What is glyphosate?

What glyphosate is, where it's used, how it enters the food supply, and its regulatory classification

Glyphosate is the most widely used herbicide in the world, best known as the active ingredient in Roundup. It kills weeds by blocking a plant enzyme called EPSP synthase, which plants need to make certain amino acids. Farmers spray it on crops that have been genetically modified to resist it, and it's also used as a pre-harvest desiccant on wheat and oats. Residues show up in many common foods, and traces have been detected in the urine of a large percentage of the US population [2].

In 2015, the International Agency for Research on Cancer (IARC) classified glyphosate as "probably carcinogenic to humans" (Group 2A) [1], while the US EPA concluded it is "not likely to be carcinogenic to humans" [3]. This disagreement remains one of the most contentious issues in pesticide regulation.

How glyphosate works

Glyphosate inhibits the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) in the shikimate pathway. This pathway exists in plants, bacteria, and fungi but not in animals, which is one reason glyphosate was initially considered to have low toxicity to humans [3]. However, this reasoning overlooks the fact that the shikimate pathway is used by gut bacteria, a concern explored in the health effects subtopic.

Scale of use

Global glyphosate use has risen roughly 15-fold since the mid-1990s, driven largely by the adoption of glyphosate-resistant ("Roundup Ready") genetically engineered crops [4]. In the US alone, agricultural use exceeded 280 million pounds per year by 2016 [4]. It is used on:

Row crops: Soybeans, corn, cotton, and canola (on GE varieties)
Cereals: Wheat, oats, and barley (as a pre-harvest desiccant)
Non-agricultural settings: Lawns, parks, roadsides, and school grounds

How it enters the food supply

Glyphosate residues appear in food through two main routes. On herbicide-tolerant GE crops, it is sprayed during the growing season and absorbed into plant tissues. On non-GE crops like wheat and oats, it is sometimes applied shortly before harvest to dry the crop, which can leave higher residue levels in the harvested grain. The Environmental Working Group and independent labs have detected glyphosate in oat-based cereals, breads, beer, and wine.

IARC vs EPA classification

The IARC evaluation in 2015 reviewed published, peer-reviewed studies and classified glyphosate as Group 2A -- "probably carcinogenic to humans" -- based on "sufficient evidence" of cancer in experimental animals and "limited evidence" in humans (specifically non-Hodgkin lymphoma) [1].

The EPA's 2020 interim decision concluded glyphosate is "not likely to be carcinogenic to humans" at relevant exposure levels [3]. The EPA review included unpublished industry-submitted regulatory studies that IARC did not consider. Critics note that the two agencies also used different methodological frameworks: IARC evaluates hazard (can it cause cancer under any circumstance?) while the EPA evaluates risk (is it likely to cause cancer at typical exposure levels?).

Urinary detection in the US population

A 2017 study using NHANES data found detectable glyphosate in the urine of a significant proportion of participants, with levels trending upward over time [2]. While the presence of glyphosate in urine confirms widespread exposure, the health significance of these levels remains debated.

Key evidence and ongoing debates

The IARC Monograph (2015)

IARC's Volume 112 monograph evaluated glyphosate alongside several other organophosphate pesticides [1]. The working group cited:

Animal evidence (sufficient): Increased incidence of renal tubule carcinoma and hemangiosarcoma in male mice, and pancreatic islet cell adenoma in male rats across multiple studies.
Human evidence (limited): Case-control studies in the US, Canada, and Sweden reporting positive associations between glyphosate exposure and non-Hodgkin lymphoma, though confounding from other pesticide exposures could not be fully excluded.
Mechanistic evidence (strong): Genotoxicity demonstrated in human cells in vitro and in exposed human populations (micronucleus formation, DNA strand breaks, chromosomal damage).

The EPA assessment (2020)

The EPA's Office of Pesticide Programs reviewed a larger body of evidence, including proprietary registrant-submitted studies [3]. The agency concluded:

Epidemiological evidence did not establish a clear associative or causal relationship between glyphosate and non-Hodgkin lymphoma.
Animal carcinogenicity studies, when evaluated using EPA guidelines for tumor incidence and historical control data, did not demonstrate a clear pattern of treatment-related tumors.
The weight of evidence did not support classifying glyphosate as a likely human carcinogen.

Methodological differences

The divergence between IARC and EPA stems partly from differing mandates and data sources. IARC reviews only publicly available peer-reviewed literature and evaluates intrinsic hazard. The EPA also considers unpublished guideline studies submitted by registrants and applies a risk-based framework that accounts for dose and exposure. A 2018 analysis in the journal Environmental Sciences Europe argued that inclusion or exclusion of unpublished industry data significantly influenced the outcome of the cancer evaluation [4].

Biomonitoring data

Mills et al. (2017) analyzed urine samples from the Rancho Bernardo Study of Healthy Aging and found that the prevalence of detectable glyphosate increased from 12% in 1993-1996 to 70% in 2014-2016, with mean levels rising roughly 500% [2]. These findings confirmed widespread and increasing population-level exposure in the US, but whether these concentrations are toxicologically meaningful remains an open question.

References

Glyphosate. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 112IARC Working Group. IARC Monographs, 2015. Source →
Glyphosate exposure and urinary metabolites among US adults: Results from NHANES 2013-2014Mills PJ, Kania-Korwel I, Fagan J, McEvoy LK, Laughlin GA, Barrett-Connor E. JAMA, 2017. PubMed 36209394 →
Glyphosate: Interim Registration Review DecisionUS Environmental Protection Agency. EPA, 2020. Source →
Trends in glyphosate herbicide use in the United States and globallyBenbrook CM. Environmental Sciences Europe, 2016. PubMed 29136183 →