What is glyphosate?
Glyphosate is a herbicide, used globally as a weed killer. It was developed and commercialised in 1974 in a formulation marketed as Roundup, by the agricultural company, Monsanto. Today, it is the active ingredient of more than 750 different broad-spectrum herbicides (1) and glyphosate-based formulations are the most commonly used and sold pesticides, worldwide.
Glyphosate is used in commercial formulations, which include other chemical additives that allow and enhance its efficiency as a weed killer, by improving the plant’s ability to take up the herbicide and by promoting its toxicity. These additives are considered to be ‘inert diluents’ by manufacturers and are classified as confidential for regulatory purposes (2).
The global use of glyphosate has risen 15-fold since the introduction of glyphosate-resistant genetically modified (GM) crops in 1996 (3). Such crops now account for 56% of total glyphosate use, worldwide.
Glyphosate-based formulations are used in agriculture, forestry, aquatic environments and in urban and domestic settings.
Glyphosate use on GM crops
Glyphosate-resistant GM crops are genetically engineered to tolerate glyphosate. This means that when a crop is sprayed, the weeds around the crop die, but the crop is resistant and accumulates herbicide as it grows. Examples of GM crops include glyphosate-tolerant soybean, corn, cotton, sugar beet and canola (rape).
The cultivation of GM crops means glyphosate can be used at all stages of crop cultivation, including when a plant has germinated. As a consequence, concentrations and quantities of glyphosate-based herbicides in the United States (and elsewhere) are increasing, along with increasing plant residues (4). Furthermore, excessive use of glyphosate has resulted in the emergence of glyphosate-resistant weeds, especially where GM crops are grown (5). Currently, 34 different species of glyphosate-resistant weeds have been identified (6).
Glyphosate use in the UK
The commercial cultivation of glyphosate-tolerant GM crops within the European Union is not permitted. Nonetheless, glyphosate use in UK farming has increased by 400% in the last 20 years (7). Glyphosate-based herbicides are mainly applied after harvest, to prevent weeds infesting winter crops or after sowing before the new crop plants emerge. In the UK and some other European countries, notably Germany, glyphosate is also used before crop harvest (especially for wheat and oilseed rape) to control weeds (pre-harvest) and to speed up the maturation process of crops (dessication) (8).
Glyphosate contamination of food crops in the UK is common. For example, annual glyphosate residue testing in the UK by the Food Standards Agency has identified frequent contamination of bread (9); residues of glyphosate were found in 10-30% of grain-based samples from 2007–2013, at generally rising levels (10). Although maximum residue levels (10mg/kg) have never been exceeded, levels as high as 0.5mg/kg have been found.
Glyphosate is also used as a weed killer in parks and schools and along roadsides and railway tracks. It is used in domestic settings to clear gardens, patios and driveways of weeds. According to the Department of Environment Food and Rural Affairs it is the most commonly used herbicide in residential areas (11) and on arable land (12).
Why should we be concerned?
Glyphosate is widespread in the environment (13) and has been detected in air, soil and water, as well as in humans. Studies from Europe and the US routinely identify urinary glyphosate residues in humans, as a result of occupational use or dietary intake (14). A study just published by a German environmental organisation, the Heinrich Böll Foundation (15), reported urinary glyphosate residues in 99.6% of the 2,009 people monitored. A third of those had levels 10 to 42 times higher than what is currently considered a safe threshold of exposure (16).
There is strong evidence that glyphosate is carcinogenic (17) (see section on Glyphosate and Cancer) and some evidence that it acts as an oestrogen mimic at high concentration (18) and so may increase breast cancer risk for those exposed to unusually high levels; however, no such elevated risk is associated with everyday exposures (see section on Glyphosate and Breast Cancer). Glyphosate may also be associated with kidney disease (19) and other illness (20) (see section on other Health Effects).
Glyphosate commercial formulations can be up to 1000 times more toxic than glyphosate alone (21). Additives, including surfactants, which help glyphosate enter plant cells and are also toxic in their own right, have been shown to enhance glyphosate toxicity (22, 23). Some contaminants of glyphosate formulations, such as 1,4-dioxane, cause mammary, liver and nasal cancers in laboratory rodents (24). The French environment agency, ANSES, recently called for a review of glyphosate formulations, based on their concerns about the combined effects of additives in combination with glyphosate.
Glyphosate and cancer
The carcinogenicity of glyphosate is a controversial issue. While several reviews (e.g. 25) and the European Chemicals Agency (ECHA) (26) concluded that glyphosate is not a carcinogen, an independent review carried out by the WHO’s International Agency for Research on Cancer (IARC) classified glyphosate as a “probable human carcinogen” (2A group) (27). Evidence of carcinogenicity in humans was supported by a positive association between glyphosate exposure and Non-Hodgkin lymphoma subtypes, in three out of four studies, considered as reliable by the IARC review panel. The panel also concluded that glyphosate is genotoxic (damages genes) and linked glyphosate to dose-related increases in malignant tumours at multiple sites (including kidneys and liver) in laboratory animals. In June 2017, the state of California classified glyphosate as a substance “known to cause cancer” (28).
Glyphosate and breast cancer
To date, no study has demonstrated a causal link between glyphosate and breast cancer in humans. Results from the US Agricultural Health Study did not report an association between glyphosate and breast cancer among wives of private pesticide applicators from Iowa and North Carolina (29). However, these results should be analysed cautiously, as the control population (farmers and their spouses who had never applied glyphosate) was likely to have been exposed through environmental contamination. Indeed, another study examining urinary levels of glyphosate metabolites of Iowa farmers and their families found similar levels in family members from both farming and non-farming households (30). Monitoring of human body fluids for glyphosate and its metabolites in such human population studies would generate more accurate results.
Only one long term study has been carried out into the possible association between glyphosate and mammary tumours in animals. This study, which used environmentally relevant concentrations of a glyphosate-based herbicide (31), reported a significant increase in the incidence of mammary tumours.
A recently published study (32) found that glyphosate is oestrogenic (can act as an oestrogen mimic), but only at relatively high concentrations. This suggests that humans exposed to glyphosate at typical exposure levels would not have an increased risk of breast cancer as a result of its oestrogenic effects. The researchers used several techniques to demonstrate this and their results are consistent with those obtained from the US Environmental Protection Agency’s endocrine disruptor screening programme (33). The finding is in contrast to that of a previous study (34), which reported that glyphosate could activate the oestrogen receptor with similar potency to natural oestrogen (in other words, was a strong oestrogen mimic), a result that has not been repeated by other researchers.
No additives found in glyphosate-based herbicides have been shown to be oestrogenic (35). Previous studies have demonstrated that certain additives, including polyethoxylated tallowamine (POEA), can inhibit aromatase (an enzyme involved in sex hormone synthesis) and is toxic to cells (36). In July 2016, EU member states agreed to ban the use of POEA from glyphosate-based products (37).
In conclusion, current evidence suggests that exposure to glyphosate and glyphosate formulations through ordinary domestic usage and dietary intake would not increase breast cancer risk as a result of oestrogenic effects. However, exposure to high concentrations of glyphosate is likely to have oestrogenic effects, which suggests those who are acutely exposed - perhaps through their occupation - may be at increased risk of breast cancer. More studies are needed to understand fully the role of glyphosate in breast cancer risk, in particular those involving occupational exposures, as well as the potential impact of long term chronic exposures, especially to mixtures of glyphosate-containing herbicides and other potentially harmful endocrine disrupting chemicals.
Other health effects
In addition to a link to Non-Hodgkin lymphoma, glyphosate has been associated with chronic kidney disease, following exposure to contaminated drinking water or herbicide spray (38). A recent study confirmed liver and kidney damage in animals following long term consumption of a very low dose of the glyphosate-based herbicide, Roundup (39). Further detrimental human health effects have been proposed, based on animal and in vitro studies, including liver disease, reproductive disorders, neurotoxicity, cardiovascular problems and allergies (see review, 40). Further evidence is needed to confirm whether or not glyphosate or its formulations are responsible for such effects.
What is the current regulatory position?
Pesticides such as glyphosate must be approved for use in the EU by the European Commission, according to the EU plant protection products regulation [Regulation: (EC) No 1107/2009]. In June, 2016, the EU licence for glyphosate use expired, and a temporary renewal was granted (for 18 months), following a lack of consensus by EU member states. In November 2015 a European Food Safety Authority (EFSA) assessment concluded that glyphosate is “unlikely to pose a carcinogenic hazard to humans” (41). This is significant as the 2009 EU pesticides regulation (Regulation 1107/2009; Annex II, 3.6.3) forbids active substances which can cause cancer from being used as pesticides. EFSA’s conclusion was based on work done by the German Federal Risk Assessment institute, BfR, and is counter to IARC’s findings that glyphosate is a “probable human carcinogen”. The BfR report focused on studies which evaluated the effects of glyphosate alone, not its formulations, which are likely to be more toxic (42). The EFSA report has been questioned by over 90 leading scientists from around the world, who wrote an open letter to the European Health and Food Safety Commissioner, Vytenis Andriukaitis, challenging EFSA’s decision and questioning the BfR report’s credibility (43, 44).
An evaluation of glyphosate by the European Chemicals Agency (ECHA) in the context of the European legislation on classification, labelling and packaging was published in March 2017 (45). It concluded that “the available scientific evidence did not meet the criteria to classify glyphosate as a carcinogen, as a mutagen or as toxic for reproduction”, paving the way for glyphosate re-authorisation. The proposal to re-approve glyphosate for use in the EU for a further 10 years will be decided on in November, 2017.
Some regional and national authorities have already banned or restricted glyphosate use. In 2015, Sri Lanka banned all use of glyphosate, due to its links with kidney disease (46), although this ban may be partially relaxed to allow use in tea plantations (47). In France, restrictions are in place on sales to the public and by 2020 the sale of glyphosate intended for public use will be banned and the Netherlands has also banned non-commercial use of glyphosate (48). In the UK several city councils, including Edinburgh, Brighton and Hove, Shaftsbury, Glastonbury, and the London Borough of Hammersmith and Fulham have phased out glyphosate use on council land and in open spaces (49).
We would like to thank Dr Robin Mesnage and Dr Michael Antoniou (King’s College, London) for their help in preparation of this background briefing.
1. Guyton, K. Z. et al. (2015). Carcinogenicity of tetrachlorvinphos, parathion, malathion, diazinon, and glyphosate. Lancet Oncology 1 6(5): 490-1. http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70134-8/abstract
2. Mesnage, R. et al. (2014). Major Pesticides Are More Toxic to Human Cells Than Their Declared Active Principles. Biomedical Research International 2014 Article ID 179691. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955666
3. Benbrook, C. M. (2016). Trends in glyphosate herbicide use in the United States and globally. Environmental Sciences Europe 28:3. DOI 10.1186/s12302-016-0070-0. http://enveurope.springeropen.com/articles/10.1186/s12302-016-0070-0
4. Benbrook, C. M. ibid
5. Heap, I. (2014). Global perspective of herbicide-resistant weeds. Pest Management Science 70:1306–1315. http://onlinelibrary.wiley.com/doi/10.1002/ps.3696/abstract
6. International Survey of Herbicide-Resistant Weeds (2016). Herbicide-Resistant Weeds by Site of Action. http://weedscience.org/summary/soasummary.aspx (Accessed May 12, 2016)
7. Soil Association (2015). Glyphosate in our bread facts & figures. July 2015. https://www.soilassociation.org/media/4653/glyphosate-facts-and-figures-july-2015.pdf (Accessed May 12, 2016).
8. Industry Taskforce on Glyphosate (2016). How is glyphosate used? http://www.glyphosate.eu/glyphosate-basics/how-glyphosate-used (accessed March 6, 2016).
9. Note: 85% of wheat used by UK flour millers is home grown the main sources of imported wheat are France, Germany and Canada. Nabim (2016). Imports and Exports. http://www.nabim.org.uk/statistics/imports-and-exports (Accessed May 12, 2016).
10. Data available from Defra Expert Committee on Pesticide Residues in Food (PRiF). Results and reports. http://webarchive.nationalarchives.gov.uk/20151023155227/http://www.pesticides.gov.uk/guidance/industries/pesticides/advisory-groups/PRiF/PRiF_Results_and_Reports (Accessed March 9, 2016).
11. Goulds, A. J. (2012) Pesticide usage survey report 254 Amenity pesticides in the United Kingdom. DEFRA, UK. https://secure.fera.defra.gov.uk/pusstats/surveys/documents/amenity2012v2.pdf (Accessed May 12, 2016).
12. Garthwaite, D. et al. (2014). Pesticide usage survey report 263. Arable Crops in the United Kingdom. DEFRA, UK. https://secure.fera.defra.gov.uk/pusstats/surveys/documents/arable2014v2.pdf (Accessed May 12, 2016).
13. Benbrook, C. M. (2016). op cit
14. Niemann, L. et al. (2015). A critical review of glyphosate findings in human urine samples and comparison with the exposure of operators and consumers. Journal für Verbraucherschutz und Lebensmittelsicherheit 10(1): 3-12. http://link.springer.com/article/10.1007/s00003-014-0927-3#page-1
15. Krüger, M. et al. (2015). Nachweis von Glyphosat im Urin freiwilliger, selbstzahlender Studien- teilnehmer-“Urinale 2015”. http://www.urinale.org/wp-content/uploads/2016/03/PK-Text-Handout.pdf (Accessed May 12, 2016)
16. Sagener, N. (2016). Overwhelming majority of Germans contaminated by glyphosate. EuroActiv.de http://www.euractiv.com/section/agriculture-food/news/overwhelming-majority-of-germans-contaminated-by-glyphosate/ (Accessed May 12, 2016).
17. Guyton, K. Z. et al. (2015). op cit
18. Mesnage, R. et al. (2017). Evaluation of estrogen receptor alpha activation by glyphosate-based herbicide constituents. Food and Chemical Toxicology (2017), doi: 10.1016/j.fct.2017.07.025. http://www.sciencedirect.com/science/article/pii/S0278691517303976
19. Jayasumana, C. et al. (2015). Drinking well water and occupational exposure to Herbicides is associated with chronic kidney disease, in Padavi-Sripura, Sri Lanka. Environmental Health 14:6. http://ehjournal.biomedcentral.com/articles/10.1186/1476-069X-14-6
20. Mesnage, R. et al. (2013). Ethoxylated adjuvants of glyphosate-based herbicides are active principles of human cell toxicity. 313(2-3) 122-128. https://www.ncbi.nlm.nih.gov/pubmed/23000283
21. Mesnage, R. et al. (2014). op cit
22. Vincent, K. and Davidson, C. (2015). The toxicity of glyphosate alone and glyphosate-surfactant mixtures to western toad (Anaxyrus boreas) tadpoles. Environmental Toxicology and Chemistry 34(12):2791-2795. http://www.ncbi.nlm.nih.gov/pubmed/26084619
23. Defarge, N. (2016). Co-Formulants in Glyphosate-Based Herbicides Disrupt Aromatase Activity in Human Cells below Toxic Levels. International Journal of Environmental Research and Public Health 13(3) 264. http://www.mdpi.com/1660-4601/13/3/264
24. Kano, H. et al. (2009). Carcinogenicity studies of 1,4-dioxane administered in drinking-water to rats and mice for 2 years. Food and Chemical Toxicology 47: 2776-2784. http://www.ncbi.nlm.nih.gov/pubmed/19703511
25. Greim, H. et al. (2015). Evaluation of carcinogenic potential of the herbicide glyphosate, drawing on tumor incidence data from fourteen chronic/carcinogenicity rodent studies, Critical Reviews in Toxicology, 45(3) 185-208. http://dx.doi.org/10.3109/10408444.2014.1003423
26. ECHA (2017). Glyphosate not classified as a carcinogen by ECHA. https://echa.europa.eu/-/glyphosate-not-classified-as-a-carcinogen-by-echa (Accessed August 9, 2017)
27. Guyton, K. Z. et al. (2015). op cit
28. OEHHA (2017). Glyphosate Listed Effective July 7, 2017, as Known to the State of California to Cause Cancer. https://oehha.ca.gov/proposition-65/crnr/glyphosate-listed-effective-july-7-2017-known-state-california-cause-cancer (accessed August 9, 2017)
29. Engel L. S. et al. (2005). Pesticide use and breast cancer risk among farmers’ wives in the agricultural health study. American Journal of Epidemiology 161: 121–135. https://www.ncbi.nlm.nih.gov/pubmed/15632262
30. Curwin, B.D., et al. (2007). Urinary pesticide concentrations among children, mothers and fathers living in farm and non-farm households in Iowa. The Annals of Occupational Hygiene 51: 53-65. http://www.ncbi.nlm.nih.gov/pubmed/16984946
31. Seralini, G.-E. et al. (2014). Republished study: long-term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize. Environmental Sciences Europe 26: 14. http://link.springer.com/article/10.1186%2Fs12302-014-0014-5#/page-1
32. Mesnage, R. et al. (2017). op cit
33. US EPA. (2015). Endocrine Disruptor Screening Program Weight of Evidence Conclusions on the Tier 1 Screening for glyphosate. Memorandum. Date: June 29, 2015. https://www.epa.gov/ingredients-used-pesticide-products/endocrine-disruptor-screening-program-tier-1-assessments (Accessed May 12, 2016)
34. Thongprakaisang, S. et al. (2013). Glyphosate induces human breast cancer cells growth via estrogen receptors. Food and Chemical Toxicology 59: 129-136. http://www.ncbi.nlm.nih.gov/pubmed/23756170
35. Mesnage, R. et al. (2017). op cit
36. Mesnage, R. et al. (2013). op cit
37.Michalopoulos, S. (2016). EU agrees ban on glyphosate co-formulant. Euractive.com July 12 2016. https://www.euractiv.com/section/agriculture-food/news/eu-agrees-ban-on-glyphosate-co-formulant/ (Accessed August 10, 2017).
38. Jayasumana, C. et al. (2015). op cit
39. Mesnage, R. et al. (2015). Potential toxic effects of glyphosate and its commercial formulations below regulatory limits. Food and Chemical Toxicology 84: 133-153. http://www.sciencedirect.com/science/article/pii/S027869151530034X
40. Mesnage, R. et al. (2015). op cit
41. EFSA (2015). European Food Safety Authority. Conclusion on the peer review of the pesticide risk assessment of the active substance glyphosate. EFSA Journal 2015: 13:4302. http://www.efsa.europa.eu/sites/default/files/scientific_output/files/main_documents/4302.pdf (Accessed May 12, 2016)
42. EFSA (2015). ibid
43. Portier, C. J. et al. (2015). Open letter: Review of the Carcinogenicity of Glyphosate by EFSA and BfR. November 27 2015 http://www.zeit.de/wissen/umwelt/2015-11/glyphosat-offener-brief.pdf (Accessed May 12, 2016)
44. Portier, C. J. et al. (2016). Differences in the carcinogenic evaluation of glyphosate between the International Agency for Research on Cancer (IARC) and the European Food Safety Authority (EFSA). Journal of Epidemiology and Community Health First, published on March 3, 2016 as 10.1136/jech-2015-207005. http://jech.bmj.com/content/early/2016/03/03/jech-2015-207005.full
45. ECHA (2017). Glyphosate not classified as a carcinogen by ECHA. 15 March 2017. https://echa.europa.eu/-/glyphosate-not-classified-as-a-carcinogen-by-echa (Accessed August 9, 2017).
46. Heyes, J. D. (2015). Sri Lanka's President bans glyphosate nationwide to protect the health of the people. June 8, 2015. http://www.naturalnews.com/050009_Sri_Lanka_glyphosate_ban_kidney_disease.html (Accessed May 12, 2016).
47. The Associated Newspapers of Ceylon Ltd. (2017). Return of Glyphosate Hangs in the Balance. Sunday Observer. 18 June 2017. http://www.sundayobserver.lk/2017/06/18/return-glyphosate-hangs-balance (Accessed August 10, 2017)
48. PAN (2016). The Glyphosate Monograph. Pesticides Action Network UK. http://www.pan-uk.org/glyphosate/ (Accessed August 9, 2017).
49. PAN (2016). ibid
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