Glyphosate and Roundup: All roads lead to cancer
A new study shows that not just glyphosate herbicides (the full formulation), but glyphosate the chemical alone, contributes to cancer. Moms Across America invites everyone to read and share this article with their loved ones and to send an urgent letter
now to the EPA to BAN glyphosate! There is no justifiable reason to be
spraying a carcinogenic, endocrine-disrupting herbicide that causes
liver disease and miscarriages on our food supply!
Clearly, we do not need a Cancer Moonshot, Biden, we need to stop spraying glyphosate and cancer-causing chemicals here on Earth! Now!
New study and article, first published on GMWatch.org:
Glyphosate and Roundup lead to changes in gene regulatory microRNAs (miRNAs or miRs) linked with
cancer, newly published data show. The analysis, of a type known as small RNA profiling, was conducted in liver tissue from rats exposed to glyphosate and Roundup MON 52276, an EU-approved formulation, over 90 days.In the new results, Roundup MON 52276 was found to reduce the levels of miR-22 and miR-17, whereas glyphosate decreased the level of miR-30 and increased the amount of miR-10. These changes in miRNAs are important because they are known to alter the expression of crucial cell growth regulator genes, which can lead to the development of cancer.
A
gene function that is central to multiple cellular processes, p53, is a
particular target of these miRNAs. The miRNA changes can lead to
alterations in p53 gene expression, as has been found in multiple types
of cancer in humans.
The link between the changes in miRNAs and
p53 gene expression is consistent with the findings within the same
study showing gene expression changes in Roundup- and glyphosate-exposed
rats. The gene expression changes strongly imply a p53 pathway DNA
damage response. DNA damage is a major risk factor for cancer
development.
Furthermore, increases in miR-10 have been found in
other studies to be associated with leukemia, a blood cancer. The
increase in mir-10 caused by glyphosate exposure in the experimental
animals may provide one mechanism by which users of Roundup have
succumbed to another blood cancer, known as non-Hodgkin lymphoma. These
results could strengthen the legal cases of the cancer sufferers in the
US who are suing Bayer/Monsanto because they believe that exposure to
Roundup caused their disease. Three such cases have already been decided
in favor of the plaintiffs.
Study lead Dr Michael Antoniou of
King's College London said, "The new data showing changes in miRNA
patterns add yet more evidence to the cancer-causing potential of
glyphosate and Roundup. What is more, our results show that it is not
just Roundup, which is a mixture of glyphosate with various additives,
that has carcinogenic potential, but also glyphosate alone."
Previously reported findings
The new data confirm and build on previously reported findings that were published as a pre-print in April 2021, which GMWatch reported on. The study with the additional findings has now passed peer review and is published in the prestigious journal, Toxicological Sciences.
The pre-print version
of the study had reported that glyphosate and glyphosate-based
herbicides such as Roundup activate mechanisms involved in cancer
development, including DNA damage – and these effects occur at doses
assumed by regulators to have no adverse effects. The data suggest that
the DNA damage was caused by oxidative stress, a destructive imbalance
in the body that can cause a long list of diseases. Oxidative stress is
the likely cause of the damage seen to the liver, leading to an
inflammatory (immune type) response, which in turn can cause DNA damage.
Crucially,
the study found that the isolated active ingredient of Roundup –
glyphosate – damaged DNA. This finding, according to the EU’s pesticide
law, should result in a ban on glyphosate and all its formulations.
All these findings are carried over into the peer-reviewed version of the study.
How the study was done
The study builds on the findings of a previous one by the same authors. In the previous study,
the researchers had compared the effects in rats of MON 52276 with
those of its "active ingredient", glyphosate, tested alone. The findings
showed that glyphosate and Roundup herbicide, given at doses that
regulators say are safe, resulted in the animals suffering gut
microbiome disturbances and oxidative stress, with indications that the
liver was affected and possibly damaged.
In the current follow-up study, the researchers analyzed the liver tissue from the same rats to see if the damage had indeed occurred.
The
researchers carried out some of the standard tests that regulators
require the pesticide industry to conduct to gain market authorization
for their products – namely blood biochemistry and kidney and liver
histopathology (microscopic examination of tissue).
They also
carried out in-depth tests (molecular profiling) that are not demanded
by regulators or typically carried out by the industry. One type of test
looked for adverse effects at a profound molecular level of biological
functioning through analysis of gene expression (transcriptomics) and
epigenetics (DNA methylation) in the liver and kidneys. Another type of
test, using specialized genetically engineered cell lines, was intended
to highlight changes in function linked with cancer formation.
In addition, the researchers carried out tests that can detect direct damage to DNA.
Roundup causes fatty liver disease – confirmed
The standard tests, histopathology, and blood biochemistry analysis found adverse
effects from the Roundup treatment, namely a dose-dependent and
statistically significant increase in fatty liver disease and liver cell
death.
The finding of fatty liver disease from exposure to the
MON 52276 formulation of Roundup confirmed the same researchers'
previous observation that an ultra-low dose of another Roundup
formulation, Roundup Grand Travaux Plus, was administered to the same
strain of Sprague-Dawley rats over a 2-year period, caused non-alcoholic
fatty liver disease.
An increase in liver and kidney lesions was
also detected in animals treated with glyphosate, although this did not
reach statistical significance. However, the authors commented that an
experiment of a longer duration using more animals may have resulted in
statistical significance.
Non-standard tests most revealing
Worryingly for public health, it was the non-standard molecular
profiling tests that are not required by pesticide regulators that were
most revealing.
First,
Roundup was found to alter the expression of 96 genes in the liver
specifically linked to DNA damage and oxidative stress, as well as
disruption of circadian rhythms or "body clocks". The most affected
genes in the liver also had their expression similarly altered in
kidneys. Crucially, a core set of genes whose expression was altered by
Roundup was similarly changed in the glyphosate-treated animals. This
strongly suggests that the key changes in gene function reflective of
oxidative stress and DNA damage were due to glyphosate and not the
additional substances (adjuvants) present in the Roundup formulation.
Second, direct DNA damage to the liver was found to increase with glyphosate exposure.
These
findings potentially constitute a bombshell that could end the
authorization of glyphosate in the EU. That’s because the EU pesticide
regulation (1107/2009) has what’s known as hazard-based cut-off
criteria. This means that if a pesticide's active ingredient is shown to
cause a certain type of harm to health at whatever dose, it must be
banned. One of the named types of harm is damage to DNA. The discovery
that glyphosate alone damages DNA in a living animal should, if
regulators follow the law, result in a ban on the chemical.
Third,
both glyphosate and Roundup were found to cause epigenetic changes
known as DNA methylation. Epigenetics describes layers of molecular
structures associated with DNA that control the underlying function of
genes. The defining feature of epigenetic changes is that they can alter
how genes work but do not involve changes to the actual DNA sequence.
These types of changes were found at over 5,000 genomic sites for
glyphosate and over 4,000 for Roundup. This is a concern because such
alterations are typically found at high frequency in cancer tissues.
All findings lead to the same conclusion
The researchers performed further laboratory tests in mouse cell
lines, which are designed to highlight effects that can lead to cancer
formation. Glyphosate and three Roundup formulations were assessed in
these tester cell lines. It was found that two formulations of Roundup
herbicide, but not glyphosate, activated oxidative stress and misfolded
protein responses, both clear markers of carcinogenicity.
Commenting
on the totality of the data, Dr. Antoniou said, "No matter what
molecular measurements we undertook, they all led to the same
conclusion: that is, both glyphosate and Roundup are potential
carcinogens."
Other studies, including the industry ones submitted to support regulatory approval of glyphosate, have also found that glyphosate causes cancer in
experimental animals. Based on studies in animals and humans, as well
as mechanistic data, in 2015 the International Agency for Research on
Cancer (IARC) classified glyphosate as a probable human carcinogen.
Other implications of the new study
1. Ending animal testing is not yet feasible
Interestingly,
in the new study, glyphosate was shown to damage DNA in living animals
but not in the cell culture system. This shows that in vitro lab tests
using isolated cells cannot fully substitute for evaluations in a living
animal because certain effects will be missed. This is because animals
(including humans) are whole organisms whose complexity cannot be
replicated in a flask, petri dish, or test tube. While many people
(GMWatch included) would like to see an end to animal testing, as long
as pesticides and other chemicals are allowed to be released into the
environment, such a move would put public health at risk.
2. Roundup is more toxic than glyphosate
In summary, Roundup was found to
be more toxic than glyphosate, confirming and building on previous
observations. However, taken together, the results from the various
assays conducted show that both glyphosate and Roundup herbicides
activate mechanisms involved in cancer development, causing gene
expression changes reflecting oxidative stress and DNA damage. Also,
glyphosate alone was clearly able to induce DNA damage.
These
findings directly challenge the global regulatory practice of only
assessing the isolated declared active ingredient (glyphosate) and not
the complete commercial formulations (Roundup) as sold and used.
The
study further highlights the power of in-depth molecular profiling
"omics" methods to detect changes that are missed by relying solely on
conventional biochemical and histopathological measurements conducted in
standardized industry tests on pesticide active ingredients. The study
paves the way for future investigations by identifying gene expression
changes and altered DNA methylation sites, which can serve as biomarkers
and potential predictors of negative health outcomes resulting from
exposure to glyphosate-based herbicides.
3. Results could allow a survey of the human population for glyphosate herbicide exposure
Commenting
on the implications of the results for human exposure monitoring, study
leads Dr. Michael Antoniou said, "The biomarkers we identified (such as
the miRNA and gene expression changes) can be tested for in people, but
we don't know if this particular pattern of biomarkers is unique to
glyphosate-based herbicide exposure. Thus the biomarkers would need to
be correlated with a history of exposure to glyphosate-based herbicides
and measurements of glyphosate in urine.
"If high levels of
glyphosate were found in the urine, and this correlated with the
biomarkers identified in the new study and the person's history of
glyphosate herbicide exposure, this would indicate that exposure to
glyphosate-based herbicides might be responsible for any health effects
that are both indicated by our findings and found in the person. These
findings should be tested first by investigations of herbicide
applicators, as their exposure can be high and details of the particular
herbicides used are often recorded, which would enable clearer results
to be obtained."
4. "Safe" and "no effect" doses were shown to be harmful
In the 90-day rat feeding study, different groups of animals were fed
three different doses of glyphosate and the glyphosate-equivalent dose
of Roundup MON 52276. The lowest dose was the concentration that
regulators assume to be safe to ingest on a daily basis over a lifetime
(the EU acceptable daily intake or ADI: 0.5 mg per kg of body weight per
day). The middle dose was the dose that EU regulators concluded had no
observable adverse effect (the "no observable adverse effect" level or
NOAEL) in industry-sponsored rat feeding studies (50 mg per kg of body
weight per day). The highest dose was 175 mg, the dose that US
regulators concluded had no observable adverse effect.
Adverse
effects were found from Roundup exposure at all dose levels in a
dose-dependent fashion. These findings show that the glyphosate ADI for
the EU – and that of the USA, which is even higher – is not safe to
ingest. Likewise, it shows that the EU and US regulators were only able
to conclude that glyphosate had "no observable adverse effect" at the
levels mentioned above because the tests that they require industry to
carry out are insufficiently sensitive.
The study supports plaintiffs in Roundup-cancer litigation
Summarising the implications of the study for
the Roundup-cancer litigation in the US, Dr. Antoniou said, “Our
results are the first to simultaneously show glyphosate and Roundup
toxicity in a whole mammalian animal model system and provide a
mechanism – oxidative stress – by which DNA damage has been observed in
other systems, such as mammalian tissue culture cells.
“These
findings show that glyphosate and Roundup score positive in various
tests of carcinogenicity – transcriptome/epigenome/miRNA changes,
oxidative stress, protein misfolding, and DNA damage – in a living
animal (rat) that is accepted as a surrogate for human health effects.
In my view, this strengthens the argument that exposure to Roundup
herbicides can lead to the type of cancer suffered by the plaintiffs in
many of the court cases – non-Hodgkin lymphoma.”
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