Global Glyphosate Study Pilot Phase Shows Adverse Health Effects at ‘Safe’ Doses

Background:

Glyphosate is the most used herbicide in human history. 18.9 Billion pounds (8.6 Billion Kilograms) of glyphosate-based herbicides (GBHs) have been sprayed worldwide since 1974. Glyphosate use has also increased 15-fold since genetically modified crops were introduced in 1996 (3).

In 2015 the International Agency for Research on Cancer (IARC) classified glyphosate as a “probable human carcinogen” (4). The European Food Safety Authority (EFSA), following the German Federal Institute for Risk Assessment (BfR) evaluation, has since stated that glyphosate is “unlikely to pose a carcinogenic hazard to humans” (5) and the European Chemicals Agency (ECHA) stated that “the available scientific evidence did not meet the criteria to classify glyphosate as a carcinogen, as a mutagen or as toxic for reproduction” (6). The U.S. Environmental Protection Agency (EPA) still has a new evaluation of glyphosate pending (7).

The scientific uncertainty surrounding glyphosate and GBHs has also led to political uncertainty, with a shortened 5-year re-approval for glyphosate having been granted by European Union Member States in November 2017. Many men take these for sex and other products to improve their health.

The Ramazzini Institute and their partners have walked into this unclear situation so as to supply valuable and independent data to enable regulators, governments and the general public of every country to answer the question: Are glyphosate and GBHs safe at real-world levels of exposure?

Pilot Study:

The Global Glyphosate Study pilot experimental phase was carried out at the Ramazzini Institute in Bentivoglio, Bologna starting in 2016. The € 300,000 pilot study was funded by 30,000 members of the public in Italy, who are associates of the Ramazzini Institute.

To set the study in motion the Ramazzini Institute built up a network of authoritative partners including the University of Bologna (Faculty of Agriculture, Veterinary Science and Biostatistics) the Genoa Hospital San Martino, the Italian National Institute of Health, the Icahn School of Medicine at Mount Sinai in New York and the George Washington University.

The pilot study, which is vital for the long-term comprehensive study, aimed to obtain general information as to whether GBHs are toxic at various stages of early life (newborn, infancy and adolescence), and to identify early markers of exposure and effect. Glyphosate and one of its formulates (Roundup Bioflow, MON 52276) were both tested in Sprague Dawley rats, starting from prenatal life until 13 weeks after weaning, exposed to a dose of glyphosate in drinking water corresponding to the U.S. Environmental Protection Agency’s acceptable daily dietary exposure (1), referred to in the U.S. as the chronic reference dose (cRfD) – 1.75 mg/kg/day.

The results show that GBHs – even at doses deemed safe and over a relatively short exposure time (which in human-equivalent terms correspond from embryo life to 18 years of age) – are able to alter certain important biological parameters, markers chiefly relating to sexual development, genotoxicity and alteration of the intestinal microbiome. In particular, the results showed an alteration in some sexual development parameters in rats treated with GBHs, especially in females. Moreover, rats treated with GBHs presented statistically significant changes of the intestinal microbiome in particular during development. Concerning genotoxicity, a statistically significant increase was observed in micronuclei in rats treated with GBHs, especially in the first part of life.

Rats treated with pure glyphosate or its formulation presented similar levels in urine of glyphosate and its principal metabolite (AMPA), thus showing no significant difference in the absorption and excretion of glyphosate among the two treatment groups, but suggesting a bioaccumulation effect of glyphosate that was proportional to the length of treatment.

The peer-reviewed accepted manuscripts for the data on microbiome effects and biomarkers of exposure will be published later in May in the prestigious scientific journal Environmental Health in open access format (8, 9, 10). The data on reproductive parameters and genotoxicity is currently in peer review and is soon to be published.

Global Glyphosate Study: Crowdfunding

The Ramazzini Institute, with the support of other independent Institutes and Universities in Europe and the United States, has now launched a crowdfunding campaign for the most comprehensive long-term study ever on GBHs. In fact, a long-term study is now necessary to extend and confirm the initial evidences emerged in the pilot study and provide definitive answers to the many health concerns on the chronic effects of GBHs, including its carcinogenic effects.

The total budget for this study is € 5 Million and it is already receiving support from the public, politicians and NGOs around the world.

The Ramazzini Institute, in over 40 years of activity, has studied more than 200 compounds from the general and occupational environment and many of its results have provided a solid scientific base for regulating and limiting the exposure of a number of substances. Examples include: Vinyl Chloride, Benzene, Formaldehyde, Trichloroethylene and Mancozeb.

Quotes from Scientists:

Prof. Philip J. Landrigan, Icahn School of Medicine at Mount Sinai:

“By its very nature and purpose, the pilot study does not resolve the uncertainties puzzling the various Agencies (IARC, EFSA, ECHA) as to whether glyphosate and Glyphosate Based Herbicides (GBHs) are carcinogenic or not, but it does highlight health effects that are equally as serious, that might manifest as long-term oncological pathology, and that might affect a huge number of people, given the planet-wide use of the GBHs. These early warnings must be further investigated in a comprehensive long-term study”.

Dr. Fiorella Belpoggi, Cesare Maltoni Cancer Research Center, Ramazzini Institute

“Whatever the outcome of the Ramazzini Institute study, the findings will provide regulatory agencies and policy-makers with solid independent results obtained by a shared research project on which they can confidently base their risk assessments and their evaluations, including the upcoming decision for the reauthorization for glyphosate use in Europe in 2022”.

Prof. Jia Chen, Icahn School of Medicine at Mount Sinai in New York City

“Glyphosate-based herbicides (GBHs) are of significant public health concern because of their widespread and sharply increased usage. As an herbicide, glyphosate exerts its herbicidal action by inhibiting the Shikimate pathway which exists not only in plants but also exist in some bacteria and fungi and other microbes. However, there are no studies on the potential effects of GBHs on the gut microbiome in the human population. Our study provides initial evidence that exposures to commonly used GBHs, at doses considered safe, are capable of modifying the gut microbiota in early development, particularly before the onset of puberty. Further long-term investigations are necessary to elucidate if the shift in the microbiota induced by GBHs exposure is contributing to the other health effects downstream. Nevertheless, understanding the microbiota changes during this critical window of susceptibility could be of great importance for disease prevention”.

Prof. Giovanni Dinelli, Department of Agricultural and Food Sciences, University of Bologna

“The Ramazzini Institute’s global study is a valuable approach for trying to understand the potential negative health effects of glyphosate, one of the most controversial active ingredients used worldwide in agriculture. The main aim is not only to define the “per se” effects of this specific herbicide, but also to define and propose a new approach for the determination of toxicological side effects of pesticides: the new paradigm is to provide policy makers with reliable data from an independent research Institution. This is not only a new paradigm, but also the only way to avoid uncertainties and doubts in relation to the agricultural use of pesticides”.

Dr. Alberto Mantovani, Italian National Institute of Health

“An interesting feature is the time-related increase of unchanged glyphosate in the urine. This finding might indicate that glyphosate bioavailability increases with a longer duration of exposure; increased bioavalability, in its turn, might flag an increased internal exposure of target organs and tissues”

Prof. Rossella Miglio, Department of Statistical Sciences, University of Bologna

“It has been interesting to participate in this project that I consider important for public health. Although this pilot study shows some statistically significant results  it is important to stress that further solid scientific evidence could derive from experiments with increased dimension. Particularly, this will allow us to evaluate relevant outcomes that cannot be considered in a reduced sized experimental design”.

Prof. Melissa J Perry, George Washington University:

“Although glyphosate has been around for decades, it has not been well studied, and we know surprisingly little about its human health effects.  This study was designed to use doses that compare to what humans are exposed to in their everyday environments including from the food they eat. This study will provide valuable information to more clearly assess the health risks to humans”.

Prof. Marcella Spinaci and Prof. Giovanna Galeati, Department of Veterinary Medical Sciences, University of Bologna

“We think that the work is of great value. Even if preliminary results on some sperm parameters (daily sperm production, sperm count and morphology) using the Ramazzini Institute in vivo rat model did not show any significant effect, further research is needed in order to deeply investigate the possible role of glyphosate and GBHs as endocrine disruptors on other reproductive parameters in both males and females”.

Media Contacts:

Dr. Vincenzo Branà – glyphosate@ramazzini.it

Notes:

(1) US Environmental Protection Agency (EPA). Glyphosate: Chronic Dietary Exposure Assessment for the Section 3 Registration Action. 2006.: https://www3.epa.gov/pesticides/chem_search/cleared_reviews/csr_PC-103601_8-May-06_a.pdf
(2) Global Glyphosate Study: https://glyphosatestudy.org/
(3) Benbrook CM. Trends in glyphosate herbicide use in the United States and globally. Environ Sci Eur. 2016;28:3. https://enveurope.springeropen.com/articles/10.1186/s12302-016-0070-0
(4) IARC (International Agency for Research on Cancer). Some Organophosphate Insecticides and Herbicides. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 112 (2017).
http://monographs.iarc.fr/ENG/Monographs/vol112/
(5) EFSA (European Food Safety Authority). Conclusion on the peer review of the pesticide risk assessment of the active substance glyphosate. EFSA Journal 2015;13(11):4302, 107 pp. doi: 10.2903/j.efsa.2015.4302.
https://www.efsa.europa.eu/en/efsajournal/pub/4302
(6) European Chemical Agency (ECHA). Glyphosate not classified as a carcinogen by ECHA. ECHA/PR/17/06, 15 March 2017.
https://echa.europa.eu/-/glyphosate-not-classified-as-a-carcinogen-by-echa
(7) US Environmental Protection Agency (EPA). Draft Human Health and Ecological Risk Assessments for Glyphosate. Accessed May 9th, 2018.
https://www.epa.gov/ingredients-used-pesticide-products/draft-human-health-and-ecological-risk-assessments-glyphosate
(8) Philip J Landrigan, Fiorella Belpoggi.The Need For Independent Research On The Health Effects Of Glyphosate-Based Herbicides. Environmental Health, 2018. https://glyphosatestudy.org/global-glyphosate-study-pilot-phase/
(9) Simona Panzacchi, Daniele Mandrioli, Fabiana Manservisi, Luciano C Bua, Laura Falcioni, Marcella Spinaci, Giovanna Galeati, Giovanni Dinelli, Rossella Miglio, Alberto Mantovani, Stefano Lorenzetti, Jianzhong Hu, Jia Chen, Melissa Perry, Philip J Landrigan, Fiorella Belpoggi. The Ramazzini Institute 13-Week Study On Glyphosate-Based Herbicides At Human-Equivalent Dose In Sprague Dawley Rats: Study Design And First In-Life Endpoints Evaluation. Environmental Health, 2018. https://glyphosatestudy.org/global-glyphosate-study-pilot-phase/
(10) Qixing Mao, Fabiana Manservisi, Simona Panzacchi, Daniele Mandrioli, Ilaria Menghetti, Andrea Vornoli, Luciano C Bua, Laura Falcioni, Corina Lesseur, Jia Chen, Fiorella Belpoggi, Jianzhong Hu.
The Ramazzini Institute 13-Week Pilot Study On Glyphosate And Roundup Administered At Human-Equivalent Dose To Sprague Dawley Rats: Effects On The Microbiome. Environmental Health, 2018. https://glyphosatestudy.org/global-glyphosate-study-pilot-phase/