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Mississippi Turfgrass – Jeffrey Derr, Ph.D. Professor of Weed Science, Virginia Tech

Glyphosate has been in the news quite a bit recently. You probably have seen the ads on television concerning glyphosate and human health. In this article I discuss some background information on this herbicide as well as scientific reports on toxicity of the chemical.

What is glyphosate?

The glyphosate molecule (Figure 1) is similar to the amino acid glycine. The chemical name is N-(phosphonomethyl) glycine, a relatively small molecule compared to newer herbicides. It is the active ingredient in products such as Roundup PROMAX, as well as in generic products sold under a variety of trade names. Since the chemical is off patent (patent expired around 2000), other companies besides Monsanto/Bayer can sell this herbicide under their own trade name. Some examples of other trade names for products that contain glyphosate include Accord, Gly Star Pro, Glyphomate 41, Razor, Rodeo and Touchdown, among others.

Formulation

The initial formation of this herbicide was an isopropylamine salt of glyphosate, which is still widely used, although other salt formulations are available now, such as the potassium salt and the dimethylamine salt. This becomes important when comparing products. We need to look at the amount of glyphosate acid in products, not the amount of active ingredient, since the different salt formulations differ in their molecular weight. For example, Roundup PROMAX contains 5.5 pounds per gallon of the potassium salt of glyphosate (ai) or 4.5 lbs/gallon glyphosate acid (ae). Roundup Pro contained 4.0 lbs/gallon of the isopropylamine salt of glyphosate (ai) or 3.0 lbs/gallon glyphosate acid (ae). So Roundup PROMAX contains 50% more glyphosate acid than Roundup Pro and applications rates in terms of fluid ounces of product per acre are lower than for Roundup Pro.

Besides glyphosate, there are other chemicals in commercial formulations, usually water and a surfactant. As an example of a formulation, Roundup PROMAX contains the potassium salt of glyphosate at 48.7% by weight, surfactant(s) approximately 9%, and water plus minor ingredients at approximately 42%.

Surfactants can aid in the absorption of herbicides by weeds. One example would be POEA (polyoxyethylene tallow amine). Concerns have been raised about the toxicity of this surfactant to aquatic organisms such as tadpoles, salamanders, and frogs. Aquatic formulations of glyphosate either do not contain a surfactant or contain a surfactant that has not shown to be an issue. That is why certain formulations of glyphosate are not labeled for aquatic use – not due to the toxicity of glyphosate but due to toxicity concerns about the surfactant to amphibians and other aquatic organisms. For glyphosate products that do not contain a surfactant, one generally needs to add an approved one for optimum weed control.

History

Glyphosate was found to control weeds by a Monsanto scientist in 1970. The herbicide was patented in 1971 and was introduced commercially as Roundup in 1974. Glyphosate use has increased over time, especially when Roundup-Ready crops were introduced, starting with Roundup Ready soybeans in 1996. These soybean lines, and later corn, cotton, and other crop cultivars, were developed to be resistant to glyphosate through biotechnology. For these genetically-modified crops, glyphosate could be applied overtop for selective weed control.

Mode of action

Glyphosate inhibits the enzyme enolpyruvyl shikimate-3-phosphate (EPSP) synthase, needed for synthesis of the aromatic amino acids tryptophan, tyrosine, and phenylalanine in plants. Animals, including people, do not make these amino acids, so they need to get these chemicals in their diet. Plants have to make these amino acids, which are the building blocks of proteins. So glyphosate inhibits a process that occurs in plants but not in  animals, resulting in a chemical that controls plants with low acute toxicity to animals, including people.

Acute toxicity of glyphosate

A measure of toxicity is the LD50 value, the dose required to kill 50% of the test animal, usually rats. The higher the LD50, the lower the toxicity. The acute oral LD50 for glyphosate in rats is greater than 5,000 mg/kg – practically non-toxic. The acute dermal LD50 rat is greater than 5,000 mg/kg – practically non-toxic. (taken from SDS sheet for Roundup PROMAX, http://www.cdms.net/ldat/mp8NJ004.pdf). For comparison the acute oral LD50 rat for caffeine is 192 mg/kg (https://psychonautwiki.org/wiki/Caffeine) so caffeine is a much more toxic chemical than glyphosate. The acute oral LD50 rat for aspirin is 950 mg/kg (aspirin SDS, https://www.caymanchem.com/msdss/70260m.pdf), also more toxic on an acute basis than glyphosate. Another point to keep in mind is that risk associated with a given pesticide is based on the toxicity of the chemical along with the exposure level.

Use

Glyphosate is a nonselective postemergence herbicide, meaning that it controls essentially all weeds. The recent development of glyphosate-resistant weeds has pushed researchers and growers to find alternative means to control these weed species. However, most weed species are still susceptible to glyphosate.

Glyphosate is systemic, so it moves into and controls underground portions of weeds (roots, rhizomes, tubers, etc.), making it the preferred product for perennial weed control in many situations. This chemical binds to soil particles and has essentially no soil activity, so crops can be planted a week after application.

Glyphosate is used for preplant weed control/site preparation, lawn renovation, spot treatment of weeds in landscape beds, as a directed spray application in fruit and nursery production, and for noncrop weed management, such as guard rails, railroad lines, and parking lots, among other uses. It controls grasses, sedges, and broadleaf weeds, making it a broad spectrum herbicide.

Recent issues about glyphosate

It has been suggested that glyphosate causes non-Hodgkin lymphoma (NHL), a type of cancer, and other diseases. In one epidemiological report, associations between pesticides and NHL subtypes were reported, including B cell lymphoma and glyphosate (Int J Environ Res Public Health. 2014 Apr 23;11(4):4449-527. doi: 10.3390/ijerph110404449). The International Agency for Research on Cancer (IARC), part of the World Health organization, listed glyphosate as a probable human carcinogen (Group 2A) in 2015 (https://monographs.iarc.fr/wp-content/uploads/2018/06/mono112-10.pdf), along with burning of wood, eating red meat, high-temperature frying, late-night work shifts, being a hairdresser or barber, spraying insecticides, and making art glass, among others (https://en.wikipedia.org/wiki/List_of_IARC_Group_2A_carcinogens).

In August 2018, a jury in San Francisco ordered Roundup’s manufacturer, Monsanto, to pay $289 million in damages to a school groundskeeper (Dewayne Lee Johnson) who argued that the glyphosate-based herbicide caused his cancer. A judge later upheld that decision but reduced Monsanto’s payout to $78 million. Recently, another jury in San Francisco ruled against Monsanto, with the jury concluding that glyphosate was a substantial factor in causing non-Hodgkin lymphoma in Edwin Hardeman, a 70-year-old Sonoma County man. Bayer, which bought Monsanto, responded by saying that there is over four decades of extensive science on glyphosate and the conclusions of regulators worldwide support the safety of their glyphosate-based herbicides and that they are not carcinogenic (https://www.bayer.us/en/newsroom/press-releases/article/?id=123290).

Harrells has decided not to sell glyphosate products (https://www.lawnandlandscape.com/article/ll-031219-harrells-discontinues-glyphosate/).Although the company feels that the weight of scientific evidence strongly supports its safety when used properly, their insurance provider would not cover any claims related to glyphosate. With apparently over 11,000 lawsuits filed against Monsanto, there is a financial risk from the insurance standpoint related to glyphosate.

Another issue that has been mentioned is that glyphosate may affect bacteria in the gut microbiome. Low levels of glyphosate have been reported in certain crops, generally in the parts per billion range, although the EPA has determined that the low levels do not pose a significant health risk to humans. Low levels of labeled pesticides can sometimes be detected in food crops, but the EPA compares these levels to the toxicity data for that pesticide to determine a no effects level and to set residue levels allowed before approving a pesticide. Certain bacteria can be adversely affected by exposure to glyphosate. A recent issue that has been reported is an impact on the gut bacteria in honey bees, resulting in adverse effects (Proc. Natl. Acad. Sci. USA. 2018 Oct 9; 115(41): 10305–10310).

What does the scientific literature say about glyphosate and cancer?

As of 2016, there were 23 epidemiological studies, 15 animal carcinogenicity studies and over 90 genotoxicity studies for glyphosate. Reviews have been written summarizing the conducted studies.

A review in 2012 found no consistent pattern of causation between glyphosate exposure and cancer (Mink et al. Reg. Toxicology & Pharmacology 63:440-452). Some conclusions of glyphosate effects are not supported by available evidence (Frontiers in Public Health 2017 Vol 5 Article 316). There was no association between glyphosate and any solid tumor, including. non-Hodgkin lymphoma (Andreotti et al. 2018 J. National Cancer Institute 110 (5): 509-516). The U.S. EPA concluded in a 2013 report that glyphosate does not pose a cancer risk to humans (2013 Federal Register Notice (FR 25396, Vol. 78, No. 84, May 1, 2013).

In 2016, EPA’s office of Pesticide Programs released a report (https://www.epa.gov/sites/production/files/2016-09/documents/glyphosate_issue_paper_evaluation_of_carcincogenic_potential.pdf). In it, EPA states that “In epidemiological studies, there was no evidence of an association between glyphosate exposure and numerous cancer outcomes; however, due to conflicting results and various limitations identified in studies investigating NHL, a conclusion regarding the association between glyphosate exposure and risk of NHL cannot be determined based on the available data.” “Increases in tumor incidence were not considered treatment-related in any of the animal carcinogenicity studies.” “The overall weight of evidence indicates that there is no convincing evidence that glyphosate induces mutations in vivo via the oral route.” EPA’s overall conclusion was that glyphosate was “’not likely to be carcinogenic to humans’ at doses relevant to human health risk assessment.”

In 2017, the EPA issued a draft assessment, which also concluded that glyphosate is not a likely carcinogen to humans (Released Draft Risk Assessments for Glyphosate, https://www.epa.gov/pesticides/epa-releases-draft-risk-assessments-glyphosate). The European Food Safety Authority and the EU member states concluded in 2015 that glyphosate is unlikely to pose a carcinogenic hazard to humans and the evidence does not support classification with regard to its carcinogenic potential (EFSA Journal 2015;13(11):4302).

The Food and Agriculture Organization of the United Nations in a 2016 summary report concluded that “in view of the absence of carcinogenic potential in rodents at human-relevant doses and the absence of genotoxicity by the oral route in mammals, and considering the epidemiological evidence from occupational exposures, the Meeting concluded that glyphosate is unlikely to pose a carcinogenic risk to humans from exposure through the diet” (https://www.who.int/foodsafety/jmprsummary2016.pdf).

Why did the ARC reach a different conclusion than EPA and the EFSA and the FAO? The IARC only looked at publicly-available reports while EPA evaluated all data, including those submitted by the registrant and those not published. The IARC did not consider dose in their analysis while the EPA considered dose to be relevant to the interpretation of data. EPA did a systemic evaluation of the quality for the studies conducted with glyphosate while the IARC did less of a quality evaluation.

There can be differing opinions on the interpretation of laboratory testing of pesticides. One cannot test chemicals on people, so scientists use a test animal such as rats. Labs will use only a limited number of test animals and may increase the dose to levels much higher than typical exposure levels of the chemical to try to force responses that may occur at low frequency or at low dosages. If cancer develops in the test animal only at doses much higher than a typical exposure would be, what do you conclude? Did the dose cause the response or did the chemical cause the effect? Can you extrapolate the data to lower doses? These are questions that arise when interpreting results from lab studies.

Alternatives to glyphosate

We do not have a ready alternative to glyphosate that provides the same level of weed control and use. The closest in my opinion is glufosinate (Finale, Cheetah Pro), another non-selective postemergence herbicide that is inactivated upon contact with soil. It works faster on weeds than glyphosate but it is not as systemic as glyphosate. So glyphosate generally provides greater control of perennial weeds, especially perennial grasses, compared to glufosinate. There are nonselective postemergence contact herbicides, such as diquat (Reward), pelargonic acid (Scythe), and acetic acid (WeedPharm). These contact herbicides will not affect the underground portions of perennial weeds so they are more effective overall on annual weeds.

Decision making

Read the literature cited in this article and determine for yourself the benefits and risks to use of glyphosate. Be careful about articles you read on the internet, in newspapers, and in other media. Sometimes claims are made about chemicals that are not supported by scientific research. Ask to see data from published, peer-reviewed articles in scientific journals.

If you plan to continue using glyphosate, as we plan to do here at the research station, follow information listed on the label. For example, the Personal Protective Equipment (PPE) for Roundup PROMAX is a long sleeve shirt, long pants, shoes, and socks (http://www.cdms.net/ldat/ld8NJ010.pdf). Read and follow all label directions. Make sure the product you use has a label for the site to be treated.

Acknowledgement –

I would like to thank Dr. Timothy Pastoor, of Pastoor Science Communications for sharing his PowerPoint “Glyphosate – Get the Facts” with me. Some of the information listed above was taken from this PowerPoint.