THIRD WORLD NETWORK BIOSAFETY INFORMATION SERVICE
Dear Friends and Colleagues
Re: New Evidence on the Health Impacts of Glyphosate
Glyphosate is the world’s most popular herbicide, applied not only on farms but also in forests, parks, public spaces and gardens. It is the active ingredient in Monsanto’s ‘Roundup’ and is regularly used in the widespread cultivation of the company’s Roundup Ready crops genetically engineered to be resistant to glyphosate. For years, industry has claimed that glyphosate is minimally toxic to humans but new studies indicate otherwise.
A new Thai in-vitro study on human cells (Item 1) shows that glyphosate induces the growth of human breast cancer cells via estrogen receptors. Even low, environmentally relevant doses were found to stimulate estrogenic activity. In addition, the study found that there was an additive estrogenic effect between glyphosate and genistein, a phytoestrogen in soybeans. This is worrying as glyphosate-based herbicides are widely used in soybean cultivation.
Another study found that acute Roundup exposure at low doses for 30 minutes disrupts male reproductive functions by triggering calcium-mediated cell death in rat testis and Sertoli cells (Item 2). Sertoli cells play an important role in sperm cell production and hence male fertility.
Glyphosate residues have been found in the main foods of the Western diet, comprised primarily of sugar, corn, soy and wheat. New research by Friends of the Earth detected glyphosate residues in the urine of 44 per cent of people tested from 18 different European countries (Item 3).
Another study (Item 4) presents evidence that glyphosate could disrupt gut bacteria, suppress the CYP enzyme class, and likely impair suphate transport, thereby inducing disease. One of the roles of CYP enzymes is to detoxify xenobiotics (foreign chemicals found in a living organism). This means that glyphosate could effectively enhance the damaging effects of other food-borne chemical residues and environmental toxins. According to the authors, the medical conditions to which glyphosate could plausibly contribute to include inflammatory bowel disease, obesity, depression, ADHD, autism, Alzheimer’s disease, Parkinson’s disease, ALS, multiple sclerosis, cancer, cachexia, infertility, and developmental malformations. The researchers call for more independent research to validate the findings presented and if verified, to take immediate action to drastically curtail the use of glyphosate in agriculture.
With best wishes,
Third World Network
131 Jalan Macalister
Website: http://www.biosafety-info.net/ and http://www.twn.my/
Glyphosate induces human breast cancer cells growth via estrogen receptors
Siriporn Thongprakaisanga, Apinya Thiantanawatb, c, Nuchanart Rangkadiloka, c, Tawit Suriyoc, Jutamaad Satayavivada, c, d
a Environmental Toxicology Program, Chulabhorn Graduate Institute, Kamphaengphet 6 Road, Laksi, Bangkok 10210, Thailand
b Applied Biological Sciences Program, Chulabhorn Graduate Institute, Kamphaengphet 6 Road, Laksi, Bangkok 10210, Thailand
c Laboratory of Pharmacology, Chulabhorn Research Institute, Kamphaengphet 6 Road, Laksi, Bangkok 10210, Thailand
d Center of Excellence on Environmental Health and Toxicology, Office of the Higher Education Commission, Ministry of Education, Bangkok, 10400, Thailand
- Glyphosate at 10-12 to 10-6 M promoted growth of T47D cells via estrogen receptors.
- Glyphosate produced the activation of ERE which can be blocked by ICI 182780.
- Glyphosate altered estrogen receptors by increasing expression ratio of ER and ER.
- Glyphosate had an additive effect with genistein on ERE activation and cell growth.
Glyphosate is an active ingredient of the most widely used herbicide and it is believed to be less toxic than other pesticides. However, several recent studies showed its potential adverse health effects to humans as it may be an endocrine disruptor. This study focuses on the effects of pure glyphosate on estrogen receptors (ERs) mediated transcriptional activity and their expressions. Glyphosate exerted proliferative effects only in human hormone-dependent breast cancer, T47D cells, but not in hormone-independent breast cancer, MDA-MB231 cells, at 10-12 to 10-6 M in estrogen withdrawal condition. The proliferative concentrations of glyphosate that induced the activation of estrogen response element (ERE) transcription activity were 5-13 fold of control in T47D-KBluc cells and this activation was inhibited by an estrogen antagonist, ICI 182780, indicating that the estrogenic activity of glyphosate was mediated via ERs. Furthermore, glyphosate also altered both ERα and β expression. These results indicated that low and environmentally relevant concentrations of glyphosate possessed estrogenic activity. Glyphosate-based herbicides are widely used for soybean cultivation, and our results also found that there was an additive estrogenic effect between glyphosate and genistein, a phytoestrogen in soybeans. However, these additive effects of glyphosate contamination in soybeans need further animal study.
Food and Chemical Toxicology
Available online 9 June 2013
Roundup Disrupted Male Reproductive Functions By Triggering Calcium-Mediated Cell Death In Rat Testis And Sertoli Cells
de Liz Oliveira Cavalli VL, Cattani D, Elise Heinz Rieg C, Pierozan P, Zanatta L, Benedetti Parisotto E, Wilhelm Filho D, Regina Mena Barreto Silva F, Pessoa-Pureur R, Zamoner A.
Free Radic Biol Med. 2013 Jun 29. pii: S0891-5849(13)00326-2. doi: 10.1016/j.freeradbiomed.2013.06.043. [Epub ahead of print]
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis-Santa Catarina, Brazil.
Open access: http://www.ncbi.nlm.nih.gov/pubmed/23820267
Glyphosate is the primary active constituent of the commercial pesticide Roundup®. The present results show that acute Roundup® exposure at low doses (36ppm, 0.036g/L) for 30min induces oxidative stress and activates multiple stress-response pathways leading to Sertoli cell death in prepubertal rat testis. The pesticide increased intracellular Ca2+ concentration by opening L-type voltage-dependent Ca2+ channels (L-VDCC) as well as endoplasmic reticulum IP3 and ryanodine receptors, leading to Ca2+ overload within the cells, which set off oxidative stress and necrotic cell death. Similarly, 30min incubation of testis with glyphosate alone (36ppm) also increased 45Ca2+ uptake. These events have been prevented by the antioxidants Trolox® and ascorbic acid. Activated protein kinase C (PKC), phosphatidylinositol-3-kinase (PI3K) and the mitogen-activated protein kinases (MAPKs), such as ERK1/2 and p38MAPK have played a role in eliciting Ca2+ influx and cell death. Roundup® decreased the levels of reduced glutathione (GSH) and increased the amounts of thiobarbituric reactive species (TBARS) and protein carbonyls. Also, exposure to the glyphosate-Roundup® has stimulated the activity of glutathione peroxidase, glutathione reductase, glutathione-S-transferase, gamma-glutamyl transferase (γGT), catalase, superoxide dismutase and glucose-6-phosphate dehydrogenase, supporting downregulated GSH levels. Glyphosate has been described as an endocrine disruptor affecting the male reproductive system; however, the molecular basis of its toxicity remains to be clarified. We could propose that Roundup® toxicity, implicating in Ca2+ overload, cell signaling misregulation, stress response of the endoplasmic reticulum and/or depleted antioxidant defenses could contribute to Sertoli cell disruption of spermatogenesis that could impact male fertility.
Growing doubts about the safety of glyphosate [extracts only]
FOE, 13 June 2013
Glyphosate is the world’s best-selling chemical herbicide. Glyphosate-containing herbicides, such as Monsanto’s Roundup, are the most widely used herbicides in Europe, applied in farming, forestry, parks, public spaces and gardens. Glyphosate-containing herbicides are also crucial to the production of genetically modified herbicide resistant crops. In recent years, a number of scientific studies have raised concerns about glyphosate’s safety and there have been calls for glyphosate-containing herbicides to be banned. New research by Friends of the Earth has detected glyphosate residues in the urine of 44 per cent of people tested, from 18 different European countries.
Conclusions and demands
New research from Friends of the Earth has shown that people from all over Europe – in EU and none EU countries – have glyphosate residues in their urine. The evidence suggests that a significant proportion of the population could have glyphosate in their bodies – and it is not clear where it is coming from. Despite the fact that glyphosate is the world’s best-selling chemical herbicide and glyphosate-containing herbicides are the most widely-used herbicides in Europe, very little testing is done for glyphosate residues in food, feed, or water. Tests for glyphosate in the body do not take place at all.
Friends of the Earth wants to know:
* Why do people have glyphosate in their urine? Where does it come from?
* Why haven’t public authorities done any testing on glyphosate residues in humans?
* Why is food, animal feeds (such as imported soy) and drinking water so rarely tested for glyphosate?
* What are the health impacts of glyphosate in our bodies? Is it guaranteed that
glyphosate residues are completely excreted? If not, what happens to the remaining
* Why haven’t there been any long-term health studies on on-going glyphosate uptake in humans?
* Why have the maximum residue levels (MRLs) for glyphosate in food and feed been
* Who is profiting from increasing glyphosate use?
* Why are authorities considering applications to grow glyphosate-resistant genetically modified crops in Europe?
Given the uncertainty about how glyphosate is entering people and the need to minimise exposure to glyphosate, Friends of the Earth demands that:
* The EU and national governments must immediately start a monitoring programme for glyphosate in food and feed, including imported animal feed crops such as GM soy. Levels of glyphosate (and its breakdown product AMPA) in the environment should also be monitored, covering aquatic systems and soil. These monitoring programmes should be comprehensive and the results should be made available to the public without delay.
* National governments must introduce a glyphosate reduction programme and desiccation (spraying crops shortly before the harvest) should be banned without delay. All other uses for glyphosate should be evaluated by 2015, existing maximum residue limits (MRLs) should be re-evaluated, and there must be no further increases in the MRLs.
* No glyphosate resistant genetically modified crops should be authorized in the EU.
* All food processors and retailers should minimise their customer ́s exposure to glyphosate residues by specifying glyphosate-free products from their suppliers. They should extend their internal pesticides monitoring programme and include glyphosate in their regular testing.
Glyphosate’s Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome: Pathways to Modern Diseases
Anthony Samsel and Stephanie Seneff
Glyphosate, the active ingredient in Roundup®, is the most popular herbicide used worldwide. The industry asserts it is minimally toxic to humans, but here we argue otherwise. Residues are found in the main foods of the Western diet, comprised primarily of sugar, corn, soy and wheat. Glyphosate's inhibition of cytochrome P450 (CYP) enzymes is an overlooked component of its toxicity to mammals. CYP enzymes play crucial roles in biology, one of which is to detoxify xenobiotics. Thus, glyphosate enhances the damaging effects of other food borne chemical residues and environmental toxins. Negative impact on the body is insidious and manifests slowly over time as inflammation damages cellular systems throughout the body. Here, we show how interference with CYP enzymes acts synergistically with disruption of the biosynthesis of aromatic amino acids by gut bacteria, as well as impairment in serum sulfate transport. Consequences are most of the diseases and conditions associated with a Western diet, which include gastrointestinal disorders, obesity, diabetes, heart disease, depression, autism, infertility, cancer and Alzheimer’s disease. We explain the documented effects of glyphosate and its ability to induce disease, and we show that glyphosate is the “textbook example” of exogenous semiotic entropy: the disruption of homeostasis by environmental toxins.
This paper presents an exhaustive review of the toxic effects of the herbicide, glyphosate, the active ingredient in Roundup®, in humans, and demonstrates how glyphosate’s adverse effects on the gut microbiota, in conjunction with its established ability to inhibit the activity of cytochrome P450 enzymes, and its likely impairment of sulfate transport, can remarkably explain a great number of the diseases and conditions that are prevalent in the modern industrialized world. Its effects are insidious, because the long-term effects are often not immediately apparent. The pathologies to which glyphosate could plausibly contribute, through its known biosemiotic effects, include inflammatory bowel disease, obesity, depression, ADHD, autism, Alzheimer’s disease, Parkinson’s disease, ALS, multiple sclerosis, cancer, cachexia, infertility, and developmental malformations. Glyphosate works synergistically with other factors, such as insufficient sun exposure, dietary deficiencies in critical nutrients such as sulfur and zinc, and synergistic exposure to other xenobiotics whose detoxification is impaired by glyphosate. Given the known toxic effects of glyphosate reviewed here and the plausibility that they are negatively impacting health worldwide, it is imperative for more independent research to take place to validate the ideas presented here, and to take immediate action, if they are verified, to drastically curtail the use of glyphosate in agriculture. Glyphosate is likely to be pervasive in our food supply, and, contrary to being essentially nontoxic, it may in fact be the most biologically disruptive chemical in our environment.