Nov 10 2017

Glyphosate Not Associated with Cancer

IARC-Headquarters_ExteriorIn March of 2015 the International Agency for Research on Cancer (IARC), part of the World Health Organization (WHO), published their assessment on glyphosate, Monsanto’s popular weedkiller, classifying it as 2a – a probable carcinogen. This was like red meat to the anti-GMO crowd, and even sparked class action suits against Monsanto and may lead to banning use of the chemical in the EU.

There were significant problems with the IARC report, however. First – it is at odds with every other expert review of the scientific literature on glyphosate. I review the evidence here, citing many expert panel reviews, all conclude that the evidence does not support a link between glyphosate and risk of cancer. The IARC conclusion is a clear outlier, which reasonably prompts questions as to why their designation stands out.

We also need to put the IARC classification of 2a – probable carcinogen, into context. This is the same classification that the IARC gave to drinking hot beverages or eating red meat. Overall they tend to err on the side of caution when making their classification.

But there were problems that go beyond where the IARC sets their threshold for “probable.” Two main criticisms have emerged. The first is the lack of transparency. Reuters has published a series of articles on the issue, outlining, for example, that when the EPA reviewed the safety of glyphosate they also published a 1300 + page document that outlines the entire deliberative process. The IARC produced no such document.

Further, Reuters was able to obtain copies of the draft report and shows that the final report differs in significant ways. They found 10 major changes or omissions from the draft to the final copy, every one in the direction of emphasizing the risks of glyphosate. It is not known who made these edits, and the IARC responded by essentially instructing their scientists not to discuss the confidential deliberative process.

Far more important, however, is the accusation that the lead IARC scientist knew of unpublished data (because he was involved in the research) that showed no correlation between glyphosate and cancer, but this data was not considered in the review. So the lead scientist excluded his own data from the final analysis.

That data has now been published. 

The study comes from the Agricultural Health Study. Here are the results:

Among 54 251 applicators, 44 932 (82.8%) used glyphosate, including 5779 incident cancer cases (79.3% of all cases). In unlagged analyses, glyphosate was not statistically significantly associated with cancer at any site. However, among applicators in the highest exposure quartile, there was an increased risk of acute myeloid leukemia (AML) compared with never users (RR = 2.44, 95% CI = 0.94 to 6.32, Ptrend = .11), though this association was not statistically significant. Results for AML were similar with a five-year (RRQuartile 4 = 2.32, 95% CI = 0.98 to 5.51, Ptrend = .07) and 20-year exposure lag (RRTertile 3 = 2.04, 95% CI = 1.05 to 3.97, Ptrend = .04).

This is the best and largest set of data to date, and it was negative. The possible association with AML requires further discussion, as I am confident it will be seized on by those with an anti-glyphosate agenda. First and most importantly, this association was not statistically significant. This means it is almost certainly noise in the data. Given the number of possible correlations being examined, non-significant possible correlations are almost inevitable.

There are two other reasons to think this association is noise – there was no difference between the 5 year and 20 year exposure lag. If this were a true cause and effect, we would expect the lag time to matter. Even more significant, however, is the fact that previous possible correlations were between glyphosate and non-Hodgkins lymphoma (NHL). That is the association that led to the IARC classification. There was no association with NHL is this data, just a non-significant association with AML. This is exactly what we expect to find with random noise – different correlations in different sets of data. Such correlations don’t mean anything until they are replicated in an independent set of data.

So the bottom line is that this large data set is essentially negative regarding any association between glyphosate and cancer. If the IARC had taken this data into consideration it may have (and it seems should have) changed their conclusions. They knew about this data, but chose to ignore it.

The issue of glyphosate is controversial because it has become a focal point for an ideological struggle. For the anti-GMO movement it is the poster-child of corporate malfeasance. For corporations this is an example of activist government overreach.

I tend to think that both sides are correct, at least to an extent. We should not trust corporations, meaning that we should not just assume they will be good corporate citizens, never abuse their power, or that they will consider the public interest over their shareholders. There is overwhelming evidence that, generally speaking, this is not a good assumption. Corporations look after their own bottom line. That is why we need regulations, transparency, and oversight to protect consumer and public interests.

I also don’t think we can trust activist organizations, nor can we assume that government agencies will act without ideological bias. Again, history tells a very different story.

What we need, therefore, are professional disinterested reviewers. We need scientific experts to review objective evidence, and investigative journalists to make sure there is transparency. They don’t always do their job optimally either, but the whole system acts as a set of checks and balances.

The story of glyphosate and the IARC review is a microcosm of all this. We see multiple different interests, each with a different narrative interpretation of reality, fighting over what is, at the end of the day, a scientific question. What is the safety of glyphosate in the context of how it is used and compared to other alternatives? The best we can do is to have multiple independent experts review all the evidence and give us a transparent assessment. If a consensus emerges and that consensus includes the opinion that there is sufficient evidence to reach a conclusion, then that conclusion is probably the most reliable answer we can get.

In the case of glyphosate we actually have a large set of data with multiple independent reviews concluding it is relatively safe as used, and is superior to most other herbicides. The IARC review is an outlier, and the process used has come under significant criticism suggesting bias.

In any case, the recent published data from the AHS renders all previous reviews obsolete. This new data argues strongly against any link between glyphosate and cancer. In light of this, the IARC should update their classification, as their now obsolete classification is actively being used as a basis of lawsuits and regulations.

 

32 responses so far

32 Responses to “Glyphosate Not Associated with Cancer”

  1. Willyon 10 Nov 2017 at 9:22 am

    Thanks for posting this, Dr. Novella.

  2. BBBlueon 10 Nov 2017 at 10:10 am

    Those who defend the anti-glyphosate, anti-pesticide, anti-GMO, anti-conventional ag narrative, will completely ignore a proper interpretation of the data as it relates to AML and work to bring more attention to their claims that not enough is known about the ecotoxicity of the formulated product and its inert ingredients.

  3. Billzbubon 10 Nov 2017 at 10:14 am

    “In light of this, the IARC should update their classification, as their now obsolete classification is actively being used as a basis of lawsuits and regulations.”

    Dr. Novella, if you had to guess, what do you think will happen?

  4. SteveAon 10 Nov 2017 at 10:44 am

    Glyphosate comes close to being the ideal weed-killer.

    Perhaps some re-branding might be in order: Navaho Organic Crop Healing Balm.

  5. chikoppion 10 Nov 2017 at 10:53 am

    [SteveA] Perhaps some re-branding might be in order: Navaho Organic Crop Healing Balm.

    As a marketing professional, I applaud the ingenuousness and style of you proposal! That ranks right up there with rebrands like the “death tax.”

  6. hardnoseon 10 Nov 2017 at 12:38 pm

    We are exposed to ever-increasing amounts of glyphosate, combined with other toxic Roundup ingredients. Plants take in these chemicals, so they can’t be washed off.

    Roundup makes agriculture much easier, because it can be sprayed liberally on crops that are genetically engineered to tolerate it. It is being used more and more.

    Cancer is not the only concern. Glyphosate is a herbicide, and it is a powerful antibiotic. Therefore, the intestinal bacteria we need for good health can be killed when we eat plants containing glyphosate, or other herbicides.

    I know you will say that Roundup is less toxic than other weed killers. But that is not the point. Other weed killers have not been used as liberally and extensively as Roundup is being used now.

  7. SFinksteron 10 Nov 2017 at 1:09 pm

    I reject your reality and substitute my own.

  8. Lane Simonianon 10 Nov 2017 at 1:18 pm

    One of the inert ingredients in Roundup–polyethoxylated tallow amine–is particularly toxic.

    https://www.ncbi.nlm.nih.gov/pubmed/24434723

    https://www.reddit.com/r/science/comments/1x07ti/glyphosate_commercial_formulation_causes/

    Polyethoxylated tallow amine produces peroxynitrite which causes DNA damage, damage to the intestinal lining, damage to beneficial bacteria in the gut, damage to the blood-brain barrier, increased risk for certain neurological diseases including Alzheimer’s disease, and increased risk for multiple myeloma and non-hodgkin’s lymphoma.

    http://www.jneurosci.org/content/17/8/2653

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2248324/

  9. Steven Novellaon 10 Nov 2017 at 1:53 pm

    HN – that was an uncharacteristically cogent comment by you. Here are some other points to consider:

    The antimicrobial effect of glyphosate is very low. Although Monsanto patented this use, they never marketed it as an antibiotic because it is too weak to use clinically. Studies of soil bacteria or animal microbiota also do not show any effect. The only studies that show an effect are in vitro, and at much higher doses than current exposure. There is no evidence glyphosate has an adverse effect on human GI bacteria, and the existing evidence indicates it is very unlikely.

    Many of the safety studies with glyphosate are in farm workers exposed to much higher doses than any consumer from eating foot, and still there is no evidence of any harm.

    But, since it is widely used, I am all in favor of more studies and tracking its effects. I just don’t agree with misrepresenting the existing evidence for a political (or corporate, for that matter) agenda.

  10. ScubaSharkyon 10 Nov 2017 at 1:59 pm

    “Cancer is not the only concern. Glyphosate is a herbicide, and it is a powerful antibiotic. Therefore, the intestinal bacteria we need for good health can be killed when we eat plants containing glyphosate, or other herbicides.”

    Ah yes. The old glyphosate harms the microbiome trope. If only someone would conduct an experiment to test this hypothesis…

    Wait… what’s this?

    http://www.sciencedirect.com/science/article/pii/S0269749117328099

    TL;DR: “…we have shown that pure glyphosate and the tested commercial formulation Glyfonova® had very limited effects on the gut microbial community composition in rats during a 2-week oral exposure trial at a concentration of 50xADI for humans. This is likely to be explained by sufficient bioavailability of aromatic amino acids in the gut environment, alleviating the effect of glyphosate blocking the Shikimate pathway.”

  11. hardnoseon 10 Nov 2017 at 2:28 pm

    Wow, rats only had limited effects after 2 whole weeks! That means we can ingest glyphosate for our whole lives with only limited problems.

  12. bachfiendon 10 Nov 2017 at 3:24 pm

    Hardnose,

    Glyphosate had very limited effect on the intestinal bacteria of rats after two weeks. Two weeks is a very long time for intestinal bacteria. The bacteria would have been ‘pooped’ many times in 2 weeks.

    Whether glyphosate would have had a greater effect on the rats if given for years wasn’t the question being asked in the study.

  13. MosBenon 10 Nov 2017 at 5:27 pm

    It’s also at 50x the acceptable daily intake. I’m not a doctor, but it seems pretty reasonable that at that dose over a 2 week period you would see an effect if there was going to be one.

  14. MosBenon 10 Nov 2017 at 5:30 pm

    But as Steve said, there are aspects of glyphosate use that we should continue to test, if only because it’s use is so ubiquitous. So sure, keep testing it, but the evidence that we currently have makes it seem pretty safe.

  15. hardnoseon 10 Nov 2017 at 6:19 pm

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3945755/

    We can trust Monsanto. After all, they care about each and every one of us.

  16. hardnoseon 10 Nov 2017 at 6:24 pm

    SN: “The antimicrobial effect of glyphosate is very low.”

    Oh really?
    “A reduction of LAB in the GIT microbiota by ingestion of strong biocides like glyphosate could be an explanation for the observed increase in levels of C. botulinum associated diseases.”

    https://www.ncbi.nlm.nih.gov/pubmed/23396248

  17. bachfiendon 10 Nov 2017 at 7:10 pm

    Hardnose,

    Hardnose,

    ‘Could be’ an explanation for the observed increase in Clostridium botulinum associated diseases.

    You do know what ‘could be’ means, don’t you?

  18. hardnoseon 10 Nov 2017 at 7:51 pm

    “You do know what ‘could be’ means, don’t you?”

    It COULD BE true that Monsanto loves you and carefully and thoroughly tests its products for safety.

  19. bachfiendon 10 Nov 2017 at 8:01 pm

    hardnose,

    ‘It COULD BE true that Monsanto loves you and carefully and thoroughly tests its products for safety.?

    Irrelevant. It could be true, but I wouldn’t accept it as a ‘given’. Public companies test their products just sufficiently to get them past the regulators – any more would reduce profits.

    It’s necessary to have sufficient regulations to ensure products are sufficiently safe for the uses they’re approved.

  20. Wolfbecketton 10 Nov 2017 at 8:27 pm

    Good data, it’s too bad it won’t have any effect whatsoever.

    You can’t reason people out of a position that they didn’t reason themselves into.

  21. Grant Jacobson 10 Nov 2017 at 10:11 pm

    “The possible association with AML requires further discussion, as I am confident it will be seized on by those with an anti-glyphosate agenda.”

    It’s always possible I’m missing something, but this is already happening. I have a guy in my Twitter feed who claimed the paper shows an association. I pointed out that the paper says it’s statistically insignificant and that means it’s neither here nor there (without more work), but he’s trying to make it true somehow.

  22. BillyJoe7on 10 Nov 2017 at 11:53 pm

    SN: “This is the best and largest set of data to date, and it was negative”

    HN: But let me just cherry pick a couple of studies that support my gut feelings about Monsanto.

  23. praktikon 11 Nov 2017 at 7:56 am

    I’ve listened to Monsanto scientists speak, I actually don’t find it that hard to imagine people who have good motivations that work there.

    Listen to 98 Fred Perlak – Inside the Mind of a Monsanto Scientist by Inquiring Minds #np on #SoundCloud
    https://soundcloud.com/inquiringminds/98-fred-perlak-inside-the-mind-of-a-monsanto-scientist

  24. daedalus2uon 11 Nov 2017 at 1:42 pm

    The paper on glyphosate effects on gut microbiome in rats measured the minimum inhibitory concentration (MIC) on a number of LAB. They were in the 2% to 4% range. The MIC for Clostridia was 1to 2%. So Clostridia are more sensitive to inhibition than are LAB, making the hypothetical risk of C. diff infection from glyphosate exposure implausible.

    The European Acceptable Daily Intake ADI is 0.5 mg/kg body weight. They tested 50x that, 25 mg/kg body weight. They measured ~50 micrograms/g in colon contents, or ~0.005%.

    It isn’t surprising that minimal effects were observed at such levels.

  25. Lane Simonianon 11 Nov 2017 at 9:20 pm

    Polyethoxylated tallow amines are likely the most toxic of the various “inert” compounds in Roundup. My links are not making it through, but here is an important study.

    Glyphosate Commercial Formulation Causes Cytotoxicity, Oxidative Effects, and Apoptosis on Human Cells Differences With its Active Ingredient

    “In the present study, the effects on oxidative balance and cellular end points of glyphosate, aminomethylphosphonic acid (AMPA), and a glyphosate formulation (G formulation) were examined in HepG2 cell line, at dilution levels far below agricultural recommendations. Our results show that G formulation had toxic effects while no effects were found with acid glyphosate and AMPA treatments. Glyphosate formulation exposure produced an increase in reactive oxygen species, nitrotyrosine formation [an indicator of peroxynitrite damage–my addition], superoxide dismutase activity, and glutathione (GSH) levels, while no effects were observed for catalase and GSH-S-transferase activities. Also, G formulation triggered caspase 3/7 activation and hence induced apoptosis pathway in this cell line. ”

    Peroxynitrite causes or contributes to DNA damage, inflammation, damage to the lining of the gut, disruption of the blood-brain barrier, and the death of neurons. As such it is linked to a wide variety of diseases:

    Nitric Oxide and Peroxynitrite in Health and Disease

    “In vivo, peroxynitrite generation represents a crucial pathogenic mechanism in conditions such as stroke, myocardial infarction, chronic heart failure, diabetes, circulatory shock, chronic inflammatory diseases, cancer, and neurodegenerative disorders. Hence, novel pharmacological strategies aimed at removing peroxynitrite might represent powerful therapeutic tools in the future. Evidence supporting these novel roles of NO and peroxynitrite is presented in detail in this review.”

    As a matter of quiet curiosity, Monsanto began to remove polyethoxylated tallow amine from Roundup while claiming they did so only for commercial reasons.

  26. BillyJoe7on 12 Nov 2017 at 12:39 am

    Lane,

    (You can provide up to a maximum of three links per comment.
    If you have more than three links, you can hit the submit button after the third link and then continue in a second comment).

    I’m not sure that a single paper can overturn what the preponderance of evidence concludes.
    You are doing no less than hardnose with his two cherry picked papers.
    Of course, if it pans out, it must be considered as part of the evidence, put against all the other evidence of lack of harm from GMOs.

    As for Monsanto removing “polyethoxylated amines from roundup while claiming they did so only for commercial reasons” (and kudos for putting “only” in the correct position in that sentence), I’m not sure why you would find that “curious” (even if “quietly”). Vaccine manufacturers did the same with mercury in vaccines. There was no evidence of harm, but there was a growing perception of harm by the public as a result of being misinformed/lied to by the anti-vaccination networks.

  27. BBBlueon 12 Nov 2017 at 2:08 am

    POEA is highly toxic to naked cells in vitro and to aquatic organisms if applied directly to aquatic environments, which is why there are no herbicide labels that include POEA for use to control weeds in aquatic environments.

    The AHS integrates potential association with inerts like POEA and human cancers because exposure to complete formulations was considered.

    In fact, the AHS integrates potential associations with every other pesticide active ingredient plus inerts used by applicators in Iowa and North Carolina, not just glyphosate-based herbicides. Headline should read: “No Association Found Between Pesticides and Cancer” rather than limiting it to just glyphosate herbicides.

  28. Lane Simonianon 12 Nov 2017 at 10:20 pm

    BillyJoe7, thanks for making me aware of the maximum number of links per comment. That will save me a great deal of frustration in the future.

  29. Insomniacon 13 Nov 2017 at 10:02 am

    Great post. However, as is often the case on this issue, it misses one crucial point: the IARC uses a classification that describes the danger associated with the substance and not the actual risk to which people are exposed. That means that they just give information about the potential carcinogenicity, which does not mean that consumers around the world are at risk of developing cancer as a result of eating products containing glyphosate residues.

    In this respect, although it can be criticized and may be erroneous, the current position of the IARC is not necessarily at odds with the review statements of other agencies. For instance, the joint FAO/WHO assessment states that glyphosate is unlikely to pose any threat to consumers who are mostly exposed to glyphosate in small quantities through the oral route.

    I think this point should be put forward more often, as it shows that the debate is not framed properly when people misrepresent what the IARC conclusion actually means.

  30. BBBlueon 13 Nov 2017 at 12:22 pm

    Insomniac- It is an easy point to miss since, as the Risk-Monger says “IARC conduct hazard assessments, they acknowledge that, but then strangely present their findings in contrast to government agencies that conduct risk assessments [such as EFSA and BfR]. https://risk-monger.com/2017/10/23/iarcgate-six-reasons-why-iarcs-head-christopher-wild-must-be-fired/

    I agree, the point about hazard-based assessments is not framed properly when people misrepresent what the IARC conclusion actually means, and that includes misrepresentations by IARC members themselves.

  31. BillyJoe7on 13 Nov 2017 at 3:17 pm

    Insomniac,

    Why make the point that glyphosate is a potentially carcinogenic when the evidence is that it is not carcinogenic? It’s like relying on basic research when the results of systematic reviews are already available.

  32. Insomniacon 19 Nov 2017 at 6:21 pm

    BBBlue,
    I agree, part of the misunderstanding comes from confusing statements and misleading communication at the IARC. There may be something fishy here, although I strive not to jump to conclusions before the whole story is known.

    BillyJoe7,
    I have not reviewed the evidence myself, maybe the IARC is mistaken. My point, however, is that whether this is the case or not, it remains the one and only source on which everyone relies when talking about glyphosate. Therefore it is important to understand what it means, even if we take the IARC conclusion at face value.

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