Long term toxicity of a Roundup herbicide and a Roundup-tolerantgenetically modiﬁed maize
, Emilie Clair
, Robin Mesnage
, Steeve Gress
, Nicolas Defarge
, Didier Hennequin
, Joël Spiroux de Vendômois
University of Caen, Institute of Biology, CRIIGEN and Risk Pole, MRSH-CNRS, EA 2608, Esplanade de la Paix, Caen Cedex 14032, France
University of Verona, Department of Neurological, Neuropsychological, Morphological and Motor Sciences, Verona 37134, Italy
University of Caen, UR ABTE, EA 4651, Bd Maréchal Juin, Caen Cedex 14032, France
a r t i c l e i n f o
Received 11 April 2012Accepted 2 August 2012Available online xxxx
GMORoundupNK603RatGlyphosate-based herbicidesEndocrine disrupting effects
a b s t r a c t
The health effects of a Roundup-tolerant genetically modiﬁed maize (from 11% in the diet), cultivatedwith or without Roundup, and Roundup alone (from 0.1ppb in water), were studied 2years in rats. Infemales, all treated groups died 2–3 times more than controls, and more rapidly. This difference was vis-ible in 3 male groups fed GMOs. All results were hormone and sex dependent, and the pathological pro-ﬁles were comparable. Females developed large mammary tumors almost always more often than andbefore controls, the pituitary was the second most disabled organ; the sex hormonal balance was mod-iﬁed by GMO and Roundup treatments. In treated males, liver congestions and necrosis were 2.5–5.5times higher. This pathology was conﬁrmed by optic and transmission electron microscopy. Markedandseverekidneynephropathieswerealsogenerally1.3–2.3greater.Malespresented4timesmorelargepalpable tumors than controls which occurred up to 600days earlier. Biochemistry data conﬁrmed verysigniﬁcant kidney chronic deﬁciencies; for all treatments and both sexes, 76% of the altered parameterswere kidney related. These results can be explained by the non linear endocrine-disrupting effects of Roundup, but also by the overexpression of the transgene in the GMO and its metabolic consequences.
2012 Elsevier Ltd. All rights reserved.
There is an ongoing international debate as to the necessarylength of mammalian toxicity studies in relation to the consump-tion of genetically modiﬁed (GM) plants including regular meta-bolic analyses (Séralini et al., 2011). Currently, no regulatoryauthority requests mandatory chronic animal feeding studies tobe performed for edible GMOs and formulated pesticides. How-ever, several studies consisting of 90day rat feeding trials havebeen conducted by the biotech industry. These investigationsmostly concern GM soy and maize that are rendered either herbi-cide tolerant (to Roundup (R) in 80% of cases), or engineered toproduce a modiﬁed
toxin insecticide, or both. As a result theseGM crops contain new pesticide residues for which new maximalresidual levels (MRL) have been established in some countries.If the petitioners conclude in general that there is no majorchange in genetically modiﬁed organism (GMO) subchronic toxic-ity studies (Domingo and Giné Bordonaba, 2011; Hammond et al.,2004, 2006a,b), signiﬁcant disturbances have been found andmay be interpreted differently (Séralini et al., 2009; Spiroux deVendômois et al., 2010). Detailed analyses have revealed altera-tions in kidney and liver functions that may be the signs of earlychronic diet intoxication, possibly explained at least in part bypesticide residues in the GM feed (Séralini et al., 2007; Spirouxde Vendômois et al., 2009). Indeed, it has been demonstrated thatR concentrations in the range of 10
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GM, genetically modiﬁed; R, Roundup; MRL, maximal residuallevels; GMO, genetically modiﬁed organism; OECD, Organization for Economic Co-operation and Development; GT, glutamyl-transferase; PCA, principal componentanalysis; PLS, partial least-squares; OPLS, orthogonal partial least-squares; NIPALS,NonlinearIterativePartialLeastSquares;OPLS-DA,OrthogonalPartialLeastSquaresDiscriminant Analysis; G, glycogen; L, lipid droplet; N, nucleus; R, rough endoplas-mic reticulum (on microscopy pictures only); U, urinary; UEx, excreted in urineduring 24h; APPT, Activated Partial Thromboplastin Time; MCV, Mean CorpuscularVolume; PT, Prothrombine Time; RBC, Red Blood Cells; ALT, alanine aminotrans-ferase; MCHC, Mean Corpuscular Hemoglobin Concentration; A/G, Albumin/Glob-ulin ratio; WBC, White Blood Cells; AST, aspartate aminotransferase.
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Food and Chemical Toxicology