Food and Chemical Toxicology
Volume 65, March 2014, Pages 394–395
Reply to letter to the editor
Editor in Chief of Food and Chemical
Toxicology answers questions on retraction
A. Wallace Hayes (Editor-in-Chief)
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Letter to the Editor
Food and Chemical Toxicology, Volume 65, March 2014, Page 389
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Referred to by
Letter to the editor
Food and Chemical Toxicology, Volume 66, April 2014, Page 385
PDF (242 K)
In November 2012, this journal published an article titled “Long term toxicity of a Roundup
herbicide and a Roundup-tolerant genetically modified maize,” by Séralini et al. (2012). The
publication of this article caused quite a stir in the media, as well as in the scientific community.
The journal received many letters expressing concerns about the validity of the findings. A
careful and time-consuming analysis found that the data were inconclusive, and therefore the
conclusions described in the article were unreliable. Accordingly, the article was retracted. Since
the public announcement of the retraction, the journal has received many letters to the editor; a
selection of these letters will be published, along with this response to those letters. Many of
these letters expressed concerns about the decision making process behind this action,
particularly what role (if any) current or former Monsanto employees played, whether or not
COPE guidelines were followed, and if the journal was also considering retraction of a similar
paper by Hammond et al. (2004). The answers to these questions are below.
The membership of the editorial board is composed of academic, government, and industrial
scientists. Contrary to what has been suggested by some, the appointment of Professor Richard
Goodman, University of Nebraska, as an Associate Editor was not influenced by Monsanto or
any other party. Members of the editorial board are chosen based on their expertise as
toxicologists/ scientists. It is the goal of this journal to have a variety of different viewpoints. In
this case, as in other cases, I as Editor-in-Chief listened to as wide and diverse a set of expertise
as possible. To wit, Professor Goodman, along with other members of the editorial board was
involved in initial discussions of the Séralini paper and the request to view raw data. When the
request was made to Dr. Séralini to review the raw data, the journal suggested to Dr. Séralini that
all parties involved sign a confidentiality agreement. This confidentiality agreement was
designed to protect Dr. Séralini and his data so that it was (A) not viewed by anyone he did not
want to view his data and (B) that it would not go beyond the people he agreed would review the
raw data. Not initially, but during the process, Dr. Séralini made a direct request that Professor
Goodman be excluded, and we at FCT readily and quickly agreed. It is understandable that Dr.
Goodman’s involvement, however small, might be cause for concern for some. However, the
decision to retract the paper was mine alone, made by me exclusively and not by a vote of the
editorial board. Further, when Dr. Séralini asked for Dr. Goodman’s involvement to stop, I
agreed, fully and promptly.
The Monsanto Company did write a letter to the editor regarding this article, and it was
published along with a number of other letters to the editor (Hammond et al., 2013); neither the
company nor any of their scientists put any pressure on the Editor-in-Chief regarding this matter.
A second concern that has been raised is whether this retraction follows the COPE guidelines.
The COPE guidelines were consulted when making this decision. According to the COPE
guidelines, “Journal editors should consider retracting a publication if … they have clear
evidence that the findings are unreliable, either as a result of misconduct (e.g. data fabrication) or
honest error (e.g. miscalculation or experimental error).” (COPE, 2009). The retraction statement
could have been clearer, and should have referred to the relevant COPE guidelines. The data are
inconclusive, therefore the claim (i.e., conclusion) that Roundup Ready maize NK603 and/or the
Roundup herbicide have a link to cancer is unreliable. Dr. Séralini deserves the benefit of the
doubt that this unreliable conclusion was reached in honest error. The review of the data made it
clear that there was no misconduct. However, to be very clear, it is the entire paper, with the
claim that there is a definitive link between GMO and cancer that is being retracted. Dr. Séralini
has been very vocal that he believes his conclusions are correct. In our analysis, his conclusions
cannot be claimed from the data presented in this article.
At this point it is very important to state that the retraction does not reflect or impact the
journal’s view on GMOs or associated organizations. Our journal would, in fact, very much
welcome the opportunity to review follow-up studies that have a greater sample size, a finetuned method, and proper controls. We are also actively searching and recruiting people to
provide a balance view on this topic to serve on the editorial board.
Finally, the letters post-retraction have questioned whether an earlier study done by Monsanto
received different treatment from our journal. This article was published in 2004, well before I
became Editor-in-Chief. However, I take the issue seriously and have reviewed this paper in
detail. The Hammond et al. article was a 13 week feeding study performed in rats feed grain
from Roundup Ready corn which is tolerant to the herbicide glyphosate (Hammond et al., 2004).
The authors reported the following: “Purina TestDiets formulated Roundup Ready corn grain
into rodent diets at levels of 11 and 33% (w/w). The responses of rats fed diets containing
Roundup Ready corn grain were compared to that of rats fed diets containing non-transgenic
grain (controls). All diets were nutritionally balanced and conformed to Purina Mills, Inc.
specifications for Certified Lab Diet 5002. There were 400 rats in the study divided into 10
groups of 20 rats/sex/group. Overall health, body weight, food consumption, clinical pathology
parameters (hematology, blood chemistry, urinalysis), organ weights, gross and microscopic
appearance of tissues were comparable between groups fed diets containing Roundup Ready and
control corn grain… This study complements extensive agronomic, compositional and farm
animal feeding studies with Roundup Ready corn grain, confirming it is as safe and nutritious as
existing commercial corn hybrids.” The authors also stated “The study design was adapted from
OECD Guideline No. 408 (1981) and the study was reported to have been conducted in general
compliance with OECD Good Laboratory Practice (GLP) guidelines at the Metabolism and
Safety Evaluation-Newstead, toxicology laboratory.”
In accordance with OECD Guideline No. 408 (OECD, 2009a), the Hammond et al. study was
limited to 90 days and used 20 rats/sex/group, and was conducted in general compliance with
OECD Good Laboratory Practice (GLP) guidelines, as previously stated. The Séralini et al. study
ran for two (2) years with only 10 rats/sex/group and was reported to be done in a GLP
environment according to OECD guidelines (which guideline is not explicitly stated in the
paper). Séralini et al. state that they had “had no reason to settle at first for a carcinogenesis
protocol using 50 rats per group,” as recommended in OECD Nos. 451 and 453 (guidelines for
Carcinogenicity Studies and Combined Chronic Toxicity/Carcinogenicity Studies, respectively)
(OECD, 2009a and OECD, 2009b), and instead seem to have opted for 10 rats/sex/group as
recommended by OECD No. 408 (guidelines for Repeated Dose 90-day Oral Toxicity Study in
Rodents). While the number of animals used may have been sufficient to reach conclusions
regarding oral toxicity, it proved insufficient for conclusions related to the carcinogenicity of the
In conclusion, FCT has retracted this article because our thorough investigations revealed that its
methods were scientifically flawed. The low number of animals, and the strain selected, rendered
the conclusions unreliable. No definitive conclusions could be drawn from the inconclusive data.
Therefore, in accordance with both the COPE guidelines and the journal policy, it was necessary
to take this action of retracting the article.
COPE, 2009 COPE, 2009. Retraction guidelines.
Hammond et al., 2004
B. Hammond, R. Dudek, J. Lemen, M. Nemeth
Results of a 13 week safety assurance study with rats fed grain from glyphosate
Food Chem. Toxicol., 42 (2004), pp. 1003–1014
Article PDF (470 K) View Record in Scopus Citing articles (73)
Hammond et al., 2013
B. Hammond, D.A. Goldstein, D. Saltmiras
Response to original research article, ‘Long term toxicity of a Roundup herbicide
and a Roundup-tolerant genetically modified maize’
Food Chem. Toxicol., 53 (2013), pp. 459–464
Article PDF (241 K) View Record in Scopus Citing articles (2)
OECD, 2009a OECD, 2009a. OECD Guideline for the Testing of Chemicals.
OECD, 2009b OECD, 2009b. Combined Chronic Toxicity Carcinogenicity Studies.
Séralini et al., 2012
G.-E. Séralini, E. Clair, R. Mesnage, S. Gress, N. Defarge, M. Malatesta, D. Hennequin, J.S.
Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically
Food Chem. Toxicol., 50 (2012), pp. 4221–4231
Article PDF (2286 K) View Record in Scopus Citing articles (123)
Copyright © 2014 The Authors. Published by Elsevier Ltd.
Food and Chemical Toxicology 50 (2012) 4221–4231
Contents lists available at SciVerse ScienceDirect
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
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 2012
Accepted 2 August 2012
Available online 19 September 2012
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 were hormone 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 and transmission 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 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.
Ó 2012 Elsevier Ltd. Open access under CC BY-NC-ND license.
Endocrine disrupting effects
a b s t r a c t
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
There is an ongoing 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 90 day 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: firstname.lastname@example.org (G.-E. Séralini).
0278-6915 Ó 2012 Elsevier Ltd. Open access under CC BY-NC-ND license.
cide tolerant (to Roundup (R) in 80% of cases), or engineered to
produce a modiﬁed Bt toxin insecticide, or both. As a result these
GM crops contain new pesticide residues for which new maximal
residual levels (MRL) have been established in some countries.
If the petitioners conclude in general that there is no major
change in genetically modiﬁed organism (GMO) subchronic toxicity studies (Domingo and Giné Bordonaba, 2011; Hammond et al.,
2004, 2006a,b), signiﬁcant disturbances have been found and
may be interpreted differently (Séralini et al., 2009; Spiroux de
Vendômois et al., 2010). Detailed analyses have revealed alterations in kidney and liver functions that may be the signs of early
chronic diet intoxication, possibly explained at least in part by
pesticide residues in the GM feed (Séralini et al., 2007; Spiroux
de Vendômois et al., 2009). Indeed, it has been demonstrated that
R concentrations in the range of 103 times below the MRL induced
endocrine disturbances in human cells (Gasnier et al., 2009) and
toxic effects thereafter (Benachour and Seralini, 2009), including
in vivo (Romano et al., 2012). After several months of consumption
of an R-tolerant soy, the liver and pancreas of mice were affected,
as highlighted by disturbances in sub-nuclear structure (Malatesta
et al., 2008a, 2002a,b). Furthermore, this toxic effect was reproduced by the application of R herbicide directly to hepatocytes in
culture (Malatesta et al., 2008b).
G.-E. Séralini et al. / Food and Chemical Toxicology 50 (2012) 4221–4231
views on GMOs (Domingo and Giné Bordonaba, 2011; Snell et al.,
2011) we had no reason to settle at ﬁrst for a carcinogenesis protocol using 50 rats per group. However we have prolonged the biochemical and hematological measurements or disease status
recommended in combined chronic studies using 10 rats per group
(up to 12 months in OECD 453). This remains the highest number
of rats regularly measured in a standard GMO diet study. We have
tested also for the ﬁrst time 3 doses (rather than two in the usual
90 day long protocols) of the R-tolerant NK603 GM maize alone,
the GM maize treated with R, and R alone at very low environmentally relevant doses starting below the range of levels permitted by
regulatory authorities in drinking water and in GM feed.
2. Materials and methods
The experimental protocol was conducted in accordance with the regulations of
our ethics in an animal care unit authorized by the French Ministries of Agriculture
and Research (Agreement Number A35-288-1). Animal experiments were performed according to ethical guidelines of animal experimentations (CEE 86/609 regulation). Concerning ﬁeld studies of plant species, no speciﬁc permits were
required, nor for the locations/activities. The maize grown (MON-00603-6 commonly named NK603) was authorized for unconﬁned release into the environment
and use as a livestock feed by the Canadian Food Inspection Agency (Decision Document 2002-35). We conﬁrm that the location is not privately-owned or protected
in any way and that the ﬁeld studies did not involve endangered or protected species. The GM maize was authorized for import into the European Union (CE 258/97
Since then, long-term and multi-generational animal feeding
trials have been performed with some possibly providing evidence
of safety, while others conclude on the necessity of further investigations because of metabolic modiﬁcations (Snell et al., 2011).
However, none of these studies have included a detailed followup of the animals with up to 11 blood and urine samples over
2 years, and none has investigated the NK603 R-tolerant maize.
Furthermore, toxicity evaluation of herbicides is generally performed on mammalian physiology through the long-term study
of only their active principle, rather than the formulation used in
agriculture, as was the case for glyphosate (Williams et al., 2000),
the active herbicide constituent of R. It is important to note that
glyphosate is only able to efﬁciently penetrate target plant organisms with the help of adjuvants present in the various commercially used R formulations (Cox, 2004). When R residues are
found in tap water, food or feed, they arise from the total herbicide
formulation, which is the most commonly used mixture in agriculture; indeed many authors in the ﬁeld have strongly emphasized
the necessity of studying the potential toxic effects of total chemical mixtures rather than single components (Cox and Surgan,
2006; Mesnage et al., 2010; Monosson, 2005). Even adjuvants
and not only glyphosate or other active ingredients are found in
ground water (Krogh et al., 2002), and thus an exposure to the diluted whole formulation is more representative of an environmental pollution than the exposure to glyphosate alone in order to
study health effects.
With a view to address this lack of information, we have performed a 2 year detailed rat feeding study. The actual guideline
408 of the Organization for Economic Co-operation and Development (OECD) was followed by some manufacturers for GMOs even
if it was not designed for that purpose. We have explored more
parameters and more frequently than recommended in this standard (Table 1) in a long-term experiment. This allowed us to follow
in details potential health effects and their possible origins due to
the direct or indirect consequences of the genetic modiﬁcation itself in GMOs, or due to the formulated herbicide mixture used on
GMOs (and not glyphosate alone), or both. Because of recent re-
2.2. Plants, diets and chemicals
The varieties of maize used in this study were the R-tolerant NK603 (Monsanto
Corp., USA), and its nearest isogenic non-transgenic control. These two types of
maize were grown under similar normal conditions, in the same location, spaced
at a sufﬁcient distance to avoid cross-contamination. The genetic nature, as well
as the purity of the GM seeds and ...
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