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Recently, the herbicide glyphosate was evaluated for its potential human carcinogenicity by two agencies: the International Agency for Research of Cancer (IARC), of the World Health Organisation (WHO) and the European Food Safety Agency (EFSA) of the European Union.
While IARC classified glyphosate as a “probably carcinogenic to humans”, EFSA did not. There were factual reasons for this difference that were underlined by each agency. This difference in classification initiated a debate and these highlights aims at clarifying factually what these differences are, and puts them into perspective.
In term of classification, “hazard” refers to the intrinsic properties of an agent (physical, chemical, biological) while “risk” takes into consideration the probability and the level of exposure to the agent considered as hazardous.
This may result in different classifications depending on the integration or not of the risk as a factor for the classification.
A simple explanation of these concepts can be found in this GreenFacts
video: www.youtube.com/watch?v=PZmNZi8bon8
Glyphosate is the common name for N-(phosphonomethyl)glycine (IUPAC), a herbicide that is most commonly known under the commercial name of ‘Roundup’, but is now also available on the market in a wide variety of products, formulations and brands. Glyphosate can be used in combination with POE-tallowamine, a co-formulant that promotes the penetration of the active substance into plants.
For the EFSA peer review of its risk assessment, the representative formulated product for the evaluation was ‘MON 52276’, a soluble concentrate containing 360 g/L glyphosate as isopropylammonium salt (486 g/L).
Glyphosate is generally used in spraying applications against emerged annual, perennial and biennial weeds in all crops, including but not restricted to vegetables, oil seeds, potatoes, cereals, orchard crops and vine. It can be used before planting fruit crops, ornamentals, trees, nursery plants, etc…, and for pre-harvest spraying of leaves for desiccation in cereals and oilseeds.
In March 2015, IARC classified glyphosate as “probably carcinogenic to humans” (Group 2A)1. This was based on “limited evidence of cancer in humans” (based on real-world exposures) and “sufficient evidence of cancer in experimental animals” (from studies of “pure” glyphosate). IARC also concluded that there was “strong” evidence for genotoxicity, both for “pure” glyphosate and for glyphosate formulations.
As underlined by the agency itself, the IARC Monographs evaluation is a hazard classification. It indicates the strength of evidence that glyphosate can cause cancer. IARC further states that the probability of developing a cancer will depend on factors such as the type and extent of exposure and the strength of the effect of the agent.
By contrast, EFSA concluded that “glyphosate is unlikely to pose a carcinogenic hazard to humans and the evidence does not support classification with regard to its carcinogenic potential according to Regulation (EC No 1272/2008)”. Based on the representative uses, that were limited to conventional crops only, chronic or acute risks for the consumers have not been identified . This conclusion was reached following a second mandate from the European Commission to consider the findings from the International Agency for Research on Cancer (IARC) regarding the potential carcinogenicity of glyphosate or glyphosate-containing plant protection products in the on-going peer review of the active substance.
EFSA also considered that glyphosate is unlikely to be genotoxic (i.e. damaging to DNA). EFSA underlies that these conclusions followed the peer review of the initial risk assessments carried out by the competent authority of Germany, which was the rapporteur Member State for this substance.
The IARC Monographs evaluation is based on the systematic assembly and review of all publicly available and pertinent studies by independent experts. It follows strict scientific criteria, and the classification system is recognized and used as a reference all around the world.
To reach these conclusions, IARC reviewed about 1000 studies and cited 269 in the Monograph, including experimental studies of both “pure” glyphosate and of glyphosate-based formulations. Some of the studies looked at the effect on people. The Monograph included studies of real-world exposures to humans exposed to different formulations in different regions at different times through their work, such as farmers. Globally, these studies reported similar and statistically significant increases in the same type of cancer: non-Hodgkin lymphoma. Others were experimental studies on cancer and cancer-related effects in experimental systems.
For the experimental studies of “pure” glyphosate, the IARC Monograph concluded that the evidence for causing cancer in experimental animals was “sufficient’’ and the evidence for causing genotoxicity was “strong”.
An important consideration in the IARC Working Group’s evaluation was that glyphosate caused unusual types of tumours in animals, which can provide important evidence of a cause-and-effect relationship.
The IARC Working Group reached the same hazard conclusion for glyphosate and for its formulations.
The EFSA’s evaluation process starts with a review of the available information by one of the member states, in this case it was Germany, followed by an extensive review process by all other member states and by the industry task force who had supplied the initial assessment, as well as a public consultation. All of this documentation is available on the EFSA’s website.
In terms of carcinogenicity, the EFSA assessment focused on the pesticide active substance, glyphosate itself, (and not its formulations) and considered all available information, including the IARC report 3.
The EFSA conclusions4 were reached on the basis of the evaluation of the representative uses of glyphosate as briefly described in the answer to question 2. The report presented the peer-reviewed, reliable endpoints that were considered to be appropriate for use in regulatory risk assessment and derived from the available studies and literature according to EFSA practices5. The information that was required by the regulatory framework but that was still missing was also listed.
Nevertheless, a series of data gaps was identified, mainly in the determination of residues and impurities. There were gaps in the analytical methods of residues, in the knowledge of influence of individual impurities in glyphosate in the results of mammalian toxicology tests, and in particular impurities that have a suspected toxicity high enough in comparison with the toxicity profile of the parent compound.
EFSA also underlined a series of concerns, including the fact that in the process of chemical compound registration, eight out of the 24 applicant companies presented specifications of their glyphosate formulation that contained elements that were not in accordance with the the toxicological assessment data that they provided to support the registration.
In November 2015, an open letter addressed by a group of scientists to the EU Commissioner for Health and Food Safety pointed out that all the information that the EFSA glyphosate assessment6 was based on was not all publicly available. EFSA published a reply, underlining7 that the background documents (around 6000 pages worth), which included the reports on which the assessment was based, as well as the comments gathered though a public consultation by EU Member states, individuals and organisations are published on the EFSA website. The group of scientists further considered in an article8 that EFSA used non-publicly available industry-provided studies and that « owing to the potential public health impact of glyphosate, which is an extensively used pesticide, it is essential that all scientific evidence relating to its possible carcinogenicity is publicly accessible and reviewed transparently in accordance with established scientific criteria».
Another groups of scientists also published a « consensus statement” about « concerns over use of glyphosate-based herbicides and risks associated with exposures »9 .
The main differences between the EFSA and IARC evaluations are explained by the fact that the EU and IARC take different approaches to the classification of chemicals. The EU scheme used by EFSA assesses each individual chemical, and each marketed mixture separately. IARC assesses generic agents, including groups of related chemicals, as well as occupational or environmental exposure, and cultural or behavioural practices.
For EFSA10, the IARC report looked at both glyphosate – an active substance – and glyphosate-based formulations, grouping all formulations regardless of their composition. The EU assessment, on the other hand, considered only glyphosate. Globally, EFSA considers that in total they assessed more evidence including additional key studies that were not considered by IARC and will suggest the European Commission to authorise its continued use as pesticides in the EU.
For IARC, many regulatory agencies rely primarily on industry data from toxicological studies that are not available in the public domain. The IARC Working Group’s evaluation of glyphosate included all relevant evidence available in the public domain for independent scientific review including any industry studies that met these criteria. However, they did not include data which did not provide enough detail for independent assessment. This was the case with some of the industry studies of cancer in experimental animals.
Regarding more specifically the genotoxic potential of glyphosate, EFSA considers that the effects observed in some glyphosate-based formulations are related to the other constituents or “co-formulants” and that, similarly, certain glyphosate-based formulations display higher toxicity than that of the active ingredient, presumably because of the presence of co-formulants.
EFSA proposes thus that the toxicity of each pesticide formulation and in particular its genotoxic potential should be further considered.
The WHO has not formally accepted the conclusions of the IARC glyphosate monograph yet, and an extraordinary meeting on pesticides residues in May 2016 is planned to address this issue11.
In an effort to clarify scientific divergences, EFSA, in line with its principles of openness and transparency, proposed to meet IARC early in 2016 to discuss the different evidence and the different methodologies that the two organisations have used.
However, an exchange of letters between the Directors of both institutions in early 2016 indicated that this could not happen12.
References
1
2
www.efsa.europa.eu/fr/efsajournal/pub/4302
3
4
www.efsa.europa.eu/en/efsajournal/pub/4302
5
www.efsa.europa.eu/interactive_pages/pesticides_authorisation/PesticidesAuthorisation
6
7
11
www.who.int/foodsafety/areas_work/chemical-risks/call_for_data_for_2016_JMPR_May_final_1.pdf?ua=1
12
www.efsa.europa.eu/sites/default/files/Letter_from_Dr_Wild_to_Bernhard_Url_160212.pdf
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