Glyphosate, or N-(phosphonomethyl)glycine, is a widely used broad-spectrum, nonselective herbicide that has been in use since 1974. Glyphosate effectively suppresses the growth of many species of trees, grasses, and weeds. It acts by interfering with the synthesis of the aromatic amino acids phenylalanine, tyrosine, and tryptophan, through the inhibition of the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). Importantly, EPSPS is not present in mammals, which obtain their essential aromatic amino acids from the diet.
Glyphosate is currently marketed under numerous trade names by more than 50 companies in several hundreds of crop protection products around the world. More than 160 countries have approved uses of glyphosate-based herbicide products.Glyphosate has now become the most heavily-used agricultural chemical in the history of the world, and its safety profile, including the potential carcinogenicity, has been heavily discussed by scientists, public media and regulatory authorities worldwide for the last several years. Given its widespread use, the key question is: could Glyphosate be toxic for humans?

In 2015, the International Agency for Research on Cancer (IARC), a research arm of the WHO, classified Glyphosate as “probably carcinogenic to humans”. It was categorized as ‘2A’, due to sufficient evidence of carcinogenicity in animals and strong evidence for two carcinogenic mechanisms but limited evidence of carcinogenicity in humans.
In contrast, the European Food Safety Authority (EFSA) concluded, based on the Renewal Assessment Report (RAR) for glyphosate that was prepared by the German Federal Institute for Risk Assessment (BfR), that ‘Glyphosate is unlikely to pose a carcinogenic hazard to humans and the evidence does not support classification with regard to its carcinogenic potential’.

Why do the IARC and the EFSA disagree?

To understand this discrepancy, it is important to note that the IARC carried out a hazard assessment, which evaluates whether a substance might pose a danger. The EFSA, on the other hand, conducted a risk assessment, evaluating whether Glyphosate actually poses risks when used appropriately. The differences between these two approaches can be explained by the following example:
Under real-world conditions, eating a normal amount of bacon (and other processed meats) raise the risk of colorectal cancer by an amount way too small to consider. However, as bacon does appear to be raising cancer by a tiny, but reproducible and measurable amount, it is currently classified in IARC’s category ‘1’ (‘carcinogenic to humans’). Therefore, the analysis done by the IARC boils down to the question ‘Is there any possible way, under any conditions at all, that Glyphosate could be a carcinogen?’ while the EFSA tries to answer the question ‘Is Glyphosate actually causing cancer in people?’

However, these differences are not clearly communicated and people are left confused by these contradicting reports. To aggravate the situation, both parties accuse each other of using inscrutable and misleading (statistical) methods:

• IARC scientists have strongly criticized the report carried out by EFSA: ‘In the EFSA report, almost no weight is given to studies from the published literature and there is an over-reliance on non-publicly available industry-provided studies using a limited set of assays that define the minimum data necessary for the marketing of a pesticide. Many of the elements of transparency do not exist for the EFSA report. For example, citations for almost all references, even those from the open scientific literature, have been redacted. The ability to objectively evaluate the findings of a scientific report requires a complete list of cited supporting evidence. As another example, there are no authors or contributors listed for either document, a requirement for publication in virtually all scientific journals where financial support, conflicts of interest and affiliations of authors are fully disclosed.’
• At the same time, the EFSA committee stated that ‘IARC’s methods are poorly understood and IARC’s conclusion is the result of the exclusion of key data from the IARC review process (animal bioassay and genotoxicity) or differences in the interpretation of the data that was assessed particularly in regard to the animal bioassay results.’

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.
To understand the implications behind the two different scientific questions being asked (is a substance hazardous vs. is there a real risk potential) is clearly important as shown above. Furthermore, the Glyphosate story has also demonstrated that science can only move forward through the careful evaluation of data and the rigorous review of findings, interpretations and conclusions. An important aspect of this process is transparency and the ability to question or debate the findings of others. This ensures the validity of the results and provides a strong basis for decisions.