ISIS Report 13/07/11

EU Regulators and Monsanto Exposed for Hiding Glyphosate Toxicity

The European Commission approved glyphosate knowing, as Monsanto did, that it causes birth defects, while the public were kept in the dark, the herbicide must now be banned Dr Eva Sirinathsinghji and Dr. Mae-Wan Ho

Please forward widely to your political representatives and demand a worldwide ban on glyphosate herbicides

A damning report co-authored by an international group of scientists and researchers for non-government organisation Open Earth Source (OES) reveals that studies from industry including those from Monsanto since the 1990s showed glyphosate caused birth defects and the European Commission approved the herbicide in full knowledge of those finding [1].

Glyphosate is the active ingredient in Monsanto’s Roundup herbicide and over a hundred other commercial formulations. It is the cause of great concern as evidence of its harmful effects keep piling up from independent scientific studies in recent years, including endocrine disruption, DNA damage, reproductive and developmental toxicities, neurotoxicity, cancer, and birth defects  (see [2] Glyphosate Toxic and Roundup Worse, SiS 26; [3] Death by Multiple Poisoning, Glyphosate and Roundup, SiS 42; [4] Ban Glyphosate Herbicide Now. SiS 43; [5] Lab Study Establishes Glyphosate Link to Birth Defects, SiS 48).

Monsanto’s Roundup formulation is the biggest selling herbicide in the world, and its use has dramatically increased since the company introduced glyphosate-tolerant genetically modified (GM) crops such as RR (Roundup Ready) soybean. Today, almost 80 percent of the world’s soy production takes place in the US, Brazil and Argentina, and in 2009, RR soybean accounted for 91 percent, 99 percent and 71 percent respectively of total soybean acreage in those countries. Since 1997, RR soy production has increased from 5 to 30 million hectares of land in the US alone [1]. Soybeans have been found to contain glyphosate residues up to 10 times as high as the doses that caused foetal malformations in chick and frog embryos.

With such widespread use of the herbicide, and the EU considering approval of GM crops tolerant to glyphosate for cultivation in Europe, there is an urgent need for a proper review of the herbicide, which is in line with the more stringent new EU pesticide regulation that came into force in June 2011. Indeed, just such a review was due to take place in 2012. But shortly after the EC was notified of the latest research on glyphosate causing birth defects (which the EC dismissed), it delayed the review on glyphosate and 38 other dangerous pesticides to 2015 [1]. Furthermore, the 2010 review will be under the old, less stringent regulations. The official reason for the delay is that they have ‘too much workload’. This means that the safety of glyphosate may not be reviewed under the new regulations until 2030.

The review delay is being challenged in a lawsuit brought against the EC by Pesticides Action Network Europe and Greenpeace. The co-authors of the OES report are also calling on the EC to conduct a prompt review without delay, and to withdraw glyphosate and Roundup from the market.

Evidence of birth defects from industry and independent studies

The OES report reveals that studies carried out by industry in the 1990s showed embryonic lethality and birth defects in laboratory animals, including dilation of the heart in rabbits at low doses of glyphosate. Higher doses were shown to cause defects in independent studies as far back as 1980.

Monsanto has responded by denying its own findings [6]: “Regulatory authorities and independent experts around the world agree that glyphosate does not cause adverse reproductive effects in adult animals or birth defects in offspring of these adults exposed to glyphosate, even at doses far higher than relevant environmental or occupational exposures.”

However, the ‘independent experts’ cited by Monsanto were mired in conflicts of interests, both financial and professional, and rely almost entirely on studies carried out by industry [1]. 

Independent studies  have revealed links to cancer, genetic damage and endocrine disruption, as well as developmental defects, for example, craniofacial and vertebrae abnormalities in rats [7] as well as craniofacial and mouth deformities, eye abnormalities and bent, curved tails in frog tadpoles [8]. The most recent study by Carrasco and colleagues found a mechanistic link between glyphosate and abnormal retinoic acid signalling in embryonic development [5, 9]

Astonishingly, these and numerous other studies cited by the OES report were dismissed by the European Commission (EC) and the German Federal Office for Consumer Protection and Food Safety (BVL), which is responsible for liaising between industry and the EC. BVL’s conclusion, communicated to the EC via Germany’s 1998 ‘draft assessment report’ (DAR), was ‘‘no evidence of teratogenicity” for glyphosate.

Draft assessment report contained damning evidence

Germany’s 1998 DAR was crucial for glyphosate gaining current EU approval. Despite concluding from industry’s dossier of studies that “glyphosate does not cause teratogenicity”, the report immediately went on to quality its conclusion by pointing out that higher doses of glyphosate caused “reduced ossification and a higher incidence of skeletal and/or visceral [internal organs] anomalies” in foetuses of rats and rabbits.  It also added that the industry studies on glyphosate given at high doses showed reduced number of viable foetuses produced by rats and rabbits, as consistent with increased birth defects. The skeletal anomalies found in those early industry studies are also consistent with the recent findings reported by Carrasco and colleagues [5, 9]. However, these abnormalities were dismissed on the spurious grounds that the high doses poisoned the mother (maternally toxic doses), and hence deemed irrelevant to human risk assessment, as poisoning the mother with any substance can affect the foetus and lead to birth defects. This absurd assumption is indeed contested in the independent scientific literature, and much debated even within industry.

A history of manipulation and near-deception by German and EU regulators

As evident from Germany’s 1998 DAR, Germany manipulated scientific evidence using various ploys bothering on deceit, and with a total disregard of the precautionary principle.

The glyphosate-treated animals in studies submitted by industry practically all showed effects of treatment compared with untreated animals, and at doses as low as 20 mg/kg body weight. So much so that UK’s Pesticide Safety Directorate (PSD), which commented on the data, supports the teratogenicity of glyphosate [1]: “Taken in isolation, none of the findings in these rabbit teratology studies would be clearly of concern. However, overall there is an indication of a pattern.”

Germany on the other hand, resorted to including ‘historical control groups’ in other (irrelevant) unpublished studies, which had the effect of increasing the variation, and hence cancelling out any statistical significance in the actual experiments submitted by industry.  UK’s PSD ended by asking Germany to make available the historical control data, but it remains unclear whether PSD ever saw the data, or if it did, how it responded. And to this day, the historical control data are hidden from the public.

As the OES report commented [1]: “The use of historical rather than concurrent controls adds variables to an experiment that aims to control variables, obscures the teratogenic effects of glyphosate, and biases any conclusion. That is why the use of historical control data is controversial. The practice should not be allowed in evaluating animal toxicological and other studies for pesticide approvals.”

Valid controls for an experiment are animals of the same genetic strain and age, reared in the same environment and studied at the same time as the treated animals. Furthermore, “the manner in which the animals are examined and evaluated, and the data recorded, must be the same.”

The OES report went on to state: “If such practices [of using historical controls] were uncovered in an independent scientific study, they could be considered scientific fraud.”

In summary, the industry and regulators appeared to have colluded in a saga of manipulating scientific evidence in approving glyphosate.

• Industry (including Monsanto) has known since the 1980s that glyphosate causes birth defects in animals at high concentrations
• Industry has known since 1993 that those effects could also occur at low to mid doses
• The German government has known that glyphosate causes birth defects since at least 1998, the year it submitted its DAR on glyphosate to the EC
• The EC’s expert scientific review panel has known since 1999 that glyphosate causes birth defects
• The EC has known that glyphosate causes birth defects since 2002, the year that its Directorate General of SANCO (Health and Consumer Protection) published the final review report for the current approval of glyphosate.

Throughout all that time, the public have been kept in the dark, and the work of independent scientists drawing attention to the teratogenic effects of glyphosate and Roundup were ignored, dismissed, or otherwise denigrated.

The LOAEL (lowest observable adverse effects level) of glyphosate was similarly identified by Germany to be 60 mg/kg body weight/day, at least 3 times higher than indicated by the industry data through a sleight of hand that considered only ‘chronic exposure’ in the ‘most sensitive species’ taken to be the rat; while independent studies indicated LOAEL as low as 5 mg/kg body weight for endocrine disruption and liver damage in rats. The LOAEL is used to set acceptable daily intake (ADI), which is 1/100 of the LOAEL. Consequently, the current ADI of 0.6 mg/kg/day is at least 10 times higher than warranted by data existing at the time the level was set.

Bad science shielded by industry’s own questionable guidelines and standards

In addition to outright manipulation of scientific evidence, industry has erected an effective shield for its bad science under the guise of  ‘Good Laboratory Practices’ (GLP) guidelines, set by the Organisation for Economic Cooperation and Development (OECD), a development and trade, not scientific, organisation. The GLP guidelines have already been strongly criticised in a paper [10] co-authored by 30 scientists who point out that the GLP “specifies nothing about the quality of the research design, the skills of the technicians, the sensitivity of the assays, or whether the methods employed are current or out-of-date.” The EC and the European Food Safety Authority (EFSA) both accept the GLP guidelines and independent research that does not conform can be ignored for assessment purposes. Thus, the research of Carrasco’s team and other independent studies showing harm from glyphosate or Roundup were dismissed on grounds that the testing systems are “unvalidated” and the studies “inappropriate and irrelevant for human health risk assessment purposes” (because they are not carried out on approved animals such as rats, mice and dogs, for example), in other words, they are not in accordance with GLP.  As the OES report remarks [1], this “raises the question: why do governments fund scientific research if they ignore its findings in almost every risk assessment?”

In fact, GLP toxicity studies have been criticised for using out of date protocols with very high doses at near poisoning levels that may have little relevance to real world exposure levels, and test animals are typically killed before old age, masking most developing diseases. In short, GLP tests use protocols that can rarely find toxicity.

 A comparison of NOAELs (no observable adverse effects levels) from industry and independent tests on dozens of chemicals found that in every case, independent studies detected important toxic effects at levels well below those that industry claimed to be safe. Yet regulators ignore the independent data in favour of those from industry because they comply with the OECD GLP guidelines. Their rejection of the recent findings of Carrasco’s team is indefensible but for the rigid adherence to the GLP guidelines, as the OES report points out at length (see also [5]).

Furthermore, the OECD set rigid and scientifically incorrect criteria regarding dose-response in toxicological tests. They fail to take into account the fact that endocrine disrupting and other effects are often stronger at low dose than at high dose, which invalidates the assumption that there is a safe dose below which there is no significant toxicity.

The new EU pesticide regulation has the potential to end the tyranny of GLP by insisting on peer-reviewed independent scientific studies in pesticide assessments. However, the new regulation obliges industry to do its own scientific literature search in preparing a pesticide dossier, thus giving industry full control of the studies it selects for inclusion and may well reinforce the tyranny of the GLP.

Human evidence of health concerns is mounting

Due to obvious restrictions of experiments on humans, human data of glyphosate toxicity is difficult to obtain in a laboratory setting.  There are, however, results obtained from human cell lines. One such experiment performed in 2009 by French scientist Giles-Eric Séralini and colleagues found that Roundup caused total cell death in umbilical, embryonic and placental cells within 24 hours [3, 11].

Further, with the widespread use of glyphosate in countries such as Argentina and Canada, evidence of harm to humans is now growing. A local Argentinean government report documented tripling in numbers of childhood cancers from 2000 to 2009, and quadrupling of birth defects in agrochemical use zones (ref see [12] Argentina’s Roundup Human Tragedy, SiS 48). Carrasco noted in his study that [9] “The findings in the lab are compatible with malformations observed in humans exposed to glyphosate during pregnancy.”

An epidemiological study in Ontario, Canada, also found high levels of premature births and miscarriages in female members of farming families that used pesticides, including glyphosate.

BVL’s response to those problems was that they are irrelevant to the situation in Europe, even as plans to grow glyphosate-tolerant crops are afoot: “Even if there were indications for an increase in malformations because of extensive exposure to pesticides in South America, the state authorities in these countries would be responsible to initiate more in-depth investigations. Taking into account the very different application conditions and the uncertainties with regard to the plant protection products and human exposure, such findings would not automatically give rise to concern about the safety of glyphosate-based herbicides in Europe.”

Additional concerns

A recent report released by a senior US scientist Dr Don Huber, Professor Emeritus, Purdue University,  warned of a novel pathogen associated with glyphosate tolerant GM crops (see [13] Emergency! Pathogen New to Science Found in Roundup Ready GM Crops?). A leaked letter written by him to the USDA expressed deep concern for this pathogen that was highly enriched in transgenic crops, and apparently associated with devastating crops diseases and high rates of infertility and miscarriages in animals. This is a novel concern that adds to the urgency with which glyphosate and GM agriculture needs to be reviewed by the EU.

Conclusion & recommendation

The authors of the OES report conclude that “the existing approval of glyphosate and Roundup is out of date and scientifically unsupportable.” They recommend the immediate withdrawal of glyphosate until a new review is performed with a full range of up-to-date tests that are independently reviewed and publicly available.

We fully agree with their conclusion and recommendation.

References

1. Antoniou M, Habib M, Howard CV, Jennings RC, Leifert C, Nodari RO, Robinson C, Fagan J. Roundup and birth defects: Is the public being kept in the dark? Earth Open Source, 2011.

2. Ho MW and Cummins J. Glyphosate toxic and Roundup worse Science in Society 26, 12, 2005.

3. Ho MW and Cherry B. Death by multiple poisoning, glyphosate and Roundup. Science in Society 42 , 14, 2009

4. Ho MW. Ban glyphosate herbicides now. Science in Society 43, 34-35, 2009.

5. Ho MW. Lab study establishes glyphosate link to birth defects. Science in Society 48, 32-33, 2010.

6. Beyond the Rows, A blog by Monsanto, St. Louis, United States of America, 9 June 2011, accessed 11 July 2011, http://www.monsantoblog.com/2011/06/09/june-2011-earth-open-source-report-on-roundup/

7. Dallegrave E, Mantese FD. et al. 2003. The teratogenic potential of the herbicide glyphosate-Roundup in Wistar rats. Toxicol Lett 142(1-2): 48

8.  Lajmanovich RC, Sandoval MT, Peltzer PM. 2003. Induction of mortality and malformation in Scinax nasicus tadpoles exposed to glyphosate formulations. Bull. Environ. Contam. Toxicol. 70, 612–18.

9. Paganelli A, Gnazzo V, Acosta H, Lopez SL and Carrasco AD. Glyphosate-based herbicides produce teratogenic effects on vertebrates by impairing retinoic acid signalling. Chem Res Toxicol, August 9. http://pubs.acs.org/doi/abs/10.1021/tx1001749

10. Myers JP, Vom Saal FS. et al. Why public health agencies cannot depend on good laboratory practices as a criterion for selecting data: The case of bisphenol A. Environmental Health Perspectives 2009, 117, 309–15.

11. Benachour N, Séralini GE. 2009. Glyphosate formulations induce apoptosis and necrosis in human umbilical, embryonic, and placental cells. Chem Res Toxicol 22: 97–105.

12. Robinson C. Argentina's Roundup human tragedy Science in Society 48, 30, 2010

13. Ho MW. Emergency! Pathogen new to science found in Roundup Ready GM crops? Science and Society 50, 10-11, 2011.

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