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Roundup (herbicide)

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Template:Chembox new Roundup is the brand name of a systemic, broad-spectrum herbicide produced by the controversial U.S. "life sciences" company Monsanto and contains the active ingredient glyphosate. It is the most used herbicide in the world [citation needed], and the top-selling agrichemical of all time [citation needed]. Monsanto developed and patented the glyphosate molecule in the 1970s, and marketed Roundup from 1973. It retained exclusive rights in the US until its US patent expired in September, 2000, and maintained a predominant marketshare in countries where the patent expired earlier.

The active ingredient of Roundup is the isopropylamine salt of glyphosate. Glyphosate's mode of action is to inhibit an enzyme involved in the synthesis of the amino acids tyrosine, tryptophan and phenylalanine. It is absorbed through foliage and translocated to growing points. Weeds and grass will generally re-emerge within one to two months after usage. Because of this mode of action, it is only effective on actively growing plants; it is not effective as a pre-emergence herbicide. Monsanto also produces seeds which grow into plants genetically engineered to be tolerant to glyphosate which are known as Roundup Ready crops. The genes contained in these seeds are patented. Such crops allow farmers to use glyphosate as a post-emergence pesticide against both broadleaf and cereal weeds. Soy was the first Roundup Ready crop and was produced at Monsanto's Agracetus Campus located in Middleton, Wisconsin. Current Roundup Ready crops include maize (corn), sorghum, cotton, soy, canola and alfalfa.

There are some concerns about the product such as weed resistance, the main current concern is a possible impact on the reproduction and fertility of mammals, including humans. Like many agricultural chemicals, there is debate about whether the potential benefits outweigh the potential harms.

The largest single user of Roundup reportedly is the U.S. Government, which sprays huge quantities of the herbicide over the northern countries of South America in an effort to discourage cultivation of the coca plant. (See article Plan Colombia).

The Active Ingredient

Glyphosate is the primary active ingredient in Monsanto's much used yet controversial herbicide, Roundup. Many crops have now been genetically engineered to be resistant to it. The chemical is only absorbed by the leaves of plants and it is not absorbed by roots from the soil. In the US 25 million applications are used every year on lawns and yards, and in US agriculture totally, estimates range from 18-48 million pounds are used yearly, with a 20% yearly growth rate in usage.

Chemistry

Glyphosate is an aminophosphonic analogue of the natural amino acid glycine and the name is a contraction of glycine, phospho-, and -ate, given the C.A.S. number 1071-83-6. It was first discovered to have herbicidal activity in 1970 by John Franz, a scientist that worked for the Monsanto company. In 1987 Franz received the National Medal of Technology from Ronald Reagan for his discoveries [1], a medal given to American companies like DOW, DuPont, and IBM, and American company and university scientists. He has received other awards, including the 1990 Perkin Medal for Applied Chemistry [2], stated as the highest honor given for advances in American industrial chemistry, for his design of an effective herbicide, relatively non-toxic compared to previous herbicides.

Biochemistry

The full action of glyphosate is not yet fully known,[3][4], yet glyphosate mainly helps kill plants by inhibiting the enzyme 5-enolpyruvoyl-shikimate-3-phosphate synthase (EPSPS), which forms the aromatic amino acids: phenylalanine, tyrosine and tryptophan.[5] The production of Chorismate is ultimately stopped by the presence of the glyphosphate, EPSPS catalyzes the reaction of shikimate 3-phosphate (S3P) and phosphoenolpyruvate (PEP) to form ESP and phosphate, the aromatic amino acids are also used to make secondary metabolites such as folates, ubiquinones and naphthoquinones.[citation needed] The shikimate pathway is not present in animals, so it was thought it would have low toxicity to them, yet it has actually later been found to affect other plant enzyme systems including detoxification enzymes, and also has been found to affect animal enzymes.[6][7][8].

Health, Ecological Concerns, & Controversy

Toxicity & Ecological Impact

Glyphosate is classed as a moderately toxic herbicide and in EPA toxicity class III. Representative of one side of the debate on toxicity, in a comprehensive scientific review citing hundreds of studies, American scientist Caroline Cox, in Journal of Pesticide Reform v. 108, n.3 [9] stated that "Glyphosate containing products are acutely toxic to animals, including humans". She goes on to state that it has conclusively demonstrated adverse effects in "all standards of laboratory toxicology testing" including medium term toxicity, long-term toxicity, genetic damage, reproductive toxicity, and carcinogenicity.[10] & she also questions the neutrality of the American EPA. On the other side a review was conducted in 2000 concluding that "under present and expected conditions of new use, there is no potential for Roundup herbicide to pose a health risk to humans"[11].The EPA, however, clearly states that in "relatively short term exposures" to concentrations in water above its limits (which it currently sets at 0.7 parts per million in water), the short term human effects so far found include congestion of lungs, increased breathing rate, and effects of long term exposures have potential to cause kidney damage and reproductive effects.[12]There is currently no true consensus on the true toxicity of glyphosate products, those that cite a consensus must cite sources that rely almost totally on Monsanto studies or studies they have funded. In terms of acute toxicity, however, it appears 100ml to 200ml ingested is fatal to humans (1/3 cup to a cup). The EUs current listing of glyphosate products is based mainly on Monsanto studies & unpublished studies, presented by Monsanto, Feinchemie, Cheminova, and other agricultural chemical companies. Still, glyphosate products are argueably less toxic than many other herbicides and pesticides.

Scientific Fraud & False Advertising

Until recently most studies of glyphosate and glyphosate product toxicty have been carried out by Monsanto or funded by them. On two occasions the American EPA has caught scientists deliberately falsifying test results at research laboratories hired by Monsanto to study glyphosate,[13][14][15] and Monsanto has also been charged with illegally advertising, (falsely and misleadingly), glyphosate products calling them "safer than table salt", prompting a law suit by the New York State attorney general[16], and prompting several action groups to form in the United States against these products.[17]In the second incident of falsifying test results in 1991, the owner of the lab (Craven Labs), and three employees were indicted the following year on 20 felony counts, the owner was sentenced to 5 years in prison and fined 50,000 dollars, the lab was fined 15.5 million dollars and ordered to pay 3.7 million in restitution.[18][19][20]Craven laboratories performed studies for 262 pesticide companies including Monsanto. In the first incident involving "Industrial Biotest Laboratories", a reviewer stated after finding "routine falsification of data" that it was "hard to believe the scientific integrity of the studies when they said they took specimens of the uterus from male rabbits".[21] The EPA performed this audit of IBT in 1976, yet the fraud did not make headlines until 1983.[22] Monsanto has also been charged in countries besides the US for false advertising of roundup and misleading the public, and just recently lost a suit in Europe, yet are appealing.[23]

Immediate symptoms of ingestion & unintentional contact exposure

The toxicity of Roundup has been questioned, in addition to its active agent (glyphosate), because of several of the inactive ingredients, including the surfactant polyoxy-ethyleneamine (POEA) [24]. These components may be responsible for some of the "acute" toxicity to humans such as eye irritation up to death. Ingestion of Roundup has been proven to cause many symptoms including diarrhea, vomitting, excess fluid in lungs, pneumonia, confusion, lung dsyfunction, erosion of the intestinal tract, kidney damage, damage to the larynx, destruction of blood cells, and other symptoms, with 200ml (less than a cup) typically leading to death and human fatality, yet cases of only 100ml (a little over 1/3 cup) of ingested glyphosate product have been fatal.[25][26][27][28][29] Unintentional low exposures cause symptoms such as, eye irritation (pain, burning, blurred vision), swollen face & eyes & joints, blisters, skin rash, rapid heartbeat & palpitations, elevated blood pressure, chest pain, congestion, coughing, headache, dizziness, fever, nausea, facial numbness, burning & itchy skin, & recurrent eczema & inhalation is considered more toxic than ingestion. [30][31][32][33][34][35][36][37]

human & mammalian toxicity

One of the difficulties with assessing true glyphosate toxicity, is the fact that it is always used in formulations with several other ingredients, and therefore studies of pure glyphosate toxicty have only partial relevance.[38]There is no product sold that is pure glyphosate and it only exists as such in the manufacturing process. Researchers looking for explanations about possible roundup and glyphosate toxicity, and as to why Canadian farm families exposed to glyphosate formulations had a possible association with increased miscarriages and pre-mature births [39], found that glyphosate roundup formulations were twice as toxic as pure glyphosate. They also found viability of human placental cells considerably reduced & with estrogen synthesis interference, in the commonly used glyphosate formulations yet not with pure glyphosate.[40]

Recent independent mammalian research indicates glyphosate induces a variety of functional abnormalities in fetuses and pregnant rats.[41]Also in recent mammalian research glyphosate has been found to cause interference in reproductive chemistry specifically interfering in male testosterone production in mice.[42]. There are currently few studies into the toxicity of glyphosate formulations, most are conducted by Monsanto or other agricultural firms. On the other side, Greenpeace put out a cautious 10 year old statement that glyphosate has little toxicity to mammals, but this came before the more recent research: on the reproductive effects of the commonly used glyphosate formulations, and on pure glyphosate toxicity to male reproductive cells. Sleep problems caused by glyphosate exposure may be caused as glyphosate appears to mimic adrenaline as reported by the WHO and the EPA [43]Sublethal effects in mammals have included decreased activity of detoxification enzymes in the liver and intestinal system.[44]Glyphosate as a pure ingredient is of far less concern than many other herbicides, pesticides, and chemicals such as those from the organochlorine family. Monsanto states glyphosate is not carcinogenic (cancer causing), yet actually qualifies this statement in their document to say the "active ingredient" in glyphosate products and roundup ready products is not carcinogenic, and makes no comment on the total product.[45] Greenpeace states that poor quality testing methods are responsible for results that usually show little glyphosate contamination on food products or in other systems, yet makes no statement as to the harms of minor glyphosate contamination on human foods and only as to harms on ecology or farmworkers.[46]However, residues have been found by Monsantos own studies on lettuce 5 months after soil treatment, in barley four months after soil treatment, and the WHO found "significant residues" on wheat with residues not lost during baking.[47]Overall, glyphosate products are a clear and vast improvement, however, from Monsantos organochlorine products such as DDT and agent orange, that were eventually forced to be discontinued and phased out of many nations, including the US and EU.

Many times issues of glyphosate toxicity may concern its co-ingredients. Its formulations are reported to cause many of the cases of toxic herbicide exposure in California, consistently rating in the top 10 most likely pesticide/herbicide formulations to cause incidents, yet these lead to few to no full hospitalizations, and many may be eye-related (it is in the severe EPA category I for eyes). In the UK it is the most frequently cited to cause incidents, yet all of this stems partly from the fact that glyphosate is one of the most frequently used herbicides, so incidents are bound to be high. Monsanto has been adjusting its formulations to address this, yet older more toxic formulations are still available, and especially in countries with lower standards than the UK. [43]Many of these cases are thought to partially be as of the many other ingredients in glyphosate formulations that have equal or greater toxicity than pure glyphosate and that are frequently unlisted as they are "trade secrets". Some report the direct toxicity of pure glyphosate to mammals and birds as reportedly low [48]. Others disagree however stating plainly "glyphosate is toxic to mammals", and also state its effect on flora can have a damaging effect on mammals and birds through habitat destruction[49]. Monsanto states its products are not harmful to anyone or anything.[50]Glyphosate formulations are also used in intentional harm situations, like suicides. A letter to The Lancet (Feb 6 1988, pg 299) reported 56 toxic exposures to glyphosate formulations in Japan between 1984-1986 with adverse repsiratory, cardiovascular, and neurotoxic effects leading to 9 deaths. Many other toxic agricultural products are used in suicides such as paraquat. It takes about 200ml (3/4cup) of glyphosate product to cause rapid human death, yet cases of just 100ml (slightly more than 1/3 cup) of ingested roundup have resulted in human death. If a mammal (including a human) ingests enough glyphosate-product it will die unpleasantly. Inhalation of glyphosate products is regarded as far more toxic than ingestion.

In terms of cancer causing effects, the US Environmental Protection Agency, the EC Health and Consumer Protection Directorate, and the UN World Health Organization have all concluded that pure glyphosate is not carcinogenic, their conclusions were all based mainly on Monsantos own studies and unpublished studies, so the independence of this result is not fully clear, yet its carcinogenicity seems to be quite minimal. The first studies submitted to the EPA by Monsanto did find an increase in testicular cancer and an increase in thyroid cancer & kidney tumors of rats. A recent Monsanto study (1990) found increase in pancreas and liver tumors and thyroid cancer, yet they were not rated as carcinogenic as Monsantos industry pathologist stated the 3 times the rate of cancer was too similar to the control group (4.5% cancer rate in control, 12.5% rate in treated).[51] Opponents of glyphosate-based pesticides frequently state that glyphosate is linked to cancer, citing a study in the British Journal of Cancer that showed three times the rate of hodgkins lymphoma in people occupationally exposed to glyphosate herbicides, and similar to the rate found in the very few animals studies that have been conducted by Monsanto.[52] There is debate over what exactly in the products would cause increases in cancers, citing the human research of Hardell and Eriksson (Cancer 1999 85:1353–1360), this paper showed a link between glyphosate and lymphoma, Monsanto states the link was not statistically significant and was within the realm of random variation. The authors themselves concluded "definite conclusions cannot be drawn for separate chemicals, such as MCPA and glyphosate, from the multivariate analysis". Opponents of glyphosate also state that Roundup has been found to cause genetic damage, citing research including Peluso et al (Environ Molec Mutag 31:55–59). The authors concluded that the damage was "not related to the active ingredient, but to another component of the herbicide mixture", so some of Roundup toxicity may be as of the total product and not only the listed active ingredient.

The evidence would suggest that roundup may be partially carcinogenic to farmworkers or those living nearby, likely only mainly in long term exposures, and of less concern than several other agricultural chemicals. However, cancer causing effects for even long term consumers of foodstuffs which have been sprayed with roundup would be minimal to non-existent, of greater concern to children than adults, and would only be relevant when taken in context with the many other chemical residues possibly present on foodstuffs, and the possible synergistic effect from these in combination and added together.

Roundup has also been found by researchers at Texas Tech University to disrupt the expression of steroidogenic acute regulatory protein (StAR) which has a role in testosterone production in males [44], causing concern about its effects on reproductive function.

Aquatic effects

Fish and invertebrates are more sensitive to formulations of glyphosate,[53] LC50s are 2ppm to 300ppm,[54] the surfactants can be responsible for much of the harm [55] leading to 20 to 70 times the toxicity of pure glyphosate,[56] young fish are more sensitive, and increased water temperatures lead to greater toxic effect.[57][58][59] This difference is interesting in that the toxicities are similar to just pure glyphosate, in soft water [60] or if the fish have not recently eaten.[61] Sublethal effects at far lower concentrations include erratic swimming & labored respiration which may impact feeding, migration, and reproduction, and also gill damage & and changes in liver structure.[62][63][64][65] In Australia, there is controversy over glyphosate formulations used in or near water, most of this stems from ingredients in the formulations other than the actual pure active ingredient: glyphosate. Monsanto corporation had adjusted its formulations for Australia in the late 1990s to address this issue with its "Biactive" line of products.[66]Glyphosate is generally less persistent in water than in soil, with 12 to 60 day persistance observed in Candian pond water, yet persistance of over a year have been observed in the sediments of ponds in Michigan & Oregon.[67]

effects on soil and on natural wild flora & fauna

An EU summary based on evidence presented by Monsanto, of Monsanto studies and unpublished studies carried out for Monsanto, that Glyphosate was not biodegradable. Of nine herbicides tested for their toxicity to soil microorganisms, glyphosate formulations were found to be the second most toxic to a range of bacteria, fungi, actinomycetes and yeasts.[68] However, when glyphosate comes into contact with the soil it can be rapidly bound to soil particles and be inactivated.[69] Unbound glyphosate can be degraded by bacteria [45] and a patent exists describing a process whereby glyphosate degradation is enhanced by immobilizing bacteria on an inert support [46]. Low activity because of binding to soil particles suggests that glyphosate's effects on soil flora will be limited.[citation needed] Other sources show that 80% of glyphosate absorbed by soil can be rapidly desorbed in just a two hour period, leading the study to conclude that the herbicide can be extensively mobile in soil.[47] Recent work shows that glyphosate can be readily released from certain types of soil particles, and therefore may leach into water or be taken up by plants. Low glyphosate concentrations can be found in many creeks and rivers in U.S. and Europe. In the US glyphosate has been called "extremely persistent" by its EPA, yet half lives vary from as little as 3 days at a soil site in Texas, 141 days at a site in Iowa, to between 1 - 3 years in Swedish forest soils being observed.[48] It appears that more northern sites have the longest soil persistances such as in Canada & Scandanavia.

The US EPA concluded that many endangered species of plants, as well as the Houston toad, may be at risk from glyphosate use. It has been reported that glyphosate formulations can persist on foods & food crops for up to two years and that they also negatively impact earthworm and beneficial insect populations and further drive farmers and gardeners away from natural farming methods to dependence on ecologically harmful crutches.[49]In New Zealand applications of glyphosate (1/20 of typically used applications), significantly affected growth and survival of earthworms, in other studies nitrogen fixing bacteria have been impaired, and also crop plant susceptibility to disease has been increased.[70][71][72][73][74][75][76]Monsanto firmly denies any negative impact on anything, including wildlife, and has many studies it has funded to back up its position. They would also be quick to point out that any possible negative impact on earthworms & nitrogen fixing bacteria, etc., would be offset by greater yields as of the elimination of weeds, and also would point to soil benefits from less mechanical cultivation of weeds by using roundup & like products.

Roundup was once believed, or at least stated by Monsanto researchers, to have no effect on animals. However, as of 2005, research has shown that, when roundup is applied directly to water in contravention of the product labeling, the surfactant polyethoxylated tallow amine (POEA) can kill tadpoles [77] by interrupting amphibian respiration through their skins. A 1995 Australian study concluded that ‘Roundup’ a popular and supposedly ecofriendly herbicide “was extremely toxic to tadpoles and adult frogs” (The New Zealand Frog Survey).

Reproductive health concerns & EDC activity

There are concerns about the effects of glyphosate (and Roundup) on possible human reproductive dysfunction.

Endocrine disruptor debate

In-vitro studies (Walsh, et al 2000) have shown glyphosate to have an effect on progesterone production in mammalian cells and can affect mortality of placental cells in-vitro (Richard, et al 2005). Whether these studies classify glyphosate as an endocrine disruptor is a matter of debate, with others pointing to studies, of even just pure glyphosate on Leydig cells showing harmful effects, to demonstrate conclusively that it is an endocrine disruptor.

Some feel that in-vitro studies are insufficient, and are waiting to see if animal studies show a change in endocrine activity, since a change in a single cell line may not occur in an entire organism. Additionally, current in-vitro studies expose cell lines to concentrations orders of magnitude greater than would be found in real conditions, and through pathways that would not be experienced in real organism. Many current toxicological studies results supportive of no endocrine activity were mainly provided by Monsantos own studies of pure glyphosate and not the chemical formulations of glyphosate that are actually used (EU 2002).

Others feel that in-vitro studies, particularly ones identifying not only an effect, but a chemical pathway, are sufficient evidence to classify glyphosate as an endocrine disruptor, on the basis that even small changes in endocrine activity can have lasting effects on an entire organism that may be difficult to detect through whole organism studies alone. Further research on the topic has been planned.

Glyphosate resistance in weeds & microorganisms

The first documented cases of weed resistance to glyphosate were found in Australia, involving rigid ryegrass near Orange, New South Wales.[78]Some farmers in the United States have expressed concern that weeds are now developing with glyphosate resistance, with 13 states now reporting resistance, and this poses a problem to many farmers, including cotton farmers, that are now heavily dependent on glyphosate to control weeds.[79][80]Farmers associations are now reporting 103 biotypes of weeds within 63 weed species with herbicide resistance, and this will continue to grow as a problem.[81][82]

Some microorganisms have a version of 5-enolpyruvoyl-shikimate-3-phosphate synthetase (EPSPS) that is resistant to glyphosate inhibition. The version used in genetically modified crops was isolated from Agrobacterium strain CP4 (CP4 EPSPS) that was resisitant to glyphosate.[83][84]. The CP4 EPSPS gene was cloned and inserted into soybeans. The CP4 EPSPS gene was engineered for plant expression by fusing the 5' end of the gene to a chloroplast transit peptide derived from the petunia EPSPS. This transit peptide was used because it had shown previously an ability to deliver bacterial EPSPS to the chloroplasts of other plants. The plasmid used to move the gene into soybeans was PV-GMGTO4. It contained three bacterial genes, two PC4 EPSPS genes, and a gene encoding beta-glucuronidase (GUS) from Escherichia coli as a marker. The DNA was injected into the soybeans using the particle acceleration method. Soybean cultivar A54O3 was used for the transformation. The expression of the GUS gene was used as the initial evidence of transformation. GUS expression was detected by a staining method in which the GUS enzyme converts a substrate into a blue precipitate. Those plants that showed GUS expression were then taken and sprayed with glyphosate and their tolerance was tested over many generations.

Genetically modified crops

In 1996, genetically modified soybeans were available commercially([50]). This greatly improved conventional farmers' ability to control weeds in soybean fields since glyphosate could be sprayed on fields without hurting the crop. As of 2005, 87% of U.S. soybean fields were planted to glyphosate resistant varieties [85].[86].

===Other uses===

Tradenames

It was first sold by Monsanto under the tradename Roundup but is no longer under patent so is now marketed under various names (for example TOP UP48 in Thailand).

Other uses

Glyphosate is one of a number of herbicides used by the United States government to spray Colombian coca fields through Plan Colombia. Its health effects, effects on legal crops, and effectiveness in fighting the war on drugs have been widely disputed.


External links

References

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