IARC's Classification of Glyphosate as a Probable Carcinogen
In March 2015, independent experts of the International Agency for Research on Cancer (IARC) of the World Health Organization (WHO) classified glyphosate as “probably carcinogenic to humans” (Group 2A), after conducting a systematic and thorough review of all publicly available and relevant studies on the carcinogenicity of the substance. The classification was based on “sufficient evidence” of cancer in laboratory animals (from studies of “pure” glyphosate) and “limited” evidence of cancer in humans (from real-world exposures that actually occurred). Additionally, IARC concluded that "strong" evidence exists that both “pure” glyphosate and glyphosate formulations can cause genotoxicity (the ability to damage genetic material, i.e. DNA) and oxidative stress, both. Both effects are recognized mechanisms of carcinogenicity.
The EU legal framework for the classification of Carcinogenic Substances
In the European Union, the Regulation on Classification, Labelling and Packaging of substances and mixtures (CLP Regulation) is the legal framework that sets out the criteria for the classification and labelling of hazardous chemicals. Under the CLP Regulation, the equivalent of the classification of a substance as Group 2A (IARC classification), would be Category 1B (“presumed to have carcinogenic potential for humans”), if there is "sufficient evidence" of its carcinogenicity. According to the EU law on pesticides, substances that meet the criteria for classification as category 1B should be removed from the EU market.
Assessing Carcinogenicity of Glyphosate: Insights into the Shortcomings of the EU Evaluation Process
Back in March 2017 the European Chemicals Agency (ECHA) published its opinion that the available evidence did not justify classifying glyphosate as carcinogenic. In June 2022, in the framework of the ongoing renewal process, ECHA’s Risk Assessment Committee concluded again that glyphosate is not carcinogenic, and that it meets the approval criteria under EU law. This failure to classify it as a category 1B carcinogen was criticised by civil society organisations, which demonstrated that this conclusion was contrary to the available scientific evidence.
Health and environmental organisations denounced ECHA’s serious scientific misconduct in the assessment of glyphosate’s carcinogenicity. The flaws in the assessment were highlighted by the work of two experts, Christopher J. Portier and Peter Clausing, who evaluated the authorities‘ draft assessment report and ECHA’s opinion which ignores its own rules and guidance to reach its conclusions. Following applicable standards and guidelines properly, Portier and Clausing concluded unequivocally that there is in fact sufficient evidence of carcinogenicity, for glyphosate to be classified as a category 1B carcinogen. It appears that the numerous cancer incidences observed in the five mice and seven rat studies provided by the industry have been systematically discounted by EU authorities in their evaluation.
Current scientific research continues to provide accumulating evidence that glyphosate exposure is associated with oxidative stress – the known mechanism of carcinogenicity (see above). This includes a recent study in humans demonstrating an increase in urinary indicators of oxidative stress after exposure to glyphosate.
Génération Futures (2022) : Glyphosate et cancer : des preuves scientifiques rejetées, sur le rapport de HEAL.
PAN EUROPE (2022) : Glyphosate ECHA classification: denial of science and disrespect of EU law
Scientific American (2015) : Widely Used Herbicide Linked to Cancer
EU Science Hub : Carcinogenicity
The Conversation (2023) : Does this cause cancer? How scientists determine whether a chemical is carcinogenic – sometimes with controversial results
PAN Germany (2018) : Europäische Behörden verletzten ihre eigenen Regeln, um Glyphosat als nicht krebserregend einzustufen, European authorities violated their own rules to classify glyphosate as non-carcinogenic
IARC Monograph on Glyphosate (2015): Classifies Glyphosate as probably carcinogenic to humans
HEAL (2022) : HOW THE EU RISKS GREENLIGHTING A PESTICIDE LINKED TO CANCER
Scientific research papers
Vicky C Chang, PhD and al., “Glyphosate exposure and urinary oxidative stress biomarkers in the Agricultural Health Study”, (JNCI: Journal of the National Cancer Institute 115(4) 2023).
Genotoxicity of glyphosate: a summary of the controversy
In 2015 the International Agency for Research on Cancer (IARC) classified glyphosate as a probable carcinogen. This conclusion was based, among others, on “strong evidence that glyphosate causes genotoxicity.” For IARC experts, “the evidence base includes studies that gave largely positive results in human cells in vitro, in mammalian model systems in vivo and in vitro and studies in other non-mammalian organisms”.
A few years later, in 2021, the French national institute for health and medical research (Inserm) reached the same conclusion about glyphosate: “Many studies show genotoxic damage (DNA breaks or changes in its structure)”. According to Inserm: “the studies showing a lack of genotoxicity from glyphosate appear to be less substantial in both qualitative and quantitative terms than those suggesting a positive effect” To reach this conclusion, both IARC and Inserm analysed published independent studies, many of which used in vitro “comet assays”, which address the occurrence of DNA damage (like DNA strand break) caused by glyphosate in various cell types (liver, kidney, lymphocytes, etc.).
IARC and Inserm linked the observed genotoxicity effect of glyphosate to the induction of oxidative stress, a proven underlying mechanism of carcinogenicity. According to Inserm, “[Genotoxic damage is] consistent with the direct or indirect induction of oxidative stress by glyphosate, observed in various species and cell systems, sometimes at exposure levels compatible with those that may be experienced by human populations”. To the IARC, “strong evidence exists that glyphosate, AMPA, and glyphosate-based formulations can induce oxidative stress”.
According to these two recognised institutions that reviewed the very large scientific literature on glyphosate genotoxicity, it is therefore clear that a scientific consensus exists on this issue: glyphosate is genotoxic and this toxic effect can be explained by the oxidative stress generated by the substance. However, no regulatory agency, including ECHA, has classified glyphosate as carcinogenic or has acknowledged its genotoxic potential.
The main reason for this discrepancy in opinions is that the regulatory agencies repeatedly underestimate the results of the in vitro comet assay and of any other non-OECD protocol studies, like studies performed on non-standard organisms such as fishes or mechanistic studies revealing an induction of oxidative stress. The OECD however sets guidelines and protocols that are directed to the industry that has an interest to commercialize a chemical or product. Therefore, by downgrading all results from non-OECD protocol studies the regulatory agencies are giving preference to the studies produced by the pesticide companies that have an interest to place their products in the market. This creates a “bias” against public scientific literature, such as oxidative stress as a mechanism of genotoxicity.
In conclusion, the genotoxicity assessment of glyphosate performed by regulatory agencies contains scientific flaws and a bias towards industry-based studies rather than independent scientific literature. It is a typical example demonstrating that a regulatory decision does not always reflect a scientific consensus.
Briefing / report :
Générations Futures (2022): LE GLYPHOSATE EST-IL GÉNOTOXIQUE ?
HEAL (2022) : Scientific evidence of glyphosate link to cancer dismissed in ongoing EU assessment, new report reveals
Génération Futures (2022): Episode 4: Le glyphosate est-il génotoxique?
HEAL (2022) : HEAL’s response to the public consultations on the EU’s initial assessment of glyphosate
HEAL (2022) : Health and environmental groups raise alarms over EU Chemicals Agency’s failure to classify glyphosate as a carcinogen for human health
Scientific research papers
INSERM, “Glyphosate and glyphosate-based herbicides” (2021).