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Cited by 299Genetically Modified Organisms ResearchPesticide Exposure and ToxicityCarcinogens and Genotoxicity Assessment

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

Open access
Séralini, Gilles-Eric, Clair, Emilie, Mesnage, Robin, Gress, Steeve, Defarge, Nicolas, Malatesta, Manuela, Hennequin, Didier, de Vendômois, Joël Spiroux·2014·Environmental Sciences Europe
DOI 10.1186/s12302-014-0014-5PMC PMC5044955
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Abstract

BACKGROUND: 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. RESULTS: Biochemical analyses confirmed very significant chronic kidney deficiencies, for all treatments and both sexes; 76% of the altered parameters were kidney-related. In treated males, liver congestions and necrosis were 2.5 to 5.5 times higher. Marked and severe nephropathies were also generally 1.3 to 2.3 times greater. In females, all treatment groups showed a two- to threefold increase in mortality, and deaths were earlier. This difference was also evident in three male groups fed with GM maize. All results were hormone- and sex-dependent, and the pathological profiles were comparable. Females developed large mammary tumors more frequently and before controls; the pituitary was the second most disabled organ; the sex hormonal balance was modified by consumption of GM maize and Roundup treatments. Males presented up to four times more large palpable tumors starting 600 days earlier than in the control group, in which only one tumor was noted. These results may be explained by not only the non-linear endocrine-disrupting effects of Roundup but also by the overexpression of the EPSPS transgene or other mutational effects in the GM maize and their metabolic consequences. CONCLUSION: Our findings imply that long-term (2 year) feeding trials need to be conducted to thoroughly evaluate the safety of GM foods and pesticides in their full commercial formulations.

AI snapshot

Written from the paper’s full text.

TL;DR

This 2-year rat feeding study reports that NK603 GM maize, with or without Roundup, and Roundup alone at low doses produced chronic kidney and liver pathology, hormone-dependent tumors, and increased mortality compared with controls. The authors conclude that long-term feeding trials are needed to evaluate GM foods and complete pesticide formulations.

Key findings

  • Biochemical analyses found chronic kidney deficiencies across all treatments and both sexes; 76% of altered parameters were kidney-related, including 82% in treated females and 87% in GM maize-treated males.
  • In treated males, liver congestions and necrosis were 2.5 to 5.5 times higher than controls; Gamma GT hepatic activity increased up to 5.4 times in GMO + R groups, and cytochrome P450 activity increased up to 5.7 times at the highest dose.
  • Females in all treatment groups showed a two- to threefold increase in mortality, with earlier deaths; maximum differences included five times more male deaths by month 17 in the 11% GM maize group and six times greater female mortality by month 21 on 22% GM maize with or without R.
  • Females developed large mammary tumors more frequently and earlier: by month 24, 50% to 80% of treated females had tumors versus 30% of controls, and R groups had 80% affected; mammary tumor incidence was significantly increased at the lowest R dose versus controls (p < 0.05, Kruskal-Wallis with Dunn’s test). Males had up to four times more large palpable tumors starting 600 days earlier than controls, in which only one tumor was noted.

Methods

  • Two-year chronic toxicity study in Sprague-Dawley rats: 100 males and 100 females, 10 per group per sex, fed NK603 GM maize at 11%, 22%, or 33% with or without Roundup, or given Roundup in drinking water at 0.1 ppb, 0.09%, or 0.5%, alongside isogenic maize controls.
  • Observations included 34 organs and 56 parameters analyzed at 11 time points for most organs, with blood and urine biochemistry, histology, electron microscopy, organ weights, and tumor monitoring.
  • Biochemical data were analyzed by OPLS-DA using models with R2(Y) ≥ 80% and Q2(Y) ≥ 60%, with discriminant variables at 99% confidence; mammary tumor differences used Kruskal-Wallis followed by Dunn’s test.

Limitations

  • The paper states it was not designed as a carcinogenicity study and did not use the OECD-required 50 rats per sex per group; it calls for larger cohorts to confirm or refute the tumor incidence and mortality trends.
  • The authors state that further transcriptomic, proteomic, and metabolomic analyses are needed to confirm endocrine and oxidative stress pathways, and that the total chemical composition of the GM maize was not measured in detail.
  • Evident from the text: group sizes were 10 per sex per group, limiting statistical power, and the study relied on multivariate modeling for many biochemical comparisons rather than pairwise survival analyses such as Kaplan-Meier.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1186/s12302-014-0014-5

Cites

71 of 71 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 71 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Marked and severe nephropathies were generally 1.3 to 2.3 times greater in treated groups.

    “Marked and severe nephropathies were also generally 1.3 to 2.3 times greater.”
    Quote in the paperSubstantial claim
  • Findingown data

    Ferulic acid was decreased in both GM maize and GM maize + R diets by 16% to 30% in comparison to the control diet.

    “Ferulic acid was decreased in both GM maize and GM maize + R diets by 16% to 30% in comparison to the control diet (889 ± 107, 735 ± 89, respectively, vs. control 1,057 ± 127 mg/kg)”
    Quote in the paperNot a substantial claim
  • Findingown data

    There was no difference in total isoflavones between the diets.

    “For example, there was no difference in total isoflavones.”
    Quote in the paperNot a substantial claim
  • Findingown data

    In the R alone treatment groups, similar trends were observed, with a partial resumption of nucleolar activity at the highest dose.

    “In the R alone treatment groups, similar trends were observed, with a partial resumption of nucleolar activity at the highest dose.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Gamma GT hepatic activity was increased by the end of the experiment, particularly in the GMO + R groups (up to 5.4 times higher).

    “In addition, by the end of the experiment, Gamma GT hepatic activity was increased, particularly in the GMO + R groups (up to 5.4 times higher), this probably being reflective of liver dysfunction.”
    Quote in the paperSubstantial claim
  • May combine two claims. 56
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 21

  • May combine two claims.

    Findingown data

    GM maize-fed groups either with or without R application showed a higher heterochromatin content and decreased nucleolar dense fibrillar components.

    “The GM maize-fed groups either with or without R application showed a higher heterochromatin content and decreased nucleolar dense fibrillar components, implying a reduced level of mRNA and rRNA transcription.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Standard biochemical compositional analysis revealed no particular differences between the different maize types and diets; GM and non-GM maize were classified as substantially equivalent, except for transgene DNA quantification.

    “Standard biochemical compositional analysis revealed no particular differences between the different maize types and diets, the GM and non-GM maize being classified as substantially equivalent, except for transgene DNA quantification.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the GMO + R group at the highest dose, the smooth endoplasmic reticulum was drastically increased and nucleoli decreased in size, becoming more compact.

    “In the GMO + R group (at the highest dose), the smooth endoplasmic reticulum was drastically increased and nucleoli decreased in size, becoming more compact.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Males presented up to four times more large palpable tumors starting 600 days earlier than the control group, in which only one tumor was noted.

    “Males presented up to four times more large palpable tumors starting 600 days earlier than in the control group, in which only one tumor was noted.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    All results were hormone- and sex-dependent, and the pathological profiles were comparable.

    “All results were hormone- and sex-dependent, and the pathological profiles were comparable.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Transmission electron microscopic observations of liver samples confirmed changes for all treated groups in relation to glycogen dispersion or appearance in lakes, increase of residual bodies and enlargement of cristae in mitochondria.

    “Transmission electron microscopic observations of liver samples confirmed changes for all treated groups in relation to glycogen dispersion or appearance in lakes, increase of residual bodies and enlargement of cristae in mitochondria (Figure 2, panels 2 to 4).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Biochemical analyses confirmed very significant chronic kidney deficiencies for all treatments and both sexes; 76% of the altered parameters were kidney-related.

    “Biochemical analyses confirmed very significant chronic kidney deficiencies, for all treatments and both sexes; 76% of the altered parameters were kidney-related.”
    • Also stated in: § Biochemical analyses of blood and urine samples · plain
      “In summary, for all treatments and both sexes, 76% of the discriminant variables versus controls were kidney-related.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There was no rejection by the animals of the diet with or without GM maize, nor any major difference in body weight.

    “There was no rejection by the animals of the diet with or without GM maize, nor any major difference in body weight (data not shown).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Females developed large mammary tumors more frequently and before controls.

    “Females developed large mammary tumors more frequently and before controls”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In females, all treatment groups showed a two- to threefold increase in mortality, and deaths were earlier.

    “In females, all treatment groups showed a two- to threefold increase in mortality, and deaths were earlier.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In GM maize-treated males (with or without R), 87% of discriminant variables were kidney-related, but the disrupted profiles were less obvious because of advanced chronic nephropathies and deaths.

    “In GM maize-treated males (with or without R), 87% of discriminant variables were kidney-related, but the disrupted profiles were less obvious because of advanced chronic nephropathies and deaths.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Up to 14 months, no control animals showed signs of palpable tumors, while 10% to 30% of treated females per group developed tumors, except one group (33% GMO + R).

    “Up to 14 months, no animals in the control groups showed any signs of palpable tumors, whilst 10% to 30% of treated females per group developed tumors, with the exception of one group (33% GMO + R).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In female animals, the largest tumors were five times more frequent than in males after 2 years, with 93% being mammary tumors.

    “In female animals, the largest tumors were in total five times more frequent than in males after 2 years, with 93% of these being mammary tumors.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    By the beginning of the 24th month, 50% to 80% of female animals had developed tumors in all treatment groups, with up to three tumors per animal, whereas only 30% of controls were affected.

    “By the beginning of the 24th month, 50% to 80% of female animals had developed tumors in all treatment groups, with up to three tumors per animal, whereas only 30% of controls were affected.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Large tumor size caused impediments to breathing or digestion and nutrition because of thoracic or abdominal location and resulted in hemorrhaging.

    “Large tumor size caused impediments to either breathing or digestion and nutrition because of their thoracic or abdominal location and also resulted in hemorrhaging (Figure 5A,B,C).”
    Quote in the paperNot a substantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    Levels of Na and Cl or urea increased in urine with a concomitant decrease of the same ions in serum, as did the levels of P, K, and Ca.

    “Levels of Na and Cl or urea increased in urine with a concomitant decrease of the same ions in serum, as did the levels of P, K, and Ca.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The largest tumors progressively increased in size and number over the experiment but not proportionally to treatment dose.

    “These tumors progressively increased in size and number, but not proportionally to the treatment dose, over the course of the experiment (Figure 4).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Tumor numbers were almost always more than in controls for all treated groups, often with a two- to threefold increase for both sexes.

    “Tumor numbers were rarely equal but almost always more than in controls for all treated groups, often with a two- to threefold increase for both sexes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Metastases were observed in only two cases: one in a group fed 11% GM maize and another in the highest dose of R treatment group.

    “Metastases were observed in only two cases; one in a group fed with 11% GM maize and another in the highest dose of R treatment group.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Tumors began to reach a large size on average 94 days before controls in treated females and up to 600 days earlier in two male groups fed GM maize (11 and 22% with or without R).

    “Tumors began to reach a large size on average 94 days before controls in treated females and up to 600 days earlier in two male groups fed with GM maize (11 and 22% with or without R).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    At the end of the experiment, internal non-palpable tumors were added, and their sums were lower in males than in females.

    “At the end of the experiment, internal non-palpable tumors were added, and their sums were lower in males than in females.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Death in male rats was mostly due to severe hepatorenal insufficiencies, confirming the first signs of toxicity observed in 90-day feeding trials with NK603 GM maize.

    “Death in male rats was mostly due to the development of severe hepatorenal insufficiencies, confirming the first signs of toxicity observed in 90-day feeding trials with NK603 GM maize [7].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [7] 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 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    All treatments in both sexes enhanced large tumor incidence by two- to threefold in comparison to controls and also the number of mammary tumors in comparison to the Harlan Sprague-Dawley strain and overall around threefold in comparison to the largest study with 1,329 Sprague-Dawley female rats.

    “All treatments in both sexes enhanced large tumor incidence by two- to threefold in comparison to our controls and also the number of mammary tumors in comparison to the Harlan Sprague-Dawley strain [56] and overall around threefold in comparison to the largest study with 1,329 Sprague-Dawley female rats [57].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [56] 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 source

      Not checked in the free run.

    • cites [57] Chandra M, Riley MG, Johnson DE: Spontaneous neoplasms in aged Sprague–Dawley rats. Arch Toxicol 1992, 66: 496–502. 10.1007/BF01970675 source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    The general causes of death were linked mostly to mammary tumors in females and to problems in other organ systems in males.

    “The general causes of death represented in histogram format within each of the panels in Figure 6, are linked mostly to mammary tumors in females and to problems in other organ systems in males.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In female cohorts, there were two to three times more deaths in all treated groups compared with controls by the end of the experiment, and deaths occurred earlier in general.

    “In the female cohorts, there were two to three times more deaths in all treated groups compared with controls by the end of the experiment and deaths occurred earlier in general.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the study, tumors developed considerably faster than in controls, even though the majority of tumors were observed after 18 months.

    “In our study, the tumors also developed considerably faster than in controls, even though the majority of tumors were observed after 18 months.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the present investigation, deeper analysis at an ultrastructural level revealed evidence of impediments in transcription and other defects in cell nuclear structure that were comparable in both sexes and dose-dependent in hepatocytes in all treatments.

    “In the present investigation, deeper analysis at an ultrastructural level revealed evidence of impediments in transcription and other defects in cell nuclear structure that were comparable in both sexes and dose-dependent in hepatocytes in all treatments.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingcitation

    The lifespan of the control group corresponded to the mean for the strain of rat used (Harlan Sprague-Dawley), but males on average died before females, except for some female treatment groups.

    “The lifespan of the control group of animals corresponded to the mean for the strain of rat used (Harlan Sprague-Dawley), but as is frequently the case with most mammals, including humans [55], males on average died before females, except for some female treatment groups.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [55] World health statistics. WHO press, Geneva, Switzerland; 2012.

      Not checked in the free run.

  • May combine two claims.

    Findingnone given

    In females, kidney ion leakage was evident at a biochemical level at month 15, when severe nephropathies were observed in dead male animals at postmortem, at the anatomopathological level.

    “In females, kidney ion leakage was evident at a biochemical level at month 15, when severe nephropathies were observed in dead male animals at postmortem, at the anatomopathological level.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The first female death occurred in the 22% GM maize feeding group and resulted from a mammary fibroadenoma 246 days before the first control female death.

    “The first female death occurred in the 22% GM maize feeding group and resulted from a mammary fibroadenoma 246 days before the first control female death.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Control male animals survived on average 624 ± 21 days, and females lived for 701 ± 20 days during the experiment, plus a 5-week starting age and a 3-week housing stabilization period.

    “Control male animals survived on average 624 ± 21 days, whilst females lived for 701 ± 20 days during the experiment, plus in each case, a 5-week starting age at reception of animals and a 3-week housing stabilization period.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The R treatment groups showed the greatest rates of tumor incidence, with 80% of animals affected in each group.

    “The R treatment groups showed the greatest rates of tumor incidence, with 80% of animals affected (with up to three tumors for one female), in each group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Before mean survival time elapsed, 30% of control males (three in total) and 20% of females (only two) died spontaneously, while up to 50% of males and 70% of females died in some groups on diets containing GM maize.

    “Before this period, 30% control males (three in total) and 20% females (only two) died spontaneously, while up to 50% males and 70% females died in some groups on diets containing the GM maize (Figure 6, panels GMO, GMO + R).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Internal non-palpable tumor sums were not significantly different from controls, although slightly increased in females.

    “They were not significantly different from controls, although slightly increased in females (Figure 4, histogram insets).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Disturbances found in the male liver are characteristic of chronic toxicity, confirmed by alterations in biochemical liver and kidney function parameters.

    “Disturbances that we found to occur in the male liver are characteristic of chronic toxicity, confirmed by alterations in biochemical liver and kidney function parameters.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    The observed effects of NK603 GM maize and R were not additive but reached a threshold.

    “This explanation also corresponds to the fact that the observed effects of NK603 GM maize and R were not additive but reached a threshold.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The classical tests of Kolmogorov-Smirnov (one-sided) and Wilcoxon-Mann-Whitney reach α values of significance of 1.40% and 2.62%, respectively.

    “The classical tests of Kolmogorov-Smirnov (one-sided) and Wilcoxon-Mann-Whitney reach α values of significance, which are respectively of 1.40% and 2.62%.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    These results may be explained by non-linear endocrine-disrupting effects of Roundup and by overexpression of the EPSPS transgene or other mutational effects in the GM maize and their metabolic consequences.

    “These results may be explained by not only the non-linear endocrine-disrupting effects of Roundup but also by the overexpression of the EPSPS transgene or other mutational effects in the GM maize and their metabolic consequences.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    Statistical analysis of results employed OPLS-DA 2-class models built between each treated group per sex and controls; only models with an explained variance R2(Y) ≥ 80%, and a cross-validated predictive ability Q2(Y) ≥ 60%, were used for selection of the discriminant variables, when their regression coefficients were significant at a 99% confidence level.

    “Statistical analysis of results employed OPLS-DA 2-class models built between each treated group per sex and controls. Only models with an explained variance R2(Y) ≥ 80%, and a cross-validated predictive ability Q2(Y) ≥ 60%, were used for selection of the discriminant variables (Figure 3), when their regression coefficients were significant at a 99% confidence level.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    R concentrations in the range of 103 times below the MRL can induce endocrine disturbances in human cells and toxic effects thereafter.

    “Indeed, it has been demonstrated that R concentrations in the range of 103 times below the MRL can induce endocrine disturbances in human cells [8] and toxic effects thereafter [9].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [8] 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 source

      Not checked in the free run.

    • cites [9] 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 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    This choice is also consistent with the recommendation of the OECD that for a chronic toxicity test, rats of the same strain should be used as in studies on the same substance but of shorter duration.

    “This choice is also consistent with the recommendation of the OECD that for a chronic toxicity test, rats of the same strain should be used as in studies on the same substance but of shorter duration [32].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] OECD guideline no. 452 for the testing of chemicals: Chronic toxicity studies:Adopted 7 September 2009. OECD Publishing, Paris, France; 2009.

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation

    Our study design was based on that of the Monsanto investigation in order to make the two experiments comparable, but we extended the period of observation from Monsanto's 90 days to 2 years.

    “Our study design was based on that of the Monsanto investigation in order to make the two experiments comparable, but we extended the period of observation from Monsanto's 90 days to 2 years.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3] 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 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    At low contaminating levels, adjuvants may be better candidates than G to explain the toxicity or endocrine disruptive side effects of R on human cells and also in vivo for acute toxicity.

    “Even if G has shown to interact directly with the active site of aromatase at high levels [19], at low contaminating levels, adjuvants may be better candidates than G to explain the toxicity or endocrine disruptive side effects of R on human cells [8,20] and also in vivo for acute toxicity [21].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [8] 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 source

      Not checked in the free run.

    • cites [20] 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 source

      Not checked in the free run.

    • cites [21] 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.

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Overall, our study is the first in-depth life-long toxicology study on the full commercial Roundup formulation and NK603 GM maize, with observations on 34 organs and measurement of 56 parameters analyzed at 11 time points for most organs, and utilizing 3 doses.

    “Overall, our study is the first in-depth life-long toxicology study on the full commercial Roundup formulation and NK603 GM maize, with observations on 34 organs and measurement of 56 parameters analyzed at 11 time points for most organs, and utilizing 3 doses.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductcitation

    Both OECD 452 and 453 specify 20 rats per sex per group but require only 50% (ten per sex per group, the same number that we used in total) to be analyzed for biochemical and hematological parameters.

    “Both OECD 452 and 453 specify 20 rats per sex per group but require only 50% (ten per sex per group, the same number that we used in total) to be analyzed for biochemical and hematological parameters.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductcitation

    We used the Sprague-Dawley strain of rat, as recommended for chronic toxicology tests by the National Toxicology Program in the USA, and as used by Monsanto in its 90-day study.

    “We used the Sprague-Dawley strain of rat, as recommended for chronic toxicology tests by the National Toxicology Program in the USA [31], and as used by Monsanto in its 90-day study [3].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [31] King-Herbert A, Sills R, Bucher J: Commentary: update on animal models for NTP studies. Toxicol Pathol 2010, 38: 180–181. 10.1177/0192623309356450 source

      Not checked in the free run.

    • cites [3] 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 source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationown data

    The data indicate that 90-day feeding studies are inadequate and that long-term (2 years) investigations are needed to evaluate the life-long impact of GM food consumption and exposure to complete pesticide formulations.

    “Our data highlight the inadequacy of 90-day feeding studies and the need to conduct long-term (2 years) investigations to evaluate the life-long impact of GM food consumption and exposure to complete pesticide formulations.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The rat model and the 2-year chronic toxicity design are adequate to predict life-long human health impacts of GM food and complete pesticide formulations.

  • May combine two claims.

    Premisecitation

    None of the previous long-term and multi-generational animal feeding trials included a detailed follow-up of the animals, including multiple (up to 11) blood and urine sampling over 2 years, and none investigated either the GM NK603 R-tolerant maize or Roundup.

    “However, in contrast with the study we report here, none of these previous investigations have included a detailed follow-up of the animals, including multiple (up to 11) blood and urine sampling over 2 years, and none has investigated either the GM NK603 R-tolerant maize or Roundup.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [16] 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 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    This is consistent with the well-documented toxic effect of very low dilutions of R on apoptosis, mitochondrial function, and cell membrane degradation, inducing necrosis of hepatocytes, and in other cell lines.

    “This is consistent with the well-documented toxic effect of very low dilutions of R on apoptosis, mitochondrial function, and cell membrane degradation, inducing necrosis of hepatocytes, and in other cell lines [8,9,44,45].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [8] 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 source

      Not checked in the free run.

    • cites [9] 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 source

      Not checked in the free run.

    • cites [44] 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 source

      Not checked in the free run.

    • cites [45] Peixoto F: Comparative effects of the Roundup and glyphosate on mitochondrial oxidativephosphorylation. Chemosphere 2005, 61: 1115–1122. 10.1016/j.chemosphere.2005.03.044 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Plant extracts containing ferulic and caffeic acids were able to promote detoxification of human embryonic kidney cells after culture in the presence of R.

    “This possibility is consistent with our previous observation that plant extracts containing ferulic and caffeic acids were able to promote detoxification of human embryonic kidney cells after culture in the presence of R [40].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [40] 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 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Females were more sensitive to the presence of R in drinking water than males, as evidenced by a shorter lifespan.

    “Females were more sensitive to the presence of R in drinking water than males, as evidenced by a shorter lifespan (Figure 6, panels R).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The observed disease may result from endocrine disruptive effects, which are known to be non-monotonic.

    “This suggests that the observed disease may result from endocrine disruptive effects, which are known to be non-monotonic.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Endocrine disruptive effects are known to be non-monotonic.

  • May combine two claims.

    Interpretationcitation

    Liver function in female animals was less negatively affected, possibly due to protection from oxidative stress conferred by estrogen.

    “The observation that liver function in female animals was less negatively affected may be due to the known protection from oxidative stress conferred by estrogen [43].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] 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 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The disturbed kidney functional parameters may have been induced by the reduced levels of phenolic acids in the GM maize feed used in the study, since caffeic and ferulic acids are beneficial to the kidney as they prevent oxidative stress.

    “Therefore, the disturbed kidney functional parameters may have been induced by the reduced levels of phenolic acids in the GM maize feed used in our study, since caffeic and ferulic acids are beneficial to the kidney as they prevent oxidative stress [38,39].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [38] 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 source

      Not checked in the free run.

    • cites [39] 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 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationreasoning

    A possible explanation for this finding is the production of specific compound(s) in the GM feed that are either directly toxic and/or cause the inhibition of pathways, which in turn generates toxic effects.

    “A possible explanation for this finding is the production of specific compound(s) in the GM feed that are either directly toxic and/or cause the inhibition of pathways, which in turn generates toxic effects.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    The NK603 and DKC 2675 maize were spaced at sufficient distance to avoid cross-contamination.

    “These two types of maize were grown under similar normal conditions, in the same location, spaced at sufficient distance to avoid cross-contamination.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The location of each cage within the experimental room was regularly changed.

    “The location of each cage within the experimental room was regularly changed.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Herbicide levels in the different drinking-water dilutions were assessed by glyphosate measurements using mass spectrometry.

    “Herbicide levels were assessed by G measurements in the different dilutions by mass spectrometry.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    It was previously known that G consumption in water above authorized limits may provoke hepatic and kidney failure.

    “It was previously known that G consumption in water above authorized limits may provoke hepatic and kidney failure [33].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33] 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).

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The experimental protocol was conducted in an animal care unit authorized by the French Ministries of Agriculture and Research (Agreement Number A35-288-1).

    “The experimental protocol was conducted in an animal care unit authorized by the French Ministries of Agriculture and Research (Agreement Number A35-288-1).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    Animal experiments were performed according to ethical guidelines of animal experimentations (CEE 86/609 regulation), including the necessary observations of all tumors, in line with the requirements for a long-term toxicological study, up to a size where euthanasia on ethical grounds was necessary.

    “Animal experiments were performed according to ethical guidelines of animal experimentations (CEE 86/609 regulation), including the necessary observations of all tumors, in line with the requirements for a long-term toxicological study [32], up to a size where euthanasia on ethical grounds was necessary.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] OECD guideline no. 452 for the testing of chemicals: Chronic toxicity studies:Adopted 7 September 2009. OECD Publishing, Paris, France; 2009.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The NK603 and DKC 2675 maize were grown in the same location.

    “These two types of maize were grown under similar normal conditions, in the same location, spaced at sufficient distance to avoid cross-contamination.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    After 20 days of acclimatization, 100 male and 100 female animals were randomly assigned on a weight basis into ten groups.

    “After 20 days of acclimatization, 100 male and 100 female animals were randomly assigned on a weight basis into ten equivalent groups.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    The 2-year life-long experiment was conducted in a Good Laboratory Practice (GLP) accredited laboratory.

    “This 2-year life-long experiment was conducted in a Good Laboratory Practice (GLP) accredited laboratory according to OECD guidelines.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The 2-year life-long experiment was conducted according to OECD guidelines.

    “This 2-year life-long experiment was conducted in a Good Laboratory Practice (GLP) accredited laboratory according to OECD guidelines.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationreasoning

    As the total chemical composition of the GM maize has not been measured in detail, the use of substantial equivalence as a concept in risk assessment is insufficient to highlight potential unknown toxins and therefore cannot replace long-term animal feeding trials for GMOs.

    “As the total chemical composition of the GM maize has not been measured in detail, the use of substantial equivalence as a concept in risk assessment is insufficient to highlight potential unknown toxins and therefore cannot replace long-term animal feeding trials for GMOs.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    R with adjuvants has been shown to disrupt aromatase, which synthesizes estrogen, and to interfere with estrogen and androgen receptors in cells.

    “In addition, R with adjuvants has been shown to disrupt aromatase, which synthesizes estrogen [19], and to interfere with estrogen and androgen receptors in cells [8].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [19] 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 source

      Not checked in the free run.

    • cites [8] 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 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    The ten groups were equivalent.

    “After 20 days of acclimatization, 100 male and 100 female animals were randomly assigned on a weight basis into ten equivalent groups.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The partitioning of the X data by OPLS results in improved model transparency and interpretability.

    “This partitioning of the X data results in improved model transparency and interpretability [75].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [75] 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.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Study design and conductnone given

    Anesthesia did not impact animal health.

    “It was first demonstrated that anesthesia did not impact animal health.”
    Quote in the paperNot a substantial claim
70 of 70

  • The paper relies on this without support.

    No regulatory authority requires mandatory chronic animal feeding studies for edible GMOs, or even short-term studies with blood analyses for the full commercial formulations of pesticides as sold and used, but only for the declared active principle alone.

    “Currently, no regulatory authority requires mandatory chronic animal feeding studies to be performed for edible genetically modified organisms (GMOs), or even short-term studies with blood analyses for the full commercial formulations of pesticides as sold and used, but only for the declared active principle alone.”

  • The paper relies on this without support.

    There was no evidence in the literature on GM food safety evaluation to indicate anything to the contrary that would require a carcinogenicity study.

    “As there was no evidence in the literature on GM food safety evaluation to indicate anything to the contrary, this initial investigation was designed as a full chronic toxicity and not a carcinogenicity study.”

  • The paper relies on this without support.

    The rat model and the 2-year chronic toxicity design are adequate to predict life-long human health impacts of GM food and complete pesticide formulations.

    “Our findings imply that long-term (2 year) feeding trials need to be conducted to thoroughly evaluate the safety of GM foods and pesticides in their full commercial formulations.”

  • The paper relies on this without support.

    This report describes the first long-term (2-year) rodent feeding study investigating possible toxic effects from consumption of R-tolerant GM maize NK603 and a complete commercial formulation of R herbicide.

    “This report describes the first long-term (2-year) rodent (rat) feeding study investigating possible toxic effects arising from consumption of an R-tolerant GM maize (NK603) and a complete commercial formulation of R herbicide.”

  • The paper relies on this without support.

    The tested levels correspond to levels likely to arise from consumption or environmental exposure, such as 11% GM maize in food or 50 ng/L G equivalent of R-formulation in contaminated drinking tap water.

    “This corresponds to levels likely to arise from consumption or environmental exposure, such as either 11% GM maize in food, or 50 ng/L G equivalent of R-formulation, a level which can be found in some contaminated drinking tap waters and which falls within authorized limits.”

  • The paper relies on this without support.

    The medium dose of R treatment tested (400 mg/Kg G equivalent) corresponds to acceptable residue levels of this pesticide in some edible GMOs.

    “In this regard, it is noteworthy that the medium dose of the R treatment tested (400 mg/Kg G equivalent) corresponds to acceptable residue levels of this pesticide in some edible GMOs.”

  • The paper relies on this without support.

    The modified EPSPS enzyme drives the first step of aromatic amino acid biosynthesis in the plant shikimate pathway.

    “This enzyme is known to drive the first step of aromatic amino acid biosynthesis in the plant shikimate pathway.”

  • The paper relies on this without support.

    This study represents the first detailed documentation of long-term deleterious effects arising from consumption of a GMO, specifically a R-tolerant maize, and of R, the most widely used herbicide worldwide.

    “This study represents the first detailed documentation of long-term deleterious effects arising from consumption of a GMO, specifically a R-tolerant maize, and of R, the most widely used herbicide worldwide.”

  • The paper relies on this without support.

    Non-cancerous tumors can be more lethal than cancerous tumors due to internal hemorrhaging or compression and obstruction of function of vital organs, or toxins or hormone secretions.

    “The real tumors were recorded independently of their grade, but dependent on their morbidity, since non-cancerous tumors can be more lethal than those of cancerous nature, due to internal hemorrhaging or compression and obstruction of function of vital organs, or toxins or hormone secretions.”

  • The paper relies on this without support.

    Endocrine disruptive effects are known to be non-monotonic.

    “This suggests that the observed disease may result from endocrine disruptive effects, which are known to be non-monotonic.”

  • The paper relies on this without support.

    DKC 2675 is the nearest isogenic non-transgenic control to NK603.

    “The varieties of maize used in this study were the DKC 2678 R-tolerant NK603 (Monsanto Corp., USA), and its nearest isogenic non-transgenic control DKC 2675.”

  • The paper relies on this without support.

    All secondary metabolites cannot be known and measured in the composition.

    “All secondary metabolites cannot be known and measured in the composition.”
12 of 12

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Some of these reports were published and then retracted, and others were never subjected to peer review.

    “Some of these reports were published and then retracted (Séralini et al., 2012), although recently and controversially republished without further peer review (Séralini et al., 2014), and others were never subjected to peer review (Ermakova, 2005; Velmirov et al., 2008).”

    From Prevalence and impacts of genetically engineered feedstuffs on livestock populations1 (2014) · cites this paper as Séralini et al., 2014

Cites

1 retracted

Flagged first, then by citations

Research works printed but not linked: 4

  1. Cox C: Herbicide factsheet - glyphosate. J Pesticide Reform 2004, 24: 10–15.
  2. Mesnage R, Clair E, Séralini GE: Roundup in genetically modified plants: regulation and toxicity in mammals. Theorie in der Ökologie 2010, 16: 31–33.
  3. 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.
  4. 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.

Cited by

Sorted by citations

Related

Authors
Séralini, G.-E., Clair, E., Mesnage, R., Gress, S., Defarge, N., Malatesta, M., Hennequin, D., & de Vendômois, J. S.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • University of Verona (IT)
ORCID
Venue
Environmental Sciences Europe
Publisher
Springer Science and Business Media LLC
Published
2014-06-24
Volume
26
Issue
1
Pages
14-14
ISSN
  • 2190-4715 (ISSN-L)
  • 2190-4707
DOI
10.1186/s12302-014-0014-5
PMC
PMC5044955
OpenAlex
W2143746117
Semantic Scholar
d1c31b767dbc03c77b99be14ddc0c7719ed29b57
Cited by
299
References
71
Citations by year
2026: 6 · 2025: 13 · 2024: 8 · 2023: 23 · 2022: 26 · 2021: 30 · 2020: 37 · 2019: 27 · 2018: 36 · 2017: 30 · 2016: 26 · 2015: 28 · 2014: 9
FWCI
36.24
Type
journal article
Language
en
Open access
Licence
Locations
  • Environmental Sciences Europe (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Genetically Modified Organisms Research
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
Keywords
Roundup, glyphosate, NK603, genetically modified crops, chronic toxicity, kidney injury, liver necrosis, mammary tumors, pituitary tumors, sex differences, endocrine disruption, GM food safety, pesticide safety, drinking water exposure

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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