Glyphosate

Preliminary post

Glyphosate is a small molecule, and it does not have chemical features of many environmental toxins. Nevertheless, don’t let that fool you. This is a mighty molecule—more harmful and more persistent than first thought.

Here we present scientific background to help to understand how glyphosate harms human and environmental health, and can even have some perverse, counter-productive effects in agriculture.

Carcinogenicity of glyphosate-based herbicides is summarized HERE.

Regulatory issues, and PCN work on glyphosate and sustainable agriculture are summarized HERE.

Glyphosate chemical structure

black=carbon; white=hydrogen; red=oxygen; blue=nitrogen; orange=phosphorus.
NOTE: glyphosate does not contain ring structures or halogens such as fluorine or chlorine atoms, that typically flag persistent, toxic chemicals.
Image from Wikipedia.

Glyphosate is by far the most-used herbicide globally. In Canada, about 50 million kilograms of the active ingredient is applied annually. In some provinces, most is used for agriculture; elsewhere more is used to eliminate early regrowth (e.g., raspberries, birch, aspen) before planting monocultures in forest clearcuts (increasing risks and severity of forest fires ¹); to clear the ground (e.g., along fence lines, rights of way, sports fields, foundations); and to alter aesthetics.

Glyphosate-based herbicides

Glyphosate is not used alone

Glyphosate is the chemical that is assessed and registered by Health Canada’s Pest Management Regulatory Agency (PMRA), but herbicide sprays are complicated mixtures. Glyphosate is the “active ingredient” in glyphosate-based herbicides (GBHs), that also include substances to make the product spread over, stick to and penetrate into plants more effectively. These ingredients can have the same effect (and possibly other impacts) when the product lands on the skin and airways of non-target life.

How glyphosate works to kill plants

Glyphosate inhibits an enzyme that is used by many species to make certain essential protein building blocks, called amino acids. This enzyme, “5-enolpyruvylshikimate-3-phosphate synthase” or EPSP synthase, is in plants and many microbes, but not in animals. This led to a simplistic conclusion that glyphosate is “safe” for everyone and everything without this enzyme. That was incorrect, because animals receive essential amino acids from the species that make them, and these are sensitive to glyphosate.

GBHs kill most plants, unless they are genetically engineered to be immune, or have adapted/evolved, due to repeated exposures over time.

What else does glyphosate do?

Glyphosate is an antibiotic, affecting microbiomes in animals and the soil

A microbiome includes a diverse collection of microbes—mostly bacteria and fungi—living together in a particular location such as the gut, skin or mucus membranes. In the environment, microbiomes are adapted to the soil in particular locations such as a farmer’s field, the woods, a swamp, a golf green, a compost heap—anywhere that is not sterile.

Glyphosate has been patented as an antibiotic, because it kills many bacteria and fungi. These microbes, that express EPSP synthase, produce essential nutrients that animals cannot make themselves. Bacteria and fungi also have many poorly-understood roles in the soil.

Glyphosate affects the gut microbiome

With low levels of essential nutrients, the young don’t develop properly and the immune system is weakened. Biochemical imbalances and higher levels of inflammation can lead to failure to thrive and to develop properly, as well as inflammatory bowel disease and cancers.

Health Canada should know. The PMRA’s confidential test data includes findings of “anal staining” and marks on cage linings, indicating intestinal distress in test animals; however the animals were not dying so the effect was discounted as “not adverse.”

The public, peer-reviewed literature finds that GBHs affect the gut in laboratory animals, for example:

• Sex-dependent impact of Roundup on the rat gut microbiome was observed at a low concentration of Roundup (0.1 ppb) that is encountered in the environment.²
• An animal study on microbiome effects from glyphosate and Roundup administered at a human-equivalent dose reported, “exposures to commonly used GBHs, at doses considered safe, are capable of modifying the gut microbiota in early development…”³

Glyphosate affects the soil microbiome

GBHs can shift the soil microbiome, decreasing soil fungal biomass and species richness.⁴

The soil microbiome includes diverse bacteria and fungi, that:

• transport water and nutrients to roots
• create essential nutrients
• break down old plant materials
• “fix” nitrogen in nodules on roots of some plants, and nourish the host plant, and
• are pathogens that:
  • infect plants and can contaminate food
  • infect beneficial species, or
  • infect and control some pests such as grasshoppers.

In farm fields, Fusarium infections contaminate foods with mycotoxins that can cause cancer and birth defects.⁵ Canadian researchers have reported that glyphosate use is associated with cereal diseases caused by Fusarium spp. in the Prairies.⁶ Fusarium has been reported to be less problematic in organic wheat.⁷

Beneficial colonies of “nitrogen-fixing” microbes in nodules on roots of particular crops (mostly legumes) can also be impacted by GBHs. Organic farmers rely naturally boosting soil nitrogen with these cover crops and rotations. Production of nitrogen containing fertilizers used in “conventional” agriculture is a significant source of greenhouse gases, and a substantial cost to growers.

Unanticipated consequence: the glyphosate – grasshoppers connection

In 2023, as forecast, crops in parts of Saskatchewan were virtually eliminated by grasshoppers.⁸ It was a stressful time, and we heard that “conventional” farmers who were spraying insecticides were upset with the organic farmers who were not. Apparently at least one organic farmer sprayed water on fields, to quell the tension with neighbours. Looking at devastated fields, organic crops were in relatively good shape (though not great). How could that be?

Plagues of locusts and grasshoppers have destroyed crops over millennia, but these and other pests rise and fall. One of the reasons is that pathogens that sicken and kill such insects increase during infestations, and then these high pathogen levels control pests over subsequent years. With fewer insects dying and replenishing the infectious microbes, the control wanes until there is another severe outbreak and the cycle repeats.

Research on effects of a fungal disease on Grasshopper Populations in Saskatchewan in 1963 ⁹ describes how soil pathogens have long been known to control pests. The role of fungi in the control of grasshoppers in 1987 ¹⁰ has been followed up with extensive research. Now an indigenous fungus discovered in Canadian Prairie (Alberta) soil, Metarhizium anisopliae var. anisopliae is being developed as an effective biocontrol for grasshoppers.¹¹

In 2001, a team of international researchers collaborated on a thorough review of Biological Control of Grasshoppers and Locusts.¹² The PMRA does not assess impacts of pesticides such as GBHs on natural pest controls such as insect pathogens, but in this case GBHs were obvious potential culprits in severe pestilence.

While the PMRA may have been oblivious, Monsanto was quick to respond. A 2002 study “Fungicidal effects of glyphosate and glyphosate formulations on entomopathogenic fungi”¹³ acknowledged that Roundup does kill grasshopper pathogens, but claimed that other chemicals in the product (“formulants”) are at fault. There has been no replication of this research, and we do not know whether reformulation has, or even could ensure that grasshopper pathogens are not affected by GBHs.

Glyphosate is a “chelator”

“Chelate” is derived from the Greek word for “claw.” Chelating chemicals have the ability to wrap around and bind a metal ion.

Glyphosate is persistent and chelation may be part of the reason

Glyphosate is claimed to have low environmental persistence, but in a study relating it to kidney disease, glyphosate was much more persistent in hard water.¹⁴ This was ascribed to chelates being less susceptible to biodegradation.

Data collected and shared by Agriculture Canada researcher Dr. Myriam Fernandez confirmed that glyphosate decreases slowly in fields after transitioning to organic practices. Moreover, glyphosate is mobile in the environment, as low levels were detected in fields that have never been sprayed.

Glyphosate in Saskatchewan soil samples

Glyphosate can mobilize both nutrients and toxic elements

As a chelator, glyphosate can mobilize minerals into the water phase, where they are translocated to roots. These include essential nutrients such as calcium, magnesium and micronutrients, as well as toxic elements such as cadmium, lead or mercury. The latter are neurotoxic, can harm many body systems, and may cause cancer.

The glyphosate – cadmium connection

Cadmium is highly toxic and is a known human carcinogen. Canada has significant naturally occurring cadmium in some prairie soils and potash and permits higher levels in fertilizer than some international trading partners.

During the 1990s Environment Canada studied natural accumulation of pollutants by plants. “Phytoremediation” is using plants to concentrate toxins on contaminated sites. Brassicas (e.g. broccoli, cabbage, kale), sunflowers and grains were noted among plants that concentrated cadmium most avidly. With high affinity for cadmium, Canadian grains have upon occasion exceeded European Union (EU) limits, and therefore have been refused entry into the EU market.

Glyphosate mobilizes cadmium from soil, making it more available to plants.¹⁵ In a wide-ranging systematic review of growing methods and crop contamination, a UK-based study found higher antioxidant levels, lower cadmium concentrations and lower incidence of pesticide residues in organically grown crops.¹⁶ Another comprehensive review focusing on human health implications of organic agriculture ¹⁷ noted that cadmium accumulates in seeds and is lower in organic grains. Authors also noted lower levels of veterinary drugs and higher levels of some nutrients in organic foods.

An important gap in protection of public health is that there is no standard for cadmium in Canadian food. Canadians’ cadmium body burdens are falling with decreasing tobacco consumption,¹⁸ but limiting cadmium in foods could benefit the growing non-smoking population.

Back to the future—check out Prevent Cancer Now’s earliest posts on glyphosate

The whole point to our work is NOT to see ongoing exposure to carcinogens. PCN’s formal submissions are summarized HERE, but for the record, we identified the major issues long ago:

• 2015 comment on the International Agency for Research on Cancer assessment that glyphosate is a probable human carcinogen. The world’s most used weed-killer is probably carcinogenic – so what?
• 2015 response of 96 scientists denouncing an EU report, and reaffirming the International Agency for Research on Cancer (IARC) finding that the world’s most commonly used herbicide, glyphosate, probably causes cancer. The Roundup turn-around
• 2017 discussion of confidential test data we examined following Canada’s reassessment of glyphosate, and found that evidence of the expected intestinal distress had been discounted. Why worry about mucky mouse butts and cancer?

References

1.         Lindsay, B. ‘It blows my mind’: How B.C. destroys a key natural wildfire defence every year | CBC News. CBC https://www.cbc.ca/news/canada/british-columbia/it-blows-my-mind-how-b-c-destroys-a-key-natural-wildfire-defence-every-year-1.4907358 (2018).

2.         Lozano, V. L. et al. Sex-dependent impact of Roundup on the rat gut microbiome. Toxicol. Rep. 5, 96–107 (2017).

3.         Mao, Q. et al. The Ramazzini Institute 13-week pilot study on glyphosate and Roundup administered at human-equivalent dose to Sprague Dawley rats: effects on the microbiome. Environ. Health 17, 50 (2018).

4.         Vázquez, M. B., Moreno, M. V., Amodeo, M. R. & Bianchinotti, M. V. Effects of glyphosate on soil fungal communities: A field study. Rev. Argent. Microbiol. 53, 349–358 (2021).

5.         Ekwomadu, T. I., Akinola, S. A. & Mwanza, M. Fusarium Mycotoxins, Their Metabolites (Free, Emerging, and Masked), Food Safety Concerns, and Health Impacts. Int. J. Environ. Res. Public. Health 18, 11741 (2021).

6.         Fernandez, M. R. et al. Glyphosate associations with cereal diseases caused by Fusarium spp. in the Canadian Prairies. Eur. J. Agron. 31, 133–143 (2009).

7.         Arnason, R. Why organic wheat escaped Fusarium last year. The Western Producer https://www.producer.com/news/why-organic-wheat-escaped-fusarium-last-year/ (2017).

8.         Grasshopper Forecast Map | Insects. Government of Saskatchewan https://www.saskatchewan.ca/business/agriculture-natural-resources-and-industry/agribusiness-farmers-and-ranchers/crops-and-irrigation/insects/grasshopper-map.

9.         Pickford, R. & Riegert, P. W. The Fungous Disease Caused by Entomophthora grylli Fres., and its Effects on Grasshopper Populations in Saskatchewan in 1963. Can. Entomol. 96, 1158–1166 (1964).

10.       Goettel, M., Johnson, D. & Inglis, G. D. The role of fungi in the control of grasshoppers. J. Am. Mosq. Control Assoc. 3, S71–S75 (1987).

11.       Canada, A. and A.-F. Research and development of a newly discovered, effective grasshopper biocontrol agent found in Canadian prairie soil. http://agriculture.canada.ca/en/science/agriculture-and-agri-food-research-centres/pest-management-centre/pesticide-risk-reduction-pest-management-centre/integrated-pest-management-projects/research-and-development-newly-discovered-effective-grasshopper-biocontrol-agent-found-canadian (2018).

12.       Lomer, C., RP Bateman, Johnson, D., Langewald, J. & Thomas, M. Biological Control of Locusts and Grasshoppers. Annu. Rev. Entomol. (2001).

13.       Morjan, W. E., Pedigo, L. P. & Lewis, L. C. Fungicidal Effects of Glyphosate and Glyphosate Formulations on Four Species of Entomopathogenic Fungi. Environ. Entomol. 31, 1206–1212 (2002).

14.       Ulrich, J. C. et al. Glyphosate and Fluoride in High-Hardness Drinking Water Are Positively Associated with Chronic Kidney Disease of Unknown Etiology (CKDu) in Sri Lanka. Environ. Sci. Technol. Lett. 10, 916–923 (2023).

15.       Zhou, D.-M., Wang, Y.-J., Cang, L., Hao, X.-Z. & Luo, X.-S. Adsorption and cosorption of cadmium and glyphosate on two soils with different characteristics. Chemosphere 57, 1237–1244 (2004).

16.       Barański, M. et al. Higher antioxidant and lower cadmium concentrations and lower incidence of pesticide residues in organically grown crops: a systematic literature review and meta-analyses. Br. J. Nutr. 112, 794–811 (2014).

17.       Mie, A. et al. Human health implications of organic food and organic agriculture: a comprehensive review. Environ. Health 16, 111 (2017).

18.       Health Canada. Cadmium in Canadians. https://www.canada.ca/en/health-canada/services/environmental-workplace-health/reports-publications/environmental-contaminants/human-biomonitoring-resources/cadmium-canadians.html (2021).

19.       Sender, R., Fuchs, S. & Milo, R. Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLOS Biol. 14, e1002533 (2016).

20.       Benchimol, E. I. et al. Trends in Epidemiology of Pediatric Inflammatory Bowel Disease in Canada: Distributed Network Analysis of Multiple Population-Based Provincial Health Administrative Databases. Am. J. Gastroenterol. 112, 1120–1134 (2017).

21.       O’Sullivan, D. E. et al. The incidence of young-onset colorectal cancer in Canada continues to increase. Cancer Epidemiol. 69, 101828 (2020).

22.       Arbuckle, T. E., Lin, Z. & Mery, L. S. An exploratory analysis of the effect of pesticide exposure on the risk of spontaneous abortion in an Ontario farm population. Environ. Health Perspect. 109, 851–857 (2001).

23.       Parvez, S. et al. Glyphosate exposure in pregnancy and shortened gestational length: a prospective Indiana birth cohort study. Environ. Health 17, 23 (2018).

24.       Klátyik, S. et al. Terrestrial ecotoxicity of glyphosate, its formulations, and co-formulants: evidence from 2010–2023. Environ. Sci. Eur. 35, 51 (2023).