| Ban-Glyphosate.Com...Home WHY GLYPHOSATE SHOULD BE BANNED Dr. Eva Sirinathsinghji
and Dr. Mae-Won Ho Note: Drs. Sirinathsinghji
and Ho are leading researchers at the Institute for
Science in Society in UK. This information was found
online at this location: http://www.permaculturenews.org/2012/11/01/why-glyphosate-should-be-banned-a-review-of-its-hazards-to-health-and-the-environment/ and
http://www.i-sis.org.uk/SS-glyphosate.php 1.
Introduction 2.
Regulators and industry both culpable 3.
How glyphosate works 4.
Health impacts 5.
Environmental and agronomic effects 6.
To conclude Executive Summary The use of glyphosate-based herbicides,
especially Monsanto’s Roundup formulation, has
increased dramatically since the introduction of
genetically modified (GM) glyphosate-tolerant crops,
resulting in the contamination of our food,
environment and water supplies. Glyphosate-based herbicides are now the
most commonly used herbicides in the world. It is
still promoted as ‘safe’, despite damning evidence of
serious harm to health and the environment. Evidence of harm to health
Evidence of negative environmental and
agronomic impacts
Conclusion The serious harm to health and the
environment caused by the use of glyphosate herbicides
is clear. There is a compelling case for banning or
phasing out glyphosate-based herbicides worldwide, in
favour of a global
transition to non-GM, herbicide-free organic
agriculture (see Food Futures Now *Organic
*Sustainable *Fossil Fuel Free,
ISIS Report). 1 Introduction A feeding trial lasting two years on rats
showed that females exposed to Monsanto’s glyphosate
formulation Round-up and/or Roundup-tolerant
genetically modified (GM) maize were 2 to 3 times as
likely to die as controls and much more likely to
develop large mammary tumours.
In males, liver congestions and necrosis were 2.5 to
5.5 times as frequent as the controls, while kidney
diseases were 1.3-2.3 times controls. Males also
presented large kidney or skin tumours
four times as often as the controls and up to 600 days
earlier. Biochemical data confirmed significant kidney
chronic deficiencies for all treatments and both
sexes. The research team, led by Giles-Eric Séralini of Caen University in
France, suggested that the results can be explained by “non-linear
endocrine-disrupting effects of Roundup” and “the
overexpression of the transgene in the GMO and its
metabolic consequences.” The results were dynamite, and the
repercussions are still to be played out [2].
Predictably, the pro-GM brigade around the world
launched a concerted campaign to discredit the
scientists and their findings (see commentary by John
Vidal on the Guardian website [3]. But contrary to the impression given in
the popular media, this is not an isolated study
suddenly to reveal that GM feed and the most widely
used herbicide in the world may be toxic. It is the
latest in a series of laboratory experiments backed up
by experience of farmers and farm workers around the
world that have found toxicity both for GM crops and
for the herbicide. It is also the most thorough study
to be carried out for the longest duration of two
years. Currently, European regulators require
companies to do feeding trials for only 90 days. Note that the new study found toxicity
not just for Roundup herbicide, but also for the
Roundup-tolerant GM maize (NK603) that had not been
sprayed with herbicide. In other words, GM maize has
toxicity independently of the herbicide. As most
Roundup tolerant GM crops have been sprayed and
contain substantial amounts of herbicide and herbicide
residues, they may also mask the toxicity of the GM
crops themselves. We review existing evidence on the health
and environmental impacts of glyphosate herbicides and
glyphosate-tolerant GM crops as the maximum permitted
levels of the herbicide and herbicide residues in food
are set to rise 100-150 times in the European Union if
Monsanto’s new proposal is approved [4]. 2 Regulators and industry both culpable Healthy food and clean water are
fundamental needs and basic human rights, but these
are being compromised by the ever
increasing use of synthetic chemicals in
agriculture. Glyphosate-based herbicides, originally
developed by Monsanto, are the most widely used in the
world and increasing numbers of studies are
documenting its link to serious illnesses and
environmental damage. Most disturbingly, both Monsanto
and the European Commission knew that the chemical
could lead to cancer and birth defects prior to its
approval for Europe in the 1980s; despite that,
glyphosate continues to be touted as a ‘safe’ chemical
[5] (see [6] EU Regulators and Monsanto
Exposed for Hiding Glyphosate Toxicity,
SiS 51). The first glyphosate-based herbicide,
Roundup®, was launched by Monsanto in 1974 and its use
has risen sharply since the introduction of
glyphosate-tolerant genetically modified (GM) crops in
1996. Following the expiry of the glyphosate patent in
the US in 1991 and outside the US in 2000, many
commercial formulations are available. Based on US
data, GM crops have been directly responsible for a 7
% increase in overall pesticide use from 1996 to 2011
[7] (see [8] Study Confirms GM crops lead to increased
Pesticide Use, to appear). This is predicted to
increase with the emergence and spread of
herbicide-resistant weeds (see section 5.1), and
insects resistant to Monsanto’s Bt
toxin insecticides, as well as the introduction of GM
crops with tolerance to multiple herbicides. Proponents of industrial chemical
agriculture and GM crops argue glyphosate increases
crop yields, providing a more efficient,
cost-effective and safe method of agriculture
necessary to tackle hunger and food insecurity across
the world. The US officially recognises
glyphosate as a safe chemical with regards to human
health [9], currently defined as a Toxicity Class III
herbicide (slightly toxic) with no carcinogenic
activity. The EU classifies it as an irritant that can
also cause severe ocular damage [10]. The accumulation of scientific
peer-reviewed publications, clinical observations and
witness reports from farmers and residents living in
glyphosate-treated areas however, refutes the official
line. Over a hundred peer-reviewed publications show
detrimental effects, proving to the scientific
community what farmers in the global South have known
for a long time. Not acknowledging those studies goes
against fundamental scientific and medical principles
as well as the basic human right to a healthy
environment, not least because the evidence challenges
the naïve assumption that governments’ primary concern
is to protect our health and not the pockets of
multinational corporations. 3 How glyphosate works Glyphosate or N-(phoshonomethyl) glycine
(molecular formula – C3H8NO5P) acts through inhibiting
the plant enzyme – EPSPS
(enolpyruvylshikimate-3-phosphate synthase) in the shikimate pathway [12] (see
[13] Glyphosate Tolerant Crops
Bring Diseases and Death, SiS 47). It catalyses the transformation
of phosphoenol pyruvate
(PEP) to shikimate-3-phosphate, required for making
essential aromatic amino acids phenylalanine, tyrosine
and tryptophan. Amino acids are essential building
blocks for all proteins. This metabolic pathway exists
in all plants, fungi, and some bacteria. Animals do
not have the shikimate
pathway, and depend on getting the essential amino
acids from their diet. Inhibition of protein synthesis
leads to rapid necrosis (premature cell death) in the
plant. As the EPSPS enzyme is present in all plants,
glyphosate can effectively kill all plant species. The
high solubility of glyphosate formulations allows it
to be taken up by the plant where it acts
systematically from roots to leaves. Figure 1 Chemical Structure of
Glyphosate Glyphosate-tolerant crops are either
engineered to carry extra copies of the EPSPS gene
isolated from the soil bacterium Agrobacterium tumefaciens, or glyphosate
intolerant versions of EPSPS. These GM crops are
therefore tolerant to the herbicide, but are not
engineered to metabolise
or get rid of it, resulting in GM crops with the
herbicide and its residues throughout the plant
destined to become food or animal feed. In addition to inhibition of EPSPS,
glyphosate disrupts many biochemical and physiological
functions of plants. Glyphosate was first patented as
a general metal chelator
and strongly chelates micronutrients such as
manganese, which is an important co-factor of the
EPSPS enzyme (see [13]). This is suggested to be the
mechanism by which glyphosate kills plants. Manganese
is a co-factor in over 25 plant enzymes. Other macro
and micronutrients are also chelated by glyphosate
such as Ca2+, Mg2+, Cu2+, Fe2+, Co2+, Ni2+ and Zn2+.
This interference with biochemical pathways goes on to
compromise biological functions including the immune
system as well as crop productivity (see [14] USDA scientist reveals All,
SiS 53). 4 Health impacts There is a wealth of evidence on the
health hazards of glyphosate. Its approval, along with
other hazardous chemicals, relies on systematic flaws
in the EU and US regulatory processes, which to this
day, do not require evaluation by independent
research, and instead rely solely on the industry’s
own studies. Approval is therefore often based on data
not available to the public or independent research
scientists. Nevertheless, raw data have been obtained
from the industry through the law courts, which, when
re-analysed by independent
scientists, also provide evidence of toxicity. Taken together, glyphosate is implicated
in birth and reproductive defects, endocrine
disruption, cancers, genotoxicity,
neurotoxicity, respiratory problems, nausea, fever, allergies and
skin problems. 4.1 Teratogenicity and reproductive
effects Evidence of teratogenicity (birth
defects) and reproductive problems stretches back to
the 1980s [5]. Observations made
by Monsanto were acknowledged by the German
government (and its agencies), acting as the
“rapporteur” state on risk assessment to the
European Commission. The German bodies
concluded that high doses (500 mg/kg) led to
significant skeletal and/or visceral (internal organ)
abnormalities in rats and rabbits including the
development of an extra 13th rib, reduced viability,
and increased spontaneous abortions. Low doses (20
mg/kg) were later shown to cause dilated hearts. The
questionable analysis and interpretation of the data
by Germany (including claims that dilated hearts had
unknown consequences and sample sizes were too small
and lacking dose-dependent results) meant that the
findings were not considered relevant to human risk
assessment. This argument has
been comprehensively rebutted in a report by Open
Earth Source (see [6]). Most importantly, the
findings have been corroborated subsequently. Independent studies confirmed birth
defects in laboratory animals. Defects in frog
development were first observed with lethal doses of
Roundup® (10mg/L, roughly equivalent to 0.003%
dilution of Roundup®) that were still below
agricultural concentrations. Effects were 700 times
more pronounced with Roundup® compared to another
formulation lacking the surfactant polyoxyethyleneamine (POEA),
which is added to maximise
glyphosate’s leaf penetration, and is thought to
increase glyphosate penetration of animal cells as
well [19]. POEA may also have independent toxic
properties. It is important to note that regulatory
approval does not require assessment of the risk of
commercial formulations, and instead relies on testing
glyphosate alone. Sub-lethal doses also led to a 15-20
% increase in gonad size and reduced egg viability in
Leopard frogs and catfish respectively [16, 17]. A definitive study conducted by Andrés
Carrasco and his colleagues in Argentina found neural
and craniofacial defects in frogs exposed to
sub-lethal doses (1/5,000 dilutions) of glyphosate and
Roundup® [18] (see [19] Lab Study Establishes
Glyphosate Link to Birth Defects,
SiS 48). These effects
correlated with over-active retinoic acid (RA), a
well-known regulator of the posterior-anterior axis
during development (Figure 2). RA is an oxidised form of vitamin A and
women are already advised against taking excess
vitamin A during pregnancy. It also regulates the
expression of genes essential for the development of
the nervous system during embryogenesis (shh, slug, otx2), which were inhibited following
glyphosate exposure. Inhibition of RA signalling prevented the teratogenic effects of
glyphosate, further confirming its involvement in the
observed abnormalities. The craniofacial defects in frogs are
similar to human birth defects linked to retinoic acid
signalling such as
anencephaly (neural tube defect), microcephaly (small
head), facial defects, myelomeningocele
(a form of spina bifida),
cleft palate, synotia
(union or approximation of the ears in front of the
neck, often accompanied by the absence or defective
development of the lower jaw), polydactily
(extra digit), and syndactily
(fusion of digits) ; these
diseases are on the rise in pesticide-treated areas
such as Paraguay [20]. Figure 2 Effect of glyphosate
injection; left to right: control embryo not
injected with glyphosate; embryo injected in one
cells only; and embryo injected in both cells. Note
the reduction of the eye, adapted from [18] Findings in mammals are consistent with
those in amphibians. According to the World Health Organisation (WHO), the
administration of high doses of glyphosate (3 500
mg/kg per day) to pregnant rats resulted in an
increased incidence of soft stools, diarrhoea, breathing rattles,
red nasal discharge, reduced activity, increased
maternal mortality (24% during the treatment period),
growth retardation, increased incidence of early resorptions, decrease of total
number of implantation and viable foetuses, and increased number
of foetuses with reduced
ossification of sternebra
[21]. Rats orally treated with sub-lethal doses of
Roundup® also showed dose-dependent reductions in
craniofacial ossification (bone development), caudal
vertebrae loss, and increased mortality [22],
consistent with amphibian data and RA signalling defects.
Prepubescent exposure led to disruption in the onset
of puberty in a dose-dependent manner, reduced
testosterone production, and abnormal testicular
morphology [23]. Reproductive effects were transgenerational, with male
offspring of exposed pregnant rats suffering from
abnormal sexual behaviour,
increased sperm count, early puberty as well as
endocrine disruption (see below) [24]. In a feeding trial, senior scientist of
the Russian Academy of Sciences Irina Ermakova found that female
rats fed rat chow plus Roundup Ready soybean gave
birth to an excess of stunted pups: 55.6 % compared
with 6.8% in litters from control rats fed rat chow
only and 9.1 % of litters from control rats fed rat
chow supplemented with non-GM soybean. The stunted
rats were dead by three weeks, but the surviving rats
in the exposed litters were sterile [25, 26] GM Soya Fed Rats: Stunted,
Dead, or Sterile (SiS 33). The experiment was
repeated with very similar results. Unfortunately, Irmakova did not succeed in
her attempt to get the Roundup Ready soybean analysed for herbicide and
herbicide residues, so the effects could be due to a
mixture of the GM soya and herbicide/herbicide
residues. The second experiment included a group of
females fed rat chow plus GM soya protein did not do
as badly as those exposed to GM soybean; the mortality
rate of pups at three weeks was 15.1 % compared with
8.1 % for controls fed rat chow only, 10 % for
controls fed rat chow plus non-GM soybean, and 51.6 %
for litters of females fed rat chow plus Roundup Ready
soybean. This suggests that extra deaths and stunting
were due to the GM soybean;
as consistent with the new findings by Séralini and colleagues [1]. Irmakova too, was fiercely attacked, and attempts
to discredit her continued for years afterwards,
orchestrated by the journal Nature Biotechnology (see
[27] Science and Scientist Abused,
SiS 36). Dr Irina Ermakov
with the Occupy Monsanto demonstration 17 September
2012 Cell culture models offer insight into a
possible mechanism of glyphosate reproductive
toxicity. Death of testicular cells [28, 29] (see [30]
Glyphosate Kills Rat Testes Cells, SiS 54) as well as embryonic,
placental and umbilical cells occurs at levels 10
times below agricultural dilutions and is exacerbated
by the presence of POEA in commercial formulations.
Endocrine disruption was also noted at lower
concentrations (see below). Clinical and epidemiological data
gathered by The Network Of Physicians Of Drop-Sprayed
Towns in Argentina show a 2- and 3-fold increase in
congenital and musculoskeletal defects respectively
between 1971 and 2003, while another doctor noted an
increase in birth defects of around 50 % among his
patients. Argentina dedicates vast areas of land to RR
soybean production, and as a result, an estimated 12
million people in rural/semi-urban areas are exposed
to glyphosate. Increases in miscarriages, difficulty
in conceiving as well as spontaneous abortions were
documented. Many other illnesses were also suspected
to have arisen as a result of pesticide spraying (see
[31] Pesticide Illnesses and GM
Soybeans. Ban on Aerial Spraying Demanded in
Argentina, SiS 53). The local physicians
confirmed that Carrasco’s laboratory results on
amphibians (see earlier) were consistent with the
illnesses of their patients. 4.2 Endocrine disruption The endocrine system consists of various
glands that release hormones into the bloodstream,
acting as chemical messengers affecting many functions
includingmetabolism,
growth and development,tissuefunction, behaviour andmood. Disruption of the
endocrine system does not commonly result in cell
death, or acute toxicity. Instead, endocrine
disruption can have serious health effects through
interference in cell signalling
and physiology, resulting in a range of developmental
impacts including sexual and other cell
differentiation, bone metabolism, liver metabolism,
reproduction, pregnancy, behaviour,
and hormone-dependent diseases such as breast or
prostate cancer. Endocrine disruption may well
underlie many of the reproductive, teratogenic, and carcinogenic
effects of glyphosate. The synthesis of sex hormones is
disrupted by glyphosate and Roundup® in both males and
females. Mouse and rat testicular Leydig cells (testosterone
producing cells) have reduced testosterone levels as
well as increased levels of aromatase, an enzyme
complex that converts testosterone into oestrogen [28, 29]. Human
placental cells, on the other hand, showed decreased
aromatase expression [32]. All these imbalances were
observed with concentrations well below agricultural
dilutions, and effects were more pronounced with
commercial formulations containing adjuvants. Abnormal expression of testosterone
and/or oestrogen
receptors as well as oestrogen regulated genes has been
documented in human liver cells exposed to both
glyphosate alone or four commercial formulations, and
breast cancer cells exposed to glyphosate [33, 34]. Other hormones were shown to be dysregulated in the presence
of glyphosate, including increased expression and
serum concentration of leutinising
hormone and increased expression of
follicle-stimulating hormone. These are both
gonadotropin hormones secreted by the pituitary glands
that regulate growth, sexual development and
reproduction [24]. Rats exposed to Roundup and/or
Roundup-tolerant maize over two years exhibited a
range of endocrine disruption effects that, typically,
differ between the sexes [1]. Thus mammary tumours were rife in exposed
females while liver pathologies predominated in
exposed males. Similarly, pathology of the pituitary
was more significantly increased in exposed females;
and big kidney and skin tumours
were confined to males. 4.3 Carcinogenicity Epidemiological studies found that
glyphosate exposure increased risk of developing
non-Hodgkin’s lymphoma, a blood cancer of the
lymphocytes [35, 36], with one study showing a
dose-dependent correlation with exposure to commercial
formulations [37]. A rise in plasma cell proliferation
associated with multiple myeloma was documented in
exposed agricultural workers [38]. The Network of
Physicians of Aerial Sprayed Towns in Argentina has
implicated glyphosate (see Figure 3), along with other
pesticides, in the startling increase in both
childhood and adult cancers in pesticide-treated
regions, particularly in the vicinity of GM soybean
plantations [31]. Increased incidence of interstitial
testicular cell tumour at
low doses of 32 mg/kg was documented in a two- year
rat feeding study [22]. Mouse experiments also showed
that glyphosate promotes skin cancer, although not
sufficient to initiate tumours
by itself [39]. These findings make the latest results
from Séralini’s team [1]
all the more significant, as the mammary cancers in
herbicide-exposed females and kidney and skin cancers
in males are further corroboration of glyphosate’s
carcinogenic potential suggested by the earlier
findings. Further epidemiological and clinical
studies are urgently needed to assess glyphosate’s
carcinogenic activity considering the growing evidence
of its genotoxic
properties. Figure 3 Aerial spraying of herbicides,
Eugene Daily News 4.4 Genotoxicity Genotoxicity refers to damage of DNA. DNA damage can
result in mutations that lead to adverse health
effects including cancer, reproductive problems, and
developmental defects. Evidence of genotoxicity not only relates
to glyphosate, but also to its principle metabolite
2-amino-3-(5-methyl-3-oxo-1,2-
oxazol-4-yl)propanoic acid
(AMPA). Epidemiological data gathered in both
Argentina [22] (exposure to glyphosate among other
pesticides) and Ecuador [40] (exposure only to
glyphosate) showed DNA damage in blood samples taken
from exposed people. Unpublished industry studies from the
1980s showed that Roundup® causes chromosomal
aberrations and gene mutations in mouse lymphoid cells
[5]. Increased frequency of DNA adducts (covalently
bound chemicals on DNA) in the presence of glyphosate
has been documented in the liver and kidney of mice in
a dose-dependent manner [41]. This was consistent with
the research team’s previous study showing increased
frequency of DNA adducts in Italian floriculturist
workers exposed to pesticides [42]. Chromosomal and
DNA damage was noted in bone marrow, liver, and kidney
of mice acutely exposed to sub-lethal doses of
Roundup®. Significant effects with glyphosate alone
were also observed in the kidney and bone marrow [43].
Human epithelial cells derived from the buccal cavity suffer DNA
damage at levels well below agricultural dilutions (20
mg/L)[44], these are the cells likely to be affected
by exposure through inhalation (see [45] Glyphosate Toxic to Mouth
Cells & Damages DNA, Roundup Much Worse,
SiS 54). Among non-mammals, glyphosate caused cell
division dysfunction and alterations in cell cycle
checkpoints in sea urchins by disrupting the DNA
damage repair machinery [46, 47]. The failure of cell
cycle checkpoints can lead to genomic instability and
cancer in humans. Glyphosate is also genotoxic in goldfish,
European eels, and Nile tilapia [48-50]. Moreover,
fruit flies showed increased susceptibility to
gender-linked lethal recessive mutations as a result
of exposure to glyphosate [51]. Not much is known regarding glyphosate’s
main breakdown product AMPA; one study suggested it
has acute genotoxic
effects [52] and should be investigated further. 4.5 Neurotoxicity Emerging evidence suggests that
glyphosate is neurotoxic, including two published
cases of Parkinsonism in humans. A 54 year old man in
Brazil was diagnosed with Parkinsonism following
accidental spraying; he developed skin lesions six
hours after being exposed to spraying, and a month
later he developed Parkinson’s disease symptoms [53].
The other case involved a woman in Serbia who ingested
500 millilitres of
glyphosate solution and developed Parkinsonism along
with lesions of the brain’s white matter and pons
(part of brain stem), and altered mental status. The
woman suffered additional non-neurological symptoms
(see acute toxicity section) and eventually died [54].
Consistently, increased oxidative stress,
mitochondrial dysfunction and loss of cell death
markers were found in the substantia
nigra, the brain region
most affected in Parkinson’s disease, of rats exposed
chronically to glyphosate at sub-lethal levels [55,
56]. Oxidative stress represents an imbalance between
the production of reactive oxygen species (ROS), also
known as free radicals, and the body’s ability to
detoxify these reactive intermediates or repair the
damage caused by them. ROS are a natural by-product of
oxygen metabolism such as mitochondrial respiration,
and have important roles in signalling
and metabolism. Excess amounts however, can have
damaging effects on many components of the cell
including lipids in cellular membranes, DNA and
proteins. Excess ROS has been implicated in the aetiology of a wide array of
diseases including Alzheimer’s disease, Parkinson’s
disease (PD), atherosclerosis, heart failure,
myocardial infarction and cancer (see [57] Cancer a Redox Disease,
SiS 54). Activation of the
tightly regulated apoptotic and autophagic
cell death pathways is also implicated in
neurodegenerative diseases and has been observed in
rat neuronal cell lines exposed to glyphosate in a
dose-dependent manner [58]. Other mechanisms of neurotoxicity include
the inhibition of acetylcholine esterase (AChE), an enzyme that metabolises the excitatory
neurotransmitter acetylcholine. AChE
inhibitors such as organophosphate pesticides are
potent nerve agents. Symptoms of AChE
inhibition include miosis
(closing of the eyes), sweating, lacrimation,
gastrointestinal symptoms, respiratory difficulties,
dyspnea, bradycardia,
cyanosis, vomiting, diarrhoea,
personality changes, aggressive events, psychotic
episodes, disturbances and deficits in memory and
attention, as well as coma and death. Further,
increased risk of neurodevelopmental, cognitive and behavioural problems such as
Attention-Deficit Hyperactive disorder (ADHD),
deficits in short-term memory, mental and emotional
problems have been associated with exposure to
glyphosate-based herbicides in children and the
newborn [59]. Although glyphosate is an
organophosphate, it is not an organophosphate ester
but a phosphanoglycine,
and therefore not been assumed to inhibit AChE. New studies suggest
otherwise. Catfish and another fish species, C. decemmaculatus, showed AChE inhibition at
environmentally relevant concentrations of Roundup®
and glyphosate respectively [60, 61]. Furthermore,
these effects were seen following acute exposure of up
to 96 hours. A tentative association between
glyphosate and ADHD in children has been made in an
epidemiological study [62]. Further studies need to be done by
independent scientists as original neurotoxicology data presented
by Monsanto was ruled invalid by the EPA [63]. 4.6 Internal organ toxicity As in the brain (see above), increases in
reactive oxygen species (ROS) have been found in the
liver, kidney and plasma of rats exposed to acute
doses of glyphosate. Concomitant decreases in enzymes
that act as powerful antioxidants such as superoxide
dismutase occur in the liver (see [64] The Case for A GM-Free
Sustainable World, ISIS
publication). Liver cells exposed to four glyphosate
formulations at low concentrations showed decreases in
oestrogen and testosterone
receptor levels, DNA damage and decreases in aromatase
enzyme activity (see [65] Ban Glyphosate Herbicides Now,
SiS 43). Other studies
suggest mitochondrial damage to rat and carp liver
cells in vitro and in vivo respectively at sub-lethal
concentrations [66, 67]. A meta-analysis of 19 feeding studies
originally conducted by Monsanto, but later re-analysed by a group of French
scientists led by Séralini,
found kidney pathology in animals fed RR soybean,
including significant ionic disturbances resulting
from renal leakage (see [68] GM Feed Toxic, Meta-analysis
Reveals, SiS
52). This is consistent with previous results from
cell cultures treated with glyphosate (see [69]Death by multiple poisoning,glyphosate and
Roundup,SiS42), suggesting
that glyphosate present in the GM food was
responsible. Liver pathology in animals fed RR soybean
included the development of irregular hepatocyte
nuclei, more nuclear pores, numerous small fibrillar centres, and abundant dense fibrillar components,
indicating increased metabolic rates. 4.7 Acute toxicity Acute toxicity of glyphosate has been
classified ‘low’ based on rat studies performed by
industry that only showed effects at concentrations of
5 000 mg/kg. However, agricultural workers exposed at
much lower concentrations have documented various
symptoms, highlighted in Argentina (see [70] Argentina’s Roundup Human
Tragedy, SiS
48). Acute toxicity of glyphosate through skin contact
and inhalation includes skin irritation, skin lesions,
eye irritation, allergies, respiratory problems and
vomiting. In cases of ingestion, severe systemic
toxicity and even death has occurred. Ingestion of
small amounts can lead to oral ulceration, oesophageal problems, hypersalivation, nausea,
vomiting and diarrhoea.
Ingestion of larger amounts (usually >85 ml) causes
signi?cant toxicity
including renal and hepatic impairment, acid–base
disturbance, hypotension and pulmonary oedema, impaired consciousness
and seizures, coma, hyperkaliemia,
encephalopathy (global brain dysfunction),
Parkinsonism, respiratory and renal failure. Suicide
attempts have been noted as 10-20 % successful with as
little as 100 ml ingested. 5 Environmental and agronomic effects Agribusiness claims that glyphosate and glyphosate-tolerant crops will improve crop yields, increase farmers’ profits and benefit the environment by reducing pesticide use. Exactly the opposite is the case. Pesticide use has actually increased in successive surveys [71](see [72] GM Crops Increase Herbicide Use in the United States, SiS45). Not only that, the evidence indicates that glyphosate herbicides and glyphosate-tolerant crops have had wide-ranging detrimental effects, including glyphosate resistant super weeds, virulent plant (and new livestock) pathogens, reduced crop health and yield, harm to off-target species from insects to amphibians and livestock, as well as reduced soil fertility. 5.1 Glyphosate resistant weeds Critics long predicted the evolution of weeds resistant to glyphosate, consistent with all previous herbicides used in the past; and they are right. This is causing huge agronomic and ecological concern as farmers are forced to abandon whole fields of crops (see [73] GM Crops Facing Meltdown in the USA, SiS 46). So much so that Monsanto has issued a statement saying it is no longer responsible for the rising costs of weeds under the Roundup® warranty. The Weed Society of America has now launched free resistance-management courses for farmers, although the solutions are clearly towing the agribusiness line of dousing crops in additional pesticides, a terribly flawed solution that will only lead to more of the same, or worse – weeds resistant to multiple herbicides. Indeed, some species have already evolved resistance to two 0r even three types of herbicides. In some cases, these “superweeds” are so resilient that the only method of destroying them is to pull them out by hand. Palmer amaranth grows at up to 3 inches a day causing an imaginable headache for farmers (see Figure 4). Figure 4 Field infested with Palmer amaranth ‘superweed’, Agweb First documented in ryegrass in 1996 in Australia, glyphosate-resistance has since been observed in 23 separate species across 16 countries by 2010, covering an estimated 120 million hectares worldwide and continuing to spread [74]. Up until 2003, 5 resistant populations had been documented worldwide. Since 2007, there has been a 5-fold increase in the spread of resistant weeds (See [75] Monsanto Defeated By Roundup Resistant Weeds, SiS 53). So far, resistant species listed by the WeedScience database include: Palmer Amaranth, Common Waterhemp, Common Ragweed, Giant Ragweed, Ripgut Brome, Australian Fingergrass, Hairy Fleabane, Horseweed, Sumatran Fleabane, Sourgrass, Junglerice, Goosegrass, Kochia, Tropical Sprangletop, Italian Ryegrass, Perennial Ryegrass, Rigid Ryegrass, Ragweed Parthenium, Buckhorn Plantain, Annual Bluegrass, Johnsongrass, Gramilla mansa and Liverseedgrass. Of all the resistant species, Palmer Amaranth and Common waterhemp have received the most attention. Waterhemp produces up to a million seeds per plant, making it difficult to prevent spreading of resistant populations. It also has a long emergence pattern, which means that multiple rounds of herbicide treatments are required. Resistant common waterhemp was first documented in fields in Missouri, US, in 2004 after at least 6 consecutive years of growing soybeans. The suggested mechanism of resistance in this population was the amplification of EPSPS genes in the plant, allowing it to compensate for glyphosate’s inhibition of the enzyme. According to Bill Johnson, an entomologist from Perdue University in Indiana US, waterhemp is a serious threat to soybean farming with the capacity to reduce yields by 30-50 % [76]. Palmer amaranth is estimated to have infested at least a million separate sites in the US alone. It is a particular hardy plant, and is considered one of the most destructive weed species in the south-eastern US. Field experiments have shown its potential to reduce cotton yields by 17-68 %, having important implications for RR cotton farmers [77]. In order to prolong the utility of herbicide-tolerant GM crops, agribusinesses are now developing crops with multiple tolerance traits, or tolerance to old herbicides like 2,4-Dichlorophenoxyacetic acid (2,4-D). Dow Agrosciences are ready to roll out 2,4-D-tolerant corn, soy and cotton even though this year saw the discovery of 2,4-D resistant waterhemp in Nebraska, making it the sixth mechanism-of-action group to which waterhemp has developed resistance [78]. The emergence of resistant weeds explains the increases in pesticide use over the last few years, as farmers apply more and more in an attempt to rid their farms of hardy weeds. As noted by the Network of Argentinian Physicians of Crop Sprayed Towns, repeated glyphosate use on the same plots of land rose from 2 litres per hectare in 1996, to almost 20 litres in 2011 [79], most likely due to the emergence of resistant weeds. The extent of damage wreaked by glyphosate-resistant weeds has been further exacerbated by the severe US drought of 2012, which dries out weeds and makes them less sensitive to herbicides [80]. Global warming and herbicide resistant weeds may therefore have synergistic effects on crop yield losses, again highlighting the unsustainable approach of intensive chemical agriculture. 5.2 Effects on crop and plant health Glyphosate use has been associated with the increased incidence and/or severity of many plant diseases and the overall deterioration of plant functions such as water and nutrient uptake [13]. As mentioned above, glyphosate’s mechanism of action is the systemic chelation of metals, including manganese, magnesium, iron, nickel, zinc and calcium, many of which are important micronutrients. They act as co-factors for many plant enzymes including those involved in the plants’ immune system [14]. While non-transgenic varieties are killed by glyphosate, glyphosate-tolerant crops do not die; but their physiology can be compromised. Manganese is a co-factor for 25 known enzymes involved in processes including photosynthesis, chlorophyll synthesis and nitrate assimilation, and enzymes of the shikimate pathway to which EPSPS belongs. The shikimate pathway is responsible for plant responses to stress and the synthesis of defence molecules against pathogens, such as amino acids, lignins, hormones, phytoalexins, flavenoids and phenols. The virulence mechanism of some pathogens, including Gaeumannomyces and Magnaporthe (which lead to ‘take-all’ and root rot respectively) involves the oxidisation of manganese at the site of infection, compromising the plant’s defence against it. Glyphosate-tolerant crops were found to have reduced mineral content, confirming glyphosates’ metal chelating activity [81-84]. Various plant diseases have reached epidemic proportions in the US, now in its fourth year of epidemics of Goss’ wilt and sudden death syndrome and eighteenth year of epidemic of Fusarium fungal colonisation resulting in root rot and Fusarium wilt. Not only does glyphosate affect disease susceptibility, there is also evidence of increased disease severity. Examples include Take All, Corynespora root rot in soybean, Fusarium spp diseases, including those caused by Fusarium species that are ordinarily non-pathogenic. Head-scab caused by Fusarium spp of cereals increases following glyphosate application is now prevalent also in cooler climates when previously it was limited to warmer climates. Nine plant pathogens have been suggested to increase in severity as a result of glyphosate treatment of crops, while some 40 diseases are known to be increased in weed control programmes with glyphosate and the list is growing, affecting a wide range of species: apples, bananas, barley, bean, canola, citrus, cotton, grape, melon, soybean, sugar beet, sugarcane, tomato and wheat [85]. USDA scientist Professor Emeritus Don Huber presented detailed evidence including a photograph (Figure 5) to the UK Parliament that glyphosate-tolerant crops are less healthy and yield less. They have a compromised immune system and require extra water, which are major problems as climate change is likely to increase infectious diseases and exacerbate water scarcity [14]. Figure 5 Effects of
long-term glyphosate on crop (wheat) health; left not
As consistent with previous findings, GM crops are suffering heavy yield losses in drought-stricken US in 2012 [86]. A farmer who has grown both GM and non-GM varieties of corn and soybean side by side reported an average of 100-120 bushels per acre harvested from non-GM corn compared to 8-12 bushels to 30-50 bushels per acre from GM corn. According to a recent report published by the Union of Concerned Scientists, GM crops have certainly not succeeded in increasing yields [87]; but there is as yet no comprehensive peer-reviewed study on GM crop yields. As with animal species, endocrine dysfunction has been suggested in plants exposed to glyphosate (see above), potentially affecting health as well as crop yields. Inhibition of auxins involved in plant growth and development, as well as reduced methionine levels have been observed; methionine is a principle substrate for fruit, flower opening and shedding of leaves [88]. Various aquatic species including microalgae, protozoa and crustaceans are susceptible to glyphosate, but more so to the surfactant POEA [89] in Roundup formulations. 5.3 Effects on soil ecology Soil fertility is fundamental in maintaining plant health and yields. However, along with the rise in industrial agrochemical farming practices, there has been a general increase in the number of plant diseases in the past 15 to 18 years. Glyphosate has been shown to stimulate the growth of fungi and increase the virulence of soil pathogens such as Xylella fastidiosa which causes citrus variegated chlorosis, while also decreasing the presence of beneficial soil organisms [90] Scientists Reveal Glyphosate Poisons Crops and Soil (SiS47). Four primary soil fungi, Fusarium, Phythium, Rhizoccccctonia, and Phytophthora, have become more active with the use of glyphosate; and concomitantly diseases caused by these fungi have increased, such as head scab in corn, or root rot in soybeans, crown rot in sugar beets. Fusarium head blight, which affects cereal crops, is a disease that produces a mycotoxin that could enter the food chain. Beneficial micro- and macro-organisms damaged by glyphosate include earthworms, microbes producing indole-acetic acid (a growth-promoting auxin), mycorrhizae associations, phosphorus & zinc uptake, microbes such as Pseudomonads and Bacillus that convert insoluble soil oxides to plant-available forms of manganese and iron, nitrogen-fixing bacteria Bradyrhizobium, Rhizobium, and organisms involved in the biological control of soil-borne diseases that reduce root uptake of nutrients (see [90, 13] (see Figure 6). In addition to soil microorganisms, Roundup® but not glyphosate alone, kills three beneficial food microrganisms (Geotrichum candidum, Lactococcus lactis subsp. cremoris and Lactobacillus delbrueckii subsp. bulgaricus) widely used as starter cultures in the dairy industry [91]. This may explain the loss of microbiodiversity in raw milk observed in recent years. Figure 6 Interactions of
glyphosate with plant and soil biology; It has been assumed that glyphosate is short-lived, degrading in two weeks, and has low accumulation and drift. However, this conventional view may only be applicable, if at all, in certain environments. Studies in northern regions of the globe have demonstrated that glyphosate and its main metabolite AMPA can remain in the soil even years after the last spraying [92]. That means the herbicide and its residues can remain active and accumulate in soils with increasingly devastating effects on soil ecology. 5.4 Effects on ecosystems Glyphosate use impacts animal biodiversity and health either directly or indirectly through destruction of habitats. It is considered to be particularly toxic to aquatic and amphibian species, due to its high water solubility. Amphibians are considered the most endangered animal class on Earth. Recent studies have highlighted glyphosate’s toxicity to frog species, with exposure killing 78 % of animals in laboratory conditions (see [93] Roundup Kills Frogs, SiS 26). A 2012 study found enlarged tails in exposed tadpoles, similar to the adaptive changes seen in response to the presence of predators. Tadpoles adapt their body shape to suit environmental conditions, so any changes not suited to the environment could put the animals at a distinct disadvantage [94]. Currently unpublished data from The Department of Herpetology at the Society of Sciences, Aranzad, Spain suggests that glyphosate concentrations below agricultural levels are sufficient to kill 10 species of amphibians in the Basque region of Spain [95]. As mentioned earlier, birth defects in frogs have also been detailed in laboratory conditions [15]. Studies in aquatic microcosms and mesocosms found that Roundup at 8 mg glyphosate/L inhibited the growth of green algae at the expense of toxic bloom-forming cyanobacteria, with potentially drastic impacts on freshwater aquatic ecosystems [96, 97]. It also accelerates the deterioration of water quality, which is already jeopardising global water supply [98] (World Water Supply in Jeopardy, SiS 56). The indirect effect of habitat destruction is exemplified by the decline of Monarch butterfly numbers (see [99] Glyphosate and Monarch Butterfly Decline, SiS 52) (Figure 7). The larvae of this species feed almost exclusively on milkweed plants, which are being destroyed through glyphosate treatment of GM crops. In the Midwest of the US, there has been a 58 % decline in milkweed plants and a resulting 17-year decline in Monarch butterfly [100]. A decline in their winter migration to Mexico has been observed stretching back 15 years. Figure 7 Monarch butterflies, University of Arkansas System 4.4 Genotoxicity Genotoxicity refers to damage of DNA. DNA damage can
result in mutations that lead to adverse health
effects including cancer, reproductive problems, and
developmental defects. Evidence of genotoxicity not only relates
to glyphosate, but also to its principle metabolite
2-amino-3-(5-methyl-3-oxo-1,2-
oxazol-4-yl)propanoic acid
(AMPA). Epidemiological data gathered in both
Argentina [22] (exposure to glyphosate among other
pesticides) and Ecuador [40] (exposure only to
glyphosate) showed DNA damage in blood samples taken
from exposed people. Unpublished industry studies from the
1980s showed that Roundup® causes chromosomal
aberrations and gene mutations in mouse lymphoid cells
[5]. Increased frequency of DNA adducts (covalently
bound chemicals on DNA) in the presence of glyphosate
has been documented in the liver and kidney of mice in
a dose-dependent manner [41]. This was consistent with
the research team’s previous study showing increased
frequency of DNA adducts in Italian floriculturist
workers exposed to pesticides [42]. Chromosomal and
DNA damage was noted in bone marrow, liver, and kidney
of mice acutely exposed to sub-lethal doses of
Roundup®. Significant effects with glyphosate alone
were also observed in the kidney and bone marrow [43].
Human epithelial cells derived from the buccal cavity suffer DNA
damage at levels well below agricultural dilutions (20
mg/L)[44], these are the
cells likely to be affected by exposure through
inhalation (see [45] Glyphosate Toxic to Mouth
Cells & Damages DNA, Roundup Much Worse,
SiS 54). Among non-mammals, glyphosate caused cell
division dysfunction and alterations in cell cycle
checkpoints in sea urchins by disrupting the DNA
damage repair machinery [46, 47]. The failure of cell
cycle checkpoints can lead to genomic instability and
cancer in humans. Glyphosate is also genotoxic in goldfish,
European eels, and Nile tilapia [48-50]. Moreover,
fruit flies showed increased susceptibility to
gender-linked lethal recessive mutations as a result
of exposure to glyphosate [51]. Not much is known regarding glyphosate’s
main breakdown product AMPA; one study suggested it
has acute genotoxic
effects [52] and should be investigated further. |