ISIS Press Release 15/07/09

Ban Glyphosate Herbicides Now

Scientists Confirm Potent Hormone Disrupting Effects

Latest evidence confirms world's top-selling herbicide used with GM crops is toxic and disrupts sex hormones at infinitesimal doses; time for a worldwide ban
Dr. Mae-Wan Ho

This report has been submitted to the US Environment Protection Agency
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Scientific evidence of glyphosate and Roundup toxicities piling up

Glyphosate is the world's top selling herbicide, and Monsanto's formulations Roundup is used with more than 80 percent of all genetically modified (GM) crops grown globally. But evidence of its extreme toxicity has been emerging within the past decade. Glyphosate was found to kill human placental cells at concentrations below that recommended for agricultural use and approved by our regulators, while Roundup was lethal at even lower concentrations [1] Glyphosate Toxic & Roundup Worse , SiS 26). The herbicide has already been linked with spontaneous abortions, Hodgkin's lymphoma and multiple myeloma in humans; and in laboratory studies glyphosate caused liver damage in rats. Roundup is also highly lethal to amphibians [2] ( Roundup Kills Frogs , SiS 26).

Recently, the research team led by Giles-Eric Séralini at Caen University in France confirmed the lethality of glyphosate and Roundup formulations to human cells at minute concentrations (down to parts per million, ppm) [3] ( Death by Multiple Poisoning, Glyphosate and Roundup , SiS 42). They also identified three main targets for killing cells: damage to the cell membrane, poisoning of energy metabolism in the mitochondria, and programmed cell death involving fragmentation of nuclear DNA.

Séralini's team joined up with colleagues at the University of Burgundy in Dijon and have now demonstrated that the herbicide and its Roundup formulations disrupt the action and synthesis of sex hormones at even lower concentrations [4].

Synergistic nonlinear effects of herbicide formulations

Glyphosate-based herbicides are now major pollutants of rivers and surface waters. Commercial glyphosate formulations contain a number of different ‘adjuvants' that are supposed to be ‘inert', but such cocktail mixtures typically exert synergistic, multiplicative and other nonlinear effects, much more potent than the separate ingredients [5] ( Super-Toxic Cocktails , SiS 42). Unfortunately, typical toxicology tests are still carried out on individual ingredients, if at all

Not surprisingly, the question of active toxic threshold of the combinations of glyphosate and adjuvants in different formations in vivo is still open, but as Séralini and colleagues state [4], “it is now well demonstrated that mixtures formulated with G [glyphosate] and adjuvants are themselves not environmentally safe, in particular for aquatic life. They can even enhance heavy metals toxicity.”

Carcinogenic, mutagenic and reprotoxic effects

The researchers decided to look into the carcinogenic mutagenic and reproductive toxicity (CMR) of glyphosate and formulations in view of previously published findings dating from the 1990s, documenting effects on reproduction, such as sperm production and pregnancy, and mutagenic and toxic effects at very low doses in embryonic, foetal and placental cells. Numerous CMR substances are also endocrine disruptors and object for specific legislations

They chose the human liver cell line HepG2 because it is the best characterized human liver cell line, and is used as a model system to study xenobiotic toxicity. The liver is the major detoxification organ for food or drinks contaminants, and Roundup has been demonstrated to damage carp and rat liver cells at low concentrations.

The endocrine disrupting effects were studied with three different sex hormone receptors (oestrogen receptors ER a , ER b and androgen receptor AR), and with aromatase, the enzyme responsible for converting androgen to oestrogen. If these functions are disturbed, they will have a range of developmental impacts including sexual and other cell differentiation, bone metabolism, liver metabolism, reproduction, pregnancy, development, behaviour and hormone-dependent diseases such as breast or prostate cancer.

Sex hormone disrupting effects at infinitesimal concentrations

The human liver cells were exposed to glyphosate (G) and four different Roundup (R) formulations, and monitored for toxicity with a combination of enzyme assays for cell damage (cytotoxicity) as in the earlier work [3].

In addition, the ability to disrupt the action of oestrogen (female sex hormone) and androgen (male sex hormone) was investigated (see above) and their ability to damage DNA monitored with a ‘comet assay', a single cell gel electrophoresis for detecting single- and double-strand breaks and other lesions.

Glyphosate (G) was purchased from Sigma-Aldrich. The Roundup formulations tested were from Monsanto, and available on the market; Roundup Express (7.2g/L of G) (R7.2), Bioforce or Extra 360 (360g/L of G) (R360), Grands Travaus (400g/L of G) (R400), Grands Travaux plus (450g/L of G) (R450).

All functions were found to be disrupted at sub-agricultural doses with all the Roundup formulations within 24 h of exposure, the effects being more dependent on the formulations than on the concentration of glyphosate. Glyphosate alone was toxic from 1 percent, but the formulations were more potent; cytotoxic effects began at 10 ppm, and DNA damages at 5 ppm. But endocrine disrupting effects came top.

The disruption of androgen-receptor binding occurred at 0.5 ppm for the most active formulation (R400), and at 2 ppm, the transcription of oestrogen receptors was inhibited. Aromatase transcription and enzyme activity were both disrupted at 10 ppm. All formulations except R450 appeared more anti-androgenic than anti-oestrogenic. The ranking in inhibition efficiencies was R400>R450>R360>R7.2, with a 300-800 fold difference between the strongest inhibitor and the weakest. The effects were clearly neither linear nor proportional to G concentration. Glyphosate alone has no effect on these endocrine-related activities.

Ban glyphosate and GMOs now

These results are devastating for health and the environment. The toxic effects of Roundup (R400) begin at 5 ppm, and the first endocrine disrupting action is already evident at 0.5 ppm, 800 times lower than the level of 400 ppm authorized by the US Environment Protection Agency in food or feed. And these latest results come in the wake of a string of evidence linking the herbicide and its formulations with cancers, miscarriages and other reproductive toxicities, liver and cell toxicities, DNA damages, lethality to amphibians [2] and lately, a range of embryonic defects in frogs [6] ( Glyphosate Herbicide Could Cause Birth Defects , SiS 43).

In 2005, we called for a urgent review of glyphosate and Roundup [1]. Argentina is now considering a ban on this herbicide and formulations used on GM soybean grown in nearly half of its agricultural land [6].

It is time for a worldwide ban on glyphosate herbicide and GM crops. There is strong evidence indicating that [7] GM is Dangerous and Futile ( SiS 40), apart from the fact that more than 80 percent of all GM crops grown globally are engineered to be glyphosate-tolerant, and have been responsible for a 15-fold increase in glyphosate use on major crops as glyphosate-resistant superweeds proliferate.

References

1. Ho MW and Cummins J. Glyphosate toxic & Roundup worse. Science in Society 26 , 12, 2005.
2. Ho MW. Roundup kills frogs. Science in Society 26 . 13, 2005.
3. Ho MW and Cherry B. Death by multiple poisoning, glyphosate and Roundup. Science in Society 42 , 14, 2009.
4. Gasnier C, Dumont C, Benchour N, Clair E, Chagnon M-C and Séralini G-E. Glyphosate-based herbicides are toxic and endocrine disruptors in human cell lines. Toxicology, doi:10.1016/j.tox.2009.06.006.
5. Saunders PT. Super-toxic cocktails. Science in Society 42 , 49, 2009.
6. Ho MW. Glyphosate herbicide could cause birth defects. Science in Society 43 (to appear).
7. Ho MW. GM is dangerous and futile, we need sustainable food and energy systems now. Science in Society 40 , 4-7, 2008.

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