10
Mar
EPA Overlooks Glyphosate and Roundup Ingredients’ Cancer, DNA Damage, and Multigenerational Effects
(Beyond Pesticides, March 10, 2022) Glyphosate and glyphosate-based herbicides (GBH) like Roundup® induce DNA damage and alter biological mechanisms (gene regulatory microRNAs [miRNAs or miRs]) associated with cancer development. According to the study published in Toxicological Sciences, DNA damage mainly occurs through oxidative stress from GBH exposure. Moreover, DNA damage and other biological mechanisms that cause carcinogenicity (cancer) occur at doses assumed “safe” by pesticide regulators such as the U.S. Environmental Protection Agency (EPA).
Glyphosate is the most commonly used active ingredient worldwide, appearing in many herbicide formulas, not just Bayer’s (formerly Monsanto) Roundup®. The use of this chemical has been increasing since the inception of crops genetically modified to tolerate glyphosate over two decades ago. The toxic herbicide readily contaminates the ecosystem with residues pervasive in food and water commodities. In addition to this study, literature proves time and time again that glyphosate has an association with cancer development, as well as human, biotic, and ecosystem harm.
Study lead author Michael Antoniou, Ph.D., cautions, “Our results are the first to simultaneously show glyphosate and Roundup toxicity in a whole mammalian animal model system and provide a mechanism – oxidative stress – by which DNA damage has been observed in other systems, such as mammalian tissue culture cells. These findings show that glyphosate and Roundup score positive in various tests of carcinogenicity – transcriptome/epigenome/miRNA changes, oxidative stress, protein misfolding, and DNA damage – in a living animal (rat) that is accepted as a surrogate for human health effects. In my view, this strengthens the argument that exposure to Roundup herbicides can lead to the type of cancer suffered by the plaintiffs in many of the court cases – non-Hodgkin lymphoma.”
This study represents a follow-up that builds on the finding of a previous one by the same authors. The previous study compared the effects of MON 5227 (an active ingredient in Roundup) and glyphosate alone in rats and found both ingredients to cause gut microbiome disruption and oxidative stress related to possible liver damage. Thus, the present study intends to determine damages in the liver by analyzing tissue samples. Following standard regulatory testing for pesticide approval, researchers investigated biochemical changes in the blood of the kidneys and liver after exposure to glyphosate and four active ingredients in Roundup formulas: MON 52276 (European Union), MON 76473 (United Kingdom), and MON 76207 (United States). Additionally, researchers performed tests not carried out by standard testing, including observation on molecular changes in the biological function of gene expression and epigenetics (e.g., DNA methylation that changes the activity but not the sequence of a DNA segment) in the kidneys and liver. To highlight changes in biological function linked to cancer, researchers used genetically engineered (GE) cell lines and tested them for direct DNA damage.
The results confirm that liver damage occurs from exposure to glyphosate and Roundup, leading to alterations of gene expression and miRNA (small RNA) in the liver. Specifically, glyphosate and MON 52276 alter nine gene expressions in the liver and kidneys responsible for oxidative stress and DNA damage, prompting cancer development. Researchers suggest changes in miRNA can disrupt the regular function of cell growth regulator genes, like p53, resulting in cancer. The changes in gene expression of p53 strongly indicate a possible pathway for DNA damage and thus a major cancer development risk factor. Furthermore, various research, including this one, demonstrates increases in small RNA, like miR-10 from GBH exposure, have an association with blood cancer development, particularly leukemia and non-Hodgkin lymphoma. Dr. Antoniou notes, “The new data showing changes in miRNA patterns add yet more evidence to the cancer-causing potential of glyphosate and Roundup. What is more, our results show that it is not just Roundup, which is a mixture of glyphosate with various additives, that has carcinogenic potential, but also glyphosate alone.”
Almost five decades of extensive glyphosate-based herbicide use has put human, animal, and environmental health at risk. The chemical’s ubiquity threatens 93 percent of all U.S. endangered species, resulting in biodiversity loss and ecosystem disruption (e.g., soil erosion, loss of services). Exposure to GBHs has implications for specific alterations in microbial gut composition and trophic cascades. Similar to this paper, past studies find a strong association between glyphosate exposure and the development of various health anomalies, including cancer, Parkinson’s disease, and autism. Although EPA classifies glyphosate herbicides as “not likely to be carcinogenic to humans,” stark evidence demonstrates links to various cancers, including non-Hodgkin lymphoma. Thus, EPA’s classification perpetuates environmental injustice among individuals disproportionately exposed to chemicals like farmworkers, especially in marginalized communities. Chemical companies knowingly failed and continue to fail to warn farmers adequately about the dangers of the pesticide, and that the manufacturer’s (Bayer/Monsanto) chemical review conclusions are supported by accurate science.
The territory for research on pesticides’ potential carcinogenicity, and other impacts on human health, is almost ridiculously complicated. Yet there is some convergence across research that exposure to certain pesticides increases the risk of developing some cancers. The association that has been in the blinding spotlight for the past few years is between exposures to glyphosate and glyphosate-based herbicides and the risk of developing cancer, particularly non-Hodgkin Lymphoma (NHL). Beyond Pesticides has covered the mounting evidence of the dangers of glyphosate, including a meta-study that suggests a compelling link between exposures to glyphosate-based herbicides and increased risk of NHL.
In addition, it has written extensively on developments in the science and regulatory arena, including:
- the International Agency for Research on Cancer (IARC) 2015 landmark designation of glyphosate as potentially carcinogenic
- evidence that the Environmental Protection Agency colluded with Monsanto (maker of Roundup, the most widely used glyphosate-based herbicide) to advantage industry and that Monsanto had ghostwritten research that countered scientific conclusions on the cancer associations of the compound
- And California’s 2017 listing of glyphosate under Proposition 65 as a probable carcinogen and a 2018 Appellate Court affirmation of its ability to do so.
Glyphosate has been the subject of a great deal of public advocacy and regulatory attention, as well as the target of thousands of lawsuits. Beyond Pesticides has covered the glyphosate tragedy extensively; see its litigation archives for multiple articles on glyphosate lawsuits. In June 2020, facing approximately 125,000 suits for Roundup’s role in cancer outcomes, Bayer announced a $10 billion settlement to resolve roughly 75% of current and potential future litigation. However, roughly 30,000 complainants ultimately did not sign on to the settlement, so the queue of potential lawsuits is still potentially enormous. Although Bayer tried for a second settlement (~ $2 billion) to handle future claims, a U.S. District Court judge for the Northern District of California rejected Bayer’s 2021 settlement proposal. The judge stated that the settlement was inadequate for future victims diagnosed with cancer after using the herbicide. Bayer has never acknowledged any harm caused by glyphosate, maintaining the chemical is safe for use. However, in July 2021, Bayer announced its plan to end sales of its glyphosate-based herbicides (including its flagship product, Roundup) in the domestic U.S. residential lawn and garden market in 2023.
For the first time, this study demonstrates epigenetic changes in DNA, proteins, and small RNA profiles in the liver of organisms exposed to glyphosate and Roundup formula MON 52276. Researchers observed activation of DNA repair mechanisms in response to DNA damage from glyphosate. Moreover, oxidative stress and the unfolding of proteins occurred at lower concentrations of Roundup, in which the same concentration of glyphosate produced no effect. The researchers recommend regulators rely on methods to detect metabolic changes that conventional biochemical and tissue analyses overlook. Glyphosate acts on the shikimate pathway, present in plants, fungi, bacteria, archaea, and protozoa. Thus, many taxonomic groups of microorganisms are sensitive to glyphosate. Moreover, chronic exposures to the herbicide could lead to the dominance of resistant strains in bacterial communities. Some glyphosate-vulnerable bacterial strains can become resistant to glyphosate (glyphosate-tolerant class II EPSPS). For instance, glyphosate-resistant bacterial strains like E. coli and Pseudomonas alter gene function to enhance the outflow of glyphosate from the bacterial cell. Thus, this resistance mechanism encourages cross-resistance against antibiotics for pathogenic bacterial species like E. coli and Salmonella, altering the microbiome.
Overall, the researchers determined oxidative stress, an imbalance between reactive oxygen species (ROS) and biological mechanisms to detoxify ROS, likely causes liver damage. This liver damage, in turn, leads to inflammation that can damage DNA and prompt carcinogenicity. Similar to this study, others suggest that glyphosate may impact other metabolic pathways beyond the known Shikimate. A report by the University of Turku, Finland stated, “Even in glyphosate-resistant species, the interference of the herbicide on mitochondrial metabolism may induce oxidative stress and lead to toxic effects.”
Although Bayer announced the end of glyphosate sales by 2023, sales of Roundup will continue with different active ingredients. It is essential to note that the study also demonstrates ingredients in Roundup are even more toxic than glyphosate itself. Therefore, new formulations without glyphosate do little to mitigate the problem, especially regarding synergistic (combined) impacts of so-called “inert” ingredients in glyphosate formulations.
Considering pesticide exposure does not affect just one part of the body, but multiple organs, more studies need to assess what other organs or biological mechanisms glyphosate targets, triggering cancer development. These results could strengthen the legal cases of cancer patients in the U.S. who are suing Bayer/Monsanto because they have evidence that their exposure to Roundup caused their disease. The authors conclude, “[A]doption by regulatory agencies of multi-omics analyses would result in more accurate evaluation of a chemical’s toxicity and therefore better protection measures being enacted with major public health benefits.”
Cancer is one of the leading causes of death worldwide, with over eight million people succumbing to the disease every year. Notably, IARC predicts an increase in new cancer cases from 19.3 million to 30.2 million per year by 2040. Therefore, studies related to pesticides and cancer will aid in understanding the underlying mechanisms that cause the disease. Beyond Pesticides challenges the registration of chemicals like glyphosate in court due to their impacts on soil, air, water, and our health. While legal battles press on, government officials must eliminate the use of toxic synthetic herbicides to avoid the adverse effects of chemical exposure and contamination. Instead, emphasis on converting to regenerative-organic systems and using least-toxic pest control to mitigate harmful exposure to pesticides, restore soil health, and reduce carbon emissions, should be the main focus. Public policy must advance a shift to organic rather than allow unnecessary reliance on pesticides. Considering glyphosate levels in the human body decrease by 70% through a one-week switch to an organic diet, purchasing organic food whenever possible—which never allows glyphosate use—can help curb exposure and resulting adverse health effects.
It is essential to understand the health implications of pesticide use and exposure for humans, especially if pesticides increase chronic disease risk. Beyond Pesticides tracks news and studies related to pesticides through the Daily News Blog and Pesticide-Induced Diseases Database (PIDD). This database supports the clear need for strategic action to shift from pesticide dependency. For more information on the adverse effects of pesticides on human health, see PIDD pages on cancer (including lymphoma) and other diseases. Moreover, Beyond Pesticides provides tools, information, and support to take local action: check out our factsheet on glyphosate/Roundup and our report, Monsanto’s Roundup (Glyphosate) Exposed. Contact us for help with local efforts and stay informed of developments through our Daily News Blog and our journal, Pesticides and You. Additionally, check out Carey Gillam’s talk on Monsanto’s corruption on glyphosate/Roundup at Beyond Pesticides’ 36th National Pesticide Forum.
All unattributed positions and opinions in this piece are those of Beyond Pesticides.
Source: GM Watch, Toxicological Sciences
