Open access to science eprints
TheSparc provides both scientists and the general public free open access to scientific papers that are important for the survival of people and planet
ISIS Report 07/03/05
Glyphosate Toxic & Roundup Worse
Dr. Mae-Wan Ho and
Prof. Joe Cummins call for urgent
regulatory review of the most widely used herbicide in the light of new
New research findings are raising serious concerns over the safety of
the most commonly used herbicide, and should be sending shockwaves through
proponents of genetically modified (GM) crops made tolerant to the herbicide,
which now account for 75% of all GM crops in the world.
Worse yet, the most common formulation of the herbicide is even more
toxic than the herbicide by itself, and is made by the same biotech giant that
created the herbicide tolerant GM crops.
Broad-spectrum herbicide glyphosate (N-(phosphonomethyl)glycine),
commonly sold in the commercial formulation Roundup (Monsanto company, St.
Louis, Missouri USA) has been frequently used both on crops and non-crops areas
world wide since it was introduced in the 1970s. Roundup is a combination of
glyphosate with other chemicals including a surfactant (detergent)
polyoxyethyleneamine that enhance the spreading of the spray droplets on the
leaves of plants. The use of Roundup has gone up especially in countries
growing Roundup-tolerant GM crops created by Monsanto.
Glyphosate kills plants by inhibiting the enzyme,
5-enolpyruvoyl-shikimate-3-phosphate synthetase (EPSPS), essential for the
formation of aromatic amino acids such as phenylalanine, tyrosine and
tryptophan; which leads onto vitamins and many secondary metabolites such as
folates, ubiquinones and naphthoquines. It is believed to be rather specific in
action and less toxic than other herbicides, because the shikimate pathway is
not present in mammals and humans. However, glyphosate acts by preventing the
binding of phosphoenol pyruvate to the active site of the enzyme, and
phosphoenol pyruvate is a core metabolite present in all organisms; thus it has
the potential to affect other metabolic pathways. This is borne out by many
reports of toxicities associated with the herbicide reviewed in the Independent
Science Panel Report, The Case for
a GM-free Sustainable World .
An epidemiological study in the Ontario farming populations showed that
glyphosate exposure nearly doubled the risk of late spontaneous abortions ,
and Prof. Eric-Giles Seralini and his research team from Caen University in
France decided to find out more about the effects of the herbicide on cells
from the human placenta.
They have now shown that glyphosate is toxic to human placental
cells, killing a large proportion of them after 18 hr of exposure at
concentrations below that in agricultural use . Moreover, Roundup is always
more toxic than its active ingredient, glyphosate; at least by two-fold. The
effect increased with time, and was obtained with concentrations of Roundup 10
times lower than agricultural use.
The enzyme aromatase is responsible for making the female hormones
estrogens from androgens (the male hormones). Glyphosate interacts with the
active site of the enzyme but its effect on enzyme activity was minimal unless
Roundup was present.
Interestingly, Roundup increased enzyme activity after 1 h of
incubation, possibly because of its surfactant effect in making the androgen
substrate more available to the enzyme. But at 18h incubation, Roundup
invariably inhibited enzyme activity; the inhibition being associated with a
decrease in mRNA synthesis, suggesting that Roundup decreased the rate of gene
transcription. Seralini and colleagues suggest that other ingredients in the
Roundup formulation enhance the availability or accumulation of glyphosate in
There is, indeed, direct evidence that glyphosate inhibits RNA
transcription in animals at a concentration well below the level that is
recommended for commercial spray application Transcription was inhibited and
embryonic development delayed in sea urchins following exposure to low levels
of the herbicide and/or the surfactant polyoxyethyleneamine. The pesticide
should be considered a health concern by inhalation during spraying .
New research shows that a brief exposure to commercial glyphosate caused
liver damage in rats, as indicated by the leakage of intracellular liver
enzymes. In this study, glyphosate and its surfactant in Roundup were also
found to act in synergy to increase damage to the liver .
Three recent case-control studies suggested an association between
glyphosate use and the risk of non-Hodgkin lymphoma [6-8]; while a prospective
cohort study in Iowa and North Carolina that includes more than 54 315 private
and commercial licensed pesticide applicators suggested a link between
glyphosate use and multiple myoeloma . Myeloma has been associated with
agents that cause either DNA damage or immune suppression. These studies did
not distinguish between Roundup and glyphosate, and it would be important for
that to be done.
There is now a wealth of evidence that glyphosate requires
worldwide health warnings and new regulatory review. Meanwhile, its use should
be reduced to a minimum as a matter of prudent precaution.
- The Case for a GM-Free Sustainable World, Chapter 7, ISIS & TWN,
London & Penang, 2003.
- Savitz DA, Arbuckle , Kaczor D, Curtis KM. Male pesticide exposure
and pregnancy outcome. Am J Epidemiol 2000, 146, 1025-36.
- Richard S, Moslemi S, Sipahutar H, Benachour N. and Seralini GE.Differential effects of glyphosate and roundup on human placental cells and aromatase.Environ Health Perspect. 2005 Jun;113(6):716-20
- Marc J, Le Breton M, CormierP, Morales J, Belle´R and
Mulner-Lorillo O. A glyphosate-based pesticide impinges on transcription.
Toxicology and Applied Pharmacology 2005, 203, 1-8.
- Benedetti AL, de Lourdes Vituri C, Trentin AG, Dominguesc MAC and
Alvarez-Silva M. The effects of sub-chronic exposure of Wistar rats to the
herbicide Glyphosate-Biocarb. Toxicology Letters 2004, 153,
- De Roos AH, Zahm SH, Cantor KP, et al. Integrative assessment of
multiple pesticides as risk factors for non-Hodgkins lymphoma among men.
Occup Environ Med 2003, 60, E11
- Hardell L, Eriksson M, Nordstrom M. Exposure to pesticides as risk
factor for non-Hodgkins lymphoma and hairy cell leukemia: pooled analysis
of two Swedish case-control studies. Leuk Lymphoma 2002,
- McDuffie HH, Pahwa P, McLaughlin JR, Spinelli JJ, Fincham S, Dosman
JA, et al. 2001. Non-Hodgkins lymphoma and specific pesticide
exposures in men: cross-Canada study of pesticides and health. 2001, Cancer
Epidemiol Biomarkers Prev 2001,10,115563.
- De Roos AJ, Blair A, Rusiecki JA, Hoppin JA, Svec M, Dosemeci M,
Sandler DP and Alavanja MC. Cancer incidence among glyphosate-exposed pesticide
applicators in the agricultural health study. Environ Health Perspect
2005, 113, 49-54.