(Beyond Pesticides, August 11, 2023) Reinforcing earlier findings, a systematic review published inÂ ChemosphereÂ finds the popular herbicide glyphosate and its formulations (glyphosate-based formulations-GBF) exhibit five out of the ten key characteristics (KC) of carcinogens (cancer-causing chemicals). Specifically, glyphosate exhibits strong evidence of genotoxicity, epigenetic alterations (heritable changes in gene expression), oxidative stress, chronic inflammation, endocrine disruption, and disturbs gut microbiota implicated in lymphomagenesis (growth and development of lymphoma). Although organizations like the International Agency for Research on Cancer (IARC) designate glyphosate as aÂ probable human carcinogen, andÂ scientific literatureÂ supports the findings on these adverse effects purported by glyphosate, the chemical remains on the U.S. market in various formulations.
GlyphosateÂ is the most commonly used active ingredient worldwide, appearing in many herbicide formulas, not just Bayerâ€™s (formerly Monsanto) RoundupÂ®. 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,Â biotic, and ecosystemÂ harm. Therefore, advocates point to the need for national policies to reassess hazards associated with disease development and diagnosis resulting from or exacerbated by exposure to chemical pollutants. The study highlights, â€śOur findings strengthen the mechanistic evidence that glyphosate is aÂ probableÂ human carcinogen and provide biological plausibility for previously reported cancer associations in humans, such as non-Hodgkin lymphoma.â€ť
UsingÂ in vivo, ex vivo, andÂ in vitroÂ human and mammalian mechanistic studies, researchers compare exposure to glyphosate/GBF with little to no exposure counterparts for evidence of the ten KCs of carcinogens. All known human carcinogens have one or more of the ten KCs, and these mechanisms cause cancer through,
- Electrophilic (an affinity towards electrons) or metabolic activation (KC1),
- Genotoxicity (KC2),
- Alterations in DNA repair, causing genome instability (KC3),
- Inducing epigenetic changes (KC4),
- Inducing oxidative stress (KC5),
- Inducing chronic inflammation (KC6),
- Immunosuppression (KC7),
- Reducing receptor-mediated effects/endocrine disruption (KC8),
- Immortalizing cancer cells (KC9),
- Alterations in cell proliferation, death, or nutrient supply (KC10).
Researchers screened allÂ in vivo, ex vivo,Â andÂ in vitroÂ studies of glyphosate/GBF exposure in humans/mammals, reporting any KC-related outcome available in PubMed before August 2021. The researchers used the selected studies to construct a matrix, analyzing the matrix in program R to determine the strength of evidence and quality assessments. Although only 175 of the 2,537 articles met inclusion criteria, the researchers extracted over 50,000 data points related to the aforementioned KC outcomes.
The results of the analysis find strong evidence for KC2, KC4, KC5, KC6, and KC8, limited evidence for KC1 and KC3, and inadequate evidence for KC7, KC9, and KC10. Specifically, genotoxicity (KC2) and endocrine disruption (KC8) from GBF have the strongest association with carcinogenicity. The reviewed studies demonstrate that the evidence of genotoxicity is stronger among humans than in animal studies, with GBF having a greater impact on both study groups than just glyphosate alone. Additionally, the review indicates glyphosate can alter hormone (endocrine) levels and receptor activity, with the estrogen receptors being most sensitive to glyphosate and GBFs.
Almost five decades of extensive glyphosate-based herbicide (GBH) use has put human, animal, and environmental health at risk. The chemicalâ€™s ubiquity threatensÂ 93 percentÂ of all U.S. endangered species,Â resultingÂ in biodiversity loss and ecosystem disruption (e.g.,Â soil erosionÂ and loss of services). Exposure to GBHs has implications for specific alterations inÂ microbial gut compositionÂ andÂ trophic cascades. Similar to this paper, past studies find a strong association between glyphosate exposure andÂ the development of various health anomalies,Â includingÂ cancer,Â Parkinsonâ€™s disease, andÂ autism. Although the U.S. Environmental Protection Agency (EPA) classifies glyphosate herbicides as â€śnot likely to be carcinogenic to humans,â€ťÂ stark evidenceÂ demonstrates links to various cancers, including non-Hodgkin lymphoma. Thus, EPAâ€™s classification perpetuates environmental injustice among individuals disproportionately exposed to chemicals like farmworkers, especially in marginalized communities. Chemical companies knowingly fail and continue to fail to warn farmers adequately about the dangers of glyphosate. Additionally, the manufacturerâ€™s (Bayer/Monsanto) discredited chemical review conclusionsÂ challenge the European Union research.
The territory for research on pesticidesâ€™ potential carcinogenicity and other impacts on human health is exceedingly 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 andÂ the risk of developing cancer, particularly non-Hodgkin LymphomaÂ (NHL). Beyond Pesticides has covered theÂ mounting evidenceÂ of the dangers of glyphosate, including aÂ meta-studyÂ that suggests a compelling link between exposures to glyphosate-based herbicides and increased risk of NHL.
In addition, Beyond Pesticides has traced the developments in the science and regulatory arena, including:
- theÂ International Agency for Research on Cancer (IARC) 2015 landmark designationÂ of glyphosate as potentially carcinogenic
- Evidence that EPA colludedÂ 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,
- andÂ Californiaâ€™s 2017 listing of glyphosate under Proposition 65 as a probable carcinogenÂ and aÂ 2018 Appellate Court affirmationÂ of its ability to do so.
Glyphosate has been the subject of public advocacy, regulatory attention, and the target of thousands of lawsuits. (Beyond Pesticides has covered the glyphosate tragedy extensively;Â 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,Â Bayer announced a $10 billion settlementÂ 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 CaliforniaÂ rejectedÂ 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,Â maintainingÂ the chemical is safe for use. However, in July 2021,Â Bayer announced its planÂ 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. Under the plan, uses in food production will continue.
The results of the systemic review highlight an all too familiar issue. Despite these concerning data, evidence of widespread exposure to a carcinogen hasÂ failed to sway regulators at EPA, necessitating meaningful change by elected officials to reform pesticide law. Scientists highlight epidemiological evidence associating glyphosate with blood cancers like non-Hodgkin lymphoma and strong evidence of carcinogenicity in laboratory animal research brought on by genotoxicity (DNA damage) andÂ oxidative stress. In 2015, the IARC Working Group demonstrated glyphosate has strong evidence of genotoxicity (KC2) and oxidative stress (KC5). However, recent studies providing additional data supports evidence of KC2 and KC5, as well as epigenetic changes (KC4), chronic inflammation (KC6), and endocrine disruption (KC8) regarding glyphosate and GBF. Thus, glyphosate presents evidence of all five KCs of carcinogens. Although there is limited or inadequate evidence for the remaining KCs, the review encourages further examination of the effects of glyphosate and other chemicals through all ten KCs and its relation to lymphoid cancers.Â
The study concludes, “Overall, the mechanistic evidence for glyphosate and GBFs possessing multiple key characteristics of carcinogens has become stronger since IARC’s evaluation in 2015 and implicates several pathways by which these substances could induce cancer, such as lymphoma, in humans. […][O]ur understanding of glyphosate’s effects using the KCs paves the way for exploring the intricate mechanisms underlying its potential pathway to lymphoma.”
CancerÂ is one of the leading causes of death worldwide, with over eight million people succumbing to the disease every year. Notably, IARCÂ predictsÂ 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 PesticidesÂ challenges the registration of chemicals like glyphosate in courtÂ 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 toÂ regenerative-organic systems, usingÂ least-toxic pest controlÂ to mitigate harmful pesticide use,Â restore soil health, reduce carbon emissions, and increase carbon sequestration should be the main focus. Public policy must advance a shift to organic, rather than allow unnecessary reliance on pesticides. ConsideringÂ glyphosateÂ levels in the human body decrease byÂ 70%Â through a one-week switch to an organic diet,Â purchasing organic food whenever possibleâ€”which never allows glyphosate useâ€”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 when pesticides increase chronic disease risk. Beyond Pesticides tracks news and studies related to pesticides through theÂ Daily News BlogÂ andÂ 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 onÂ cancerÂ (includingÂ lymphoma) and other diseases. Moreover, Beyond Pesticides provides tools, information, and support to take local action: check out ourÂ factsheet on glyphosate/RoundupÂ and our report,Â Monsantoâ€™s Roundup (Glyphosate) Exposed. Contact us for help with local efforts and stay informed of developments through ourÂ Daily News BlogÂ and our journal,Â Pesticides and You. Additionally, check outÂ Carey Gillamâ€™s talk on Monsantoâ€™s corruptionÂ on glyphosate/Roundup at Beyond Pesticidesâ€™ 36th National Pesticide Forum. Help convert your town to organic land management through Beyond Pesticidesâ€™ Parks for a Sustainable Future program.
All unattributed positions and opinions in this piece are those of Beyond Pesticides.