DNA Damage?

Summary

DNA damage in humans can result in cancer, reproductive problems, infertility in men, birth defects in offspring, and decreased lifespan. The pesticide industry claims that glyphosate does not damage DNA. However, glyphosate and glyphosate herbicides have been found to damage DNA in animal studies, as well as in human cells tested in vitro (not in living humans). Genetic damage has been found in soybean workers exposed to agrochemicals including glyphosate herbicides, as well as in Ecuadorian people exposed only to glyphosate herbicides.

Under European law, pesticides that damage DNA (are “genotoxic”) are not allowed to be marketed.1

The “Glyphosate Facts” website, which is run by pesticide companies, claims that glyphosate does not damage DNA (is not genotoxic).2 But these claims are based on old studies carried out by the pesticide industry, submitted to regulators for regulatory authorization of glyphosate. The studies are kept hidden from the public and independent scientists on grounds of commercial confidentiality.3 4

“Glyphosate Facts” claims that these tests’ adherence to OECD (Organisation for Economic Cooperation and Development) test guidelines is a sign of “data integrity and reliability”.2

What “Glyphosate Facts” fails to mention is that OECD test guidelines were put in place in the 1970s by regulators and industry in response to the discovery of widespread fraud at laboratories commissioned by industry to test chemicals and drugs for regulatory purposes.5 OECD test guidelines only apply to industry tests performed for regulatory purposes. While there is undoubted value in forcing industry to carry out standardized tests, OECD guidelines are based on old, outdated, insensitive methodologies. They are irrelevant to academic scientists, who prefer to use the most sensitive and most up-to-date methodologies for their research.6 7 8

A major drawback to all industry studies on glyphosate is that they tested the isolated ingredient glyphosate, not the complete formulations that people and animals are exposed to (see “Roundup is more toxic than glyphosate”). Yet independent toxicological research shows that the formulations as sold and used are much more toxic than the isolated ingredient glyphosate. Therefore assurances of safety based on tests on glyphosate alone are worthless in any assessment of toxicity of the complete formulations.

In contrast to outdated industry tests, independent studies show that glyphosate, and the formulated herbicides based on it, do damage DNA.

Findings include:

  • Glyphosate-based herbicides such as Roundup activate mechanisms involved in cancer development, including DNA damage in rats – and these effects occur at doses assumed by regulators to have no adverse effects, a 2021 study has shown.
  • Glyphosate herbicides altered cell cycle checkpoints in sea urchin embryos by interfering with the DNA repair machinery. Cell cycle dysfunction was seen from the first cell division in the sea urchin embryos.9 10 11 12 The failure of cell cycle checkpoints is known to lead to genomic instability and cancer in humans.
  • Glyphosate and its main metabolite AMPA have been found to cause irreversible damage to DNA in human cells in vitro and in mice in vivo.13 14 Such damage to DNA may increase the risk of cancer and birth defects. AMPA damaged DNA in human cells in vitro at doses of 2.5-7.5mM and caused breaks in chromosomes at 1.8mM.14
  • An in vitro study showed that irradiation corresponding to a few minutes of sun exposure greatly amplified the DNA-damaging effects of glyphosate on mammalian cells. The glyphosate metabolite AMPA proved even more damaging, provoking cellular toxic effects from 0.5 ppb, a low environmentally relevant dose that can be found in European rivers and even in drinking water. The effects were even greater when glyphosate was mixed with other pesticides (the so-called “cocktail effect”), including atrazine. The authors concluded that “the Directive Standards for Pesticides in Drinking Water should be re-evaluated according to these underestimated factors of risk”.15
  • Glyphosate and Roundup caused DNA damage in human mouth cells in vitro after a single 20-minute exposure at much lower doses than those used in agriculture. Roundup was much more toxic than glyphosate alone. The study showed that in principle, people who are exposed to Roundup through inhalation (as in South American soy-producing countries) could suffer DNA damage. With both glyphosate and Roundup, DNA damage occurred at concentrations below those required to cause cell damage, suggesting that the DNA damage was caused directly by these substances instead of being an indirect result of cell toxicity.16
  • Glyphosate and Roundup caused damage to DNA and chromosomes in the bone marrow of mice in vivo and in human cells in vitro. Roundup was only slightly more toxic than glyphosate.17
  • Roundup caused mutations in the DNA of fruit flies.18
  • Roundup increased the frequency of DNA adducts (cancer-causing chemicals that link to DNA), which can mark the onset of cancer, in the liver and kidneys of mice.19
  • Genetic damage was found in soybean workers exposed to pesticides, glyphosate herbicides among them, in Brazil.20
  • Ecuadorian people exposed to aerial glyphosate herbicide spraying showed a higher degree of DNA damage in blood cells than a control population. The researchers ruled out tobacco, alcohol, non-prescription drugs and asbestos as causes. None of the individuals had used or been exposed to other herbicides or pesticides when the samples were taken. The study also found acute poisoning reactions to the glyphosate herbicide spraying, including intestinal pain and vomiting, diarrhoea, fever, heart palpitations, headaches, dizziness, numbness, insomnia, burning eyes, blurred vision, difficulty in breathing, and skin rash.21

References

  1. European Parliament and Council. Regulation (EC) No 1107/2009 of 21 October 2009 concerning the placing of plant protection products on the market and repealing Council Directives 79/117/EEC and 91/414/EEC. Off J Eur Union. 2009:1–50.
  2. Glyphosate Task Force. Is glyphosate toxic to human DNA? Glyphosate Facts. 2013.
  3. Antoniou M, Habib MEM, Howard CV, et al. Teratogenic effects of glyphosate-based herbicides: Divergence of regulatory decisions from scientific evidence. J Env Anal Toxicol. 2012;S4:006. doi:10.4172/2161-0525.S4-006.
  4. Antoniou M, Habib M, Howard CV, et al. Roundup and Birth Defects: Is the Public Being Kept in the Dark? Earth Open Source; 2011. Available at: http://earthopensource.org
  5. World Health Organization. Good Laboratory Practice: Training Manual.; 2008:1. Available at: https://www.who.int.
  6. Tweedale AC. Uses of “Good Laboratory Practices” by regulated industry and agencies, and the safety of bisphenol A. J Epidemiol Community Health. 2011;65:475–476. doi:10.1136/jech.2010.127761.
  7. Tweedale T. Enhancing credibility of chemical safety studies: no consensus. Env Health Perspect. 2011;119:A507-8; author reply A508-9. doi:10.1289/ehp.1104130.
  8. Myers JP, vom Saal FS, Akingbemi BT, et al. Why public health agencies cannot depend on good laboratory practices as a criterion for selecting data: The case of bisphenol A. Environ Health Perspect. 2009;117:309-315.
  9. Marc J, Mulner-Lorillon O, Belle R. Glyphosate-based pesticides affect cell cycle regulation. Biol Cell. 2004;96:245-9. doi:10.1016/j.biolcel.2003.11.010.
  10. Bellé R, Le Bouffant R, Morales J, Cosson B, Cormier P, Mulner-Lorillon O. Sea urchin embryo, DNA-damaged cell cycle checkpoint and the mechanisms initiating cancer development. J Soc Biol. 2007;201:317–27.
  11. Marc J, Mulner-Lorillon O, Boulben S, Hureau D, Durand G, Bellé R. Pesticide Roundup provokes cell division dysfunction at the level of CDK1/cyclin B activation. Chem Res Toxicol. 2002;15(3):326-31.
  12. Marc J, Bellé R, Morales J, Cormier P, Mulner-Lorillon O. Formulated glyphosate activates the DNA-response checkpoint of the cell cycle leading to the prevention of G2/M transition. Toxicol Sci. 2004;82:436-42. doi:10.1093/toxsci/kfh281.
  13. Mañas F, Peralta L, Raviolo J, et al. Genotoxicity of glyphosate assessed by the Comet assay and cytogenic tests. Env Toxicol Pharmacol. 2009;28:37–41.
  14. Mañas F, Peralta L, Raviolo J, et al. Genotoxicity of AMPA, the environmental metabolite of glyphosate, assessed by the Comet assay and cytogenetic tests. Ecotoxicol Env Saf. 2009;72:834-7. doi:10.1016/j.ecoenv.2008.09.019.
  15. Roustan A, Aye M, De Meo M, Di Giorgio C. Genotoxicity of mixtures of glyphosate and atrazine and their environmental transformation products before and after photoactivation. Chemosphere. 2014;108:93-100. doi:10.1016/j.chemosphere.2014.02.079.
  16. Koller VJ, Furhacker M, Nersesyan A, Misik M, Eisenbauer M, Knasmueller S. Cytotoxic and DNA-damaging properties of glyphosate and Roundup in human-derived buccal epithelial cells. Arch Toxicol. 2012;86:805–813. doi:10.1007/s00204-012-0804-8.
  17. Bolognesi C, Bonatti S, Degan P, et al. Genotoxic activity of glyphosate and its technical formulation Roundup. J Agric Food Chem. 1997;45:1957–1962.
  18. Kale PG, Petty BT, Walker S, et al. Mutagenicity testing of nine herbicides and pesticides currently used in agriculture. Env Mol Mutagen. 1995;25:148-53.
  19. Peluso M, Munnia A, Bolognesi C, Parodi S. 32P-postlabeling detection of DNA adducts in mice treated with the herbicide Roundup. Env Mol Mutagen. 1998;31:55-9. doi:10.1002/(SICI)1098-2280(1998)31:1<55::AID-EM8>3.0.CO;2-A.
  20. Benedetti D, Nunes E, Sarmento M, et al. Genetic damage in soybean workers exposed to pesticides: evaluation with the comet and buccal micronucleus cytome assays. Mutat Res. 2013;752:28-33. doi:10.1016/j.mrgentox.2013.01.001.
  21. Paz-y-Miño C, Sánchez ME, Arévalo M, et al. Evaluation of DNA damage in an Ecuadorian population exposed to glyphosate. Genet Mol Biol. 2007;30:456–460.

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