Carcinogenicity

Summary

In 2015 the World Health Organization’s International Agency for Research on Cancer (IARC) declared that glyphosate is “probably carcinogenic to humans”. Claims that glyphosate herbicides (which contain mixtures of chemicals) do not cause cancer are based on government regulators’ interpretations of industry’s own, commercially confidential, studies on glyphosate alone. In contrast, studies on Roundup and glyphosate published by independent scientists suggest that they cause cancer in laboratory animals. An in vitro study (not performed in living animals or humans) found that glyphosate disrupts hormones and made breast cancer cells proliferate at a level far below that permitted in drinking water in the EU. Controlled laboratory studies in rats are widely considered to be a good indicator of possible human cancer-causing effects of a chemical.

In 2015 the World Health Organization’s International Agency for Research on Cancer (IARC) declared that glyphosate is “probably carcinogenic to humans”.1 In a statement, the IARC said it based its conclusion on “limited evidence of carcinogenicity in humans for non-Hodgkin lymphoma and lung cancer” and “convincing evidence” that glyphosate “can cause cancer in laboratory animals”.2

Monsanto disagreed with the IARC’s verdict, citing “conclusions reached by regulatory authorities” in various countries that glyphosate does not cause cancer.3 However, the studies on which these regulatory authorities based their verdicts were conducted or commissioned by pesticide companies in support of their applications for regulatory authorizations. The studies themselves are kept secret from the public and independent scientists and are based on old, outdated methodologies [see “Glyphosate and Roundup damage DNA”].

Based on these industry studies, the EU’s 2002 review of industry studies on glyphosate claimed “no evidence” of carcinogenicity (ability to cause cancer).4 But two long-term studies on rats indicating possible carcinogenic effects already existed at this time. These long-term studies on rats were conducted in 1979–1981 and 1988–1990.5 The rats received relatively low doses of glyphosate per day in the first study and higher doses in the second. The first study found an increase in tumours in the testes of rats fed glyphosate, but the same effect was not found in the second test using the higher doses. On this basis, glyphosate was excluded from the carcinogenic category of chemicals.5,6

However, this move was based on outdated and incorrect assumptions about toxicology. Cancers can be triggered by the endocrine disruptive effects of a chemical, which can occur at extremely low doses. Endocrine disrupting chemicals (EDCs) can have more potent endocrine disruptive effects at lower doses than higher doses. Sometimes a disruptive effect seen at the lower dose is not seen at all at a higher dose.7

Low-dose effects cannot be predicted by effects at higher doses, such as are tested in regulatory tests performed on pesticides, including glyphosate. Regulatory tests do not require low doses to be tested for possible endocrine disrupting effects.8 Therefore the findings of the long-term cancer studies on rats discussed above5 should be re-evaluated in light of up-to-date scientific knowledge.

In the 1980s the US Environmental Protection Agency (EPA) became embroiled in a dispute with Monsanto over the interpretation of findings of an increased incidence of kidney tumours in mice exposed to glyphosate in the company’s own long-term study, conducted in support of regulatory authorisation for the chemical. Data supplied by Monsanto to support its position that the tumours were not related to glyphosate exposure was considered by the EPA to be “not… convincing”.9

A laboratory study on Roundup by independent researchers in mice also revealed cancer-promoting effects. Roundup was found to promote cancerous tumour growth in the skin of the mice.10

A laboratory study in human cells with glyphosate alone showed that the chemical is an endocrine disruptor in vitro. Glyphosate was found to increase the proliferation of estrogen-dependent breast cancer cells by estrogenic mechanisms11 at a level far below that permitted in drinking water in the EU (see “Potentially dangerous levels of glyphosate found in GM soy”).

Unexpected tumour findings must be followed up

An in vivo study of Roundup administered to rats in drinking water diluted to 50ng/L glyphosate equivalence – half of the level permitted in drinking water in the EU12 and 14,000 times lower than that permitted in drinking water in the USA13 – resulted in severe organ damage and a trend of increased incidence of mammary tumours in female animals over a 2-year period of exposure.14

This study was not a dedicated carcinogenicity study but a chronic toxicity study that unexpectedly found tumours. Because chronic toxicity studies use lower numbers of animals than carcinogenicity studies, the tumour findings need to be followed up with a full-scale carcinogenicity study using a larger number of animals (50 per sex per group). Roundup has never been tested for long-term toxicity in animals for regulatory purposes; only glyphosate alone has been tested, with the concerning results detailed above.

Human epidemiological studies confirm cancer risk

Studies in human populations have found an association between Roundup exposure and two types of blood cancer:

  • An epidemiological study of pesticide applicators in the USA found that exposure to glyphosate herbicide was associated with higher incidence of multiple myeloma.15
  • Epidemiological studies conducted in Sweden found that exposure to glyphosate herbicide was linked with a higher incidence of non-Hodgkin’s lymphoma.16 17 18 A systematic review of the literature published in 2014 concluded that there was an association between exposure to glyphosate herbicides and non-Hodgkin’s lymphoma.19

Glyphosate Facts misrepresents cancer study

Strangely, the pesticide industry’s Glyphosate Facts website completely misrepresents one of the above studies on non-Hodgkin’s lymphoma. The website states:

“Another publication reported an association between non-Hodgkin’s lymphoma and glyphosate but this finding was not reproduced in a later study by the same group of researchers.”20

The first study cited (Hardell et al. 2002) did indeed find an increased risk of non-Hodgkin’s lymphoma for people exposed to glyphosate herbicides,17 just as the Glyphosate Facts site says. But quite contrary to the website’s second claim, the second study cited (Eriksson et al. 2008) actually confirmed the association between non-Hodgkin’s lymphoma and glyphosate herbicides found in the earlier study and added that the link “was considerably strengthened”.18

The authors of the Glyphosate Facts site appear to have misrepresented this study.

Rats are a good human cancer model

Data collected over 30 years at the Ramazzini Institute in Italy shows that the Sprague-Dawley strain of rat used at the Institute and in many toxicological studies worldwide is a good model for human cancer, provided the studies are well-designed.21 In other words, if a chemical causes cancer in this type of rat, there is a high likelihood that it will cause cancer in humans, too.

References:

  1. Guyton K, Loomis D, Grosse Y, El Ghissassi F, Benbrahim-Tallaa L. Carcinogenicity of tetrachlorvinphos, parathion, malathion, diazinon, and glyphosate. Lancet Oncol. 2015. http://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045%2815%2970134-8.pdf.
  2. International Agency for Research on Cancer. IARC Monographs Volume 112: Evaluation of Five Organophosphate Insecticides and Herbicides. Lyon, France: World Health Organization; 2015. https://www.documentcloud.org/documents/1690645-iarc-monographs-volume-112-evaluation-of-five.html.
  3. Monsanto. Monsanto disagrees with IARC classification for glyphosate. 2015. http://www.monsanto.ca/newsviews/Pages/NR-2015-03-20.aspx.
  4. European Commission Health & Consumer Protection Directorate-General. Review report for the active substance glyphosate. 2002. http://bit.ly/HQnkFj.
  5. International Programme on Chemical Safety. Environmental health criteria 159: Glyphosate. 1994. http://www.inchem.org/documents/ehc/ehc/ehc159.htm.
  6. Dallegrave E, Mantese FD, Coelho RS, Pereira JD, Dalsenter PR, Langeloh A. The teratogenic potential of the herbicide glyphosate-Roundup in Wistar rats. Toxicol Lett. 2003;142:45-52.
  7. Vandenberg LN, Colborn T, Hayes TB, et al. Hormones and endocrine-disrupting chemicals: Low-dose effects and nonmonotonic dose responses. Endocr Rev. 2012;33(3):378-455. doi:10.1210/er.2011-1050.
  8. Vom Saal FS, Akingbemi BT, Belcher SM, et al. Chapel Hill bisphenol A expert panel consensus statement: integration of mechanisms, effects in animals and potential to impact human health at current levels of exposure. Reprod Toxicol. 2007;24:131-138. doi:10.1016/j.reprotox.2007.07.005.
  9. Dykstra W. Memorandum from William Dykstra to Robert J. Taylor: Subject: Glyphosate – EPA Registration Nos. 524–318 and 524–333 – Historical Control Data for Mouse Kidney Tumours. Washington, DC: US Environmental Protection Agency (EPA); 1989. http://www.epa.gov/pesticides/chem_search/cleared_reviews/csr_PC-103601_19-Jun-89_249.pdf.
  10. George J, Prasad S, Mahmood Z, Shukla Y. Studies on glyphosate-induced carcinogenicity in mouse skin: A proteomic approach. J Proteomics. 2010;73:951-964. doi:10.1016/j.jprot.2009.12.008.
  11. Thongprakaisang S, Thiantanawat A, Rangkadilok N, Suriyo T, Satayavivad J. Glyphosate induces human breast cancer cells growth via estrogen receptors. Food Chem Toxicol. 2013;59:129-136. doi:10.1016/j.fct.2013.05.057.
  12. Council of the European Union. Council directive 98/83/EC of 3 November 1998 on the quality of water intended for human consumption. Off J Eur Communities. 1998. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:1998:330:0032:0054:EN:PDF.
  13. US Environmental Protection Agency (EPA). Basic information about glyphosate in drinking water. 2014. http://water.epa.gov/drink/contaminants/basicinformation/glyphosate.cfm#four.
  14. Séralini G-E, Clair E, Mesnage R, et al. Republished study: long-term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize. Environ Sci Eur. 2014;26(14). doi:10.1186/s12302-014-0014-5.
  15. De Roos AJ, Blair A, Rusiecki JA, et al. Cancer incidence among glyphosate-exposed pesticide applicators in the Agricultural Health Study. Env Health Perspect. 2005;113:49-54.
  16. Hardell L, Eriksson M. A case-control study of non-Hodgkin lymphoma and exposure to pesticides. Cancer. 1999;85:1353-1360. doi:10.1002/(SICI)1097-0142(19990315)85:6<1353::AID-CNCR19>3.0.CO;2-1.
  17. Hardell L, Eriksson M, Nordstrom M. Exposure to pesticides as risk factor for non-Hodgkin’s lymphoma and hairy cell leukemia: Pooled analysis of two Swedish case-control studies. Leuk Lymphoma. 2002;43:1043-1049.
  18. Eriksson M, Hardell L, Carlberg M, Akerman M. Pesticide exposure as risk factor for non-Hodgkin lymphoma including histopathological subgroup analysis. Int J Cancer. 2008;123:1657-1663. doi:10.1002/ijc.23589.
  19. Schinasi L, Leon ME. Non-Hodgkin lymphoma and occupational exposure to agricultural pesticide chemical groups and active ingredients: a systematic review and meta-analysis. Int J Environ Res Public Health. 2014;11(4):4449-4527. doi:10.3390/ijerph110404449.
  20. Glyphosate Task Force. Is there any evidence that glyphosate causes cancer? Glyphosate Facts. 2013. http://www.glyphosate.eu/there-any-evidence-glyphosate-causes-cancer.
  21. Soffritti M, Belpoggi F, Degli Esposti D. Cancer prevention: The lesson from the lab. In: Biasco G, Tanneberger S, eds. Cancer Medicine at the Dawn of the 21st Century: The View from Bologna. Bologna: Bononia University Press; 2006:49-64. http://www.ramazzini.it/ricerca/pdfUpload/Cancer%20Medicine%2049-64_2006.pdf.

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