Food And Chemical Toxicology

Food and Chemical Toxicology xxx (2012) xxx–xxx

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Food and Chemical Toxicology
journal homepage: www.elsevier.com/locate/foodchemtox

Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize
Gilles-Eric Séralini a,⇑, Emilie Clair a, Robin Mesnage a, Steeve Gress a, Nicolas Defarge a, Manuela Malatesta b,Didier Hennequin c, Joël Spiroux de Vendômois a
a b c

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

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The health effects of a Roundup-tolerant genetically modified maize (from 11% in the diet), cultivated with or without Roundup, and Roundup alone (from 0.1 ppb in water), were studied 2 years in rats. In females, all treated groups died 2–3 times more than controls, and more rapidly. This difference was visible in 3 male groups fed GMOs. All results werehormone and sex dependent, and the pathological profiles were comparable. Females developed large mammary tumors almost always more often than and before controls, the pituitary was the second most disabled organ; the sex hormonal balance was modified by GMO and Roundup treatments. In treated males, liver congestions and necrosis were 2.5–5.5 times higher. This pathology was confirmed by optic andtransmission electron microscopy. Marked and severe kidney nephropathies were also generally 1.3–2.3 greater. Males presented 4 times more large palpable tumors than controls which occurred up to 600 days earlier. Biochemistry data confirmed very significant kidney chronic deficiencies; for all treatments and both sexes, 76% of the altered parameters were kidney related. These results can be explainedby the non linear endocrine-disrupting effects of Roundup, but also by the overexpression of the transgene in the GMO and its metabolic consequences. Ó 2012 Elsevier Ltd. All rights reserved.

Article history: Received 11 April 2012 Accepted 2 August 2012 Available online xxxx Keywords: GMO Roundup NK603 Rat Glyphosate-based herbicides Endocrine disrupting effects

1. Introduction There is anongoing international debate as to the necessary length of mammalian toxicity studies in relation to the consumption of genetically modified (GM) plants including regular metabolic analyses (Séralini et al., 2011). Currently, no regulatory authority requests mandatory chronic animal feeding studies to be performed for edible GMOs and formulated pesticides. However, several studies consisting of 90day rat feeding trials have been conducted by the biotech industry. These investigations mostly concern GM soy and maize that are rendered either herbiAbbreviations: GM, genetically modified; R, Roundup; MRL, maximal residual levels; GMO, genetically modified organism; OECD, Organization for Economic Cooperation and Development; GT, glutamyl-transferase; PCA, principal component analysis; PLS,partial least-squares; OPLS, orthogonal partial least-squares; NIPALS, Nonlinear Iterative Partial Least Squares; OPLS-DA, Orthogonal Partial Least Squares Discriminant Analysis; G, glycogen; L, lipid droplet; N, nucleus; R, rough endoplasmic reticulum (on microscopy pictures only); U, urinary; UEx, excreted in urine during 24 h; APPT, Activated Partial Thromboplastin Time; MCV, Mean Corpuscular Volume;PT, Prothrombine Time; RBC, Red Blood Cells; ALT, alanine aminotransferase; MCHC, Mean Corpuscular Hemoglobin Concentration; A/G, Albumin/Globulin ratio; WBC, White Blood Cells; AST, aspartate aminotransferase. ⇑ Corresponding author. Tel.: +33 (0)231565684; fax: +33 (0)231565320. E-mail address: criigen@unicaen.fr (G.-E. Séralini). 0278-6915/$ - see front matter Ó 2012 Elsevier Ltd. All rights...