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

Seralini G-E, Mesnage R, Clair E, Gress S, de Vendomois J, Cellier D: Genetically modified crops safety assessments: present limits and possibleimprovements. Environ Sci Eur 2011, 23: 10. 10.1186/2190-4715-23-10

Domingo JL, Gine Bordonaba J: A literature review on the safety assessment of genetically modified plants. Environ Int 2011, 37: 734–742. 10.1016/j.envint.2011.01.003

Hammond B, Dudek R, Lemen J, Nemeth M: Results of a 13 week safety assurance study with rats fed grain fromglyphosate tolerant corn. Food Chem Toxicol 2004, 42: 1003–1014. 10.1016/j.fct.2004.02.013

Hammond B, Lemen J, Dudek R, Ward D, Jiang C, Nemeth M, Burns J: Results of a 90-day safety assurance study with rats fed grain from cornrootworm-protected corn. Food Chem Toxicol 2006, 44: 147–160. 10.1016/j.fct.2005.06.008

Hammond BG, Dudek R, Lemen JK, Nemeth MA: Results of a 90-day safety assurance study with rats fed grain from cornborer-protected corn. Food Chem Toxicol 2006, 44: 1092–1099. 10.1016/j.fct.2006.01.003

Seralini GE, Cellier D, de Vendomois JS: New analysis of a rat feeding study with a genetically modified maize revealssigns of hepatorenal toxicity. Arch Environ Contam Toxicol 2007, 52: 596–602. 10.1007/s00244-006-0149-5

Spiroux de Vendômois J, Roullier F, Cellier D, Seralini GE: A comparison of the effects of three GM corn varieties on mammalian health. Int J Biol Sci 2009, 5: 706–726. 10.7150/ijbs.5.706

Gasnier C, Dumont C, Benachour N, Clair E, Chagnon MC, Seralini GE: Glyphosate-based herbicides are toxic and endocrine disruptors in human celllines. Toxicology 2009, 262: 184–191. 10.1016/j.tox.2009.06.006

Benachour N, Seralini GE: Glyphosate formulations induce apoptosis and necrosis in human umbilical,embryonic, and placental cells. Chem Res Toxicol 2009, 22: 97–105. 10.1021/tx800218n

Romano MA, Romano RM, Santos LD, Wisniewski P, Campos DA, de Souza PB, Viau P, Bernardi MM, Nunes MT, de Oliveira CA: Glyphosate impairs male offspring reproductive development by disruptinggonadotropin expression. Arch Toxicol 2012, 86: 663–673. 10.1007/s00204-011-0788-9

Krüger M, Schrödl W, Neuhaus J, Shehata A: Field investigations of glyphosate in urine of Danish dairy cows. J Environ Anal Toxicol 2013, 3: 5.

Malatesta M, Boraldi F, Annovi G, Baldelli B, Battistelli S, Biggiogera M, Quaglino D: A long-term study on female mice fed on a genetically modified soybean: effects onliver ageing. Histochem Cell Biol 2008, 130: 967–977. 10.1007/s00418-008-0476-x

Malatesta M, Caporaloni C, Gavaudan S, Rocchi MB, Serafini S, Tiberi C, Gazzanelli G: Ultrastructural morphometrical and immunocytochemical analyses of hepatocytenuclei from mice fed on genetically modified soybean. Cell Struct Funct 2002, 27: 173–180. 10.1247/csf.27.173

Malatesta M, Caporaloni C, Rossi L, Battistelli S, Rocchi MB, Tonucci F, Gazzanelli G: Ultrastructural analysis of pancreatic acinar cells from mice fed on geneticallymodified soybean. J Anat 2002, 201: 409–415. 10.1046/j.0021-8782.2002.00103.x

Malatesta M, Perdoni F, Santin G, Battistelli S, Muller S, Biggiogera M: Hepatoma tissue culture (HTC) cells as a model for investigating the effects oflow concentrations of herbicide on cell structure and function. Toxicol In Vitro 2008, 22: 1853–1860. 10.1016/j.tiv.2008.09.006

Snell C, Bernheim A, Berge JB, Kuntz M, Pascal G, Paris A, Ricroch AE: Assessment of the health impact of GM plant diets in long-term andmultigenerational animal feeding trials: a literature review. Food Chem Toxicol 2012, 50: 1134–1148. 10.1016/j.fct.2011.11.048

Williams GM, Kroes R, Munro IC: Safety evaluation and risk assessment of the herbicide Roundup and its activeingredient, glyphosate, for humans. Regul Toxicol Pharmacol 2000, 31: 117–165. 10.1006/rtph.1999.1371

Cox C: Herbicide factsheet - glyphosate. J Pesticide Reform 2004, 24: 10–15.

Richard S, Moslemi S, Sipahutar H, Benachour N, Seralini GE: Differential effects of glyphosate and roundup on human placental cells andaromatase. Environ Health Perspect 2005, 113: 716–720. 10.1289/ehp.7728

Mesnage R, Bernay B, Seralini GE: Ethoxylated adjuvants of glyphosate-based herbicides are active principles ofhuman cell toxicity. Toxicology 2013, 313: 122–128. 10.1016/j.tox.2012.09.006

Adam A, Marzuki A, Abdul Rahman H, Abdul Aziz M: The oral and intratracheal toxicities of ROUNDUP and its components to rats. Vet Hum Toxicol 1997, 39: 147–151.

Mesnage R, Defarge N, Spiroux De Vendômois J, Séralini GE: Major pesticides are more toxic to human cells than their declared activeprinciples. Biomed Res Int 2014, Vol 2014: Article ID 179691. 10.1155/2014/179691

Jobling S, Burn RW, Thorpe K, Williams R, Tyler C: Statistical modeling suggests that antiandrogens in effluents from wastewatertreatment works contribute to widespread sexual disruption in fish living inEnglish rivers. Environ Health Perspect 2009, 117: 797–802. 10.1289/ehp.0800197

Krogh KA, Vejrup KV, Mogensen BB, Halling-Sørensen B: Liquid chromatography-mass spectrometry method to determine alcohol ethoxylatesand alkylamine ethoxylates in soil interstitial water, ground water and surfacewater samples. J Chromatogr A 2002, 957: 45–57. 10.1016/S0021-9673(02)00077-8

Giesy J, Dobson S, Solomon K: Ecotoxicological risk assessment for Roundup® herbicide. In In Reviews of Environmental Contamination and Toxicology. Edited by: Ware G. Springer, New York; 2000:35–120. Reviews of Environmental Contamination and Toxicology Reviews of Environmental Contamination and Toxicology

Cox C, Surgan M: Unidentified inert ingredients in pesticides: implications for human andenvironmental health. Environ Health Perspect 2006, 114: 1803–1806.

Mesnage R, Clair E, Séralini GE: Roundup in genetically modified plants: regulation and toxicity in mammals. Theorie in der Ökologie 2010, 16: 31–33.

Monosson E: Chemical mixtures: considering the evolution of toxicology and chemicalassessment. Environ Health Perspect 2005, 113: 383–390. 10.1289/ehp.6987

Doull J, Gaylor D, Greim HA, Lovell DP, Lynch B, Munro IC: Report of an Expert Panel on the reanalysis by of a 90-day study conducted byMonsanto in support of the safety of a genetically modified corn variety (MON863). Food Chem Toxicol 2007, 45: 2073–2085. 10.1016/j.fct.2007.08.033

Opinion of the scientific panel on genetically modified organisms on a requestfrom the commission related to the safety of foods and food ingredients derivedfrom herbicide-tolerant genetically modified maize NK603 for which a request forplacing on the market was submitted under Article 4 of the Novel Food Regulation(EC) No 258/97 by Monsanto (QUESTION NO EFSA-Q-2003–002) EFSA J 2003, 9: 1–14.

King-Herbert A, Sills R, Bucher J: Commentary: update on animal models for NTP studies. Toxicol Pathol 2010, 38: 180–181. 10.1177/0192623309356450

OECD guideline no. 452 for the testing of chemicals: Chronic toxicity studies:Adopted 7 September 2009. OECD Publishing, Paris, France; 2009.

EPA: Basic information about glyphosate in drinking water. 2014, (lastaccess March)., [ http://www.waterepagov/drink/contaminants/basicinformation/glyphosatecfm ] EPA: Basic information about glyphosate in drinking water. 2014, (lastaccess March).

COUNCIL DIRECTIVE 98/83/EC of 3 November 1998 on the quality of water intended forhuman consumption Off J Eur Commun L 1998, 330(32):51298.

German Federal Agency CPFS: Monograph on glyphosate by the German federalagency for consumer protection and food safety. Annex B-5: Toxicol Metabol 1998. German Federal Agency CPFS: Monograph on glyphosate by the German federalagency for consumer protection and food safety.Annex B-5: Toxicol Metabol 1998.

Vandenberg LN, Colborn T, Hayes TB, Heindel JJ, Jacobs DR Jr, Lee DH, Shioda T, Soto AM, Vom Saal FS, Welshons WV, Zoeller RT, Myers JP: Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonicdose responses. Endocr Rev 2012, 33: 378–455. 10.1210/er.2011-1050

Hard GC, Khan KN: A contemporary overview of chronic progressive nephropathy in the laboratory rat,and its significance for human risk assessment. Toxicol Pathol 2004, 32: 171–180. 10.1080/01926230490422574

Srinivasan M, Rukkumani R, Ram Sudheer A, Menon VP: Ferulic acid, a natural protector against carbon tetrachloride-inducedtoxicity. Fundam Clin Pharmacol 2005, 19: 491–496. 10.1111/j.1472-8206.2005.00332.x

Sultana S: Attenuation of oxidative stress, inflammation and early markers of tumor promotionby caffeic acid in Fe-NTA exposed kidneys of Wistar rats. Mol Cell Biochem 2011, 357: 115–124. 10.1007/s11010-011-0881-7

Gasnier C, Laurant C, Decroix-Laporte C, Mesnage R, Clair E, Travert C, Seralini GE: Defined plant extracts can protect human cells against combined xenobioticeffects. J Occup Med Toxicol 2011, 6: 3. 10.1186/1745-6673-6-3

El-Shenawy NS: Oxidative stress responses of rats exposed to Roundup and its active ingredientglyphosate. Environ Toxicol Pharmacol 2009, 28: 379–385. 10.1016/j.etap.2009.06.001

Collotta M, Bertazzi PA, Bollati V: Epigenetics and pesticides. Toxicology 2013, 307: 35–41. 10.1016/j.tox.2013.01.017

Vina J, Borras C, Gambini J, Sastre J, Pallardo FV: Why females live longer than males? Importance of the upregulation oflongevity-associated genes by oestrogenic compounds. FEBS Lett 2005, 579: 2541–2545. 10.1016/j.febslet.2005.03.090

Benachour N, Sipahutar H, Moslemi S, Gasnier C, Travert C, Seralini GE: Time- and dose-dependent effects of roundup on human embryonic and placentalcells. Arch Environ Contam Toxicol 2007, 53: 126–133. 10.1007/s00244-006-0154-8

Peixoto F: Comparative effects of the Roundup and glyphosate on mitochondrial oxidativephosphorylation. Chemosphere 2005, 61: 1115–1122. 10.1016/j.chemosphere.2005.03.044

Jiao Z, Si XX, Li GK, Zhang ZM, Xu XP: Unintended compositional changes in transgenic rice seeds ( Oryza sativa L.)studied by spectral and chromatographic analysis coupled with chemometricsmethods. J Agric Food Chem 2010, 58: 1746–1754. 10.1021/jf902676y

Zhou J, Ma C, Xu H, Yuan K, Lu X, Zhu Z, Wu Y, Xu G: Metabolic profiling of transgenic rice with cryIAc and sck genes: an evaluation ofunintended effects at metabolic level by using GC-FID and GC-MS. J Chromatogr B Analyt Technol Biomed Life Sci 2009, 877: 725–732. 10.1016/j.jchromb.2009.01.040

Zolla L, Rinalducci S, Antonioli P, Righetti PG: Proteomics as a complementary tool for identifying unintended side effectsoccurring in transgenic maize seeds as a result of genetic modifications. J Proteome Res 2008, 7: 1850–1861. 10.1021/pr0705082

Latham JR, Wilson AK, Steinbrecher RA: The mutational consequences of plant transformation. J Biomed Biotechnol 2006, 2006: 25376. 10.1155/JBB/2006/25376

Wilson AK, Latham JR, Steinbrecher RA: Transformation-induced mutations in transgenic plants: analysis and biosafetyimplications. Biotechnol Genet Eng Rev 2006, 23: 209–237. 10.1080/02648725.2006.10648085

Rosati A, Bogani P, Santarlasci A, Buiatti M: Characterisation of 3′ transgene insertion site and derived mRNAs in MON810YieldGard maize. Plant Mol Biol 2008, 67: 271–281. 10.1007/s11103-008-9315-7

Abdo E, Barbary O, Shaltout O: Feeding study with Bt corn (MON810: ajeeb YG) on rats: biochemical analysis andliver histopathology. Food Nutri Sci 2014, 5: 185–195. 10.4236/fns.2014.52024

Zhang L, Hou D, Chen X, Li D, Zhu L, Zhang Y, Li J, Bian Z, Liang X, Cai X, Yin Y, Wang C, Zhang T, Zhu D, Zhang D, Xu J, Chen Q, Ba Y, Liu J, Wang Q, Chen J, Wang J, Wang M, Zhang Q, Zhang J, Zen K, Zhang CY: Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence ofcross-kingdom regulation by microRNA. Cell Res 2012, 22: 107–126. 10.1038/cr.2011.158

Markaverich BM, Crowley JR, Alejandro MA, Shoulars K, Casajuna N, Mani S, Reyna A, Sharp J: Leukotoxin diols from ground corncob bedding disrupt estrous cyclicity in rats andstimulate MCF-7 breast cancer cell proliferation. Environ Health Perspect 2005, 113: 1698–1704. 10.1289/ehp.8231

World health statistics. WHO press, Geneva, Switzerland; 2012.

Brix AE, Nyska A, Haseman JK, Sells DM, Jokinen MP, Walker NJ: Incidences of selected lesions in control female Harlan Sprague–Dawley ratsfrom two-year studies performed by the National Toxicology Program. Toxicol Pathol 2005, 33: 477–483. 10.1080/01926230590961836

Chandra M, Riley MG, Johnson DE: Spontaneous neoplasms in aged Sprague–Dawley rats. Arch Toxicol 1992, 66: 496–502. 10.1007/BF01970675

Hayes TB: There is no denying this: defusing the confusion about atrazine. Biosciences 2004, 54: 1139–1149. 10.1641/0006-3568(2004)054[1138:TINDTD]2.0.CO;2

Desaulniers D, Leingartner K, Russo J, Perkins G, Chittim BG, Archer MC, Wade M, Yang J: Modulatory effects of neonatal exposure to TCDD, or a mixture of PCBs, p, p'-DDT,and p-p'-DDE, on methylnitrosourea-induced mammary tumor development in therat. Environ Health Perspect 2001, 109: 739–747.

Schecter AJ, Olson J, Papke O: Exposure of laboratory animals to polychlorinated dibenzodioxins andpolychlorinated dibenzofurans from commercial rodent chow. Chemosphere 1996, 32: 501–508. 10.1016/0045-6535(95)00328-2

Kozul CD, Nomikos AP, Hampton TH, Warnke LA, Gosse JA, Davey JC, Thorpe JE, Jackson BP, Ihnat MA, Hamilton JW: Laboratory diet profoundly alters gene expression and confounds genomic analysisin mouse liver and lung. Chem Biol Interact 2008, 173: 129–140. 10.1016/j.cbi.2008.02.008

Howdeshell KL, Peterman PH, Judy BM, Taylor JA, Orazio CE, Ruhlen RL, Vom Saal FS, Welshons WV: Bisphenol A is released from used polycarbonate animal cages into water at roomtemperature. Environ Health Perspect 2003, 111: 1180–1187. 10.1289/ehp.5993

Harvell DM, Strecker TE, Tochacek M, Xie B, Pennington KL, McComb RD, Roy SK, Shull JD: Rat strain-specific actions of 17beta-estradiol in the mammary gland: correlationbetween estrogen-induced lobuloalveolar hyperplasia and susceptibility toestrogen-induced mammary cancers. Proc Natl Acad Sci USA 2000, 97: 2779–2784. 10.1073/pnas.050569097

Thongprakaisang S, Thiantanawat A, Rangkadilok N, Suriyo T, Satayavivad J: Glyphosate induces human breast cancer cells growth via estrogen receptors. Food Chem Toxicol 2013, 59C: 129–136. 10.1016/j.fct.2013.05.057

Popovics P, Rekasi Z, Stewart AJ, Kovacs M: Regulation of pituitary inhibin/activin subunits and follistatin gene expressionby GnRH in female rats. J Endocrinol 2011, 210: 71–79. 10.1530/JOE-10-0485

Walf AA, Frye CA: Raloxifene and/or estradiol decrease anxiety-like and depressive-like behavior,whereas only estradiol increases carcinogen-induced tumorigenesis and uterineproliferation among ovariectomized rats. Behav Pharmacol 2010, 21: 231–240. 10.1097/FBP.0b013e32833a5cb0

Deheuvels P: On testing stochastic dominance by exceedance, precedence and otherdistribution-free tests, with applications. Chapter 10 in Statistical Models and Methods for Reliability and SurvivalAnalysis John Wiley & Sons 2013.

Duke SO, Rimando AM, Pace PF, Reddy KN, Smeda RJ: Isoflavone, glyphosate, and aminomethylphosphonic acid levels in seeds ofglyphosate-treated, glyphosate-resistant soybean. J Agric Food Chem 2003, 51: 340–344. 10.1021/jf025908i

Kuenzig W, Chau J, Norkus E, Holowaschenko H, Newmark H, Mergens W, Conney AH: Caffeic and ferulic acid as blockers of nitrosamine formation. Carcinogenesis 1984, 5: 309–313. 10.1093/carcin/5.3.309

Baskaran N, Manoharan S, Balakrishnan S, Pugalendhi P: Chemopreventive potential of ferulic acid in7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis inSprague–Dawley rats. Eur J Pharmacol 2010, 637: 22–29. 10.1016/j.ejphar.2010.03.054

Chang CJ, Chiu JH, Tseng LM, Chang CH, Chien TM, Wu CW, Lui WY: Modulation of HER2 expression by ferulic acid on human breast cancer MCF7cells. Eur J Clin Invest 2006, 36: 588–596. 10.1111/j.1365-2362.2006.01676.x

Eriksson L, Johansson E, Kettaneh-Wold N, Wold S: Multi and Megavariate Data Analysis Part I - Principles andApplications. Umetrics AB, Umea, Sweden; 2006.

Weljie AM, Bondareva A, Zang P, Jirik FR: (1)H NMR metabolomics identification of markers of hypoxia-induced metabolicshifts in a breast cancer model system. J Biomol NMR 2011, 49: 185–193. 10.1007/s10858-011-9486-4

Wiklund S, Johansson E, Sjostrom L, Mellerowicz EJ, Edlund U, Shockcor JP, Gottfries J, Moritz T, Trygg J: Visualization of GC/TOF-MS-based metabolomics data for identification ofbiochemically interesting compounds using OPLS class models. Anal Chem 2008, 80: 115–122. 10.1021/ac0713510

Eriksson L, Johansson E, Kettaneh-Wold N, Trygg J, Wikström C, Wold S: Multi- and Megavariate Data Analysis Part II. Advanced Applications and MethodExtensions. Umetrics, Umea, Sweden; 2006.