Roundup products, herbicides that contain the chemical glyphosate, have been brought to attention for their potential role in causing cancer in humans. There is evidence from cell studies in the lab, animal studies, and human population studies that associate Roundup exposure with non-Hodgkin lymphoma in humans. A combination of these factors led the International Agency for Research on Cancer (IARC) to classify glyphosate as a group 2A (probable) carcinogen.
Since an association does not mean causation, we will address the research available regarding Roundup, as well as alternatives for both agriculture and home gardening.
What Is Roundup?
Roundup is a very popular herbicide—or weed killer—that is most commonly used in agriculture. The key ingredient in Roundup is glyphosate, a compound with a molecular structure similar to the amino acid glycine.
Background on Roundup (Glyphosate)
Glyphosate, the active ingredient in Roundup products was first sold as an herbicide in 1974. Since that time, it has grown to become the most widespread herbicide used in the United States. While in use since 1974, it’s estimated that as of 2016, two-thirds of the volume of glyphosate applied to crops had been sprayed in only the preceding decade.1
How It Works
Glyphosate works by inhibiting an enzyme in plants that is needed to manufacture a few amino acids (the building blocks of proteins). Since this enzyme and pathway are present only in plants (not humans or other animals) it was thought to be relatively non-toxic. Glyphosate also appears to bind (chelate) some minerals (such as calcium, magnesium, manganese, and iron) that are important for plant growth.2
In the U.S., Roundup is applied to control weeds and may also be used as a desiccant—a hygroscopic substance used as a drying agent. In the U.S. it is used along with crops that are genetically modified (GMO). In this setting, the GMO crops are resistant to the enzyme inhibition while nearby weeds in the vicinity are not. These “Roundup Ready” crops include:
In Europe, GMO crops are not approved, so it is used somewhat differently.
Human exposure to glyphosate has increased significantly since it was first used. Levels (measured by urine samples) in people over the age of 50 increased by 500% between the years 1993 and 1996 and follow-up measurements done between 2014 and 2015.3
Role in Cancer
In considering whether Roundup may play a role in cancer, it’s important to look at the evidence in several different ways. After all, it would be unethical to expose one group of people to large amounts of Roundup and another to none (the control group) to see if the group exposed developed more cancers. There are a number of different types of evidence that scientists use in addressing cancer risk.
Some of the lines of evidence that might support the role of a chemical in causing cancerinclude:
Mechanism: Does the chemical cause the type of damage to DNA in cells that could lead to cancer?
In vitro (lab) cell studies: What effect does Roundup have on cells, including cancer cells, grown in a dish in the lab?
Animal studies: Does the substance cause cancer in laboratory animals?
Human studies: Since it would be unethical to expose one group of people to Roundup and not another, research looks at population studies. For example, do people living in regions where Roundup is more commonly used have a higher incidence of any types of cancer? Is there a correlation between Roundup use and the incidence of any cancers over time? Does the incidence of a type of cancer correlate with measurements of glyphosate residual in people, for example, in urine specimens?
How roundup affects plants: Could Roundup alter plants so that they are more or less likely to cause disease when subsequently ingested?
Correlation of cancer incidence and use of glyphosate over time: Are there any cancers that began to increase when glyphosate use was started in the U.S. or other regions of the world?
The reason that several angles of research are needed is that correlation doesn’t necessarily mean causation. For example, the incidence of cancer may increase at the same time that Roundup use was increasing, but there are a number of other things that could be responsible as well.
An example often used by epidemiologists is that of ice cream and drownings. People tend to consume more ice cream in the summer and there are also more drownings in the summer, but this does not mean that ice cream causes drownings.
In 2015, glyphosate was classified as a probable human carcinogen (group 2A) by the International Agency for Research (IARC).
In Vitro Cell Studies and Mechanisms of Carcinogenicity
Scientists have looked at the effect of glyphosate on lymphocytes (a type of white blood cell) grown in a dish in the lab (in vitro) to evaluate potential DNA damage, as well as the type of damage that occurs if found.
Exposure to glyphosate was found to cause DNA damage (and other changes) similar to that seen with exposure to the common chemotherapy drug VePesid (etoposide). This was an acute change, but the authors postulated that chronic exposure could result in cumulative damage over time. Other studies have also shown evidence of damage to DNA as well as chromosomes in human cell lines as well as the ability of glyphosate to trigger oxidative stress.4
In an in-vitro study using human breast cancer cells, low concentrations of glyphosate (similar to what would be found in an average adult), resulted in more rapid growth (proliferative effects) of tumors that were hormone-dependent (estrogen/progesterone receptor-positive cancer cells). More rapid growth was not seen, however, in breast cancer cells that were not hormone dependent, suggesting that glyphosate has estrogen-like activity at least in this setting. (Glyphosate also altered estrogen receptor expression.)5
While studies thus far have only been done in vitro, this should be evaluated further. Estrogen receptor-positive breast cancer is the most common type of breast cancer. In addition, it is the type of breast cancer that can recur many years or decades after the initial treatment of early-stage cancer (late recurrence), and it’s largely unknown why some tumors recur and others do not. Whether the anti-estrogen therapies many women use after primary treatment would counteract any potential effect of glyphosate is unknown.
Affect of Roundup on Animals
Roundup (glyphosate) is thought to have “sufficient evidence” of being carcinogenic (cancer-causing) in animals according to the IARC.6
In a 2020 review of several studies on rats and mice (looking at chronic exposure and carcinogenicity), there was relatively strong evidence that glyphosate can lead to hemangiosarcomas (tumors of blood vessels), kidney tumors, and lymphomas. Other tumors that were found to be increased included basal cell cancers of the skin, tumors of the adrenal gland, and liver tumors.7
Looking at the underlying mechanism (at least with lymphomas), a different study found that glyphosate was able to induce the mutations in B cells that can play a role both in B-cell non-Hodgkin’s lymphoma and multiple myeloma.8
Population Studies (Human)
A number of epidemiological (population-based) studies have now shown an association between Roundup and non-Hodgkin lymphoma (NHL). Non-Hodgkin’s lymphoma is a cancer of the type of white blood cells called lymphocytes (either T cell or B cells) and is relatively common. Roughly 2.1% of people are expected to develop NHL over their lifetime, with the incidence slightly higher in men than in women.9
While correlation does not mean causation, it’s been noted that the incidence of NHL doubled between 1975 and 2006. In addition, the incidence of NHL is higher in people who have had occupational exposure to glyphosate-containing herbicides or who live near farmland that is routinely treated with herbicides.10
Other potential exposures have been looked at with the rise in NHL, including that of radon exposure in the home as regions that tend to have high levels of radon in the soil also tend to have high levels of NHL.11
A number of studies looking at NHL and glycophate have been done in the US and Europe since 2001. In 2008, a Swedish study looking at people between the age of 18 and 74 found a strong association between herbicides in general, glyphosate specifically, and non-Hodgkin lymphoma (those with exposure to glyphosate were twice as likely to have developed NHL).12
A 2019 meta-analysis of six studies supports this association further. Overall, those exposed to the highest level of glyphosate were 41% more likely to develop non-Hodgkin lymphoma The authors note that, in addition to the epidemiological association, evidence for a role in NHL is supported by links between glyphosate exposure and immunosuppression, endocrine disruption, and the type of genetic alterations often seen with NHL.13
Relative Risk vs. Absolute Risk
When looking at cancer risk, it’s important to describe what the statistics surrounding increased risk really mean. Relative risk refers to how much more likely a person might be to develop cancer than someone who is not exposed to a carcinogen. In this case, relative risk was 41%. Absolute risk, however, refers to how much more likely that means that you might develop NHL. In this case, the absolute risk is 0.8%. If your lifetime risk of developing NHL (on average, as there are other risk factors) is 2%, it might increase to 2.8% with exposure to glyphosate.
Not all studies, however, have shown an association between Roundup (glyphosate) and NHL. A large 2018 study published in the Journal of the National Cancer Institute did not find any apparent association between glyphosate exposure and any solid tumors or blood-borne cancers overall. There was some evidence of an elevated risk of acute myelogenous leukemia in those who had the greatest exposure, but this would require confirmation. This study was done with the use of questionnaires, and due to a high incidence of failure to complete the study, no solid conclusions could be drawn.14
These findings in which some studies, but not all, suggest a link between exposure and cancer are very common when looking for the causes of cancer. This is where it is very helpful to look not only at population studies, but animal studies, cell studies, and potential mechanisms to determine if the positive findings are likely significant.
Glyphosate and Plant Nutrients
Yet another angle to look at when studying glycophate exposure and cancer risk is not related to the exposure to glyphosate, but rather how glyphosate may affect the nutrients in the foods that are grown or their toxicity.
Some researchers are concerned that glyphosate, by binding with minerals in the soil (chelation), could make plants more toxic or reduce the plant’s uptake of nutrients from the soil. In turn, the foods that people eat that have been treated with glyphosate could potentially be toxic or lack the nutrients (some of which may be linked to cancer reduction) present in plants not grown with the use of glyphosate. Whether this is a concern to humans is unknown at this time, but is something that should be considered if glyphosate use is going to continue to increase in the US.2
Other Medical Concerns
In addition to cancer risk, the use of Roundup has raised concern over other medical problems as well. Some of these include:
Fatty liver disease: Mice fed a dose of glyphosate estimated to be 100 times lower than that found in the average human were found to develop liver dysfunction similar to nonalcoholic fatty liver disease.15 It’s important, of course, to note that the effect of a chemical in rodents doesn’t necessarily translate to effects in humans.
Birth defects: A study in Argentina found that regions where glyphosate concentrations in the soil were high had twice the rate of birth defects and three times the rate of miscarriages compared with regions that had lower concentrations of the chemical. Again this was correlation and doesn’t necessarily imply causation16 Birth defects have also been noted in baby pigs that have been fed soybeans containing glyphosate residue, and similar birth defects have been seen in humans who live near farmland where Roundup is used.10
Effects in pregnancy: In rats, it was found that exposure to glyphosate during pregnancy altered the expression of some genes associated with oxidant defense, inflammation, and fat metabolism. In theory, it’s possible that exposure to Roundup in utero could result in long-term neurological effects (but again, this study was only done on rodents).17
There are also reports that suggest a potential impact of Roundup on the liver, kidneys, general metabolic processes, as well as the composition of the gut microbiome.
Regulations and Additional Concerns
In addition to medical concerns the increasing use of Roundup, and especially with larger volumes being needed as resistance develops, raises other issues including both ecological and environmental concerns. These may be due to glyphosate, the metabolic product AMPA, both, or the effect when combined with genetically engineered proteins.
Studies have found that Roundup can alter the normal bacterial content of soil, as well as organisms such as earthworms, monarch butterflies, and honeybees.
With regard to human health, the Environmental Protection Agency (EPA) has set a glyphosate daily chronic Reference Dose (cRfD) of 1.75 milligrams (mg)/kilogram (kg) of body weight daily. The European Union (EU) also has a cRfD, though the cut-off is lower than the US at 0.5 mg/kg/day. In EU the scientists have now recommended the cut-off level for operators to be 0.1 mg/kg/day.
Despite these numbers, it can be hard to grasp what level of exposure might be concerning with respect to cancer. According to the EPA, a carcinogen is thought to have an “acceptable risk” if it is thought to “only” lead to cancer in 1:10,000-1 million people over their lifetime. That said, in the occupational setting, a higher risk (up to 1:1000) is generally allowed.1
Alternatives to Roundup
There are potential alternatives to the use of Roundup products both in agriculture and in home gardens.
In your home garden there are a number of alternatives to using herbicides. These can include:
Hand pulling weeds
Using very hot water (but it’s important to be careful to avoid burns)
Depending on the weeds, your local horticulture association can probably give you non-toxic ideas for removing weeds, ranging from vinegar to other solutions
Researchers have been looking into a number of alternatives to Roundup on an agricultural scale, especially with some countries banning or limiting the use of glyphosate (such as Austria, France, Germany, and Vietnam).
Even where Roundup is fully allowed, it’s recommended that contingency plans be formulated beginning now. Even without limitations, the growing resistance of weeds to glyphosate will likely result in the need for alternative methods of weed control in the near future.
Physical/mechanical methods (such as tilling and cutting) are one option. Cultural methods such as covering crops, changing planting times, and reseeding may also reduce the need for chemical control.18
If you use products such as Roundup at home or at work or if you live near a farm where Roundup is applied, there are a number of measures you can take to reduce your exposure.
When applying Roundup, wear protective clothing (our skin is not an impermeable barrier as evidenced by the multiple medications now available in patch form). Practice caution when removing the clothes you wear as well to avoid exposing family members who may be doing your laundry.
Some people like to wear gloves, but whether you do or not, always wash your hands thoroughly (for at least 20 seconds with soap and water) after you are done.
Consider the use of eye protection, especially if you will be applying herbicides under pressure.
Do not walk barefoot for at least 24 hours and preferably wait until after it has rained (or been watered) once Roundup is applied. Keep pets away as well.
Do not eat, drink, or smoke while applying any type of herbicides or pesticides
Consider your application method: high-pressure sprayers may result in greater exposure.
Review the material data safety sheets on any chemical you work with on-the-job and follow recommendations for protection.
General Measures to Limit Exposure:
Wash all produce before eating
Avoid home herbicides whenever possible, especially on houseplants
Keep children and pets away from fields that are treated with Roundup (this may require some awareness in places such as parks and playgrounds)
Keep in mind that Roundup is only one chemical in the environment, and it is often a combination of factors rather than one single cause that leads to cancer. There are many potential concerns in the environment (such a Roundup), but well-known concerns as well. Make sure to focus the bulk of your prevention efforts on major risk factors (such as not smoking, avoiding excess sun exposure, and eating a wide variety of fruits and vegetables).
While potential risks and lessening effectiveness may be concerning, this is also an opportunity for researchers to develop alternative weed management techniques that are not only more sustainable and safer, but healthier for the environment as well. There’s no need to wait to take action yourself. While the agricultural industry looks into alternative options, people can begin practices that minimize the use of and exposure to glyphosate in their own gardens today.
As a final note, don’t limit your consumption of vegetables due to concerns over Roundup residues on your food. When it comes to your daily routine, increasing your intake of vegetables (at least up to 600 grams/day) is one of the easier ways to reduce your risk of cancer in the future.19
verywellhealth.com, 19 January 2021