GM-free Scotland

GM issues | Is GM soya safe?


CONTENTS

Part   I  –   Review of feeding experiments on GM soya

Part  II  –  Roundup: safe as salt?

Part III  –  Roundup: reproductive effects


Part I

Review of feeding experiments on GM soya.

(Review of the science, 2008)

'Roundup Ready' soya has been one of the biggest success stories in the short history of GM agriculture.  Genetically transformed to make it resistant to Monsanto's Roundup weedkiller, this crop has the added attraction that sales of the seed can be lucratively linked to the marketing of the herbicide.

The sales-pitch for Roundup Ready (RR) seed is simple. The active ingredient of Roundup is glyphosate which is the least unfriendly to the environment of all the weedkillers, degrading to harmless end-products, and rapidly becoming inactivated in the soil.  Roundup technology benefits the farmer and his yields through cheap and easy weed control.  It allows no-till agriculture to the benefit of the soil, and the transgenic protein produced by the GM plant is non-toxic and non-allergenic.

Any initial questions about safety of RR soya were easily dismissed by three studies, which Monsanto commissioned and part-paid for their publication in a scientific journal(1,2,3).  These demonstrated that the compositional and feeding value are equivalent to conventional soya and that the novel protein was easily digested.

In summary, Roundup Ready soya hit the market with all benefit to the farmer, no problem for environment, and human health problems just weren't in the picture at all.

The reality, twelve years down the line, is beginning to look a little different.

Eleven years after GM soya entered our food chain, an attempt to review the citations in the scientific literature on human and animal toxicological risks from GM food drew the comment that “ ... it is quite amazing to note ... the number (of articles) was particularly small ... and) surprisingly limited”.  This review concluded with the question “where is the scientific evidence showing that GM foods are toxicologically safe?”(4)

How and where?  Indeed.  Let's look at the evidence.

The study commissioned by Monsanto for publication way back in 1996 focused on feeding value for commercial livestock, but also included a very short (28 day) trial on young rats(2) .  This assessed gross symptoms of disease on the basis of organ weights and general appearance.  Beyond this, only  the pancreas received some extra attention because soya produces a number of known anti-nutrients which can adversely affect this organ.  Observed organ differences were declared not “meaningful”.

In 1999, a short (140 day) Russian study was published which looked at liver function in rats fed Roundup Ready soya protein concentrate(5) .  Since this organ deals with toxins entering, or produced by, the body, it is an obvious place to look for signs of unusual activity.  The authors noted modifications to the liver cell membrane function and enzyme activity, but these were considered to be “within physiological standards”.  
COMMENT  This paper was a translation from the Russian, and slightly difficult to follow, but it sounds like another version of Monsanto's not “meaningful” mentioned above. 

In 2000, a short (105 day) study on rats and mice fed Roundup Ready soya looked at the immune-system because harmful qualities in the food will tend to provoke protective mechanisms in the physiology(6) .  No adverse effects on immune-related organs were found.

In summary, by 2001, when people had already been eating Roundup Ready soya for 5 years, the 'proof' of safety seems to have amounted to three brief industry-commissioned feeding studies.  A single belated experiment had been performed on each of three key areas of the physiology which might reasonably be affected by untoward qualities in the food: pancreatic-based digestion, the liver-based detoxification, and the immune system.

Since then, other approaches using multigenerational experiments and more refined cellular and subcellular techniques have been pursued.

On the basis that the high rate of proliferation and unique cell differentiation in a normal testis make this organ very sensitive to toxins, two experiments were published in 2004 which looked at mice whose mothers were fed Roundup Ready soya chow during gestations and lactation, and who were then fed the GM chow after weaning. 

In one, testicular cell development was used as a bioindicator of exposure to toxins by an American team who measured the proportions of different cell types present  in the testis as the testis matured(10).  Their measurements were repeated on the fourth generation of mice fed GM chow.  No differences were detected in cell growth or differentiation in any of the animals.

The second study, by an Italian team, used immuno-electron microscopy to identify subtle alterations in the ultrastructure of the different cell types found in the testes(12) .  Signs of reduced nuclear activity similar to those caused by stress factors or drugs were evident, some of which normalised with age.

Another line of research has emerged from various Italian teams who took a much closer look at organ changes at the sub-cellular level in response to Roundup Ready soya:


One last published paper has not been mentioned.  A short (91 day) rat feeding study appeared in 2004 which found more 'not meaningful' differences, including no adverse effects even at GM soya levels as high as 90% of the diet(11) .  This was surprising because previous work had indicated that maximum levels of soya compatible with health in the rodent diet were much lower: Monsanto's study in 1996 used 24% processed soya, the American mouse testis study used 21%,  the Italian mouse testis and rat studies used 14%. 

One possible explanation for this contradiction tends to jump uncomfortably out of the literature.  The experiments which failed to identify any problems, including the one which tried 90% soya chow, were short-term and used young animals.  The experiments which suggested problems involved longer-term feeding.  For example, the American four-generation mouse-testis study used young animals of 63-87 days-old, while in the Italian experiments which revealed evidence of harm, extended to 140 and 224 days.

You might be getting the impression by now that half the published toxicological studies on RR soya have been designed to be too short, too superficial in the parameters measured, and have used too healthy animals to pick up on problems.

To go back to the original question of 'where's the evidence' of toxicological safety to base any decision on, the sum total of evidence seems to be twelve published studies.  Two concluded no adverse findings, three concluded no meaningful differences and seven concluded something odd, inexplicable and potentially harmful to health was apparent.  This looks like seven-to-five against (or, seven against, two for, and three inconclusive maybe/maybe-nots).  Is this sufficient evidence for you to make an informed decision on whether RR soya is safe to eat?  Or, is it a reason to urgently require more detailed, systematic and comprehensive study?

The question, of course, doesn't stop there because there are other confounding implications of RR soya which are just beginning to see the light of day.  For example, RR soya is, not surprisingly, sprayed with Roundup.  Is Roundup really as benign as Monsanto has repeatedly suggested?  The Italian researchers mentioned above are beginning to question this.  See Part II, Glyphosate – Safe as Salt?

SOURCES

  1. Padgette et al. (1996) The Composition of Glyphosate-Tolerant Soybean seeds Is Equivalent to That of Conventional Soybeans, Journal of Nutrition 126

  2. Hammond et al. (1996) The Feeding Value of Soybeans Fed to rats, Chickens, Catfish and Dairy Cattle Is Not Altered by Genetic Incorporation of Glyphosate Tolerance, Journal of Nutrition 126

  3. Harrison et al. (1996) The Expressed Protein in Glyphosate-Tolerant Soybean, 5-Enolypyruvylshikimate-3-Phosphate Synthase from Agrobacterium sp. Strain CP4, Is Rapidly Digested In Vitro and Is Not Toxic to Acutely Gavaged Mice, Journal of Nutrition, 126

  4. Domingo J. L. (2007), Toxicity Studies of Genetically Modified Plants: A Review of the Published Literature, Critical Reviews in Food Science and Nutrition 47

  5. Tutel'ian et al. (1999) Medical and biological evaluation of safety of protein concentrate from genetically-modified soybeans, www.ncbi.nlm.gov, Vopr Pitan 68

  6. Teshima et al. (2000) Effect of GM and Non-GM Soybeans on the Immune System of BN Rats and B10A Mice, Journal of Food Hygiene Society Japan, 41:3

  7. Malatesta et al.(2002) Ultrastructural Morphometrical and Immunocytochemical Analyses of Hepatocyte Nuclei from Mice Fed on Genetically Modified Soybean, Cell Structure and Function 27

  8. Malatesta et al.(2002) Ultrastructural analysis of pancreatic acinar cells from mice fed on genetically modified soybean, Journal of Anatomy, 201(5)

  9. Malatesta et al.(2003) Fine structural analyses of pancreatic acinar cell nuclei from mice fed on gentically modified soybean, Letter to the Editor, European Journal of Histochemistry, 47:4

  10. Brake and Evenson (2004) A generational study of glyphosate-tolerant soybeans on mouse fetal, postnatal, pubertal and adult testicular development, Food and Chemical Toxicology 42,

  11. Zhu et al.(2004) Nutritional assessment and fate of DNA of soybean meal from Roundup Ready or conventional soybeans using rats, Archives of Animal Nutrition, 58:4

  12. Vecchio et al. (2004) Ultrastructural analysis of testes from mice fed on genetically modified soybean, European Journal of Histochemistry, 48:4

  13. Tudisco et al.(2006) Genetically modified soya bean in rabbit feeding: detection of DNA fragments and evaluation of metabolic effects by enzymatic analysis, Animal Science, 82

  14. Malatesta et al.(2008) A long-term study on female mice fed on a genetically modified soybean: effects on liver ageing, Histochemical Cell Biology, 130

  15. Ermakova (2009), Influence of Soy with the Gene EPSPS CP4 on the Physiological State and Reproductive Functions of Rats, Russian Academy of Natural Sciences – Modern problems of science and education, 5

Part II

Roundup: safe as salt?                                                                                        

Consider the following claims(1,2):

These are very reassuring.  They tell us that Roundup herbicide has been around for years all over the world, long before the GM crops designed to be sprayed with it came on the scene.  It's safe to eat, environmentally friendly, naturally disappears to negligible levels, and saves any need for additional weed-killers.

Comforting.  But is it true?

The final claim has been the first one to unravel.

Between 1994 (pre-GM) and 2005 (nine years post-GM), US government data reveal a 15-fold increase in the use of glyphosate; the following year, glyphosate use jumped a further substantial 28%(3,12).

This has been due to a number of Roundup-related changes in farming practice:

The result has been, as predicted right from the start of RR crops, the emergence of some very problematic Roundup-resistant weeds, and a spiraling cycle of increased spraying using more Roundup plus some very less ‘friendly’ weedkillers.

Monsanto's promised elimination of the “need for additional herbicides” was short-lived.

The Company's assertion that 'Glyphosate is rapidly broken down in soil' also needs qualification.

If glyphosate is actually in the soil, and if the soil conditions are conducive, and if the right micro-organisms are there, glyphosate can be degraded in a few days.

However, most of the 'disappearance' of glyphosate from the soil is due to dissapation rather than degradation.  Glyphosate readily washes away in soil water, and tends to attach itself to minerals such as soil particles, or magnesium or calcium in solution.  Under the wrong soil conditions, microbial breakdown of glyphosate can take several weeks, and the total clearance of the herbicide from soil can take several months.

Monsanto's natural rapid breakdown of glyphosate by soil micro-organisms isn't untrue, it's just a very small part of the bigger picture.

The successful history of widespread use of Roundup is true.  However, again it needs qualification.

Look at the US government figures for increased use of Roundup quoted above, and the changes in agricultural practice which have led to them.

The suggested long history applies to the use of the weedkiller on weeds, not on the crops you eat.  A significant part of that 15-fold increase is now going into the plants which produce your food.

But, you may well ask, if Roundup is safe as salt and generally dissipates quickly from the environment, does it really matter if there's a bit more of it around and some of that bit is in our food?

Monsanto's claim that Roundup is 'no more toxic ... than table salt' is supported by a report on the safety of glyphosate prepared jointly by the UN Environment Programme, International Labour Organisation and the World Health Organisation in 1994(5).  This summarised the data available at the time.  It noted low toxicity in a wide range of animal species, and few effects in most tests except at very high dosages of the herbicide.

There are, however, a few alarm bells in this report.  For example:

The resulting deleterious effects of glyphosate on nitrogen-fixation in RR soya roots have since been confirmed.  This is a cause for concern for agriculture in the long-term because “even a small reduction in nitrogen fixation potential may have long-term effects on sustainable soil nitrogen pools, considering the widespread adoption of the (glyphosate resistant) soyabean system”(6)

In the field, glyphosate is taken into the leaves of the plants from where it is actively moved to different parts of the shoot and root where it accumulates unchanged.

The overall impression from all the above descriptions of the fate of the herbicide in the soil, in water, in animals, and in plants, is that glyphosate hangs around in the system: it isn't metabolised in plants or animal (including food-animals), once consumed it isn't processed by the digestive or immune systems, so the only way to get rid of it is by slowly flushing it out.  Glyphosate has a habit of attaching itself to things in the soil which have parallels in the living system.  What mischief might it get up to inside you during the days before it is cleared?  And of course, if you're eating traces of glyphosate at every meal, it suggests there would be small amounts perpetually flowing through your body.

This hanging around in the environment and inside us raises a safety question, especially if no one knows exactly how much we're consuming.

A reviewer of data on glyphosate residue levels in 2005 commented “surprisingly little has been published on herbicide residues in (glyphosate resistant crop) foods ...”.  He noted a single published study which reported, as Monsanto assured us, that glyphosate residues are “within established tolerance levels” in harvested seeds.  Beyond this, it seems all we have to rely on are the herbicide residue data presented for regulatory approval as supplied by Monsanto.  Tolerance levels are of course set at many times below measured concentrations toxic to animals.  But, see below.

The single published study on herbicide residues inexplicably found greater amounts of AMPA than glyphosate in the seeds despite the science which has shown that plants are unable to degrade the herbicide.  This begs the question, are the glyphosate levels in food being kept below tolerance standards because the herbicide is being replaced by something else no one's testing for?  Which brings us to a  more obviously serious alarm bell.


This is a bit of an understatement of the situation because 'Roundup' is marketed in several formulations containing anything from 7 to 45 percent glyphosate and a varying cocktail of secret chemicals (such as surfactants) all designed to get glyphosate into the plant and to kill it more effectively.  Newer Roundup formulations also have additional more toxic herbicides added in.

Another piece of this jigsaw was added when Italian researchers noted that cellular toxic responses in laboratory animals fed Roundup Ready soya were very similar to those caused by glyphosate.  While some animal feeding studies have identified adverse effects from RR-spiked chow, others have not (see Part I - Review of feeding experiments on GM soya) but none of these studies measured the levels of glyphosate or Roundup in the feed used.

Four pivotal scientific papers looking at physiological effects of Roundup in animal cells have given real cause to question the safety of the formulations(8,9,10,11).  Two found modifications in the membranes of mitochondria (these are vital cellular bodies which generate the energy to power all cell functions) after treatment with Roundup suggestive of a decline in mitochondrial activity.  One found other signs of decreased activity, for example, in the cell nucleus.  The third study found Roundup interferes with the pathway for endocrine hormone synthesis.  The fourth found Roundup induced cell death.  There was clear evidence that the problems were attributable to Roundup, and not to glyphosate.

Ominously, similar harmful effects were observed with one of the few known adjuvants in Roundup, and with AMPA, glyphosate's breakdown product which is inexplicably turning up in harvested seed.  The authors noted “surprisingly (or, perhaps, politely speaking) Roundup is always more toxic than its active ingredient, glyphosate”(8).

Glyphosate may indeed be no more toxic than table salt, but that's a claim which doesn't extend to the actual mixture of chemicals being sprayed on our crops.

One further alarm bell from the 1994 joint review needs to be mentioned:

Which leads us to Part III – Roundup: reproductive effects. 


SOURCES

  1. Monsanto quotes from Monsanto Information Pack, January 1997

  2. Pat Thomas, Behind the label: Roundup Weedkiller, The Ecologist, April 2008

  3. Euroabio admits increased chemical to fight superweed, Thin Ice 10, March 2008

  4. Hetherington et al. (1999) The absorption, translocation and distribution of the herbicide glyphosate in maize expressing the CP-4 transgene, Journal of Experimental Botany, 50:339

  5. International Programme on Chemical Safety, Environmental Health Criteria 159, GLYPHOSATE, jointly sponsored by UN Environment Programme, International Labour Organization, World Health Organization, Geneva 1994

  6. Zablotowicz and Reddy (2004) Impact of Glyphosate on the Bradyrhizobium japonicaum Symbiosis with Glyphosate-Resistant Transgenic Soybean, Journal of Environmental Quality, 33

  7. Cerdeira and Duke (2006) The Current Status and Environmental Impacts of Glyphosate-Resistant Crops, Journal of Environmental Quality, 35

  8. Benachour and Seffralini (2009) Glyphosate Formulations Induce Apoptosis and Necrosis in Human Umbilical, Embryonic, and Placental Cells, Chemical research in Toxicology, 22:1

  9. Richard et al. (2005) Differential effects of Glyphsate and Roundup on Human Placental cells and Aromatase, Environmental Health Perspectives, 113:6

  10. Peixoto (2005) Comparative effects of Roundup and glyphosate on mitochondrial oxidative phosphorylation, Chemosphere, 61:8

  11. Malatesta et al.(2008) Hepatoma tissue culture (HTC) cells as a model for investigating the effects of low concentrations of herbicide on cell structure and function, Toxicology in Vitro, 18

  12. Who Benefits from GM Crops? Friends of the Earth Europe, February 2009

Part III

Roundup: reproductive effects

A study by Russian scientist, Irina Ermakova, which found that feeding rats on Roundup Ready (RR) soya led to stunted growth, small litter size and pup deaths was published in 2009 (1).  Ermakova's data had earlier been examined and dismissed by the UK Food Standards Agency (FSA) on the basis that an American study on mice published in 2004 had recorded no pup survival, health or litter size problems at all (2).

Using mouse testicular development as a sensitive biomonitor of toxic effects, the American study looked at what happened when the mice were given a diet of RR herbicide-tolerant soya (3).  The authors measured the various cell types present in testicular tissue, and concluded that the transgenic diet had no negative effect.

That same year, a preliminary study by an Italian team, also using mouse testis as a bio-indicator, appeared in the literature.  This team took a close look at subcellular features in the testes of mice fed RR soya (4).  They observed cellular changes typical of those previously linked to stress factors or drugs. 

The similarity of the test material of these two studies coupled to their contradictory findings and the FSA's apparent eagerness to ignore a study which suggested GM-linked problems in favour of one which found no problems, led us to take a closer look at the two pieces of research.

In the US paper, all background introductory information is derived from Monsanto.  Its 'Materials' section specifically mentions that “Glyphosate degrades to harmless products, is inactivated rapidly in soil and has low toxicity to animals”.  After this statement establishing safety, the weedkiller is not mentioned again and formed no part of the study.  

COMMENT  Note the side-lining of 'Roundup' in favour of the more innocuous 'glyphosate': this seems to be a typical industry slight-of-hand, and one which scientists shouldn't fall for.  The testimonial of safety appearing in the description of the materials was presumably an excuse for the absence of data on pesticide applications or residue levels in the test diet.  The authors seem to be trying uncommonly hard to draw attention away from herbicide effects. Was someone steering the FSA towards the US study to make sure it got the right message? 

There's no hint anywhere in the US paper of any relevant background reading into other  work suggesting reproductive effects linked to RR soya.

The Italian authors on the other hand cite a number of studies indicating adverse reproductive effects from the herbicide, and point out that these suggest glyphosate could have a role in the toxicity they observed.  These references were obviously available and relevant to the American team.

The studies noted by the Italians don't make comfortable reading:

Also in the literature at the time:

And subsequent to these, more evidence has emerged:

This last study tested Roundup at concentrations as low as 1 part per million (or 0.0001%), which is  five times the permissible level of glyphosate residues.  To put this into context, the maximum level of a contaminant allowed would normally be set at a hundredth of the measured toxic amounts.  A five-fold margin is not acceptable as this could too easily be detrimental in exceptional circumstances.

Human experiences with glyphosate-containing herbicides are filtering in from abroad.  South American countries, caught in the grip of soya monoculture fever, have made many of their communities into unwilling test-animals for the effects of Roundup.  For example:

COMMENT  The South American examples of harm are from very extreme levels of exposure which you're not going to get from your daily soya pinta.  However, more limited but cumulative DNA damage from repeated trace doses of the same toxic formulae may simply take longer to kill you.

To go back to Irina Ermakova's rat study in which the levels of harm caused to reproduction and to the pups were so extreme that the work was treated with derision by pro-GM scientists and the scientific press.  As the FSA said at the time “there are a number of possible explanations for the results obtained in this preliminary study, apart from the GM and non-GM origin of the test materials.  Without information on a range of important factors, conclusions cannot be drawn from this work.”  True, so how much Roundup was in the diet of these rats?  While all other feeding studies used highly processed RR soya, Ermakova used simple ground soya, along with anything else it might contain.  For example, a Japanese team (Teshima et al.)(18), which found no problems in the immune systems of rats or mice fed GM soya chow, used heat-treated soyabean meal, and the American mouse testicular cell study used frozen GM soya chow for the long-term feeding part of the study.   Glyphosate is not normally stable at extremes of temperature and the effects of processing the many secret ingredients in the various Roundup formulations are complete unknowns.  What was actually fed to the laboratory animals in experiments where the chow had been heated or frozen might be very different from a ground soya paste.  The modern human diet often contains soya flour and whole soya-beans.

A review of the evidence on the safety of glyphosate and Roundup in 2000 found “There was no convincing evidence for direct DNA damage in vitro or in vivo”, and concluded that, “under present and expected conditions of use” there was no increased risk of cancer or reproductive effects associated with the herbicide(12).  How does the evidence look now?  Is it looking like we are eating bits of Roundup in our food and drink, and even in meat and diary, and are creating fertility problems and cancers in the generation just born?

Note

The next generation of herbicide-tolerant GM crops is being genetically transformed to resist two herbicides: glyphosate and glufosinate.  Glufosinate is an established 'high risk' to mammals, insects and wild plants (even outside the sprayed field), 'unsafe' for farmers at the concentrations handled (even when protective equipment is in use), an 'acute risk' for young children (at levels found in potatoes after the leafy part of the plant has been destroyed by glufosinate before harvesting), and a possible risk for the unborn child and for fertility.  The US Environmental Protection Agency has reported glufosinate and its metabolites in all processed rice commodities.  Glufosinate is not destroyed by boiling nor by cooking.  Glufosinate is banned for use in the EU, but imported products may harbour a cocktail of weedkillers which are synergistically toxic to children, to the unborn child and to the fertility of the parents(19).

SOURCES

  1. Ermakova (2009), Influence of Soy with the Gene EPSPS CP4 on the Physiological State and Reproductive Functions of Rats, Russian Academy of Natural Sciences – Modern problems of science and education, 5

  2. Statement on the affect of GM soya on newborn rats, Food Standards Agency Advisory Committee for Novel Foods and Processes, 5.12.05

  3. Brake and Evenson (2004) A generational study of glyphosate-tolerant soybeans on mouse fetal, postnatal, pubertal and adult testicular development, Food and Chemical Toxicology 42

  4. Vecchio et al. (2004)  Ultrastructural analysis of testes from mice fed on genetically modified soybean, Letter to the Editor, European Journal of Histochemistry, 48:4

  5. Peluso et al. (1998) 32P-postlabeling detection of DNA adducts in mice treated with the herbicide Roundup, Environment. Mol. Mut. 31

  6. Walsh et al. (2002) Roundup inhibits steroidogenesis by disrupting steroidogenic acute regulatory (StAR) protein expression, Environmental Health Perspectives, 108

  7. Marc et al. (2002) Pesticide Roundup provokes cell division dysfunction at the level of CDK1/cyclin B activation, Chemical Research in Toxicology, 15

  8. Daruich et al. (2001) Effect of the Herbicide Glyphosate on enzymatic Activity in Pregnant Rats and Their Fetuses, Environmental Research Section A, 85

  9. Richard et al., Differential effects of Glyphosate and Roundup on Human Placental Cells and Aromatase, Environmental Health Perspectives, 113:6, 2005

  10. Benachour et al. (2007) Time- and Dose-Dependent Effects of Roundup on Human Embryonic and Placental Cells, Archives of Environmental Contamination and Toxicology LLC

  11. Benachour et al. (2009) Glyphosate formulations Induce Apoptosis and Necrosis in Human Umbilical, Embryonic, and Placental Cells, Chemical Research in Toxicology, 22(1)

  12. Williams et al. (2000) Safety Evaluation and Risk Assessment of the Herbicide Roundup and Its Active Ingredient, Glyphosate, for Humans, Regulatory Toxicology and Pharmacology, 31:2

  13. Paz-y-Miňo et al. (2007) Evaluation of DNA damage in an Ecuadorian population exposed to glyphosate, Genetics and Molecular Biology, 30:2

  14. Lisbeth Fog, Aerial spraying could damage locals' health, www.scidev.net/news, 17.05.07;

  15. Marcela Valente, Residents Say “Stop the Spraying!”, Inter Press Service, 17.11.06

  16. Marco Castillo and others, Campesino Leader Charged for Confronting Crop Spraying, www.lasoyamata.org 2;7.03.08

  17. David Vargas, Effects of soy expansion in Paraguay, www.lasojamata.org, 8.11.07

  18. Teshima et al. (2000)  Effect of GM and non-Gm soybeans on the immune system of BN rats and B10A mice, J. Food Hyg. Soc. Japan 41:3

  19. Bayer's Double Trouble, Greenpeace 6.04.09

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