US EPA Ignored Substantial Scientific Evidence of Glyphosate’s Genotoxicity

THIRD WORLD NETWORK BIOSAFETY INFORMATION SERVICE

 

Dear Friends and Colleagues

US EPA Ignored Substantial Scientific Evidence of Glyphosate’s Genotoxicity

A new analysis has been published in the journal Environmental Science Europe entitled, ‘How did the US EPA and IARC reach diametrically opposed conclusions on the genotoxicity of glyphosate-based herbicides?’. Genotoxicity refers to a substance’s destructive effect on a cell’s genetic material. Genotoxins can cause mutations in cells that can lead to cancer. While the US Environmental Protection Agency (EPA) evaluates glyphosate as “not likely to be carcinogenic to humans” and not genotoxic, the WHO’s International Agency for Research on Cancer (IARC) considers glyphosate as “probably carcinogenic to humans” and genotoxic.

Compared to the EPA’s genotoxicity review, the paper says that the IARC review is grounded on more recent, more sensitive, and more sophisticated genotoxic studies, and more accurately reflects real-world exposures.

The paper shows that only by framing and constraining its genotoxicity assessment in a highly selective way was the EPA able to conclude that glyphosate was not genotoxic. It also demonstrates that the EPA disregarded substantial scientific evidence of genotoxicity of glyphosate and glyphosate-based herbicides (GBHs). Overall, the way pesticides are assessed for risk is not fit for purpose and exposes people and the environment to unacceptable risks. The paper explains that the EPA and IARC reached diametrically opposed conclusions on glyphosate genotoxicity for three primary reasons:

  1. The EPA relied heavily on unpublished regulatory studies commissioned by pesticide manufacturers, 99% of which found that glyphosate was not genotoxic, while the IARC relied on peer-reviewed published studies and public literature reports, 70% of which found that glyphosate was genotoxic.

    2. The EPA focused its analysis on glyphosate in its pure chemical form (“glyphosate technical”). However, almost no one is exposed to glyphosate alone. Applicators and the public are exposed to complete herbicide formulations consisting of glyphosate plus added ingredients (adjuvants). The IARC considered a total of 118 genotoxicity assays on glyphosate technical, GBHs, and aminomethylphosphonic acid (AMPA), glyphosate’s primary metabolite. The EPA’s analysis encompassed only 51 of these 118 assays (43%). The IARC further analyzed another 81 assays exploring other possible genotoxic mechanisms, of which 62 (77%) reported positive results.

    3. The EPA’s analysis was limited to typical, general population dietary exposures assuming legal, food-crop uses, and did not take into account nor address generally higher occupational exposures and risks. The IARC’s assessment encompassed data from typical dietary, occupational, and elevated exposure scenarios. Elevated exposure events caused by spills, a leaky hose or fitting, or wind are actually common for people who apply herbicides several days a week, for several hours, as part of their work.

The editor-in-chief of Environmental Sciences Europe and a co-author have offered a list of “lessons to be learned” from the paper for the risk assessment of pesticides and other chemicals (see https://doi.org/10.1186/s12302-019-0187-z). They recommend that studies relating to both glyphosate and glyphosate-based herbicide formulations be taken into account in risk assessments. Also, all studies used in the risk assessment and the data underlying them must be made public and available for independent scrutiny.

With best wishes,

Third World Network
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Email: twn@twnetwork.org
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Item 1

HOW DID THE US EPA AND IARC REACH DIAMETRICALLY OPPOSED CONCLUSIONS ON THE GENOTOXICITY OF GLYPHOSATE-BASED HERBICIDES?

Charles M. Benbrook
Environ Sci Eur (2019) 31article_1588
https://doi.org/10.1186/s12302-018-0184-7
14 January 2019
https://hygeia-analytics.com/wp-content/uploads/2019/01/FINAL_Published_1-14-19.pdf

ABSTRACT

Background

The US EPA considers glyphosate as “not likely to be carcinogenic to humans.” The International Agency for Research on Cancer (IARC) has classified glyphosate as “probably carcinogenic to humans (Group 2A).” EPA asserts that there is no convincing evidence that “glyphosate induces mutations in vivo via the oral route.” IARC concludes there is “strong evidence” that exposure to glyphosate is genotoxic through at least two mechanisms known to be associated with human carcinogens (DNA damage, oxidative stress). Why and how did EPA and IARC reach such different conclusions?

Results

A total of 52 genotoxicity assays done by registrants were cited by the EPA in its 2016 evaluation of technical glyphosate, and another 52 assays appeared in the public literature. Of these, one regulatory assay (2%) and 35 published assays (67%) reported positive evidence of a genotoxic response. In the case of formulated, glyphosate-based herbicides (GBHs), 43 regulatory assays were cited by EPA, plus 65 assays published in peer-reviewed journals. Of these, none of the regulatory, and 49 published assays (75%) reported evidence of a genotoxic response following exposure to a GBH. IARC considered a total of 118 genotoxicity assays in six core tables on glyphosate technical, GBHs, and aminomethylphosphonic acid (AMPA), glyphosate’s primary metabolite. EPA’s analysis encompassed 51 of these 118 assays (43%). In addition, IARC analyzed another 81 assays exploring other possible genotoxic mechanisms (mostly related to sex hormones and oxidative stress), of which 62 (77%) reported positive results. IARC placed considerable weight on three positive GBH studies in exposed human populations, whereas EPA placed little or no weight on them.

Conclusions

EPA and IARC reached diametrically opposed conclusions on glyphosate genotoxicity for three primary reasons: (1) in the core tables compiled by EPA and IARC, the EPA relied mostly on registrant-commissioned, unpublished regulatory studies, 99% of which were negative, while IARC relied mostly on peer-reviewed studies of which 70% were positive (83 of 118); (2) EPA’s evaluation was largely based on data from studies on technical glyphosate, whereas IARC’s review placed heavy weight on the results of formulated GBH and AMPA assays; (3) EPA’s evaluation was focused on typical, general population dietary exposures assuming legal, food-crop uses, and did not take into account, nor address generally higher occupational exposures and risks. IARC’s assessment encompassed data from typical dietary, occupational, and elevated exposure scenarios. More research is needed on real-world exposures to the chemicals within formulated GBHs and the biological fate and consequences of such exposures.

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Item 2

NEW ANALYSIS RAISES QUESTIONS ABOUT EPA’S CLASSIFICATION ON GLYPHOSATE WEED KILLER

Researcher says the EPA has disregarded substantial evidence that the popular herbicide is linked to cancer

Carey Gillam
Environmental Health News
15 January 2019
https://www.ehn.org/glyphosate-cancer-epa-2625974133.html

A little more than a month ahead of a first-ever federal trial over the issue of whether or not Monsanto’s popular weed killers can cause cancer, a new analysis raises troubling questions about the U.S. Environmental Protection Agency’s (EPA) handling of pertinent science on glyphosate safety.

According to the report, which examines the opposing positions taken by the EPA and an international cancer research agency on glyphosate-based herbicides, the EPA has disregarded substantial scientific evidence of genotoxicity associated with weed killing products such as Roundup and other Monsanto brands. Genotoxicity refers to a substance’s destructive effect on a cell’s genetic material. Genotoxins can cause mutations in cells that can lead to cancer.

The EPA classifies glyphosate as not likely to be carcinogenic while the International Agency for Research on Cancer (IARC), which is part of the World Health Organization, classifies it as “probably carcinogenic.”

The paper was authored by Charles Benbrook, a former research professor who served at one time as executive director of the National Academy of Sciences board on agriculture, and was published in the journal Environmental Sciences Europe on Monday. It is based on Benbrook’s review of EPA and IARC records regarding the types and numbers of glyphosate studies each organization evaluated.

“Clearly, compared to EPA’s genotoxicity review, the IARC review is grounded on more recent, more sensitive, and more sophisticated genotoxic studies, and more accurately reflects real-world exposures,” Benbrook told EHN.

Benbrook testified as an expert witness in the first lawsuit to go to trial against Monsanto over claims its glyphosate herbicides cause cancer. The plaintiff in that case, Dewayne “Lee” Johnson, won a unanimous jury award of $289 million last year that the judge in the case cut to $78 million. Thousands of additional cancer victims have sued Monsanto and the second trial begins Feb. 25 in federal court in San Francisco. Benbrook is also expected to testify for the plaintiff in that case.

Monsanto is seeking to exclude Benbrook’s testimony at trial, saying he has no expertise in any physical science or field of medicine and no training or degree in toxicology and has never worked at the EPA or other regulatory body.

The EPA did not respond to a request for comment. The agency has maintained, however, that its review of glyphosate has been robust and thorough. Glyphosate has low toxicity for humans and glyphosate products can be safely used by following directions on labeled products, according to the EPA.

In the new analysis, Benbrook is critical of the EPA’s scrutiny of glyphosate herbicides, noting that little weight was given to research regarding the actual formulations sold into the marketplace and used by millions of people around the world. Instead, the EPA and other regulators have mostly pointed to dozens of studies paid for by Monsanto and other companies selling glyphosate herbicides that found no cancer concerns. The EPA has given little attention to several independent research projects that have indicated the formulations can be more toxic than glyphosate alone, according to Benbrook.

Indeed, the EPA only started working in 2016—some 42 years after the first glyphosate herbicides came to market – with the U.S. National Toxicology Program to evaluate the comparative toxicity of the formulations. Early results disclosed in 2018 supported concerns about enhanced toxicity in formulations.

Several scientists, including from within the EPA’s Office of Research and Development (ORD), and from a panel of scientific experts convened by the EPA, have cited deficiencies and problems with the EPA’s decision to classify glyphosate as not likely to be carcinogenic to humans. But Benbrook’s analysis is the first to look deeply at how and why the EPA and IARC drew such divergent conclusions.

Benbrook looked at the citations for genotoxicity tests discussed in the EPA and IARC reports, both those that were published in peer-reviewed journals and the unpublished ones that were presented to the EPA by Monsanto and other companies.

Some studies looked at glyphosate alone, and/or glyphosate-based herbicide formulations and some included findings about a substance called aminomethylphosphonic acid (AMPA), which is glyphosate’s primary metabolite.

Benbrook’s analysis found that within the body of available evidence, the EPA relied on 151 studies, 115 of which showed negative results, meaning no evidence of genotoxicity, and only 36 that had positive results. IARC cited 191 studies, only 45 of which showed negative results and 146 of which showed evidence of genotoxicity.

IARC said within these studies it found “strong evidence that exposure to glyphosate or glyphosate-based formulations is genotoxic…”

Benbrook’s analysis reports that over the last three years at least 27 additional studies have been published addressing possible mechanisms of genotoxic action for glyphosate and/or formulated glyphosate-based herbicides and all but one of the 27 studies reported one or more positive result. There were 18 positives arising from DNA damage, six associated with oxidative stress, and two with other genotoxicity mechanisms, his paper states.

According to Benbrook, the EPA’s failure to focus on formulated glyphosate-based herbicides is dangerous because these formulations “account for all commercial uses and human exposures (no herbicide products contain just glyphosate).”

More research is needed on real-world exposures, Benbrook concludes.

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Item 3

HOW DID THE US EPA AND IARC REACH OPPOSITE CONCLUSIONS ABOUT GLYPHOSATE’S GENOTOXICITY?

GM Watch
14 January 2019
https://www.gmwatch.org/en/news/archive/2019/18699

Many people around the world still struggle to understand how and why the US EPA and the European Food Safety Authority (EFSA) concluded that the herbicide active ingredient glyphosate is not genotoxic (damaging to DNA) or carcinogenic, whereas the World Health Organisation’s cancer agency IARC came to the opposite conclusion. IARC stated that the evidence for glyphosate’s genotoxic potential is “strong” and that glyphosate is a probable human carcinogen.

These agencies’ opposing views on glyphosate’s genotoxic potential played a crucial role in their differing conclusions about glyphosate’s carcinogenicity, since genotoxicity is one of two mechanisms through which glyphosate was deemed by the IARC to be carcinogenic (the other being oxidative stress).

Now a new peer-reviewed article answers the question of how and why the US EPA and EFSA reached diametrically opposed conclusions to IARC about glyphosate’s genotoxicity.[1] The article shows that the EPA relied on unpublished industry studies, 99% of which found that glyphosate was not genotoxic, whereas IARC relied on published studies, 74% of which found that glyphosate was genotoxic.

The EPA’s “no genotoxicity risk” judgement on glyphosate was essential to its “no carcinogenic risk” classification of the chemical. The article shows that only by framing and constraining its genotoxicity assessment in a highly selective and biased way was the EPA able to conclude that glyphosate was not genotoxic. It also demonstrates that the EPA’s cancer classification – as well as EFSA’s, which was based on the same data and was reached in a similar way – is scientifically baseless. Overall, the article shows that the way pesticides are assessed for risk is not fit for purpose and exposes people and the environment to unacceptable risks.

The paper is authored by Dr Charles Benbrook and is published in Environmental Sciences Europe.

The article’s key findings in detail are as follows.

1. EPA relied on secret and biased industry studies, whereas IARC used published studies

While IARC referenced only peer-reviewed studies and reports available in the public literature, EPA relied heavily on unpublished regulatory studies commissioned by pesticide manufacturers. In fact, 95 of the 151 genotoxicity assays cited in EPA’s evaluation were from industry studies (63%), while IARC cited 100% public literature sources.

There is a stark difference in the outcomes of industry-sponsored assays versus those in the public literature. Of the 95 industry assays taken into account by EPA, only one reported a positive result (i.e. that glyphosate had a genotoxic effect), or just 1%. Among the total 211 published studies (right circle in the graphic below), 156 reported at least one positive result, or 74%!

A closer look at the assays referenced by EPA but not IARC, and by IARC but not the EPA, also helps explain why EPA and IARC reached opposite conclusions.

EPA cited 109 total assays not included in the IARC report, 87% of which were regulatory studies commissioned by industry, and all but one was negative (i.e. no genotoxic effect).

IARC included the results from 67 assays not included in EPA’s analysis, all of which were from peer-reviewed publications, and 82% of which had at least one positive result for genotoxicity.

2. EPA analyzed a substance that almost no one is exposed to, whereas IARC looked at the real thing

Another important difference is that EPA focused its analysis on glyphosate in its pure chemical form, or “glyphosate technical”. The problem with that is that almost no one is exposed to glyphosate alone. Applicators and the public are exposed to complete herbicide formulations consisting of glyphosate plus added ingredients (adjuvants). The formulations have repeatedly been shown to be more toxic than glyphosate in isolation.

IARC, in contrast to the EPA, placed considerable weight on 85 studies focused on formulated glyphosate-based herbicides that people actually use and are exposed to. A massive 79% of the glyphosate-based herbicide assays published in the public literature reported one or more positive result.

While the EPA did list studies on formulated glyphosate-based herbicides in Appendix F of its report, EPA acknowledges it placed little to no weight on glyphosate-based herbicide assay results.

This difference is reflected in the overall percent of positive assays. Just 24% of the 151 assays cited by EPA reported positive results, while 76% of those cited by IARC had at least one positive result.

3. The EPA didn’t consider occupational exposure, whereas IARC did

The EPA’s analysis was limited to typical dietary exposure to the general public as a result of legal uses on food crops, and did not address occupational exposure and risks.

IARC’s assessment encompassed data from typical dietary, occupational, and elevated exposure scenarios. Elevated exposure events caused by spills, a leaky hose or fitting, or wind are actually common for people who apply herbicides several days a week, for several hours, as part of their work.

“Important” article – journal editor

In an unusual step, the editor-in-chief of Environmental Sciences Europe, Prof Henner Hollert, and his co-author Prof Thomas Backhaus, weighed in with a strong statement in support of the acceptance of Dr Benbrook’s article for publication. In a commentary published in the same issue of the journal, they wrote, “We are convinced that the article provides new insights on why different conclusions regarding the carcinogenicity of glyphosate and GBHs [glyphosate-based herbicides] were reached by the US EPA and IARC. It is an important contribution to the discussion on the genotoxicity of GBHs.”

Profs Hollert and Backhaus explained that it is usual practice to send manuscripts submitted to the journal to 2-4 peer reviewers. But due to the fact that the discussion on the carcinogenicity of glyphosate has become a “toxic issue”, the journal sent the article to no less than 10 reviewers, all but one of whom recommended publication.

Journal editor and co-author call for reform of pesticide approvals

In their commentary, Profs Hollert and Backhaus offered a list of “lessons to be learned” from Dr Benbrook’s article for the risk assessment of pesticides and other chemicals. Those lessons include recommendations for reform – many of which have long been demanded by GMWatch and other NGOs. In sum, these are:

* Studies relating to both glyphosate and glyphosate-based herbicide formulations must be taken into account in risk assessments.

* The problem formulation step of the risk assessment is critical to an understanding of the outcome. Thus it must be made clear to everyone, including laypersons, which substance is being assessed – as well as which exposure scenarios, endpoints, and protection goals are being considered.

* As different evaluators give different weights and reliability scores to different studies, all studies used in the risk assessment and the data underlying them must be made public and thus available for independent scrutiny. Thus the problem formulation, assessment protocols and data analysis also must be published. Pesticide assessments should implement the systematic review methodology already promoted by EFSA

* New studies must be registered, in the same way as clinical trials, to ensure that ‘no effect’ findings (which are notoriously hard to publish in journals), as well as unwelcome results, are equally considered in the assessment.

* Given that glyphosate-based herbicide formulations are more toxic than glyphosate alone, mixture effects must be considered during the risk assessment, in line with Article 4.3(b) of the EU’s pesticide regulation 1107/2009. However, this poses a challenge to transparent assessment, since the co-formulants in commercial pesticide formulations are not generally disclosed by manufacturers and are largely unknown.

NGOs and EU Parliamentary committee back editor’s call for reform

GMWatch welcomes Dr Benbrook’s article and the commentary by Profs Hollert and Backhaus as highly informative analyses of what is wrong with the regulatory assessments of pesticides and how the system needs to change. These new publications reinforce and in many aspects reflect the demands for reform of the pesticide risk assessment process put forward last year by Citizens for Science in Pesticide Regulation, a coalition of 120 NGOs, including GMWatch.

Further support for many of these measures comes from the European Parliament’s PEST Committee, which was set up in response to the concerns raised by the European Citizens’ Initiative to ban glyphosate, the Monsanto Papers (internal Monsanto documents disclosed in cancer litigation in the USA revealing how industry has subverted science), and the discrepancies in the cancer assessments of glyphosate between the European institutions and the IARC.

Note: Since September 2017, Dr Charles Benbrook has served as an expert witness in litigation involving the contribution of Roundup (a glyphosate-based herbicide) to non-Hodgkin lymphoma. He testified on behalf of Lee (Dewayne) Johnson during his trial in San Francisco in the summer of 2018.

Reference

1. Benbrook C (2019). How did the U.S. EPA and IARC reach diametrically opposed conclusions on the genotoxicity of glyphosate-based herbicides? Environmental Sciences Europe, January 15. DOI: 10.1186/s12302-018-0184-7. https://link.springer.com/article/10.1186/s12302-018-0184-7

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