Glyphosate for Breakfast?

If you are sitting down to a bowl of Cheerios this morning you may want to push it aside while we pick through some research on glyphosate.

The Environmental Working Group, an American activist group, recently shared findings that 21 General Mills oat-based cereal and snack products contain traces of glyphosate, 17 of which exhibited levels above what the group deems safe for children’s consumption. The studied food items included six varieties of Cheerios and 14 Nature Valley products, such as granola bars. The EWG established a threshold of 160 parts per billion (ppb) of glyphosate residue in food products, yet Honey Nut Cheerios Medley Crunch and Cheerios exhibited the highest traces, weighing in at 833 and 729 ppb, respectively.

In response, Bayer, the parent company of glyphosate-producing subsidiary Monsanto, maintained that these levels are “far below” EPA limits, and that an adult would have to eat 158 pounds of oat-based food every day for the rest of their life to reach these EPA limits. They also contend that the EWG has a “long history of spreading misinformation about pesticide residues”.

This news may hit close to home for many, but it isn’t out of the blue: in 2011, the USDA found higher glyphosate residues in over 90% of soybean samples. They also found residues of glyphosate’s metabolism product, AMPA.

Myers et al. (2016) notes that studies have found significant traces of GBHs in drinking water and groundwater, likely regularly exposing millions of people worldwide to glyphosate without their knowledge.

Monsanto currently faces up to 11,000 lawsuits now, many of which claim that Roundup causes cancer. Alva and Alberta Pilliod, a gardening couple in California, sprayed Roundup for over two years to keep weeds off their driveway while wearing flip flops, shorts, and tank tops. They have both been diagnosed with non-Hodgkin’s lymphoma, a type of blood cancer; in May of this year, a California jury awarded them $2 billion in damages from Monsanto. This comes after a San Francisco jury ordered Monsanto to pay $289 million to former school groundskeeper in August 2018, who developed non-Hodgkin’s lymphoma after years of Roundup use.

What is glyphosate?

Glyphosate was accidentally discovered in 1950 by Dr. Henri Martin, and it was originally used as a pipe cleaner. However, in the early 1970s, Dr. John Franz, who later founded Monsanto, demonstrated its herbicidal capability. Since then, for the past three decades, glyphosate has been the most widely used herbicide worldwide [Bai 2016]. In 1996, Monsanto began to sell genetically modified crops that could tolerate glyphosate, termed “Roundup Ready” — including soybeans, corn, and cotton.

The volume of glyphosate-based herbicides (GBHs) has increased about 100-fold since then [Myers 2016]. GBHs were initially touted as a safer alternative to earlier herbicides that were known to cause problems with both crop efficiency and human health. Its use continues to skyrocket due to both the widespread evolution of glyphosate-resistant weeds and new pre-harvest drying patterns. More than 250 pounds of GBHs were sprayed in 2016.

Monsanto’s GBH patent ended in 2000, so many companies worldwide now manufacture GBHs.

Glyphosate acts on enzymes that disrupt the shikimic acid pathway, a biochemical pathway found exclusively in green plants through which they produce amino acids [Bai 2016].

When/how/why it’s used

In the U.S., glyphosate is mostly used in the Midwest for corn, soybean, and wheat production. It’s used to prevent weeds from interfering with crop growth before and after planting and harvesting. GBHs are now widely used in a variety of crops including maize, soy grain, barley, wheat, canola, edible beans, and other crops. When glyphosate is applied pre-planting and post-harvest to keep weed growth at bay, there are rarely detectable residues in grain, oilseeds, or forage crops [Myers 2016].

Recent years have seen an increase in “green burndown”, in which GBHs are applied late in the season as a harvest aid to dry out the crops sooner. Unfortunately, these late-season applications typically lead to much higher glyphosate residues in the final harvested product. For example, Duke et al. (2012) found that genetically modified soybeans sprayed at full bloom contained 5-10 times more glyphosate and 10-25 times more AMPA than plants sprayed only early in the growing season [Duke 2012]. This use applies to non-GMO crops as well.

Debate over its classification

The EPA classifies glyphosate as “practically non-toxic and not an irritant”, according to its acute toxicity classification system. They derived this classification based on toxicity data and the fact that the shikimic acid pathway upon which glyphosate acts is only found in green plants. Furthermore, the European Food Safety Authority (EFSA) also deems glyphosate safe.

However, research now indicates that glyphosate can linger and accumulate in the environment, which complicates assessing its health risks. For example, in 2015, the European Food Safety Authority found that glyphosate and its major metabolite, AMPA, may be present in food consumed by humans.

On the other hand, the International Agency for Research on Cancer (IARC), a branch of the World Health Organization (WHO), classifies glyphosate as a “probable human carcinogen.”

Initial industry toxicity testing indicated that GBHs posed minimal risks to non-plant species, which led to regulatory authorities around the world establishing high acceptable exposure limits.

Further stirring the pot (no pun intended) is that in practice, multiple herbicides are often mixed together in large tanks, yet regulators only require each pesticide be tested for safety individually.

What the science tells us

The University of California published a biomonitoring study in which the measured glyphosate levels in over 1,000 adults from 2014 to 2017, and found that at least 70% of people had detectable traces of glyphosate in their bodies. Compare this with a cohort from 1993 to 1996, in which only 12% of participants had detectable traces.

In the lab, glyphosate has been shown to disturb endocrine (hormone) function and induce toxicity in multiple human cell lines and tissue samples.

When frog embryos were grown with an extremely diluted commercial GBH (and with glyphosate alone), the researchers found the embryos had an abnormal shape [Paganelli et al. 2010]. The authors note that these direct effects of glyphosate on early embryonic development raise concern for human offspring in populations exposed to GBH in agricultural fields.

When pregnant mice were given water with 0.5% glyphosate, they exhibited negative changes in body weight and ovary function [Ren 2018]. Exposure to high doses of daily glyphosate in mice caused memory problems and nervous system dysfunction [Ait bali 2019].

In vitro, glyphosate and GBHs disrupted estrogen signaling and DNA damage in liver cells beginning at 2ppm [Gasnier 2009]. By 10ppm, they both induced toxic effects; as with other findings, these effects were more pronounced with GBHs than with glyphosate alone.

Glyphosate induced breast cancer-like activity in vitro by increasing estrogen activity; interestingly, in an estrogen-depleted environment, glyphosate only caused proliferation in hormone-dependent breast cancer cells, but not hormone-independent [Thongprakaisang 2013]. This group points out that GBHs are often used for soybean cultivation, and they found a synergistic estrogenic effect between glyphosate and genistein, a form of estrogen in soybeans. The concentration of glyphosate used in this study that exhibited estrogenic activity and interfered with normal estrogen signaling were relevant to those reported in environmental conditions and exposed individuals.

Benedetti et al. (2004) delivered Glyphosate-Biocarb in water to rats and found that even the lowest dose caused “irreversible damage” to liver cells, including enzyme leakage and tissue structure changes [Benedetti 2004].

A two-year toxicity study in rodents demonstrated adverse effects of glyphosate in the liver and kidney [Myers 2016]. Other studies using GBHs at doses considered “safe” for humans have caused hepatorenal damage.

Young pigs fed GBH residue-contaminated food from birth showed congenital malformations that are somewhat similar to those reported in human populations living near farming regions with GBH-resistant crops [Kruger 2014, Laborde 2014].

Conversely, other groups maintain that there is no link between glyphosate and reported adverse effects in cells, animals, or humans. For example, a 2012 review from the engineering consulting firm exponent concluded that there is no consistent effect of glyphosate exposure on reproductive health or on offspring health, and that the estimated exposure concentrations in humans are 500-fold less than the maximum threshold established by the EPA [Williams 2012]. The longitudinal Agricultural Health study also found no significant hazard of glyphosate exposure following a group of adults to explore any potential link between glyphosate exposure and non-Hodgkin’s lymphoma [Andreotti 2017].

Glyphosate is a chelating agent, meaning it can sequester vital micronutrient metals like zinc, cobalt, and manganese, thereby altering their bioavailability for crops, people, wildlife, livestock, and pets [Myers 2016]. These metals are important for kidney and liver function, so their loss could have detrimental effects for these organs.

Epigenetic’s

When pregnant rats were exposed to sublethal doses of GBHs, their male offspring had impaired reproductive development, suggesting a potential epigenetic effect.

Moreover, in a study published just this year, Michael Skinner’s group at the University of Washington fed glyphosate to rats and found that adverse effects didn’t manifest until two generations later. The affected offspring rats exhibited greater propensity for prostate disease, obesity, kidney disease, ovarian disease, and birth abnormalities, even though they never came into contact with glyphosate [Kubsad 2019].

Microbiome

In addition to targeting plants, glyphosate and GBHs go after fungi and some bacteria. In a 2013 study, Shehata et al. found that pathogenic bacteria like different varieties of Salmonella and Clostridium are actually highly resistant to glyphosate, yet beneficial bacteria — including species of Enterococcus, Lactobacillus, and Bifidobacterium — were quite susceptible. This could perturb the delicate balance in our GI tract’s bacterial community.

Glyphosate alone vs in formulations

Emerging evidence suggests that many of the deleterious effects associated with GBHs arise from non-glyphosate additives. For example, a group of researchers in Vienna, Austria demonstrated that both pure glyphosate and Roundup UltraMax caused DNA damage, cell membrane damage, and impaired mitochondrial function [Koller 2012]. However, they found that Roundup was overall more active than the active principle glyphosate alone, inducing the same adverse effects as glyphosate but at much lower doses. Importantly, they looked at buccal epithelial cells — aka cheek cells — which are translatable to inhaled exposure for agricultural workers.

Benachour and Seralini (2008) showed that four different Roundup formulations at dilutions starting at 105-fold caused mitochondrial damage, cell membrane impairment, DNA fragmentation, and eventual cell death in multiple human cell types. Interestingly, they found that these negative effects were less related to the amount of glyphosate itself, but rather to the nature of the adjuvants like AMPA and POEA (surfactant). These two additives separately caused cell membrane damage, and the mixtures were more potent with glyphosate present. The authors concluded that Roundup additives like POEA can affect cell permeability and amplify toxicity that is already caused by glyphosate.

Chaufan et al. found that GBH had toxic effects — including oxidative stress and cell death — on a human liver cell sample, yet no effects were seen with glyphosate or AMPA alone [Chaufan 2014].

Benachour et al. (2007) found that Roundup was overall more toxic to cells than glyphosate alone, which may suggest a synergistic effect bolstered by additives present in Roundup. Further, at lower non-toxic doses, Roundup was found to be an aromatase disruptor. Aromatase is an enzyme involved in making estrogen, indicating that Roundup may impair estrogen functioning.

Limitations on what we know

We need more research examining realistic glyphosate exposures. Studies tend to focus on aggressive glyphosate or GBH dosing that is magnitudes more potent than one would typically experience by eating contaminated food or even by working directly with the herbicide.

For example, a 2004 study from the University of Lodz in Poland dosed human red blood cells with toxic levels of either Roundup or glyphosate and found that both had deleterious effects on blood cells [Pieniążek 2004]. However, 10 years later, members from this group concluded that the glyphosate-induced changes in human red blood cells would only occur in the context of poisoning.

We need to learn more about the toxicity of GBH additives, particularly the surfactant POEA, alone and in conjunction with glyphosate.

There haven’t been enough robust studies examining any causal link between GBH exposure and non-Hodgkin’s lymphoma.

Current human data is limited and precludes a full understanding of where glyphosate accumulates in the body, although preliminary animal studies point to the liver and kidney.

In June of this year, Bayer announced it will devote $5.6 billion to researching glyphosate alternatives over the next decade.

Finding middle ground

While many activists and researchers discount studies funded by companies including Monsanto, others contend that financial interests alone shouldn’t be grounds to dismiss thousands of independently-verified studies, since the labs still have to follow strict policies on data integrity and practices.

German Chancellor Angela Merkel recently announced to the country’s lower house that use of glyphosate will be phased out completely. This is particularly interesting since parent company Bayer is based in Germany.

Dietary recommendations

One study found that glyphosate residues were significantly lower in organically-grown grains than in conventionally grown wheat bran and barley grain [Granby 2003].

Take it with a GRAIN of salt.

Cooking or other thermal processing usually breaks down herbicide residues due to the high temperature. However, because of glyphosate’s unique salt-based composition, it isn’t as likely to be degraded during cooking [Xu 2019].

Non-dietary considerations

In addition to its effects on human health, Roundup also exerts deleterious effects on soil health. The evolution of herbicide-tolerant “superweeds” poses a threat to both farmers and consumers. In order to produce glyphosate, phosphate ore is extracted from mines and refined into elemental phosphorus. Despite Bayer’s claims of sustainable mining, environmentalists contend that this process involves stripping soil off mountaintops. This damages vegetation, contaminates water, and causes noise and air pollution that is detrimental to both wildlife and the environment [Wozniacka 2019].

More research is needed to fully understand how glyphosate may be impacting the health of people who apply the product in residential and agricultural settings, as well as people who may not come in direct contact with the chemical.

References

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