basse Normandie; FranciaFil: Séralini, Gilles Eric. CRIIGEN; Francia. Universite de Caen Basse Normandie; FranciaFil: Amiel, Caroline. CRIIGEN; Francia. Universite de Caen Basse Normandie; Franci

    Dig1 protects against locomotor and biochemical dysfunctions provoked by Roundup

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    International audienceBACKGROUND: Plant medicinal extracts may be claimed to prevent or cure chemical intoxications. Few of these are tested for their mechanisms of actions in vivo and for their cellular impacts. In 2011, we demonstrated that hepatic cell mortality induced by environmentally realistic levels of the widely used herbicide Roundup (R) in vitro can be almost entirely prevented by plant extracts called Dig1 (D, Digeodren).METHODS: We tested the in vivo effects of D alone (1.2 ml/kg bw/d), but also prior to and during 8 days of R intoxication (at 135 mg/kg bw/d) in a total of 4 groups of 40 adult Sprague-Dawley male rats each. After treatments, horizontal and vertical locomotor activities of the animals were measured by use of actimeters. Brain, liver, kidneys, heart and testes were collected and weighted. Body weights as well as feed and water consumption were recorded. Proteins, creatinine, urea, phosphate, potassium, sodium, calcium, chloride ions, testosterone, estradiol, AST and ALT were measured in serum. In liver S9 fractions, GST, GGT, and CYP450 (1A2, 2C9, 2C19, 2D6, 3A4) were assessed.RESULTS: D did not have any physiological or biochemical observable impact alone at 2 %. Out of a total of 29 measured parameters, 8 were significantly affected by R absorption within only 8 days. On these 8 parameters, only 2 were not restored by D (GGT activity and plasmatic phosphate), 5 were totally restored (horizontal and vertical locomotor activities, CYP2D6 activity, plasmatic Na + and estradiol), and the 6th was almost restored (plasmatic K+). The specificities of the toxic effects of R and of the therapeutic effects of D treatment were thus demonstrated, both at the behavioural and biochemical levels.CONCLUSIONS: D, without any side effect observable in these conditions, presented strong preventive and therapeutic properties in vivo after a short-term intoxication by the widely used pesticide Roundup

    Impact of antibiotics on efficacy of Cry toxins produced in two different genetically modified Bt maize varieties in two lepidopteran herbivore species, Ostrinia nubilalis and Spodoptera littoralis

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    The insecticidal crystal proteins from Bacillus thuringiensis (Bt) are widely-used biopesticides that are used both as Bt spore-crystal preparations in sprayable formulations and as activated toxins in genetically modified (GM) plants. Models for their modes of action have been proposed but many issues remain unresolved. Among those is the role of commensal gut bacteria in target insect death: previous studies showed that antibiotics attenuate the toxicity of Bt sprays. We tested whether antibiotics interfere with the effects of GM plant-produced Bt toxins in larvae of two Lepidopteran species, the European corn borer Ostrinia nubilalis and the cotton leafworm Spodoptera littoralis. The larvae were reared on artificial diet with or without antibiotics and, thereafter, fed two varieties of Bt GM maize in comparison to conventional non-Bt maize leaves sprayed with antibiotic solution and/or with a Bt formulation. Antibiotics significantly reduced or delayed the toxicity of Cry toxins, although to a lesser extent than previously reported for Bt-sprays. This supports the hypothesis that Cry toxins induce mortality by themselves in the absence of Bt bacteria and spores, and of commensal gut bacteria. However, larvae that were not treated with antibiotics died faster and at a higher rate which was further compounded by plant variety and species sensitivity. These findings support a hypothesis that toxicemia alone can inflict significant mortality. However, in the absence of antibiotics, the gut bacteria likely enhance the Cry toxin effect by inflicting, additionally, bacterial septicemia. This has important implications in field situations where antibiotic substances are present—e.g., from manure of animals from conventional production systems—and for ecotoxicological testing schemes of Bt toxins and nontarget organisms that are often using artificial diets enriched with high concentrations of antibiotics

    Laboratory Rodent Diets Contain Toxic Levels of Environmental Contaminants: Implications for Regulatory Tests.

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    The quality of diets in rodent feeding trials is crucial. We describe the contamination with environmental pollutants of 13 laboratory rodent diets from 5 continents. Measurements were performed using accredited methodologies. All diets were contaminated with pesticides (1-6 out of 262 measured), heavy metals (2-3 out of 4, mostly lead and cadmium), PCDD/Fs (1-13 out of 17) and PCBs (5-15 out of 18). Out of 22 GMOs tested for, Roundup-tolerant GMOs were the most frequently detected, constituting up to 48% of the diet. The main pesticide detected was Roundup, with residues of glyphosate and AMPA in 9 of the 13 diets, up to 370 ppb. The levels correlated with the amount of Roundup-tolerant GMOs. Toxic effects of these pollutants on liver, neurodevelopment, and reproduction are documented. The sum of the hazard quotients of the pollutants in the diets (an estimator of risk with a threshold of 1) varied from 15.8 to 40.5. Thus the chronic consumption of these diets can be considered at risk. Efforts toward safer diets will improve the reliability of toxicity tests in biomedical research and regulatory toxicology

    Hazard quotients (HQ) and ΣHQ for 13 rodent diets used worldwide.

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    <p>HQ were calculated for each contaminant according to regulatory guidelines for chronic non-cancer risk characterization (EPA, Risk Assessment Guidance for Superfund RAGS Part A, Chapter 8, <a href="http://www.epa.gov/oswer/riskassessment/ragsa/" target="_blank">http://www.epa.gov/oswer/riskassessment/ragsa/</a>). HQ is the ratio of the chronic daily exposure and the ADI of each contaminant. The sum of calculated HQ (ΣHQ) is indicated.</p

    Pesticides and agricultural GMOs used worldwide.

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    <p>Data from ‘Pesticides Industry Sales and Usages Report: 2006 and 2007 Market Estimates’ [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0128429#pone.0128429.ref013" target="_blank">13</a>] and ‘Global Status of Commercialized Biotech/GM Crops: 2013 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0128429#pone.0128429.ref014" target="_blank">14</a>]. (A) Data for pesticides represent 2006 and 2007 EPA estimates based on Cropnosis Limited and USDA/NASS. Others include nematicides, fumigants, other miscellaneous conventional pesticides, and chemicals used as pesticides such as sulfur, petroleum oil and sulfuric acid. Wood preservatives, specialty biocides, and chlorine/hypochlorites are not included. (B) Data for cultivated GMOs come from ISAAA global status of commercialized biotech/GM crops. The herbicide tolerance is usually to Roundup, and the modified insecticides are usually from mutated Bt genes.</p
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