The Ramazzini Institute research project

Pilot study

A ‘pilot’ experimental study of the toxicity of GBHs was carried out at the Ramazzini Institute in 2016 (Ministerial Authorization N° 710/2015-PR, issued on 17/7/2015) where both glyphosate alone and its formulation Roundup have been tested. In fact glyphosate alone and its formulations could have different effects. For example, the adjuvants present in the formulation might potentiate the toxic effects of glyphosate [13]. To set this study in motion, the Institute built up a network of authoritative partners including the University of Bologna (Departments of Agriculture, Veterinary Science and Biostatistics), the Genoa Istituto Tumori, the Istituto Superiore di Sanità (ISS), the Icahn School of Medicine at Mount Sinai, New York, and the George Washington University, Washington, DC.

The study was designed to assess the techniques and methods for detecting glyphosate and its metabolites in different matrices [14] and to develop methods for assessing organ toxicity, genotoxicity, molecular toxicity, reproductive/developmental toxicity, endocrine disruption and microbiome alteration [15]. In this pilot study, glyphosate and Roundup were both tested at a dose considered to be “safe”- corresponding to the ADI of glyphosate currently allowed in the US, defined as the chronic Reference Dose (cRfD) determined by the US EPA [16], namely 1.75 mg/kg bw/day.

Initial results from this pilot study were presented during the Annual Ramazzini Days (26–29 October 2017). These preliminary findings suggest that glyphosate and Roundup – even at doses deemed safe, i.e., at doses equivalent to the current ADI and with relatively short exposure time, from pregnancy until 13 weeks after weaning in human-equivalent terms from pregnancy to approximately 18 years of age – might be able to alter certain important biological parameters related to sexual development, genotoxicity and alteration of the intestinal bacterial flora. Other important parameters are under investigation that pertain to effects on target organs such as mammary gland, kidney and liver, the hormonal status in the blood, and chromosome alterations in sperm. All the results will be submitted for publication in this journal [14, 15].

A pilot study is, by definition, of short duration and involves fewer animals than a comprehensive experiment. Therefore, it can provide only limited information and is not designed to detect chronic effects and diseases of late onset such as cancer. Thus the Ramazzini Institute pilot study is not able to resolve the current regulatory uncertainty around glyphosate. However, the findings of the pilot study do highlight potentially serious health effects that might manifest as long-term oncologic pathology and could affect very large numbers of people, given the great and growing global use of the GBHs. Clearly these findings deserve further follow-up.

Future research

To follow up on the Ramazzini Institute pilot study, a more comprehensive investigation is necessary and it must examine the effects of a range of different environmentally relevant doses of glyphosate alone and GBHs. Therefore, in 2015, the Ramazzini Institute designed a comprehensive, integrated experimental approach to a long-term project following an already published protocol through which numerous parameters bearing on human health might be simultaneously monitored, thereby sparing animals [17]. In fact, proprietary studies conducted on behalf of the manufacturers often represent a limited investigation of the various toxicological effects now studied by academic and government scientists. The integrated study proposed by the Ramazzini Institute is based on a stepwise process that includes the priority end points of the Economic Co-operation and Development and the National Toxicology Program guidelines on carcinogenicity and chronic toxicity in addition to developmental and reproductive toxicity, exploring multiple windows of susceptibility of specific interest for risk assessments and public health decision-making such as prenatal, lactational and neonatal exposures. Such an integrated toxicological study is needed, together with further epidemiological evidence, for an independent and comprehensive assessment of the possible risks resulting from the ubiquitous exposure to GBHs.

As in the pilot study, both glyphosate and the commercial formulation Roundup will be tested in the integrated study. A human-equivalent model will be used to determine the dose-levels to be administered and the exposure period, which will include mating and gestation. Detailed assessments will examine the toxic effects in terms of the intestinal microbiome, gene expression and parameters relating to fertility, defects in development, effects on the nervous system and any treatment-related differences in the incidence of various tumours. This will be the most comprehensive study on GBHs to date and it will last 3–4 years.

To preserve independence from the pesticide-manufacturing industry and from its competitor (i.e. organic food industry), this integrated study will be supported through a global crowd-funding campaign that will be open to the world’s citizens, non-governmental organizations (NGOs) and national/international institutions. Details of this campaign are available at: www.glyphosatestudy.org.

To provide ongoing review of the integrated study, we intend to set up an external international scientific committee that will evaluate the study plan, the conduct of the study and review study results as they become available. We also plan to gather together all stakeholders interested in using our results to ascertain the degree of hazard involved in GBH exposure. These will include: IARC, EFSA, ISS, the National Institute of Environmental Health Sciences, and others, including NGOs representatives. Study results will be available by the time of the next EU decision on the reauthorization of glyphosate in 2022.