RetractedArticle

RETRACTED: Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

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.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... This means that most publications remains inconclusive, i.e. do not provide hard facts for or against GMO and GM plants. Research providing some evidence of GM environmental and health risks [8,9,10,11] is hectically debated [12,13] indicating lack of sound methodology and objectivity [14]. Consequently, one may suggest developing adequate methodology and procedures which could be used in experiments and implemented/intensified studies on the log-term health effects of GM plants introduce long-term experiments. ...
... Here the case of Séralini et al. [9,14] seems to be the most recent, the contribution of an in-depth analysis of 94 scientific articles by Diels et al. [3] notwithstanding. Séralini et al. study [9] investigated the long-term effects in rats of consumption of two Monsanto products, a genetically modified (GM) maize (NK603) and its associated pesticide, Roundup, together and separately. ...
... Here the case of Séralini et al. [9,14] seems to be the most recent, the contribution of an in-depth analysis of 94 scientific articles by Diels et al. [3] notwithstanding. Séralini et al. study [9] investigated the long-term effects in rats of consumption of two Monsanto products, a genetically modified (GM) maize (NK603) and its associated pesticide, Roundup, together and separately. The findings suggested both the maize and the Roundup herbicide it is grown with, pose serious health risks. ...
Article
Genetically modified organisms (GMOs) is a topic of intense debate across the globe since they are widely used in several commercial products and the GMO industry counts for billions of US dollars. Genetically modified crops can assist to mitigate problems in commercial agriculture with proven case studies in Indian cotton and Australian canola [1]. The success of the GMO industry has been impeded by negative information concerning health and environmental risks. The aim of the paper is to assess the current research (from 2010-2019) on the health risk of GMOs (with a special emphasis on genetically modified plants). EBSCOhost (including Medline) and ScienceDirect databases were used for review of the literature. The paper concludes that research on GMO health risk is still lacking in sound methodology, complexity, continuity, objectivity and remains inconclusive.
... "Ultimately, CSA neither mandates nor excludes the use of biotechnology or GMOs for any specific user of the approach, but it can provide a basis for helping potential users identify the risks and benefits of its use in addressing the challenges of achieving food security under climate change." (FAO, 2018) However, during the (extensive) research for this seminar paper, the circumstances in which a certain paper (Séralini et al., 2012) showing concerning health effects was defamed and eventually shut down (Fagan et al., 2014; was actually more damning than the findings themselves. The main contentious paper, by Séralini et al. (2012), was finally retracted following strong pressure from Monsanto, as released papers (Baum Hedlund Law, 2017) show with evidence of concerted pressure (Chassy, 2012) and (attempted) bribes to the editor (Monsanto, 2012). ...
... (FAO, 2018) However, during the (extensive) research for this seminar paper, the circumstances in which a certain paper (Séralini et al., 2012) showing concerning health effects was defamed and eventually shut down (Fagan et al., 2014; was actually more damning than the findings themselves. The main contentious paper, by Séralini et al. (2012), was finally retracted following strong pressure from Monsanto, as released papers (Baum Hedlund Law, 2017) show with evidence of concerted pressure (Chassy, 2012) and (attempted) bribes to the editor (Monsanto, 2012). The retraction caused so much controversy that it was finally republished, extended and with all data (and re-reviewed to ensure there was no change from the original paper) (Casassus, 2014;. ...
Research
Full-text available
Launched by the Food and Agriculture Organisation (FAO) in 2009, Climate Smart Agriculture (CSA) has become prominent in many of the discussions on how to respond to the future challenges posed by population growth, climate change and food insecurity. Seeking to find synergies between mitigation, productivity and resilience to climate change, CSA represents an intuitively "common sense" idea. However, it has been the centre of much controversy, and this paper seeks to understand and challenge these controversies, and to better understand whether CSA is the best direction for us to follow. At this critical point of human history, we cannot afford to be misled. CSA implementation decisions must be made with solid understanding of the situation (both global and local), as well as clear consultation with those who will enact and be affected by such decisions. A balance must be struck between increasing productivity to meet projected food demand, whilst lowering emissions, without in turn promoting socially, economically or even environmentally unsustainable practices. There is no time left for business as usual, which includes challenging the spectre of corporate influence in policy direction, as well as discussing the accepted paradigms in our food production system.
... A few reports are quoted here to point out the pitfalls in study design and interpretation. Common deficiencies include inadequate experimental design (identity of test and control substances), inappropriate control crops or little information on controls, the presence of contaminants not being reported, nutritionally balanced diets not being confirmed, inadequate information on the study design and methods used, statistical analysis being either omitted or inappropriate, sample sizes being too small, and studies not being published in peer reviewed journals (Arjó et al., 2013;Ermakova, 2005;Evans and Pusztai, 1999;Séralini et al., 2007Séralini et al., , 2012. Such studies have produced unreliable results and inappropriate conclusions: the paper from Séralini et al. (2012) was retracted. ...
... Common deficiencies include inadequate experimental design (identity of test and control substances), inappropriate control crops or little information on controls, the presence of contaminants not being reported, nutritionally balanced diets not being confirmed, inadequate information on the study design and methods used, statistical analysis being either omitted or inappropriate, sample sizes being too small, and studies not being published in peer reviewed journals (Arjó et al., 2013;Ermakova, 2005;Evans and Pusztai, 1999;Séralini et al., 2007Séralini et al., , 2012. Such studies have produced unreliable results and inappropriate conclusions: the paper from Séralini et al. (2012) was retracted. The ILSI best practice guidelines (ILSI, 2003;ILSI, 2007) provide detailed protocols for wholesomeness studies, which can be adapted for feeding studies with rodents and other animal species ...
Chapter
The study of the safety and risk of genetically engineered (GE) food [also described as genetically modified organisms (GMO)] is focused on determining whether intended and/or unintended effects have arisen from their use. Comparison of the unknown with the known has been a major approach to food safety, and is also applied for GE foods. A distinction should be made between the concept of safety and risk. Zero risk is not possible. International bodies have played significant roles in guiding the interpretation of these concepts. Analysis and interpretation of the composition of GE food is key to the targeted approach of assessment. The environmental effects on component concentration are becoming better understood through metaanalyses of crop data. The current global focus is on the value of rodent toxicology studies, nontarget "omics" approaches, trait stacking, and safety studies for foods produced using gene editing techniques.
... Kenyan GM field trials started in 2004 and have continued since, but till now not a single GM crop has been approved for commercialization (ISAAA, 2017). Furthermore, in November 2012 Kenya imposed a ban on GMO crop imports based on a publication of Séralini et al. (2012) that stated that eating GMOs causes cancer. The experimental design and the conclusions of that paper were heavily criticized and the paper was retracted, but the damage had been done. ...
Article
Full-text available
Genetically modified (GM) crops are cultivated globally on more than 185 million hectares, but the use of GM crops in Europe and Africa is very limited. Politicians are reluctant to allow such crops because they fear negative public reaction. The political hostility in the EU towards GM crops also has a significant impact on how African policy makers form their opinions for accepting GM crops in their own countries. However, studies reveal that specific types of GM food are welcomed by consumers and that few Europeans avoid GM labels when buying food. Similarly, African farmers and consumers are generally positive about GM crops. Policy makers should take these results into account when a decision needs to be made on whether or not to allow GM crop cultivation in their country. KEY WORDS: ACCEPTANCE, AFRICA, CONSUMERS, EUROPE, FARMERS, GM CROPS
... A publication by the Seralini laboratory Seralini G.E. et al. 58 (subsequently retracted by the journal) claiming that glyphosate-tolerant Maize NK603 induced tumors was widely discredited by many international organizations including EFSA: 59 , 60 , 61--64 and researchers like Jany K. 2012 65 , ARIO G. 66 , Snell et al. 67 , and three important papers analyzing rat experiments from the GRACE framework program 68--70 came to conclusions which exclude the Séralini experiments from serious evaluation: Herbicide tolerant crops analysed are nutritionally equivalent to the conventional crops nad 90-day rat experiments, they are scientifically sound and sufficient, an extention to 2--3 years is scientifically not justified. Also the statistics of the cited Séralini paper is deeply flawed according to Panchin A: 71,72 . ...
Article
Full-text available
1. In this review, current EU GMO regulations are subjected to a point-by point analysis to determine their suitability for agriculture in modern Europe. Our analysis concerns present GMO regulations as well as suggestions for possible new regulations for genome editing and New Breeding Techniques (for which no regulations presently exist). Firstly, the present GMO regulations stem from the early days of recombinant DNA and are not adapted to current scientific understanding on this subject. Scientific understanding of GMOs has changed and these regulations are now, not only unfit for their original purpose, but, the purpose itself is now no longer scientifically valid. Indeed, they defy scientific, economic, and even common, sense. A major EU regulatory preconception is that GM crops are basically different from their parent crops. Thus, the EU regulations are “process based” regulations that discriminate against GMOs simply because they are GMOs. However current scientific evidence shows a blending of classical crops and their GMO counterparts with no clear demarcation line between them. Canada has a “product based” approach and determines the safety of each new crop variety independently of the process used to obtain it. We advise that the EC re-writes it outdated regulations and moves towards such a product based approach. Secondly, over the last few years new genomic editing techniques (sometimes called New Breeding Techniques) have evolved. These techniques are basically mutagenesis techniques that can generate genomic diversity and have vast potential for crop improvement. They are not GMO based techniques (any more than mutagenesis is a GMO technique), since in many cases no new DNA is introduced. Thus they cannot simply be lumped together with GMOs (as many anti-GMO NGOs would prefer). The EU currently has no regulations to cover these new techniques. In this review, we make suggestions as to how these new gene edited crops may be regulated. The EU is at a turning point where the wrong decision could destroy European agricultural competitively for decades to come.
... Toxicities and detrimental effects seen in lab and farm animals feeding studies clearly indicate the harms of long term feeding of GM crops. There have been reports of severe organ damage and increased rate of large tumor formation (Séralini et al., 2012;EndScience, 2014) various other deleterious effects. There is no evidence that commercialized GM food are safe to eat over the long term. ...
Article
Full-text available
Biotechnology is a modern science with old roots. It can be considered a game changer in many ways as it has inherent solutions for many hurdles modern society is facing today. One of the most important branches of Biotechnology is Green or Agro-biotechnology, which is the application of biotechnological tools and techniques to genetically improve organisms, crops for the betterment of ever burgeoning population. Green biotechnology holds promise in producing crops with high yields and nutritional content, insect resistance, longer shelf life, and various other traits like production of vaccines (edible vaccines), monoclonal antibodies phytoremediation and so on. Biotech crops are supposed to need lesser water, fertilizers, herbicides, almost nil tillage requirement, lesser need to spray so less fuel consumption, reduced CO2 and N2O emissions. Inspite of all these advantages, the acceptance of genetically modified plants have become mired in controversies regarding their safety, applicability and their effects on the environment. This review deals with various positive and negative aspects of green biotechnology, trying to shed an unbiased light on the actual scenario because this technology actually has the potential to feed millions of poverty stricken, undernourished people on the earth. How far this goal is reached, still remains to be seen.
... There are prominent examples of subsequently discredited research claims causing permanent shifts in entire fields of thought, for example the claimed link between Bt corn, RoundUp herbicide and tumour growth. A molecular biologist, Gilles-Eric Seralini published, retracted and republished a study presenting a two year Bt corn and RoundUp feeding study in rats and reported an increase in tumours in the rats fed the Bt corn and RoundUp (Seralini et al., 2012). Other scientists and regulatory agencies criticised the design of the study as inherently flawed and its findings statistically unsubstantiated due to the low number of rats used. ...
Article
There is an apparent incongruence between businesses and researchers targeting insects for food and feed. With the Novel Foods Application looming, legislative hurdles to insects in animal feed and the uncertainty of Brexit, businesses and researchers find themselves questioning whether a collaborative partnership is worth pursuing. Discussion with experts on both sides highlighted the main tension points and possible paths to reconciliation. The key differences were established as views on end goals, access to resources, inherent personal risk and communication of findings. Ultimately, for the marriage of business and research to survive it must be recognised how similarities, however limited, work together rather than how differences divide.
... However, it is not our job to be overly encompassing and give equal weight to all objections; we also must be willing to learn from past experiences (such as the disastrous effects of the perception of possible military involvement in the WHO program in India) and to rationally disagree when we reason this to be the case. For example, despite claims to the contrary (Séralini et al., 2012), there is no scientific evidence that herbicide resistant maize is carcinogenic. There is a great deal of misinformation and misconceptions surrounding who would or would not benefit, and to what degree, from golden rice (Harmon, 2013). ...
Article
Full-text available
The Indo-Pacific region contains a unique mix of opportunities for the development and use of genetic-pest-management, gene-drive, and gene-drive-like technologies. Here I collectively refer to these technologies as Evolutionary Genetic Engineering (EGE). Indo-Pacific Islands have some of the world's highest rates of endemism and extinction---species and entire ecosystems are at risk. This threat to the natural world is coupled with the burden of human diseases, many of which are new and emerging or neglected tropical diseases. The same factors which have led to high rates of endemism also, in some ways, make this region an ideal testing ground for some types of EGE's. There is great potential for positive humanitarian, economic, and conservation applications of EGE's. However, these types of new technologies will be initially viewed from the perspective of the recent history of a loss of self determination, issues of social justice, and the testing of new technologies (e.g., biocontrol, agricultural, nuclear) in the Indo-Pacific---a region of the world that is still extensively colonized and controlled by Western Nations. Experience with successes and failures in related technologies suggests a path to move forward---a set of eight recommendations---to maximize the potential payoffs and minimize unintended negative effects of EGE's.
... En contraste, los estudios sobre el efecto nocivo de los transgénicos, en particular del maíz transgénico consumido por generaciones, no han sido fructíferos ni contundentes, ya que no existe información actual en la literatura científica que demuestre su asociación con el desarrollo de la DM2. Al contrario, se han observado una pérdida de la objetividad, inconsistencias y posibles manipulaciones que los vinculan al desarrollo de enfermedades consideradas problemas de salud pública mundiales 46 . Este hecho podría estar asociado a conflictos de intereses puramente comerciales y no científicos. ...
Article
Full-text available
La diabetes mellitus tipo2 (DM2) es un problema de salud pública mundial. La etiología de la enfermedad es multifactorial y se caracteriza por una gran heterogeneidad de alteraciones metabólicas. Las más frecuentes son la producción de insulina insuficiente, la resistencia a la insulina y el deterioro en el sistema de incretinas. El especialista en el área de la salud debe comprender la naturaleza multi-causal de la DM2en la era post-genómica. Dicha naturaleza está determinada por el efecto aditivo de genes así como del medio ambiente, por ello no existe un modelo genético epidemiológico simple que explique su patrón de herencia. De este hecho parte la necesidad de establecer la proporción de DM2 que es determinada por los genes y la contribución de los factores ambientales, cuya combinación regula el umbral o nivel de tolerancia para que se desarrolle. Dada la complejidad de la DM2 en este trabajo se analizan las diversas teorías existentes sobre la causalidad de esta pandemia. Esto permitirá comprenderla interacción del ambiente con el genoma humano y, también conocer como los factores de riesgo o predisposición a esta enfermedad interactúan con el ambiente con el genoma.
... Toxicities and detrimental effects seen in lab and farm animals feeding studies clearly indicate the harms of long term feeding of GM crops. There have been reports of severe organ damage and increased rate of large tumor formation (Séralini et al., 2012;EndScience, 2014) various other deleterious effects. There is no evidence that commercialized GM food are safe to eat over the long term. ...
... Rat liver tissues were obtained 15 from animals described in a previous report 16 . Eriksson tries to discredit the findings of our study by association with this previous investigation 16 , which sparked much controversy [17][18][19][20][21][22][23] . Livers were freshly excised from euthanized animals, snap frozen and appropriately stored to maintain integrity. ...
Article
Full-text available
The opinion expressed by Eriksson and colleagues' fails to recognise that there are no standard experimental designs for academic investigations involving omics analyses of genetically modified crops and that the only valid comparator to determine the effect of the process of transgenesis is a near isogenic variety grown at the same time and location, as was the case in our investigation of NK603 maize. Eriksson does not acknowledge that the quality of the rat liver tissues in our chronic Roundup toxicity study has neither been questioned nor branded as unsuitable for further investigation. In addition, Eriksson fails to appreciate that the statistical methods we used to analyse the liver metabolomics dataset are recognised as appropriate as some of a number of approaches that can be taken. Moreover, Eriksson neglects to mention that the proteomics analysis of the liver tissues highlights structural and functional damage from Roundup exposure. Thus our results are sound and the claims by Eriksson and colleagues of experimental flaws are unfounded.Replying to: Eriksson et al. Sci Rep 8 (2018); https://doi.org/10.1038/s41598-018-30440-7 .
... In contrast, studies on transgenic foods noxious effect, in particular of transgenic corn, consumed for generations, have not been fruitful or conclusive, since there is no current information in the scientific literature demonstrating their association with the development of DM2. On the contrary, a loss of objectivity, inconsistencies and possible manipulations have been observed associating them with the development of diseases regarded as global health problems 46 . This fact might be related to purely commercial and not scientific conflicts of interests. ...
... A number of studies concerning this issue have previously been published concluding absence of any detrimental effects on human and animal health (Cao et al., 2012;Hu, Zhuo, Gong, Piao, & Yang, 2017;Mao et al., 2016;Mo et al., 2015;Morera, Basirico, Ronchi, & Bernabucci, 2016;Shahid et al., 2016;Xu, Liu, Xing, & Yang, 2011;Yuan et al., 2017;Zhou et al., 2014). Opposite opinions, however, do exist and are experimentally documented (Kulikov, 2005;Malatesta et al., 2008Malatesta et al., , 2002Séralini et al., 2012;Świątkiewicz et al., 2011;Tudisco et al., 2010). In order to carefully assess the risk associated with Bt crops, extensive animal feeding thus becomes necessary especially on the basis of case assessment rule (Mo et al., 2015). ...
Article
Full-text available
Genetically modified (GM) crops expressing insect resistance and herbicide tolerance provide a novel approach for improved crop production but their advent at the same time presents serious challenges in terms of food safety. Although prevailing scientific proof has suggested that transgenic crops are analogous to their conventional counterparts, their use in human and animal diet gave rise to emotional public discussion. A number of studies had been conducted to evaluate the potential unintended effects of transgenic crops expressing single transgene, but very few studies for those with multiple transgenes. As the crops with single and multiple transgenes could impart different effects on non‐target organisms, thus, risk evaluation of transgenic crops expressing more than one transgene is required to declare their biosafety. The present study was therefore designed to assess the effects of different levels of dietary transgenic cottonseed expressing recombinants proteins produced by Cry1Ac, Cry2A and Cp4epsps genes on haematological indices of growing rabbits. A total of 48 rabbits were assigned to four dietary treatments containing different levels of transgenic cottonseeds (i.e., 0% w/w, 20% w/w, 30% w/w and 40% w/w) with 0% w/w serving as control. Haematological parameters were measured at periodic intervals (0, 45, 90, 135 and 180) days. No significant (p > 0.05) dose‐dependent effects were observed in most of the haematological parameters evaluated. Though, significant differences (p < 0.05) were recorded in the level of MCHC, MCH and HCT in some of experimental male and female rabbits, yet, they were not biologically significant, as all the differences were within the normal reference values. Our study suggested that feeding transgenic cottonseed of up to 40% could not adversely affect rabbit's haematological profile. However, further study needs to be conducted with different cotton genotypes expressing both single and polygenic traits before recommending the utilization of transgenic cottonseed in routine livestock feeding.
... It increased the British public's perception of risk with respect to food safety and lowered the level of public trust in science. Another example is that Séralini et al. (2012) conclude that GM corn caused health hazards in rats, although this study was retracted due to concerns about research methodology. It captured international headlines and caused consumers to scrutinize GM foods (Xia et al., 2015). ...
Article
Purpose The purpose of this paper is to examine Chinese consumers’ attitudes toward genetically modified (GM) foods and the impact that consumers’ trust in different actors – GM scientists, non-GM scientists or individuals, the government and the media, has on their attitudes. Design/methodology/approach Consumers in Beijing were surveyed about their attitudes toward GM foods and their trust in different actors. The surveys were conducted from June to July of 2015. The sample size is 1,460 people. Given the potential endogeneity of trust variable, bivariate probit models are employed to estimate the impact of trust in different actors on consumers’ attitudes. Findings The results show that 55 percent of the Chinese consumers are opposed to GM foods and nearly 60 percent do not trust GM scientists. In total, 42 percent of Chinese consumers trust in the government and 39 percent trust the non-GM scientists or individuals. Around 35 percent of consumers believe the misinformation on GM technology that were provided by the media. Trust in the GM scientists and trust in the government have a significant positive impact on consumers’ acceptance of GM foods while trust in the non-GM scientists or individuals and believing the misinformation have a significant negative effect on the acceptance. Nearly 70 percent of Chinese consumers acquired information about GM food safety from the internet or via WeChat. Consumers who acquired GM technology information from the internet or via WeChat are less likely to embrace GM foods than those who obtain information from other sources. Originality/value Consumer trust plays a crucial role to accept biotech products in the market and it is crucial for producers, policy makers and consumers to have faith in new biotech products. The results of this study suggest that the government and GM scientists should make more effort to gain the trust and support of consumers, while the media should provide objective reports on GM products based on scientific evidence.
... The likelihood of chronic health issues related to pesticide exposure is supported by a large number of data collected from laboratory animals [114][115][116]. However, epidemiological data are not available for all health issues. ...
Article
Full-text available
Pesticides play an important role in agricultural development. However, pesticide application can result in both acute and chronic human toxicities, and the adverse effects of pesticides on the environment and human health remain a serious problem. There is therefore a need to discuss the application methods for pesticides, the routes of pesticide exposure, and the health risks posed by pesticide application. The health problems related to pesticide application and exposure in developing countries are of particular concern. The purpose of this paper is to provide scientific information for policymakers in order to allow the development of proper pesticide application technics and methods to minimize pesticide exposure and the adverse health effects on both applicators and communities. Studies indicate that there are four main pesticide application methods, including hydraulic spraying, backpack spraying, basal trunk spraying, and aerial spraying. Pesticide application methods are mainly selected by considering the habits of target pests, the characteristics of target sites, and the properties of pesticides. Humans are directly exposed to pesticides in occupational, agricultural, and household activities and are indirectly exposed to pesticides via environmental media, including air, water, soil, and food. Human exposure to pesticides occurs mainly through dermal, oral, and respiratory routes. People who are directly and/or indirectly exposed to pesticides may contract acute toxicity effects and chronic diseases. Although no segment of the general population is completely protected against exposure to pesticides and their potentially serious health effects, a disproportionate burden is shouldered by people in developing countries. Both deterministic and probabilistic human health risk assessments have their advantages and disadvantages and both types of methods should be comprehensively implemented in research on exposure and human health risk assessment. Equipment for appropriate pesticide application is important for application efficiency to minimize the loss of spray solution as well as reduce pesticide residuals in the environment and adverse human health effects due to over-spraying and residues. Policymakers should implement various useful measures, such as integrated pest management (IPM) laws that prohibit the use of pesticides with high risks and the development of a national implementation plan (NIP) to reduce the adverse effects of pesticides on the environment and on human health
... Currently, the attempts to publish the retracted work in other journals are likely sporadic. The most prominent example includes the 2012 paper on the long-term toxicity of Roundup herbicide and a Roundup-tolerant genetically modified maize, first retracted by Food and Chemical Toxicology (Séralini et al. 2012) and later published in unchanged form in the Environmental Sciences Europe (Séralini et al. 2014). However, in this controversial case, the journal editors were fully aware of resubmission, and the republication was acknowledged in the paper's title (Resnik 2015). ...
Article
In case of scientific misconduct, the papers can be retracted at the request of the journal’s editors and/or authors. However, the retracted articles continue to be fully available through online resources, including journals websites. This paper argues that a classical retraction is insufficient to mitigate the adverse effect some retracted papers continue to have on critical issues, e.g. public health. The more strict approach, ‘Hard Retraction’, is presented for consideration. Its implementation would lead to (1) complete deletion of the full text of the retracted paper, (2) substitution of the original abstract with a detailed retraction notice, (3) removal of the paper from the citation databases, (4) deposition of the retracted paper in the dedicated repository accessible for registered members. The benefits and risks of such an approach are discussed. Nevertheless, it should only be reserved for cases of fraud or grave errors with broad impacts.
... Séralini (Séralini, et al. 2012 " Sin embargo el científico de Monsanto David Saltmiras admitió haber orquestado esta campaña y con ayuda de "expertos externos", científicos aparentemente independientes de Monsanto, bombardear con cartas al editor en jefe de la revista Food and ChemicalToxicology (FCT), A. Wallace Hayes, exigiendo que se retracte del estudio."http://monsantopapers.lavaca.org/2018/02/16/monsanto-al-descubierto-la-campana-para-lograr-laretractacion-del-estudio-seralini/ Dentro de las investigaciones validadas científicamente se encuentran Poverene y Cantamutto (2003) y Trigo y Cap (2003) las que señalan que, aunque desde mediados de 1990 la cantidad total de herbicidas utilizados aumentó, no es grave en general debido a que, para ellos, el glifosato ha suplido a otros herbicidas más tóxicos. ...
Thesis
Full-text available
Esta tesis es el resultado de una investigación interdisciplinaria sobre una de las problemáticas agrarias del sigo XX y XXI en nuestro país: las transformaciones territoriales producidas por el agronegocio. Se realizó un estudio etnográfico sobre las estrategias de resistencia e integración durante la consolidación del agronegocio en el Partido de Junín. Provincia de Buenos Aires entre 1996-2016. La investigación tuvo lugar entre junio de 2015 y diciembre de 2019, incluyó entrevistas y observación participante para generar datos cualitativos, se utilizaron herramientas cartográficas para ubicar espacialmente los lugares de estudio. También se incorporó la técnica de mapeo colectivo en un taller participativo con la construcción de cartografía social (Iconoclasistas, 2013) para poder identificar en una imagen satelital de la zona los lugares que los actores de esta tesis consideran son afectados (o no) por las fumigaciones. La generación de datos cuantitativos se realizó a partir de fuentes secundarias y revisión bibliográfica. En este sentido, se analizan los usos hegemónicos del territorio del agronegocio, específicamente el uso de semillas genéticamente modificadas, siembra directa (incluyendo maquinaria agrícola) y uso de agrotóxicos. Se estudian los procesos de incorporación de estas semillas en el territorio y se presentan las magnitudes en que se utilizan los agrotóxicos en la producción agraria en la zona de estudio, se caracterizan los riesgos de los productos químicos para la salud humana descriptos en la literatura científica y se explora dentro de esa producción de conocimiento la dinámica hegemonía-contra hegemonía caracterizando los actores sociales que encarnan esa dinámica en el Partido de Junín. En base a esos datos se interpretan los sentidos que circulan localmente sobre los agrotóxicos y el riesgo que comportan para la salud y el ambiente. Se concluye que la tensión entre hegemonía contra hegemonía al interior de la práctica científica no es ajena a las políticas públicas ni a las relaciones de poder con las empresas trasnacionales, y se expresa localmente en distintos actores sociales. Estas tensiones y relaciones de poder hacen que hipotetizar, o comprobar con evidencia científica fundada, que los agrotóxicos pueden ser peligrosos para la salud humana, aun bien aplicados y en dosis subóptimas, no gane poder en las relaciones sociales. Esto es válido aun cuando se trate de evidencias publicadas como poster en un congreso, como paper o como libro, sea cual fuera la valoración de la editorial o revista dentro de la comunidad científica. El dispositivo de legitimación de la ciencia demuestra tener poco poder para construir hegemonía en la política del agronegocio pampeano. La palabra autorizada para quiénes portan el discurso hegemónico circula por otros canales: charlas de idóneos en ferias de producción como Expoagro, folletos, páginas web, redes sociales de empresas o corporaciones de productores, las agronomías, y la llamada literatura gris. Con relación a las estrategias de resistencias descubrimos que las mismas transitan por distintos caminos, la solidaridad y lealtad de los productores, el discurso oculto (Scott, 2003), la acción colectiva contra las fumigaciones y la transformación del modo de producción con la implementación de la agroecología. Entendemos las relaciones de lealtad y solidaridad entre productores rurales como una práctica social que permite resistir y no perder su producción. En este sentido, la construcción social de los sentidos nativos del riesgo está atravesada por la dinámica hegemonía-contra hegemonía. Tres categorías nativas dan cuenta de esa dinámica localmente, son ellas matayuyo, remedio y veneno. La denominación local del glifosato y otros agrotóxicos como matayuyo o remedio implica que la agencia de la sustancia se representa contra la vegetación y no contra la vida animal o humana, invisibilizando las consecuencias de la exposición permanente a él y por lo tanto minimizando la percepción del riesgo. Por otra parte, las categorías nativas de remedio o veneno para referirse a las mismas sustancias marcan un cambio de agencia. En este caso se trata del pasaje de la sumisión a la acción colectiva, pues se reconoce que pasa de curar a matar. Por ello se afirma que nombrar veneno a los agrotóxicos es una de las formas que adopta la resistencia al modelo. Esta resistencia se manifiesta como discurso oculto (Scott, 2003) y en privado, ya que en Junín la hegemonía performática de las Buenas Prácticas Agrícolas impide que se exprese el riesgo de enfermar por agrotóxicos como sufrimiento social, siendo las intoxicaciones un relato permanente de casos aislados relegados al secreto en el interior de los hogares. En este sentido, también forman parte de la resistencia a las acciones colectivas organizadas en pos de establecer límites a las fumigaciones y los profesionales de la salud y científicos que se comprometen estudiando las consecuencias de los agrotóxicos a la salud y el ambiente. A su vez, los registros de producciones agroecológicas en la zona ("El Huerto Interior") permiten pensar que hay una oportunidad de transformaciones territoriales en pro de un uso solidario del territorio, garantizando la seguridad y soberanía alimentaria argentina.
... Kenyan GM field trials started in 2004 and have continued since, but till now not a single GM crop has been approved for commercialization (ISAAA, 2017). Furthermore, in November 2012 Kenya imposed a ban on GMO crop imports based on a publication of Séralini et al. (2012) that stated that eating GMOs causes cancer. The experimental design and the conclusions of that paper were heavily criticized and the paper was retracted, but the damage had been done. ...
Article
Full-text available
Genetically modified (GM) crops are cultivated globally on more than 185 million hectares, but the use of GM crops in Europe and Africa is very limited. Politicians are reluctant to allow such crops because they fear negative public reaction. The political hostility in the EU towards GM crops also has a significant impact on how African policy makers form their opinions for accepting GM crops in their own countries. However, studies reveal that specific types of GM food are welcomed by consumers and that few Europeans avoid GM labels when buying food. Similarly, African farmers and consumers are generally positive about GM crops. Policy makers should take these results into account when a decision needs to be made on whether or not to allow GM crop cultivation in their country.
... Un ejemplo claro de la intrincada relación entre el sistema científico, el Estado y las empresas es el caso del paper publicado por el grupo de investigación francés dirigido por el Dr. Séralini (Séralini, et al. 2012), fue publicado en la revista Food and Chermical Toxicology y mencionaba los hallazgos ligados a los daños a la salud sufridos por las ratas de laboratorio luego del consumo de dos productos de Monsanto/Bayer (Maíz GM NK603 TM y el herbicida Roundup Ready TM ). Al tiempo de su publicación este artículo fue retractado por los editores de la revista (en los buscadores académicos en el título figura "Retracted"), alegan que la revista recibió cartas al Editor expresando la preocupación de los hallazgos, la cantidad de ratas utilizadas en el ensayo y el uso de las mismas. ...
Thesis
Full-text available
Esta tesis expone los resultados de un estudio etnográfico de los discursos y las prácticas de los habitantes de Morse (Partido de Junín, Bs. As). Se describen los sentidos nativos del riesgo en torno al uso de agrotóxicos en un contexto de afianzamiento del agronegocio. El trabajo de campo se realizó entre 2015-2017. Se analiza la magnitud en la que los diferentes actores sociales utilizan los agrotóxicos en la zona de estudio y se caracterizan los estudios científicos hegemónicos y contrahegemónicos sobre las implicancias en la salud y el medioambiente. Se concluye que la evidencia científica sobre los daños en la salud no es suficiente para convertirse en un dispositivo de legitimación, sin embargo, las categorías nativas de matayuyo, remedio y veneno dan cuenta de un cambio de agencia en la dinámica hegemonía contrahegemonía. Referirse a los agrotóxicos como remedio invisibiliza las consecuencias de la exposición y minimiza la percepción del riesgo mientras que denominarlos veneno marca el pasaje de la sumisión a la acción colectiva, se reconoce que pasa de curar a matar. Este reconocimiento se manifiesta como discurso oculto y en secreto en el interior de los hogares.
... On ScienceNet.cn and other Chinese public platforms, articles and texts to refute the dissenting studies on GMO safetysuch as the rejected Séralini et al. (2012) were widely circulated among peer scientists and science communicators. After the 2009/2010 controversy on the biosafety certificate of GM rice, agricultural biologists' efforts to reject domestically published papers (e.g., Z. Zhang et al., 2015) were also enhanced (INT20161215, INT20170617). ...
... On ScienceNet.cn and other Chinese public platforms, articles and texts to refute the dissenting studies on GMO safetysuch as the rejected Séralini et al. (2012) were widely circulated among peer scientists and science communicators. After the 2009/2010 controversy on the biosafety certificate of GM rice, agricultural biologists' efforts to reject domestically published papers (e.g., Z. Zhang et al., 2015) were also enhanced (INT20161215, INT20170617). ...
... On ScienceNet.cn and other Chinese public platforms, articles and texts to refute the dissenting studies on GMO safetysuch as the rejected Séralini et al. (2012) were widely circulated among peer scientists and science communicators. After the 2009/2010 controversy on the biosafety certificate of GM rice, agricultural biologists' efforts to reject domestically published papers (e.g., Z. Zhang et al., 2015) were also enhanced (INT20161215, INT20170617). ...
Chapter
Full-text available
Article
Modern agriculture provides the potential for sustainable feeding of the world's increasing population. Up to the present moment, genetically modified (GM) products have enabled increased yields and reduced pesticide usage. Nevertheless, GM products are controversial amongst policy makers, scientists and the consumers, regarding their possible environmental, ecological, and health risks. Scientific-and-political debates can even influence legislation and prospective risk assessment procedure. Currently, the scientifically-assessed direct hazardous impacts of GM food and feed on fauna and flora are conflicting; indeed, a review of literature available data provides some evidence of GM environmental and health risks. Although the consequences of gene flow and risks to biodiversity are debatable. Risks to the environment and ecosystems can exist, such as the evolution of weed herbicide resistance during GM cultivation. A matter of high importance is to provide precise knowledge and adequate current information to regulatory agencies, governments, policy makers, researchers, and commercial GMO-releasing companies to enable them to thoroughly investigate the possible risks.
Article
Full-text available
The paper discusses the use of term 'advocacy science' which is communication of science which goes beyond simple reporting of scientific findings, using the case study of biotechnology. It argues that advocacy science should be used to distinguish the engagement of modern civil society organizations to interpret scientific knowledge for their lobbying. It illustrates how this new communicative process has changed political discourse in science and general perception of the role of science in contemporary society.
Article
The importance of food security and nourishment is recognized in Southern African region and in many communities, globally. However, the attainment of food security in Southern African countries is affected by many factors, including adverse environmental conditions, pests and diseases. Scientists have been insistently looking for innovative strategies to optimize crop production and combat challenges militating against attainment of food security. In agriculture, strategies of increasing crop production include but not limited to improved crop varieties, farming practices, extension services, irrigation services, mechanization, information technology, use of fertilizers and agrochemicals. Equally important is genetic modification (GM) technology, which brings new prospects in addressing food security problems. Nonetheless, since the introduction of genetically modified crops (GMOs) three decades ago, it has been a topic of public discourse across the globe, conspicuously so in Southern African region. This is regardless of the evidence that planting GMOs positively influenced farmer’s incomes, economic access to food and increased tolerance of crops to various biotic and abiotic stresses. This paper looks at the issues surrounding GMOs adoption in Southern Africa and lack thereof, the discourse, and its potential in contributing to the attainment of food security for the present as well as future generations.
Article
Full-text available
GM crops are the most studied crops in history. Approximately 5% of the safety studies on them show adverse effects that are a cause for concern, and tend to be featured in media reports. Although these reports are based on just a handful of GM events, they are used to cast doubt on all GM crops. Furthermore, they tend to come from just a few laboratories and are published in less important journals. Importantly, a close examination of these reports invariably shows methodological flaws that invalidate any conclusions of adverse effects. Twenty years after commercial cultivation of GM crops began, a bona fide report of an adverse health effect due to a commercialized modification in a crop has yet to be reported. This article is protected by copyright. All rights reserved.
Article
Full-text available
The application of gene drives to achieve public health goals, such as the suppression of Anopheles gambiae populations, or altering their ability to sustain Plasmodium spp. infections, has received much attention from researchers. If successful, this genetic tool can contribute greatly to the wellbeing of people in regions severely affected by malaria. However, engineered gene drives are a product of genetic engineering, and the experience to date, gained through the deployment of genetically engineered (GE) crops, is that GE technology has had difficulty receiving public acceptance in Africa, a key region for the deployment of gene drives. The history of GE crop deployment in this region provides good lessons for the deployment of gene drives as well. GE crops have been in commercial production for 24 years, since the planting of the first GE soybean crop in 1996. During this time, regulatory approvals and farmer adoption of these crops has grown rapidly in the Americas, and to a lesser extent in Asia. Their safety has been recognized by numerous scientific organizations. Economic and health benefits have been well documented in the countries that have grown them. However, only one transgenic crop event is being grown in Europe, and only in two countries in that region. Europe has been extremely opposed to GE crops, due in large part to the public view of agriculture that opposes “industrial” farming. This attitude is reflected in a highly precautionary regulatory and policy environment, which has highly influenced how African countries have dealt with GE technology and are likely to be applied to future genetic technologies, including gene drives. Furthermore, a mistrust of government regulatory agencies, the publication of scientific reports claiming adverse effects of GE crops, the involvement of corporations as the first GE crop developers, the lack of identifiable consumer benefit, and low public understanding of the technology further contributed to the lack of acceptance. Coupled with more emotionally impactful messaging to the public by opposition groups and the general tendency of negative messages to be more credible than positive ones, GE crops failed to gain a place in European agriculture, thus influencing African acceptance and government policy. From this experience, the following lessons have been learned that would apply to the deployment of gene drives, in Africa: It will be important to establish trust in those who are developing the technology, as well as in those who are making regulatory decisions. Engagement of the community, where those who are involved are able to make genuine contributions to the decision-making process, are necessary to achieve that trust. The use of tools to facilitate participatory modeling could be considered in order to enhance current community engagement efforts. Trusted, accurate information on gene drives should be made available to the general public, journalists, and scientists who are not connected with the field. Those sources of information should also be able to summarize and analyze important scientific results and emerging issues in the field in order to place those developments in the proper context. Engagement should involve more opportunities for participation of stakeholders in conceptualizing, planning, and decision-making. Diversifying the source of funding for gene drive research and development, particularly by participation of countries and regional bodies, would show that country or regional interests are represented. Efforts by developers and neutral groups to provide the public and decisionmakers with a more thorough understanding of the benefits and risks of this technology, especially to local communities, would help them reach more informed decisions. A better understanding of gene drive technology can be fostered by governments, as part of established biosafety policy in several African countries. Developers and neutral groups could also be helpful in increasing public understanding of the technology of genetic engineering, including gene drives. Effective messaging to balance the messaging of groups opposed to gene drives is needed. These messages should be not only factual but also have emotional and intuitive appeal.
Chapter
Using plants as factories for protein production is a proven technology that works well for vaccine, pharmaceutical, and industrial enzyme production. Although the proteins express well and have the correct characteristics, very few have been commercialized due to various concerns about their safety and quality. Nevertheless, the technology is a viable one with a large potential for excellent products at competitive costs. This volume presents several product examples from the plant production platform that are either being sold or are near commercialization. Each case study presents the challenges and advantages of using the plant system for the product.
Chapter
This chapter explores the construction and deployment of the “sound science” defense of GMOs: examining the way in which proponents of GMOs use the supremacy of science as a means to silence critiques of the technology. Whereas political constraints force antagonists of GMOs to resort to alternative, and in some respects innovative, rhetorical strategies in order to politicize the issue of GM, proponents of GMOs adopt a discourse of “sound science,” which professes itself as a neutral, objective mechanism to evaluate GMOs. By refusing to label products as containing GMOs, producers and manufacturers of the technology attempt to render the product invisible through a political and rhetorical strategy to “depoliticize” the debate over the technology. 1
Article
The use of chemical pesticides have damaged the environment and human health over the past 50 years. Biotechnological alternatives include genetically modified plants such as Bt cultures and recently those based on RNAi and CRISPR-Cas9, although resistance may appear in some insects, and also there are restrictions due to legal regulations. Microbial biopesticides based on conidia from entomopathogenic fungi are an excellent choice to face the present situation. In addition to high conidial yields, the quality of conidia should be assured in production processes. Sublethal stress during cultures may lead to cross protection, by which conidia acquire tolerance to other sort of stresses like those found in open fields. These stress response mechanisms involve G proteins and MAPK pathways. These current challenges are discussed here.
Article
Full-text available
Feeding experiments with juvenile grass carp (Ctenopharyngodon idella) fed with genetically modified maize MON 810 or DAS-59122 dried leaf biomass were carried out with 1-, 3- and 6-month exposures. Dosages of 3–7 μg/fish/day Cry1Ab or 18-55 μg/fish/day Cry34Ab1 toxin did not cause mortality. No difference occurred in body or abdominal sac weights. No differences appeared in levels of inorganic phosphate, calcium, fructosamine, bile acids, triglycerides, cholesterol, and alanine and aspartame aminotransferases. DAS-59122 did not alter blood parameters tested after 3 months of feeding. MON 810 slightly decreased serum albumin levels compared to the control, only in one group. Tapeworm (Bothriocephalus acheilognathi) infection changed the levels of inorganic phosphate and calcium. Cry34Ab1 toxin appeared in blood (12.6 ± 1.9 ng/mL), but not in the muscle. It was detected in B. acheilognathi. Cry1Ab was hardly detectable in certain samples near the limit of detection. Degradation of Cry toxins was extremely quick in the fish gastrointestinal tract. After 6 months of feeding, only mild indications in certain serum parameters were observed: MON 810 slightly increased the level of apoptotic cells in the blood and reduced the number of thrombocytes in one group; DAS-59122 mildly increased the number of granulocytes compared to the near-isogenic line.
Article
Using data Pub Med Medline, Science Direct, Endocrine Society, Argentine Society of Andrology, a bibliographic review was made to study and interpret the effect of environmental factors such as pesticides, toxic, solvents, heat and electromagnetic radiation on reproduction. Most of these factors behave as endocrine disruptors altering the homeostasis and causing hormonal unbalance during development and offspring. Monoculture of transgenic sprayed with poisons negatively impacts on male reproductive health. Elevated temperature by exposure to sources that radiate heat or remain seated for many hours alters the spermatogenesis. Electronic articles emit harmful radiation by increasing environmental exposure to electromagnetic fields that testicular function. Exposed men increase the risk of infertility by presenting dysfunctional membrane, increased DNA fragmentation and alterations in sperm morphology, motility and concentration. These effectors in the work environment must be evaluated in male infertility.
Article
Using data Pub Med Medline, Science Direct, Endocrine Society, Argentine Society of Andrology, a bibliographic review was made to study and interpret the effect of environmental factors such as pesticides, toxic, solvents, heat and electromagnetic radiation on reproduction. Most of these factors behave as endocrine disruptors altering the homeostasis and causing hormonal unbalance during development and offspring. Monoculture of transgenic sprayed with poisons negatively impacts on male reproductive health. Elevated temperature by exposure to sources that radiate heat or remain seated for many hours alters the spermatogenesis. Electronic articles emit harmful radiation by increasing environmental exposure to electromagnetic fields that testicular function. Exposed men increase the risk of infertility by presenting dysfunctional membrane, increased DNA fragmentation and alterations in sperm morphology, motility and concentration. These effectors in the work environment must be evaluated in male infertility.
Article
Full-text available
Genetic engineering and plant transformation have played a pivotal role in crop improvement via introducing beneficial foreign gene(s) or silencing the expression of endogenous gene(s) in crop plants. Genetically modified crops possess one or more useful traits, such as, herbicide tolerance, insect resistance, abiotic stress tolerance, disease resistance, and nutritional improvement. To date, nearly 525 different transgenic events in 32 crops have been approved for cultivation in different parts of the world. The adoption of transgenic technology has been shown to increase crop yields, reduce pesticide and insecticide use, reduce CO2 emissions, and decrease the cost of crop production. However, widespread adoption of transgenic crops carrying foreign genes faces roadblocks due to concerns of potential toxicity and allergenicity to human beings, potential environmental risks, such as chances of gene flow, adverse effects on non-target organisms, evolution of resistance in weeds and insects etc. These concerns have prompted the adoption of alternative technologies like cisgenesis, intragenesis, and most recently, genome editing. Some of these alternative technologies can be utilized to develop crop plants that are free from any foreign gene hence, it is expected that such crops might achieve higher consumer acceptance as compared to the transgenic crops and would get faster regulatory approvals. In this review, we present a comprehensive update on the current status of the genetically modified (GM) crops under cultivation. We also discuss the issues affecting widespread adoption of transgenic GM crops and comment upon the recent tools and techniques developed to address some of these concerns. FULL TEXT Link: https://rdcu.be/b3leO
Article
Full-text available
Weeds, which have been the bane of agriculture since the beginning of civilization, are managed manually, mechanically, and, more recently, by chemicals. However, chemical control options are rapidly shrinking due to the recent rise in the number of herbicide-resistant weeds in crop fields, with few alternatives on the horizon. Therefore, there is an urgent need for alternative weed suppression systems to sustain crop productivity while reducing our dependence on herbicides and tillage. Such a development will also allay some of the negative perceptions associated with the use of herbicide-resistance genes and heavy dependence on herbicides. Transgenic plants expressing the bacterial phosphite dehydrogenase (ptxD) gene gain an ability to convert phosphite (Phi) into orthophosphate [Pi, the metabolizable form of phosphorus (P)]. Such plants allow for a selective fertilization scheme, based on Phi as the sole source of P for the crop, while offering an effective alternative for suppressing weed growth. Here, we show that, when P is supplied in the form of Phi, ptxD-expressing cotton (Gossypium hirsutum L.) plants outcompete, in both artificial substrates and natural soils from agricultural fields, three different monocot and dicot weed species intentionally introduced in the experiments, as well as weeds naturally present in the tested soils. Importantly, the ptxD/Phi system proved highly efficacious in inhibiting the growth of glyphosate-resistant Palmer amaranth. With over 250 weed species resistant to currently available herbicides, ptxD-transgenic plants fertilized with Phi could provide an effective alternative to suppressing the growth of these weeds while providing adequate nutrition to the crop.
Article
Since its initial sales in the 1970s, the herbicide glyphosate attained widespread use in modern agriculture, becoming the most commercially successful and widely used herbicide of all time as of 2016. Despite a primary mechanism that targets a pathway absent from animal cells and regulatory studies showing safety margins orders of magnitude better than many other, more directly toxic herbicides, the safety status of glyphosate, has recently been brought into question by a slow accumulation of studies evincing more insidious health risks, especially when considered in combination with the surfactants it is usually applied with. Current, official views of respected international regulatory and health bodies remain divided on glyphosate's status as a human carcinogen, but the 2015 IARC decision to reclassify the compound as Category 2a (probably carcinogenic to humans) marked a sea change in the scientific community's consensus view. The goal of this review is to consider the state of science regarding glyphosate's potential as a human carcinogen and genotoxin, with particular focus on studies suggesting mechanisms which would go largely undetected in traditional toxicology studies, such as microbiome disruption and endocrine mimicry at very low concentrations.
Article
Full-text available
Roundup is the most widely used herbicide in agriculture. It contains glyphosate as the ‘active ingredient’, together with formulants. There are various versions of Roundup, with somewhat different effects depending on the formulants. Most genetically-modified crops are designed to tolerate Roundup, thus allowing spraying against weeds during the growing season of the crop without destroying it. Having been so heavily used, this herbicide is now found in the soil, water, air, and even in humans worldwide. Roundup may also remain as a residue on edible crops. Many studies have found harm to the environment and to health, making it imperative to regulate the use of Roundup and to ensure that its various formulations pose no danger when used in the long-term. Unfortunately, regulators may only assess the ‘active ingredient’, glyphosate, and ignore the toxicity of the formulants, which can be far more toxic than the active ingredient. This omission is in violation of a ruling by the Court of Justice of the European Union. There are close ties between the regulators and the industry they are supposed to regulate. Objectionable practices include ‘revolving doors’ between the regulators and the industry, heavy reliance on unpublished papers produced by the industry while dismissing papers published by independent scientists, and strong covert influence on the regulatory process by industry. Although this paper focuses on the European Union (EU), the situation is much the same in the United States.
Article
Full-text available
In 2012, a controversial study on the long-term toxicity of a Roundup herbicide and the glyphosate-tolerant genetically modified (GM) maize NK603 was published. The EC-funded G-TwYST research consortium tested the potential subchronic and chronic toxicity as well as the carcinogenicity of the glyphosate-resistant genetically modified maize NK603 by performing two 90-day feeding trials, one with GM maize inclusion rates of 11 and 33% and one with inclusion rates of up to 50%, as well as a 2-year feeding trial with inclusion rates of 11 and 33% in male and female Wistar Han RCC rats by taking into account OECD Guidelines for the testing of chemicals and EFSA recommendations on the safety testing of whole-food/feed in laboratory animals. In all three trials, the NK603 maize, untreated and treated once with Roundup during its cultivation, and the conventional counterpart were tested. Differences between each test group and the control group were evaluated. Equivalence was assessed by comparing the observed difference to differences between non-GM reference groups in previous studies. In case of significant differences, whether the effects were dose-related and/or accompanied by changes in related parameters including histopathological findings was evaluated. It is concluded that no adverse effects related to the feeding of the NK603 maize cultivated with or without Roundup for up to 2 years were observed. Based on the outcome of the subchronic and combined chronic toxicity/carcinogenicity studies, recommendations on the scientific justification and added value of long-term feeding trials in the GM plant risk assessment process are presented.
Article
Full-text available
Background: Glyphosate is the most widely used herbicide in the USA and worldwide. There has been considerable debate about its carcinogenicity. Epidemiological studies suggest that multiple myeloma (MM) and non-Hodgkin lymphoma (NHL) have a positive and statistically significant association with glyphosate exposure. As a B cell genome mutator, activation-induced cytidine deaminase (AID) is a key pathogenic player in both MM and B cell NHL. Methods: Vk*MYC is a mouse line with sporadic MYC activation in germinal center B cells and considered as the best available MM animal model. We treated Vk*MYC mice and wild-type mice with drinking water containing 1000 mg/L of glyphosate and examined animals after 72 weeks. Results: Vk*MYC mice under glyphosate exposure developed progressive hematological abnormalities and plasma cell neoplasms such as splenomegaly, anemia, and high serum IgG. Moreover, glyphosate caused multiple organ dysfunction, including lytic bone lesions and renal damage in Vk*MYC mice. Glyphosate-treated wild-type mice developed benign monoclonal gammopathy with increased serum IgG, anemia, and plasma cell presence in the spleen and bone marrow. Finally, glyphosate upregulated AID in the spleen and bone marrow of both wild-type and Vk*MYC mice. Conclusions: These data support glyphosate as an environmental risk factor for MM and potentially NHL and implicate a mechanism underlying the B cell-specificity of glyphosate-induced carcinogenesis observed epidemiologically.
Article
Full-text available
Abstract The current/traditional human health risk assessment paradigm is challenged by recent scientific and technical advances, and ethical demands. The current approach is considered too resource intensive, is not always reliable, can raise issues of reproducibility, is mostly animal based and does not necessarily provide an understanding of the underlying mechanisms of toxicity. From an ethical and scientific viewpoint, a paradigm shift is required to deliver testing strategies that enable reliable, animal‐free hazard and risk assessments, which are based on a mechanistic understanding of chemical toxicity and make use of exposure science and epidemiological data. This shift will require a new philosophy, new data, multidisciplinary expertise and more flexible regulations. Re‐engineering of available data is also deemed necessary as data should be accessible, readable, interpretable and usable. Dedicated training to build the capacity in terms of expertise is necessary, together with practical resources allocated to education. The dialogue between risk assessors, risk managers, academia and stakeholders should be promoted further to understand scientific and societal needs. Genuine interest in taking risk assessment forward should drive the change and should be supported by flexible funding. This publication builds upon presentations made and discussions held during the break‐out session ‘Advancing risk assessment science – Human health’ at EFSA's third Scientific Conference ‘Science, Food and Society’ (Parma, Italy, 18–21 September 2018).
Article
Traditionally, cognition and emotion were believed to be independent systems; however, research in the cognitive and neurobiological sciences has shown that the relationship between cognition and emotion is both interdependent and extensive. This intimate connection between emotion and cognition is leading to a number of insights that have the potential to inform and transform educational practices at all levels—from the classroom to the curriculum to educational policy. The question that has been on my mind (and on my heart) is, as a teacher, how can I both embrace and harness the power of emotion to help my students’ learning be more meaningful, useful, and intrinsically motivated? In this article, I would like to share with you some of the effective practices that I have implemented in my classroom and how I have worked to intentionally embed the emotional aspect of learning into the framework of the courses I teach.
Article
Full-text available
The Genetically Modified (GMO) Corn Experiment was performed to test the hypothesis that wild animals prefer Non-GMO corn and avoid eating GMO corn, which resulted in the collection of complex image data of consumed corn ears. This study develops a deep learning-based image processing pipeline that aims to estimate the consumption of corn by identifying corn and its bare cob from these images, which will aid in testing the hypothesis in the GMO Corn Experiment. Ablation uses mask regional convolutional neural network (Mask R-CNN) for instance segmentation. Based on image data annotation, two approaches for segmentation were discussed: identifying whole corn ears and bare cob parts with and without corn kernels. The Mask R-CNN model was trained for both approaches and segmentation results were compared. Out of the two, the latter approach, i.e., without the kernel, was chosen to estimate the corn consumption because of its superior segmentation performance and estimation accuracy. Ablation experiments were performed with the latter approach to obtain the best model with the available data. The estimation results of these models were included and compared with manually labeled test data with R ² = 0.99 which showed that use of the Mask R-CNN model to estimate corn consumption provides highly accurate results, thus, allowing it to be used further on all collected data and help test the hypothesis of the GMO Corn Experiment. These approaches may also be applied to other plant phenotyping tasks (e.g., yield estimation and plant stress quantification) that require instance segmentation.
Article
Food and agricultural policy research is often challenged with the issue of commercializing the application of transgenic technology in food production. There is a need for an enhanced understanding of how risk and benefit information influence the general attitudes of farmers towards genetically modified (GM) technology. This paper contributes to existing literature by studying the various adoption factors that influence Ghanaian farmers’ attitudes toward GM crop technology by using risk perception as a mediating tool. An empirical choice of methodology which is structural equation analysis was incorporated in this study. We report that, after conducting a survey among 325 respondents, Ghanaian farmers’ negative attitudes toward GM technology is as a result of the influence of risk perception on the attributes of the innovative technology (relative advantage, trialability, mass media, and interpersonal relations). We employ a conceptual framework that incorporates Innovation Diffusion Theory (IDT) and Risk analysis to assess the relationships between the attributes and attitudes towards GM technology. It was revealed in the structural equation modeling (SEM) analysis that, risk perception exerts a significant influence on the effects of the attributes of GM technology adoption thus reflecting a negative attitude towards the adoption of the related technology. We further discussed the implications for emphasizing the need for a positive attitude toward the acceptance and adoption of GM technology in Ghana.
Article
Repeated health and environmental scandals, the loss of biodiversity and the recent burst of chronic diseases constantly remind us the inability of public authorities and risk assessment agencies to protect health and the environment. After reviewing the main shortcomings of our evaluation system of chemicals and new technologies, supported by some concrete examples, we develop a number of proposals to reform both the risk assessment agencies and the evaluation processes. We especially propose the establishment of an independent structure, a High Authority of Expertise, supervising, either at European level or at national level, all the evaluation agencies, and ensuring the transparency, the methodology and the deontology of the expertise. In addition to modifying the evaluation protocols, both in their nature and in their content, especially in order to adapt them to current pollutants such as endocrine disruptors, we propose a reform of the expertise processes based on transparency, contradiction, and greater democracy, including close collaboration between the institutional and scientific parties on the one hand and the whole civil society on the other. All the proposals we make are inspired by the desire to prevent, through appropriate mechanisms, the human, health, ecological, but also economic consequences of contemporary technological choices.
Chapter
Since 2011 we have been developing a participatory problem-based learning (PBL) methodology to teach about the nature of science (NOS) and, also, to foster the development of some practical and attitudinal dimensions of scientific practice. This methodology entails a participatory knowledge-centered approach where the teacher plays a key mediating role in the relationship between students and knowledge, with more guidance than usual in active methodologies, which employ a student-centered approach. Here we present a report on how we are using this methodology in higher education courses devoted to NOS, based on experiences in different teaching contexts: an undergraduate course on history and philosophy of science and a professional master course offering an introduction to scientific knowledge to environmental managers and decision-makers. We discuss some findings derived from teachers’ diaries and students’ problem-solving reports in order to indicate how the participatory PBL approach has been working as a basis for our teaching practice and how the students have been engaging in problem-solving and learning in the classroom.
Article
Full-text available
Article
Full-text available
Transgene insertion is infrequently, if ever, a precise event and it therefore causes various alterations to the plant genome. Mutations present at transgene insertion sites include insertion of superfluous DNA and deletion and rearrangement of host chromosomal DNA. These mutations vary in frequency depending in particular on the method of delivery. Transgene insertion sites introduced using Agrobacterium tumefaciens tend to be simpler but can be associated with very large chromosomal rearrangements, while transgenes delivered by particle bombardment appear invariably to be associated with deletion and extensive scrambling of inserted and chromosomal DNA. Nevertheless, the frequency and impact of these mutations are poorly understood, especially those caused by particle bombardment. This is exemplified by the fact that only a single functional transgene insertion site resulting from particle bombardment has been comprehensively analysed for insertion-site mutations. Additionally, most data on insertion-site mutations come from the model organism Arabidopsis thaliana, and it is not yet clear if there are important species-specific differences in patterns of insertion-site mutation. Genetic mutations, linked and unlinked to the transgene insertion-site, also arise from procedures associated with plant transformation, such as tissue culture and infection with A. tumefaciens. These genome-wide mutations can number from hundreds to many thousands per diploid genome, and are likely to be important sources of phenotypic variation. The potential phenotypic consequences of genetic damage from insertion-site mutations and genome-wide mutations are discussed and recommendations for safety assessments are made. A better understanding of the genetic consequences of plant transformation should improve the quality and interpretation of scientific experiments that rely on plant transformation and should advance the debate on the safety of transgenic crops. Correction to the text: The 3rd paragraph on page 212, should read: In Medicago truncatula, 4/8 lines analysed had filler sequences of 3, 22, 38 and 392 bp. The 38 bp filler DNA corresponded to internal T-DNA sequence while the others were of unknown origin (Scholte et al. 2002).
Article
Full-text available
Plant transformation has become an essential tool for plant molecular biologists and, almost simultaneously, transgenic plants have become a major focus of many plant breeding programs. The first transgenic cultivar arrived on the market approximately 15 years ago, and some countries have since commercially approved or deregulated (e.g. the United States) various commodity crops with the result that certain transgenic crop plants, such as herbicide resistant canola and soya and pest resistant maize, are currently grown on millions of acres
Article
Full-text available
For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of "the dose makes the poison," because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from the cell culture, animal, and epidemiology literature. We illustrate that nonmonotonic responses and low-dose effects are remarkably common in studies of natural hormones and EDCs. Whether low doses of EDCs influence certain human disorders is no longer conjecture, because epidemiological studies show that environmental exposures to EDCs are associated with human diseases and disabilities. We conclude that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses. Thus, fundamental changes in chemical testing and safety determination are needed to protect human health.
Article
Full-text available
The aim of this systematic review was to collect data concerning the effects of diets containing GM maize, potato, soybean, rice, or triticale on animal health. We examined 12 long-term studies (of more than 90 days, up to 2 years in duration) and 12 multigenerational studies (from 2 to 5 generations). We referenced the 90-day studies on GM feed for which long-term or multigenerational study data were available. Many parameters have been examined using biochemical analyses, histological examination of specific organs, hematology and the detection of transgenic DNA. The statistical findings and methods have been considered from each study. Results from all the 24 studies do not suggest any health hazards and, in general, there were no statistically significant differences within parameters observed. However, some small differences were observed, though these fell within the normal variation range of the considered parameter and thus had no biological or toxicological significance. If required, a 90-day feeding study performed in rodents, according to the OECD Test Guideline, is generally considered sufficient in order to evaluate the health effects of GM feed. The studies reviewed present evidence to show that GM plants are nutritionally equivalent to their non-GM counterparts and can be safely used in food and feed.
Article
Full-text available
Sexual differentiation in the brain takes place from late gestation to the early postnatal days. This is dependent on the conversion of circulating testosterone into estradiol by the enzyme aromatase. The glyphosate was shown to alter aromatase activity and decrease serum testosterone concentrations. Thus, the aim of this study was to investigate the effect of gestational maternal glyphosate exposure (50 mg/kg, NOAEL for reproductive toxicity) on the reproductive development of male offspring. Sixty-day-old male rat offspring were evaluated for sexual behavior and partner preference; serum testosterone concentrations, estradiol, FSH and LH; the mRNA and protein content of LH and FSH; sperm production and the morphology of the seminiferous epithelium; and the weight of the testes, epididymis and seminal vesicles. The growth, the weight and age at puberty of the animals were also recorded to evaluate the effect of the treatment. The most important findings were increases in sexual partner preference scores and the latency time to the first mount; testosterone and estradiol serum concentrations; the mRNA expression and protein content in the pituitary gland and the serum concentration of LH; sperm production and reserves; and the height of the germinal epithelium of seminiferous tubules. We also observed an early onset of puberty but no effect on the body growth in these animals. These results suggest that maternal exposure to glyphosate disturbed the masculinization process and promoted behavioral changes and histological and endocrine problems in reproductive parameters. These changes associated with the hypersecretion of androgens increased gonadal activity and sperm production.
Article
Full-text available
Our previous studies have demonstrated that stable microRNAs (miRNAs) in mammalian serum and plasma are actively secreted from tissues and cells and can serve as a novel class of biomarkers for diseases, and act as signaling molecules in intercellular communication. Here, we report the surprising finding that exogenous plant miRNAs are present in the sera and tissues of various animals and that these exogenous plant miRNAs are primarily acquired orally, through food intake. MIR168a is abundant in rice and is one of the most highly enriched exogenous plant miRNAs in the sera of Chinese subjects. Functional studies in vitro and in vivo demonstrated that MIR168a could bind to the human/mouse low-density lipoprotein receptor adapter protein 1 (LDLRAP1) mRNA, inhibit LDLRAP1 expression in liver, and consequently decrease LDL removal from mouse plasma. These findings demonstrate that exogenous plant miRNAs in food can regulate the expression of target genes in mammals.
Article
Full-text available
Our previous studies have demonstrated that stable microRNAs (miRNAs) in mammalian serum and plasma are actively secreted from tissues and cells and can serve as a novel class of biomarkers for diseases, and act as signaling molecules in intercellular communication. Here, we report the surprising finding that exogenous plant miRNAs are present in the sera and tissues of various animals and that these exogenous plant miRNAs are primarily acquired orally, through food intake. MIR168a is abundant in rice and is one of the most highly enriched exogenous plant miRNAs in the sera of Chinese subjects. Functional studies in vitro and in vivo demonstrated that MIR168a could bind to the human/mouse low-density lipoprotein receptor adapter protein 1 (LDLRAP1) mRNA, inhibit LDLRAP1 expression in liver, and consequently decrease LDL removal from mouse plasma. These findings demonstrate that exogenous plant miRNAs in food can regulate the expression of target genes in mammals.
Article
Full-text available
Liver represents a suitable model for monitoring the effects of a diet, due to its key role in controlling the whole metabolism. Although no direct evidence has been reported so far that genetically modified (GM) food may affect health, previous studies on hepatocytes from young female mice fed on GM soybean demonstrated nuclear modifications involving transcription and splicing pathways. In this study, the effects of this diet were studied on liver of old female mice in order to elucidate possible interference with ageing. The morpho-functional characteristics of the liver of 24-month-old mice, fed from weaning on control or GM soybean, were investigated by combining a proteomic approach with ultrastructural, morphometrical and immunoelectron microscopical analyses. Several proteins belonging to hepatocyte metabolism, stress response, calcium signalling and mitochondria were differentially expressed in GM-fed mice, indicating a more marked expression of senescence markers in comparison to controls. Moreover, hepatocytes of GM-fed mice showed mitochondrial and nuclear modifications indicative of reduced metabolic rate. This study demonstrates that GM soybean intake can influence some liver features during ageing and, although the mechanisms remain unknown, underlines the importance to investigate the long-term consequences of GM-diets and the potential synergistic effects with ageing, xenobiotics and/or stress conditions.
Article
Full-text available
Pituitary inhibin B, activin B, and follistatin are local regulators of FSH. Activin B is a homodimeric molecule (β(B)-β(B)), while inhibin B contains an α and a β(B) subunit. The regulation of gene expression of α, β(B), and follistatin by local and endocrine hormones was examined in pituitaries from female rats and in perifused pituitary cells by RT-PCR. Ovariectomy (OVX) induced an elevation in the mRNA level of α and β(B) subunits and follistatin. Short-term (4 h) treatment of pituitary cells with GnRH decreased both the inhibin α and the inhibin/activin β(B) subunit mRNA levels, while long-term treatment (20 h) with 100 nM GnRH stimulated the expression of both subunits. In contrast, the mRNA level of follistatin was elevated after the short-term GnRH treatment. Long-term exposure of pituitary cells to estradiol and inhibin B suppressed the mRNA expression of β(B) and had no effect on the expression of α subunit and follistatin. Our results demonstrate that the increased expressions of inhibin/activin subunits and follistatin in the post-OVX period can be induced by the lack of gonadal negative feedback, resulting in a high GnRH environment in the pituitary. This study reports for the first time that GnRH administered in high doses and for a long period stimulates the gene expression of inhibin/activin subunits and thereby may contribute to the stimulatory effect of OVX on the expression of these genes.
Article
Full-text available
In recent years, there has been a notable concern on the safety of genetically modified (GM) foods/plants, an important and complex area of research, which demands rigorous standards. Diverse groups including consumers and environmental Non Governmental Organizations (NGO) have suggested that all GM foods/plants should be subjected to long-term animal feeding studies before approval for human consumption. In 2000 and 2006, we reviewed the information published in international scientific journals, noting that the number of references concerning human and animal toxicological/health risks studies on GM foods/plants was very limited. The main goal of the present review was to assess the current state-of-the-art regarding the potential adverse effects/safety assessment of GM plants for human consumption. The number of citations found in databases (PubMed and Scopus) has dramatically increased since 2006. However, new information on products such as potatoes, cucumber, peas or tomatoes, among others was not available. Corn/maize, rice, and soybeans were included in the present review. An equilibrium in the number research groups suggesting, on the basis of their studies, that a number of varieties of GM products (mainly maize and soybeans) are as safe and nutritious as the respective conventional non-GM plant, and those raising still serious concerns, was currently observed. Nevertheless, it should be noted that most of these studies have been conducted by biotechnology companies responsible of commercializing these GM plants. These findings suggest a notable advance in comparison with the lack of studies published in recent years in scientific journals by those companies. All this recent information is herein critically reviewed.
Article
Full-text available
Pollutants representative of common environmental contaminants induce intracellular toxicity in human cells, which is generally amplified in combinations. We wanted to test the common pathways of intoxication and detoxification in human embryonic and liver cell lines. We used various pollutants such as Roundup residues, Bisphenol-A and Atrazine, and five precise medicinal plant extracts called Circ1, Dig1, Dig2, Sp1, and Uro1 in order to understand whether specific molecular actions took place or not. Kidney and liver are major detoxification organs. We have studied embryonic kidney and hepatic human cell lines E293 and HepG2. The intoxication was induced on the one hand by a formulation of one of the most common herbicides worldwide, Roundup 450 GT+ (glyphosate and specific adjuvants), and on the other hand by a mixture of Bisphenol-A and Atrazine, all found in surface waters, feed and food. The prevention and curative effects of plant extracts were also measured on mitochondrial succinate dehydrogenase activity, on the entry of radiolabelled glyphosate (in Roundup) in cells, and on cytochromes P450 1A2 and 3A4 as well as glutathione-S-transferase. Clear toxicities of pollutants were observed on both cell lines at very low sub-agricultural dilutions. The prevention of such phenomena took place within 48 h with the plant extracts tested, with success rates ranging between 25-34% for the E293 intoxicated by Roundup, and surprisingly up to 71% for the HepG2. By contrast, after intoxication, no plant extract was capable of restoring E293 viability within 48 h, however, two medicinal plant combinations did restore the Bisphenol-A/Atrazine intoxicated HepG2 up to 24-28%. The analysis of underlying mechanisms revealed that plant extracts were not capable of preventing radiolabelled glyphosate from entering cells; however Dig2 did restore the CYP1A2 activity disrupted by Roundup, and had only a mild preventive effect on the CYP3A4, and no effect on the glutathione S-transferase. Environmental pollutants have intracellular effects that can be prevented, or cured in part, by precise medicinal plant extracts in two human cell lines. This appears to be mediated at least in part by the cytochromes P450 modulation.
Article
Full-text available
Worldwide used pesticides containing different adjuvants like Roundup formulations, which are glyphosate-based herbicides, can provoke some in vivo toxicity and in human cells. These pesticides are commonly found in the environment, surface waters and as food residues of Roundup tolerant genetically modified plants. In order to know their effects on cells from liver, a major detoxification organ, we have studied their mechanism of action and possible protection by precise medicinal plant extracts called Dig1. The cytotoxicity pathways of four formulations of glyphosate-based herbicides were studied using human hepatic cell lines HepG2 and Hep3B, known models to study xenobiotic effects. We monitored mitochondrial succinate dehydrogenase activity and caspases 3/7 for cell mortality and protection by Dig1, as well as cytochromes P450 1A1, 1A2, 3A4 and 2C9 and glutathione-S-transferase to approach the mechanism of actions. All the four Roundup formulations provoke liver cell death, with adjuvants having stronger effects than glyphosate alone. Hep3B are 3-5 times more sensitive over 48 h. Caspases 3/7 are greatly activated in HepG2 by Roundup at non-cytotoxic levels, and some apoptosis induction by Roundup is possible together with necrosis. CYP3A4 is specifically enhanced by Roundup at doses 400 times less than used in agriculture (2%). CYP1A2 is increased to a lesser extent together with glutathione-S-transferase (GST) down-regulation. Dig 1, non cytotoxic and not inducing caspases by itself, is able to prevent Roundup-induced cell death in a time-dependant manner with an important efficiency of up to 89%, within 48 h. In addition, we evidenced that it prevents Caspases 3/7 activation and CYP3A4 enhancement, and not GST reduction, but in turn it slightly inhibited CYP2C9 when added before Roundup. Roundup is able to provoke intracellular disruption in hepatic cell lines at different levels, but a mixture of medicinal plant extracts Dig1 can protect to some extent human cell lines against this pollutants. All this system constitutes a tool for studying liver intoxication and detoxification.
Article
Full-text available
We present for the first time a comparative analysis of blood and organ system data from trials with rats fed three main commercialized genetically modified (GM) maize (NK 603, MON 810, MON 863), which are present in food and feed in the world. NK 603 has been modified to be tolerant to the broad spectrum herbicide Roundup and thus contains residues of this formulation. MON 810 and MON 863 are engineered to synthesize two different Bt toxins used as insecticides. Approximately 60 different biochemical parameters were classified per organ and measured in serum and urine after 5 and 14 weeks of feeding. GM maize-fed rats were compared first to their respective isogenic or parental non-GM equivalent control groups. This was followed by comparison to six reference groups, which had consumed various other non-GM maize varieties. We applied nonparametric methods, including multiple pairwise comparisons with a False Discovery Rate approach. Principal Component Analysis allowed the investigation of scattering of different factors (sex, weeks of feeding, diet, dose and group). Our analysis clearly reveals for the 3 GMOs new side effects linked with GM maize consumption, which were sex- and often dose-dependent. Effects were mostly associated with the kidney and liver, the dietary detoxifying organs, although different between the 3 GMOs. Other effects were also noticed in the heart, adrenal glands, spleen and haematopoietic system. We conclude that these data highlight signs of hepatorenal toxicity, possibly due to the new pesticides specific to each GM corn. In addition, unintended direct or indirect metabolic consequences of the genetic modification cannot be excluded.
Article
Full-text available
Chronic health effects are increasing in the world such as cancers, hormonal, reproductive, nervous, or immune diseases, even in young people. During regulatory toxicological subchronic tests to prevent these on mammalian health, prior commercialization of chemicals, including pesticides and drugs, or GMOs, some statistically significant findings may be revealed. This discussion is about the need to investigate the relevant criteria to consider those as biologically significant. The sex differences and the non linear dose or time related effects should be considered in contrast to the claims of a Monsanto-supported expert panel about a GMO, the MON 863 Bt maize, but also for pesticides or drugs, in particular to reveal hormone-dependent diseases and first signs of toxicities.
Article
Full-text available
Incidence of neoplastic lesions in untreated Sprague-Dawley rats (1340 males and 1329 females) used as controls in 17 carcinogenicity studies are tabulated and evaluated. In male rats, the most common neoplasms were benign pheochromocytomas and keratoacanthomas (4.0% in each case) followed by pancreatic islet cell adenomas (3.7%), thyroid parafollicular cell adenomas (3.6%), fibromas and squamous cell papillomas of the skin and hepatocellular adenomas (2.0% in each), malignant lymphoma lymphocytic (1.9%), histiocytic sarcomas (1.4%), and adrenal cortical adenomas (1.2%). In female rats, the most common neoplasms were of mammary gland origin (31.3%: fibroadenoma 19.0%, adenocarcinomas 8.8%, and adenomas 3.5%) followed by thyroid parafollicular cell adenomas (2.9%), uterine endometrial stromal polyps (2.6%), adrenal cortical adenomas (1.9%), malignant lymphoma lymphocytic (1.6%), fibromas in the skin (1.3%), and pancreatic islet cell adenoma (1.1%). Metastases were observed from pheochromocytomas, hepatocellular carcinomas, nephroblastomas, renal pelvis transitional cell carcinoma, interstitial cell tumor and seminoma of the testes, Zymbal's gland adenocarcinomas, and mammary adenocarcinomas.
Article
Full-text available
The genetically related ACI and Copenhagen (COP) rat strains display diametrically opposed susceptibilities to mammary cancer development when treated chronically with 17beta-estradiol (E2). Here, we compare the actions of E2 on cell proliferation and lobuloalveolar development in the mammary glands of female ACI and COP rats. After 12 wk of E2 treatment, the mammary glands of ACI rats exhibited a significantly greater proliferative response to E2, compared with COP rats, as evidenced by quantification of S phase fraction and development of lobuloalveolar hyperplasia. Focal regions of atypical epithelial hyperplasia were observed in ACI, but not COP, rats. These strain differences were not because of differences in circulating E2, progesterone or, prolactin. Two-thirds of the induced mammary cancers in ACI rats exhibited aneuploidy. The E2-induced mammary cancers regressed when hormone treatment was discontinued, indicating that they were estrogen-dependent. Progesterone receptor was expressed by the great majority of epithelial cells within the E2-induced atypical hyperplastic foci and the mammary carcinomas, suggesting a link between these lesions. These data demonstrate a correlation between E2 action in the induction of mammary cell proliferation and atypical epithelial hyperplasia and genetically conferred susceptibility to E2-induced mammary cancers.
Article
Full-text available
CPN (chronic progressive nephropathy) is a spontaneous age-related disease that occurs in high incidence in the strains of rat commonly used in preclinical toxicology studies, exhibiting a male predisposition. Although increasing in incidence and severity with age, evidence indicates that CPN should be regarded as a specific disease entity and not just a manifestation of the aging process. A number of factors, mainly dietary manipulations, have been shown to modify the expression of CPN. Amongst these, restriction of caloric intake is the most effective for inhibiting the disease process. The precise etiology of CPN and the mechanism(s) underlying its pathogenesis remain unknown, but the long-standing assumption that glomerular dysfunction is the primary basis is challenged in the light of contemporary developments in understanding filtration and postglomerular cellular processing of albumin. CPN is not only a degenerative disease, but also has regenerative aspects with a high cell proliferative rate in affected tubules. Accordingly, evidence is emerging that advanced, particularly end-stage CPN, is a risk factor for a marginal increase in the background incidence of renal tubule tumors. Many chemicals are known to exacerbate the severity of CPN to an advanced stage, and this interaction between chemical and CPN can result in a small increase in the incidence of renal adenomas in 2-year carcinogenicity bioassays. Review of the pathological entities associated with chronic renal failure in man emphasizes that this rodent condition has no strict human counterpart. Because CPN is a rodent-specific entity, the finding of a small, statistically significant increase in renal tubule tumors, linked to exacerbation of CPN by a test chemical in a preclinical study for carcinogenicity, can be regarded as having no relevance for extrapolation in human risk assessment.
Article
Full-text available
The assessment of chemical mixtures is a complex topic for toxicologists, regulators, and the public. In this article the linkage between the science of toxicology and the needs of governmental regulatory agencies in the United States is explored through an overview of environmental regulations enacted over the past century and a brief history of modern toxicology. One of the goals of this overview is to encourage both regulators and scientists to consider the benefits and limitations of this science-regulatory relationship as they tackle existing issues such as chemical mixtures. It is clear that a) over the past 100 years chemical regulation and toxicologic research, have in large part, shared a common emphasis on characterization and regulation of individual chemicals. But chemical mixtures have been, and continue to be, evaluated at hazardous waste sites around the United States. For this reason the current U.S. Environmental Protection Agency guidelines for chemical mixtures assessment are also reviewed. These guidelines highlight the current practice of mixtures assessment, which relies primarily on the existing single-chemical database. It is also clear that b) the science and assessment of chemical mixtures are moving forward through the combined efforts of regulatory agencies and scientists from a broad range of disciplines, including toxicology. Because toxicology is at this exciting crossroads, particular attention should be paid to the forces (e.g., public demands, regulatory needs, funding, academic interests) that both promote and limit the growth of this expanding discipline.
Article
Full-text available
Roundup is a glyphosate-based herbicide used worldwide, including on most genetically modified plants that have been designed to tolerate it. Its residues may thus enter the food chain, and glyphosate is found as a contaminant in rivers. Some agricultural workers using glyphosate have pregnancy problems, but its mechanism of action in mammals is questioned. Here we show that glyphosate is toxic to human placental JEG3 cells within 18 hr with concentrations lower than those found with agricultural use, and this effect increases with concentration and time or in the presence of Roundup adjuvants. Surprisingly, Roundup is always more toxic than its active ingredient. We tested the effects of glyphosate and Roundup at lower nontoxic concentrations on aromatase, the enzyme responsible for estrogen synthesis. The glyphosate-based herbicide disrupts aromatase activity and mRNA levels and interacts with the active site of the purified enzyme, but the effects of glyphosate are facilitated by the Roundup formulation in microsomes or in cell culture. We conclude that endocrine and toxic effects of Roundup, not just glyphosate, can be observed in mammals. We suggest that the presence of Roundup adjuvants enhances glyphosate bioavailability and/or bioaccumulation.
Article
Full-text available
The NTP has a long history of using Fischer rats and has compiled a large database of incidences of lesions seen in control animals. Such a database is lacking for Harlan Sprague-Dawley (SD) rats. The intention of this paper is to report spontaneous lesions observed in female vehicle control Harlan SD rats, and to compare the incidence in 2 strains of rats (Fischer and Harlan SD) used in NTP studies. Female Harlan SD rats served as the test animals for a special series of 2-year studies. Male rats were not used in these studies. Complete histopathology was performed on all animals, and the pathology results underwent comprehensive NTP pathology peer review. The most commonly observed neoplasms in these female control Harlan SD rats were mammary gland fibroadenoma (71%), tumors of the pars distalis of the pituitary (41%) and thyroid gland C-cell tumors (30%). Female Fischer rats had incidences of 44% for mammary gland fibroadenomas, 34% for tumors of the pars distalis, and 16% for thyroid gland C-cell tumors. Fischer rats had a 15% incidence of clitoral gland tumors, while the Harlan SD rats had an incidence of < 1%. In contrast to Fischer F344 rats, the Harlan SD rats had a high incidence of squamous metaplasia of the uterus (44.2%). Squamous metaplasia is not a lesion commonly observed in NTP control Fischer rats. The Harlan SD rats had a very low incidence of mononuclear cell leukemia (0.5%), compared with an incidence of 24% in female Fischer rats.
Article
Full-text available
The results of a 90-day rat feeding study with YieldGard (YieldGard Rootworm Corn is a registered trademark of Monsanto Technology, LLC.) Rootworm corn (MON 863) grain that is protected against feeding damage caused by corn rootworm larvae are presented. Corn rootworm-protection was accomplished through the introduction of a cry3Bb1 coding sequence into the corn genome for in planta production of a modified Cry3Bb1 protein from Bacillus thuringiensis. Grain from MON 863 and its near isogenic control were separately formulated into rodent diets at levels of 11% and 33% (w/w) by Purina Mills, Inc. Additionally, six groups of rats were fed diets containing grain from different conventional (non-biotechnology-derived) reference varieties. The responses of rats fed diets containing MON 863 were compared to those of rats fed grain from conventional corn varieties. All diets were nutritionally balanced and conformed to Purina Mills, Inc. specifications for Certified LabDiet 5002. There were a total of 400 rats in the study divided into 10 groups of 20 rats/sex/group. Overall health, body weight gain, food consumption, clinical pathology parameters (hematology, blood chemistry, urinalysis), organ weights, gross and microscopic appearance of tissues were comparable between groups fed diets containing MON 863 and conventional corn varieties. This study complements extensive agronomic, compositional and farm animal feeding studies with MON 863 grain, confirming that it is as safe and nutritious as existing conventional corn varieties.
Article
Full-text available
No direct evidence that genetically modified (GM) food may represent a possible danger for health has been reported so far; however, the scientific literature in this field is still quite poor. Therefore, we carried out an ultrastructural morphometrical and immunocytochemical study on hepatocytes from mice fed on GM soybean, in order to investigate eventual modifications of nuclear components of these cells involved in multiple metabolic pathways related to food processing. Our observations demonstrate significant modifications of some nuclear features in GM-fed mice. In particular, GM fed-mice show irregularly shaped nuclei, which generally represents an index of high metabolic rate, and a higher number of nuclear pores, suggestive of intense molecular trafficking. Moreover, the roundish nucleoli of control animals change in more irregular nucleoli with numerous small fibrillar centres and abundant dense fibrillar component in GM-fed mice, modifications typical of increased metabolic rate. Accordingly, nucleoplasmic (snRNPs and SC-35) and nucleolar (fibrillarin) splicing factors are more abundant in hepatocyte nuclei of GM-fed than in control mice. In conclusion, our data suggest that GM soybean intake can influence hepatocyte nuclear features in young and adult mice; however, the mechanisms responsible for such alterations remain unknown.
Article
Full-text available
Previous studies in our laboratory demonstrated that high-performance liquid chromatography (HPLC) analysis of ground corncob bedding extracts characterized two components (peak I and peak II) that disrupted endocrine function in male and female rats and stimulated breast and prostate cancer cell proliferation in vitro and in vivo. The active substances in peak I were identified as an isomeric mixture of 9,12-oxy-10,13-dihydroxyoctadecanoic acid and 10,13-oxy-9,12-dihydroxyoctadecanoic acid, collectively designated tetrahydrofurandiols (THF-diols). Studies presented here describe the purification and identification of the HPLC peak II component as 9,10-dihydroxy-12-octadecenoic acid (leukotoxin diol; LTX-diol), a well-known leukotoxin. A synthetic mixture of LTX-diol and 12,13-dihydroxy-9-octadecenoic acid (iso-leukotoxin diol; i-LTX-diol) isomers was separated by HPLC, and each isomer stimulated (p < 0.001) MCF-7 cell proliferation in an equivalent fashion. The LTX-diol isomers failed to compete for [3H]estradiol binding to the estrogen receptor or nuclear type II sites, even though oral administration of very low doses of these compounds (> 0.8 mg/kg body weight/day) disrupted estrous cyclicity in female rats. The LTX-diols did not disrupt male sexual behavior, suggesting that sex differences exist in response to these endocrine-disruptive agents.
Article
Article
Previous studies on mice fed genetically modified (GM) soybean demonstrated modifications of the mitochondrial functions and of the transcription/splicing pathways in hepatocytes. The cause(s) of these alterations could not be conclusively established but, since the GM soybean used is tolerant to glyphosate and was treated with the glyphosate-containing herbicide Roundup™, the possibility exists that the effects observed may be due to herbicide residues. In order to verify this hypothesis, we treated HTC cells with 1–10 mM Roundup and analysed cellular features by flow cytometry, fluorescence and electron microscopy.Under these experimental conditions, the death rate and the general morphology of HTC cells were not affected, as well as most of the cytoplasmic organelles. However, in HTC-treated cells, lysosome density increased and mitochondrial membranes modified indicating a decline in the respiratory activity. Moreover, nuclei underwent morpho-functional modifications suggestive of a decreased transcriptional/splicing activity.Although we cannot exclude that other factors than the presence of the herbicide residues could be responsible for the cellular modifications described in GM-fed mice, the concordance of the effects induced by low concentrations of Roundup on HTC cells suggests that the presence of Roundup residues could be one of the factors interfering with multiple metabolic pathways.
Article
We reviewed 19 studies of mammals fed with commercialized genetically modified soybean and maize which represent, per trait and plant, more than 80% of all environmental genetically modified organisms (GMOs) cultivated on a large scale, after they were modified to tolerate or produce a pesticide. We have also obtained the raw data of 90-day-long rat tests following court actions or official requests. The data obtained include biochemical blood and urine parameters of mammals eating GMOs with numerous organ weights and histopathology findings. We have thoroughly reviewed these tests from a statistical and a biological point of view. Some of these tests used controversial protocols which are discussed and statistically significant results that were considered as not being biologically meaningful by regulatory authorities, thus raising the question of their interpretations. Several convergent data appear to indicate liver and kidney problems as end points of GMO diet effects in the above-mentioned experiments. This was confirmed by our meta-analysis of all the in vivo studies published, which revealed that the kidneys were particularly affected, concentrating 43.5% of all disrupted parameters in males, whereas the liver was more specifically disrupted in females (30.8% of all disrupted parameters). The 90-day-long tests are insufficient to evaluate chronic toxicity, and the signs highlighted in the kidneys and livers could be the onset of chronic diseases. However, no minimal length for the tests is yet obligatory for any of the GMOs cultivated on a large scale, and this is socially unacceptable in terms of consumer health protection. We are suggesting that the studies should be improved and prolonged, as well as being made compulsory, and that the sexual hormones should be assessed too, and moreover, reproductive and multigenerational studies ought to be conducted too.
Article
Iron nitrilotriacetate (Fe-NTA), a chief environmental pollutant, is known for its extensive toxic manifestations on renal system. In the present study, caffeic acid, one of the most frequently occurring phenolic acids in fruits, grains, and dietary supplements was evaluated for its shielding effect against the Fe-NTA-induced oxidative, inflammatory, and pathological damage in kidney. Fe-NTA was administered (9 mg Fe/kg body weight) intraperitoneally to the Wistar male rats on 20th day while caffeic acid was administered orally (20 and 40 mg/kg body weight) before administration of Fe-NTA. The intraperitoneal administration of Fe-NTA-enhanced lipid peroxidation, xanthine oxidase, and hydrogen peroxide generation with reduction in renal glutathione content, antioxidant enzymes, viz., catalase, glutathione peroxidase, and glutathione reductase. A sharp elevation in the levels of myloperoxidase, blood urea nitrogen (BUN), and serum creatinine has also been observed. Tumor promotion markers viz., ornithine decarboxylase (ODC) and [(3)H] thymidine incorporation into renal DNA were also significantly increased. Treatment of rats orally with caffeic acid (20 and 40 mg/kg body weight) resulted in a significant decrease in xanthine oxidase (P < 0.001), lipid peroxidation (P < 0.001), γ-glutamyl transpeptidase (P < 0.01), and H(2)O(2) (P < 0.01). There was significant recovery of renal glutathione content (P < 0.001) and antioxidant enzymes (P < 0.001). There was also a reversal in the enhancement of renal ODC activity, DNA synthesis, BUN, and serum creatinine (P < 0.001). All these changes were supported by histological observations. The results indicate that caffeic acid may be beneficial in ameliorating the Fe-NTA-induced oxidative damage and tumor promotion in the kidney of rats.
Article
Hypoxia can promote invasive behavior in cancer cells and alters the response to therapeutic intervention as a result of changes in the expression many genes, including genes involved in intermediary metabolism. Although metabolomics technologies are capable of simultaneously measuring a wide range of metabolites in an untargeted manner, these methods have been relatively under utilized in the study of cancer cell responses to hypoxia. Thus, (1)H NMR metabolomics was used to examine the effects of hypoxia in the MDA-MB-231 human breast cancer cell line, both in vitro and in vivo. Cell cultures were compared with respect to their metabolic responses during growth under either hypoxic (1% O(2)) or normoxic conditions. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to identify a set of metabolites that were responsive to hypoxia. Via intracardiac administration, MDA-MB-231 cells were also used to generate widespread metastatic disease in immuno-compromised mice. Serum metabolite analysis was conducted to compare animals with and without a large tumor burden. Intriguingly, using a cross-plot of the OPLS loadings, both the in vitro and in vivo samples yielded a subset of metabolites that were significantly altered by hypoxia. These included primarily energy metabolites and amino acids, indicative of known alterations in energy metabolism, and possibly protein synthesis or catabolism. The results suggest that the metabolite pattern identified might prove useful as a marker for intra-tumoral hypoxia.
Article
We summarize the major points of international debate on health risk studies for the main commercialized edible GMOs. These GMOs are soy, maize and oilseed rape designed to contain new pesticide residues since they have been modified to be herbicide-tolerant (mostly to Roundup) or to produce mutated Bt toxins. The debated alimentary chronic risks may come from unpredictable insertional mutagenesis effects, metabolic effects, or from the new pesticide residues. The most detailed regulatory tests on the GMOs are three-month long feeding trials of laboratory rats, which are biochemically assessed. The tests are not compulsory, and are not independently conducted. The test data and the corresponding results are kept in secret by the companies. Our previous analyses of regulatory raw data at these levels, taking the representative examples of three GM maize NK 603, MON 810, and MON 863 led us to conclude that hepatorenal toxicities were possible, and that longer testing was necessary. Our study was criticized by the company developing the GMOs in question and the regulatory bodies, mainly on the divergent biological interpretations of statistically significant biochemical and physiological effects. We present the scientific reasons for the crucially different biological interpretations and also highlight the shortcomings in the experimental protocols designed by the company. The debate implies an enormous responsibility towards public health and is essential due to nonexistent traceability or epidemiological studies in the GMO-producing countries.
Article
Controversy surrounds the efficacy and safety of 17beta-estradiol (E2)-mimetic therapies to women for treatment of menopausal symptoms. An important question is the nature of the trophic actions of E2-mimetics in the brain for behavioral processes versus in the periphery for beneficial effects related to osteoporosis, or unwanted proliferative effects in the reproductive tissues, such as mammary glands and uterus. Of recent interest are the effects of selective estrogen receptor modulators, which can have tissue specific actions, for these processes. In the present study, the effects were determined of E2 alone, or co-administered with a selective estrogen receptor modulator, raloxifene, for anxiety-like, depression-like, and trophic peripheral effects in ovariectomized rats that were exposed to a chemical carcinogen (7,12-dimethylbenz(a)anthracene), or not. Once per week, rats were administered vehicle, E2 (0.09 mg/kg) and/or raloxifene (1 mg/kg) subcutaneously 44-48 h before testing in a positive control, E2-dependent behavior (lordosis), depression (forced swim test), and anxiety (elevated plus maze) behavioral assays. In addition to behavioral endpoints, incidence and number of tumors, and tumor, pituitary gland, and uterine weight 14 weeks after carcinogen-exposure, and weekly hormone treatments, were analyzed. Rats administered 7,12-dimethylbenz(a)anthracene had an increased number and size of tumors, compared with vehicle treatment. E2 + raloxifene increased the number of tumors. Administration of E2 or E2 +raloxifene, but not raloxifene alone, increased pituitary and uterine weight, compared with vehicle administration. E2 or E2 + raloxifene, but not raloxifene alone, also increased the incidence of lordosis and reduced the depression-like behavior in the forced swim test (i.e. decreased time spent immobile) compared with vehicle administration. However, administration of E2 or raloxifene reduced anxiety behavior in the elevated plus maze (i.e. increased time spent on the open arms of the maze), compared with vehicle treatment. Together these data show that E2 and/or raloxifene can have some effects to alter the behavior of ovariectomized rodents, depending upon the task. As well, E2, with or without raloxifene, can also have clear trophic actions in peripheral tissues, such as carcinogen-induced tumors, uterus, and pituitary glands.
Article
Aim of the present study was to investigate the chemopreventive potential of ferulic acid on 7,12-dimethylbenz[a]anthracene (DMBA) induced mammary carcinogenesis in Sprague-Dawley rats. The chemopreventive potential of ferulic acid was assessed by monitoring the tumor incidence, as well as analyzing the status of biochemical (enzymatic and non-enzymatic antioxidants and phase II detoxification enzymes) and molecular (p53 and bcl-2) markers during DMBA-induced mammary carcinogenesis. Mammary carcinogenesis was induced in Sprague-Dawley rats by providing a single subcutaneous injection of 25 mg of DMBA in 1 ml emulsion of sunflower oil (0.75 ml) and physiological saline (0.25 ml) to each rat. Oral administration of ferulic acid at a dose of 40 mg/kg body weight to rats treated with DMBA significantly prevented the tumor formation in 80% of animals (8/10). Also, oral administration of ferulic acid significantly protected the biochemical and molecular abnormalities in DMBA treated rats. Although the exact mechanism for the chemopreventive potential of ferulic acid in DMBA-induced mammary carcinogenesis is unclear, its antigenotoxic and antioxidant potential as well as modulatory effect on phase II detoxification cascade could play a possible role.
Article
Unintended compositional changes in transgenic rice seeds were studied by near-infrared reflectance, GC-MS, HPLC, and ICP-AES coupled with chemometrics strategies. Three kinds of transgenic rice with resistance to fungal diseases or insect pests were comparatively studied with the nontransgenic counterparts in terms of key nutrients such as protein, amino acids, fatty acids, vitamins, elements, and antinutrient phytic acid recommended by the Organization for Economic Co-operation and Development (OECD). The compositional profiles were discriminated by chemometrics methods, and the discriminatory compounds were protein, three amino acids, two fatty acids, two vitamins, and several elements. Significance of differences for these compounds was proved by analysis of variance, and the variation extent ranged from 20 to 74% for amino acids, from 19 to 38% for fatty acids, from 25 to 57% for vitamins, from 20 to 50% for elements, and 25% for protein, whereas phytic acid content did not change significantly. The unintended compositional alterations as well as unintended change of physical characteristic in transgenic rice compared with nontransgenic rice might be related to the genetic transformation, the effect of which needs to be elucidated by additional studies.
Article
Glyphosate is a herbicide widely used to kill weeds both in agricultural and non-agricultural landscapes. Its reproductive toxicity is related to the inhibition of a StAR protein and an aromatase enzyme, which causes an in vitro reduction in testosterone and estradiol synthesis. Studies in vivo about this herbicide effects in prepubertal Wistar rats reproductive development were not performed at this moment. Evaluations included the progression of puberty, body development, the hormonal production of testosterone, estradiol and corticosterone, and the morphology of the testis. Results showed that the herbicide (1) significantly changed the progression of puberty in a dose-dependent manner; (2) reduced the testosterone production, in semineferous tubules' morphology, decreased significantly the epithelium height (P < 0.001; control = 85.8 +/- 2.8 microm; 5 mg/kg = 71.9 +/- 5.3 microm; 50 mg/kg = 69.1 +/- 1.7 microm; 250 mg/kg = 65.2 +/- 1.3 microm) and increased the luminal diameter (P < 0.01; control = 94.0 +/- 5.7 microm; 5 mg/kg = 116.6 +/- 6.6 microm; 50 mg/kg = 114.3 +/- 3.1 microm; 250 mg/kg = 130.3 +/- 4.8 microm); (4) no difference in tubular diameter was observed; and (5) relative to the controls, no differences in serum corticosterone or estradiol levels were detected, but the concentrations of testosterone serum were lower in all treated groups (P < 0.001; control = 154.5 +/- 12.9 ng/dL; 5 mg/kg = 108.6 +/- 19.6 ng/dL; 50 mg/dL = 84.5 +/- 12.2 ng/dL; 250 mg/kg = 76.9 +/- 14.2 ng/dL). These results suggest that commercial formulation of glyphosate is a potent endocrine disruptor in vivo, causing disturbances in the reproductive development of rats when the exposure was performed during the puberty period.
Article
Glyphosate-based herbicides are the most widely used across the world; they are commercialized in different formulations. Their residues are frequent pollutants in the environment. In addition, these herbicides are spread on most eaten transgenic plants, modified to tolerate high levels of these compounds in their cells. Up to 400 ppm of their residues are accepted in some feed. We exposed human liver HepG2 cells, a well-known model to study xenobiotic toxicity, to four different formulations and to glyphosate, which is usually tested alone in chronic in vivo regulatory studies. We measured cytotoxicity with three assays (Alamar Blue, MTT, ToxiLight), plus genotoxicity (comet assay), anti-estrogenic (on ERalpha, ERbeta) and anti-androgenic effects (on AR) using gene reporter tests. We also checked androgen to estrogen conversion by aromatase activity and mRNA. All parameters were disrupted at sub-agricultural doses with all formulations within 24h. These effects were more dependent on the formulation than on the glyphosate concentration. First, we observed a human cell endocrine disruption from 0.5 ppm on the androgen receptor in MDA-MB453-kb2 cells for the most active formulation (R400), then from 2 ppm the transcriptional activities on both estrogen receptors were also inhibited on HepG2. Aromatase transcription and activity were disrupted from 10 ppm. Cytotoxic effects started at 10 ppm with Alamar Blue assay (the most sensitive), and DNA damages at 5 ppm. A real cell impact of glyphosate-based herbicides residues in food, feed or in the environment has thus to be considered, and their classifications as carcinogens/mutagens/reprotoxics is discussed.
Article
The cryIAc and sck genes were introduced to the rice for the purpose of improving the insect resistance. Metabolic profiles of wild and transgenic rice were compared to assess the unintended effects related to gene modification. Wild samples with different sowing dates or sites were also examined to determine the environmental effects on metabolites. The polar compounds of grains were extracted, trimethylsilylated and analyzed by gas chromatography-flame ionization detection (GC-FID). Partial least squares-discriminant analysis (PLS-DA) and principal component analysis (PCA) were applied to differentiate transgenic and wild rice grains. The significantly distinguishable metabolites were picked out, and then identified by gas chromatography-mass spectrometry (GC-MS). It was found that both the environment and gene manipulation had remarkable impacts on the contents of glycerol-3-phosphate, citric acid, linoleic acid, oleic acid, hexadecanoic acid, 2,3-dihydroxypropyl ester, sucrose, 9-octadecenoic acid (Z)-, 2,3-dihydroxypropyl ester and so on. Sucrose, mannitol and glutamic acid had a significant increase in transgenic grains in contrast to those in non-genetically modified (GM) rice.