Regulatory toxicology
"Some of the most important publications by scientific teams supported by CRIIGEN or by CRIIGEN members who have participated in them.
Traditionally, when a scientific study is cited, only the name of the first author is given. Exceptionally, all authors are cited to thank them for their efforts, cooperation and support of CRIIGEN.
(Authors who are members of CRIIGEN are underlined)
2022
Comparative analysis of detection techniques for glyphosate in urine and in water. Velot C, Poitou F, Spiroux de Vendômois J. (2022) Environmental Sciences Europe. DOI 10.1186/s12302-022-00637-9
" Comparative analysis of glyphosate detection techniques in urine and water ".
Glyphosate is the declared active ingredient in the world's most widely used herbicides, and is therefore widely present in the environment. Urinary glyphosate levels represent a relevant biomarker for individual exposure to glyphosate-based herbicides. However, the measurement of GLY levels in urine is controversial, as different detection methods have led to contradictory results...
... notably in the case of enzyme-linked immunosorbent assay (ELISA) versus liquid chromatography coupled with tandem mass spectrometry (LC/MS-MS) for urine, and ELISA versus high-performance liquid chromatography coupled with fluorescence detection (HPLC/Fluo) for water.
We compared ELISA to LC/MS-MS or HPLC/Fluo by submitting identical urine and water samples to two laboratories (Biocheck, Germany and Labocéa, France respectively), spiked or unspiked with precise concentrations of glyphosate, but also with two chemically similar molecules: glycine and aminomethylphosphonic acid, respectively analogue and primary metabolite of GLY.
Both laboratories claimed a similar threshold of quantification (LOQ) for glyphosate: 0.08 and 0.05 ng/mL respectively. Each of the methods tested was found to be specific for glyphosate and therefore gave no results.
cross-detection with glycine and aminomethylphosphonic acid. However, these methods showed differences in both reproducibility and reliability depending on the matrix used (water or urine).
Although the ELISA method gave less precise results than the HPLC/Fluo technique when applied to water samples, the glyphosate concentrations measured in urine were much more reliable and reproducible with ELISA technology than those obtained with LC/MS-MS.
2021
Trans-disciplinary diagnosis for an in-depth reform of regulatory expertise in the field of environmental toxicology and security. Joël Spiroux de Vendômois, Jean-Paul Bourdineaud, Arnaud Apoteker, Nicolas Defarge, Emilie Gaillard, Corinne Lepage, Jacques Testart , Christian Vélot. Review Toxicol Res. 2021. Doi: 10.1007/s43188-020-00075-w.
" Transdisciplinary diagnosis for an in-depth reform of regulatory expertise in the field of environmental toxicology and safety ".
Repeated health and environmental scandals, the loss of biodiversity and the recent explosion in chronic diseases are constant reminders of the inability of public authorities and risk assessment agencies to protect health and the environment...
After reviewing the main shortcomings of our assessment system for chemicals and new technologies, backed up by a few concrete examples, we draw up a number of proposals aimed at reforming both risk assessment agencies and assessment processes. In particular, we propose the creation of an independent structure, a High Authority for Expertise, to supervise all assessment agencies, either at European or national level, and to guarantee the transparency, methodology and ethics of expertise. In addition to modifying the nature and content of assessment protocols, in particular to adapt them to current pollutants such as endocrine disruptors, we propose a reform of expert assessment processes based on transparency, contradiction and greater democracy, including close collaboration between institutional and scientific players on the one hand, and civil society as a whole on the other. All our proposals are inspired by the desire to prevent, through appropriate mechanisms, the human, health, ecological and economic consequences of contemporary technological choices.
2019
Insight into the confusion over surfactant co-formulants in glyphosate-based herbicides. Robin Mesnage, Charles Benbrook, Michael N Antoniou. Review Food Chem Toxicol. 2019 Jun. Doi: 10.1016/j.fct.2019.03.053.
Overview of the confusion surrounding surfactant co-formulants in glyphosate-based products
Glyphosate is the active ingredient in glyphosate-based herbicides (GBH). Other chemicals in GBHs are presumed inert by regulatory authorities and are largely ignored in pesticide safety assessments. We identified surfactants in a representative sample of GBH formulations and compared their acute toxic effects...
... The first-generation polyethoxylated amine (POEA) surfactants (POE-tallowamine) contained in Roundup are significantly more toxic than glyphosate, and have raised concerns about human health risks, particularly for highly exposed applicators. From the mid-1990s onwards, first-generation POEAs were gradually replaced by other POEA surfactants, ethoxylated etheramines, which showed less non-targeted toxic effects. Persistent concerns about surfactant toxicity were at least partially alleviated in the European Union by the introduction of propoxylated quaternary ammonium surfactants. This class of POEA surfactants is around 100 times less toxic to aquatic ecosystems and human cells than previous GBH-POEA surfactants. As the composition of GBH is legally classified as confidential business information, confusion over the identity and concentrations of co-formulants is common, and descriptions of the substances tested in published studies are often erroneous or incomplete. In order to clear up this confusion, legislation requiring disclosure of the chemical composition of pesticide products could be enacted. Research is needed to understand the health implications of ingesting these substances.
2018
Ignoring Adjuvant Toxicity Falsifies the Safety Profile of Commercial Pesticides. Robin Mesnage, Michael N Antoniou. Review Front Public Health. 2018. Doi: 10.3389/fpubh.2017.00361.
Commercial pesticide formulations do not always contain a single ingredient. Rather, they are cocktails of chemicals, composed of a designated pesticidal "active ingredient" and "other ingredients", the latter also collectively referred to as "adjuvants". These include surfactants, antifoaming agents, colorants and so on. Some adjuvants are added to influence the absorption and stability of the active ingredient, and thus enhance its pesticidal action...
... Currently, health risk assessment for pesticides in the European Union and the USA focuses almost exclusively on the declared active ingredient. However, adjuvants can also be toxic in their own right, with numerous adverse health effects reported in humans and the environment. Despite the known toxicity of adjuvants, they are regulated differently from active ingredients, their toxic effects being generally ignored. Adjuvants are not subject to an acceptable daily intake and are not included in the assessment of health risks associated with dietary exposure to pesticide residues. Here, we illustrate this gap in risk assessment with reference to glyphosate, the most widely used pesticide active ingredient. We also study the case of neonicotinoid insecticides, strongly suspected of being involved in bee and bumblebee colony collapse disorder. Study authors sometimes use the name of the active ingredient (e.g. glyphosate) when testing a commercial formulation containing several ingredients (active ingredient plus adjuvant). This leads to confusion in scientific literature and regulatory circles, and misrepresents the safety profile of commercial pesticides. Urgent action is needed to lift the veil on the presence of adjuvants in human food and body fluids, as well as in the environment (such as air, water and soil), and to characterize their toxicological properties. This must be accompanied by precautionary regulatory measures to protect the environment and the human population in general from certain toxic adjuvants currently lacking in risk assessments.
2017
Facts and Fallacies in the Debate on Glyphosate Toxicity. Robin Mesnage, Michael N Antoniou. Front Public Health. 2017. Doi: 10.3389/fpubh.2017.00316
Facts and errors in the glyphosate toxicity debate
The safety profile of the herbicide glyphosate and its commercial formulations is controversial. Criticism has been published by consultants and employees of companies marketing glyphosate-based herbicides in support of glyphosate's re-approval by regulatory agencies...
...These authors conclude that glyphosate is safe at levels below permitted regulatory limits. On the other hand, studies conducted by academic scientists independent of the industry report toxic effects below regulatory limits, as well as shortcomings in the current regulatory assessment of risks associated with glyphosate exposure. Two authors in particular (Samsel and Seneff) have published a series of commentaries proposing that long-term exposure to glyphosate is responsible for numerous chronic diseases (including cancers, diabetes, neuropathies, obesity, asthma, infections, osteoporosis, infertility and birth defects). ). The aim of this review is to examine the evidence for these alleged negative health effects, and the mechanisms that are thought to underlie them. We found that these authors inappropriately employ a deductive reasoning approach based on syllogism. We found that their conclusions are not supported by the available scientific evidence. Thus, the mechanisms and wide range of conditions proposed as resulting from glyphosate toxicity presented by Samsel and Seneff in their comments are at best unsubstantiated theories, speculation or simply incorrect. This misrepresentation of glyphosate toxicity misleads the public, the scientific community and regulators alike. Although there is evidence that glyphosate-based herbicides are toxic below regulatory safety limits, Samsel and Seneff's arguments largely serve to distract rather than give rational direction to much-needed future research into the toxicity of these pesticides, particularly at ingestion levels. which are typical of human populations.
2016
Concerns over use of glyphosate-based herbicides and risks associated with exposures: a consensus statement. John Peterson Myers, Michael N Antoniou, Bruce Blumberg, Lynn Carroll, Theo Colborn, Lorne G Everett, Michael Hansen, Philip J Landrigan Bruce P Lanphear, Robin Mesnage, Laura N Vandenberg, Frederick S Vom Saal, Wade V Welshons, Charles M Benbrook. Environ Health. 2016. Doi: 10.1186/s12940-016-0117-0.
Concerns about the use of glyphosate herbicides and the risks associated with exposures: a consensus statement.
Glyphosate, a broad-spectrum herbicide under the common trade name "Roundup", was first sold to farmers in 1974. Since the late 1970s, the volume of glyphosate-based herbicides (GBH) applied has increased 100-fold, and further increases in the volume applied are likely to be due to increasingly high application rates in response to the widespread emergence of glyphosate-resistant weeds, and new patterns of pre-harvest desiccant use...
... GBHs were developed to replace or reduce the use of herbicides, causing well-documented problems associated with crop drift and damage, slip efficiency and human health risks. Early industry toxicity tests suggested that GBHs presented relatively low risks to non-target species, including mammals, leading regulatory authorities worldwide to set high acceptable exposure limits. To accommodate changes in GBH use patterns associated with genetically modified herbicide-tolerant crops, regulators have significantly increased tolerance levels for corn, oilseeds (soybean and canola) and alfalfa crops and associated livestock feeds. Animal and epidemiological studies published over the last decade, however, underline the need for a fresh look at glyphosate toxicity. In addition, the World Health Organization's International Agency for Research on Cancer recently concluded that glyphosate is "probably carcinogenic to humans". In response to changing patterns of GBH use and advances in scientific understanding of their potential hazards, we have produced a statement of concern based on emerging scientific knowledge relevant to GBH safety. Our statement of concern takes into account current published literature describing GBH uses, mechanisms of action, toxicity in laboratory animals and epidemiological studies. It also examines the development of current human safety standards. We conclude that: (1) GBHs are the most widely used herbicide in the world and their use continues to increase; (2) Worldwide, GBHs often contaminate drinking water sources, precipitation and air, particularly in agricultural areas; (3) The half-life of glyphosate in water and soil is longer than previously thought ; (4) Glyphosate and its metabolites are widely present in the global soybean supply; (5) Human exposures to GBH are increasing; (6) Glyphosate is now authoritatively classified as a probable human carcinogen; (7) Regulatory estimates of tolerable daily intakes for glyphosate in the US and EU are based on outdated science. We propose a series of recommendations related to the need for new investment in epidemiological studies, biomonitoring and toxicological studies that draw on the principles of endocrinology to determine whether the effects of GBHs are due to endocrine-disrupting activities. We suggest that current commercial formulations of GBH be included as a priority in government-led toxicology testing programs, such as the U.S. National Toxicology Program, as well as for biomonitoring conducted by the U.S. Centers for Disease Control and Prevention.
2015
Control rats are sick rats!
Laboratory Rodent Diets Contain Toxic Levels of Environmental Contaminants: Implications for Regulatory Tests. Mesnage R, Defarge N, Rocque LM, Spiroux de Vendômois J, Séralini GE. PLoS One. 2015. Doi : 10.1371/journal.pone.0128429.
" Diets of laboratory rodents contain toxic levels of environmental contaminants: implications for regulatory testing ".
Regulatory toxicological studies compare the impact of a product on a group of "test" animals against a group of "control" animals. Is the food of the "control" animals free of potentially toxic products? That's the question answered by this publication...
With the help of accredited laboratories, we have analyzed laboratory animal feed using standardized methods. This food, sourced from all five continents, is usually considered balanced and hygienic. The scope of the study is exceptional: 13 common samples of rat kibble were examined for traces of 262 pesticides, 4 heavy metals, 17 dioxins and furans, 18 PCBs and 22 GMOs. All the samples were contaminated with very high doses of some of these substances. These pollutants, which are typical of industrial food, can explain the level of tumors and diseases classified as natural in rats by the industry, allowing them to overlook the visible side effects of the industrial products they process. If this knowledge were to be taken into account by regulations, it could have far-reaching consequences for understanding the health effects of additives, contaminants and pesticides in food produced by intensive agriculture. Here again, CRIIGEN is open to comments from companies developing quality products, and from NGOs, to bring this issue to the attention of the authorities.
2014
Conflicts of interests, confidentiality and censorship in health risk assessment: the example of an herbicide and a GMO. Gilles-Eric Séralini, Robin Mesnage, Nicolas Defarge, Joël Spiroux de Vendômois. Editorial Environ Sci Eur. 2014. doi: 10.1186/s12302-014-0013-6.
" Conflicts of interest, confidentiality and censorship in health risk assessment: the example of a herbicide and a GMO ".
We studied the long-term toxicity of Roundup-tolerant GM maize (NK603) and a whole formulation of Roundup pesticide at environmentally relevant levels from 0.1 ppb. This has caused turmoil in the scientific editorial world, highlighting conflicts of interest...
Our study was first published in Food and Chemical Toxicology (FCT) on September 19, 2012. The first wave of criticism arrived within a week, mainly from plant biologists with no toxicology experience. We responded to all these criticisms. The debate then encompassed scientific arguments, and a wave of ad hominem and potentially defamatory comments appeared in various journals by authors with serious but undisclosed conflicts of interest. At the same time, FCT recruited a former Monsanto employee as its new Associate Editor for Biotechnology after he had sent a letter to FCT complaining about our study. Not least because of this, FCT requested a post-hoc analysis of our raw data. On November 19, 2013, the editor requested the withdrawal of our study while acknowledging that the data were not incorrect and that there was no fault, fraud or intentional misinterpretation in our raw data set - an unusual, if not unprecedented, action in scientific publishing. The publisher argued that no conclusions could be drawn because we studied 10 rats per group for 2 years, because they were Sprague Dawley rats and because the data were inconclusive on cancer. This, however, was known at the time our study was submitted. However, our study was never considered a carcinogenicity study. We never used the word "cancer" in our paper. The present opinion is a summary of the debate that led to this retraction, as it is a historical example of conflicts of interest in scientific assessments of products marketed worldwide. We also show that the decision to retract cannot be rationalized on any discernible scientific or ethical basis. Censorship of health risk research undermines the value and credibility of science, so we are republishing our article.