Roundup

Template:Chembox new Roundup is the brand name of a systemic, broad-spectrum herbicide produced by the U.S. company Monsanto and contains the active ingredient glyphosate. Glyphosate is the most used herbicide in the USA^[1] and is the most-sold agrichemical of all time.^{[citation needed]} In the US 5-8 million pounds are used every year on lawns and yards and 85-90 million pounds are used annually in US agriculture.^[1]

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. In May 2007, a federal court decision barred new plantings of Roundup Ready alfalfa and the resale of seeds, due to the failure of regulators to complete an environmental impact statement examining the potential that genetically-modified alfalfa would contaminate non-GM alfalfa crops, encourage new weeds tolerant to herbicides and limit export markets.

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).

Glyphosate is an aminophosphonic analogue of the natural amino acid glycine and the name is a contraction of glycine, phospho- and -ate. It was first discovered to have herbicidal activity in 1970 by John Franz, a scientist that worked for the Monsanto company. Franz received the National Medal of Technology in 1987 from Ronald Reagan for his discoveries^[2] and in 1990 received the Perkin Medal for Applied Chemistry.^[3]

Glyphosate kills plants by inhibiting the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), which catalyzes the reaction of shikimate-3-phosphate (S3P) and phosphoenolpyruvate to form 5-enolpyruvyl-shikimate-3-phosphate (ESP). ESP is subsequently dephosphorylated to chorismate an essential precursor in plants for the aromatic amino acids: phenylalanine, tyrosine and tryptophan.^[4][5] These amino acids are used as building blocks in peptides and to produce secondary metabolites such as folates, ubiquinones and naphthoquinone. X-ray crystallographic studies of Glyphosate and EPSPS shows that glyphosate functions by occupying the binding site of the phosphoenol pyruvate, mimicking an intermediate state of the ternary enzyme substrates complex.^[6] The shikimate pathway is not present in animals, which obtain aromatic amino acids from their diet. Glyphosate has also been shown to inhibit other plant enzymes^[7][8] and also has been found to affect animal enzymes.^[9]

Glyphosate is classed as a moderately toxic herbicide and in EPA toxicity class III. A 2000 review of the available literature concluded that "under present and expected conditions of new use, there is no potential for Roundup herbicide to pose a health risk to humans".^[10] The Northwest Coalition for Alternatives to Pesticides disputes this classification.^[11]

On two occasions the American EPA has caught scientists deliberately falsifying test results at research laboratories hired by Monsanto to study glyphosate.^[12][13][14] 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".^[15][16][17] In the second incident of falsifying test results in 1991, the owner of the lab (Craven Labs), and three employees were indicted 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. Monsanto has been accused of false and misleading advertising of glyphosate products, prompting a law suit by the New York State attorney general.^[21] Monsanto has also been accused of the false advertising of roundup in Europe where it is currently appealing a law suit on the issue.^[22]

Outside its intended use, glyphosate can be lethal. For example, with intentional poisonings (e.g. suicide), there is approximately a 10% mortality for those ingesting Roundup, compared to 70% for those ingesting paraquat.^[23]

A review of the toxicological data on Roundup shows that there are at least 58 studies of the effects of Roundup itself on a range of organisms.^[24] This review concluded that "for terrestrial uses of Roundup minimal acute and chronic risk was predicted for potentially exposed nontarget organisms". It also concluded that there were some risks to aquatic organisms exposed to Roundup in shallow water. More recent research indicates glyphosate induces a variety of functional abnormalities in fetuses and pregnant rats.^[25] Also in recent mammalian research, glyphosate has been found to interfere with an enzyme involved testosterone production in mouse cell culture^[26] and to interfere with an estrogen biosynthesis enzyme in cultures of Human Placental cells.^[27]

In controlled residue studies the WHO found "significant residues" on wheat with residues not lost during baking.^[28]

Concerns have been raised abouts Roundup's effect on flora, mammals and birds brought about through habitat destruction.^[29]

The United States Environmental Protection Agency,^[30] the EC Health and Consumer Protection Directorate, and the UN World Health Organization have all concluded that pure glyphosate is not carcinogenic. Opponents of glyphosate claim that Roundup has been found to cause genetic damage, citing Peluso et al.^[31] The authors concluded that the damage was "not related to the active ingredient, but to another component of the herbicide mixture.

Fish and aquatic invertebrates are more sensitive to roundup than terrestrial organisms.^[24] Glyphosate is generally less persistent in water than in soil, with 12 to 60 day persistence observed in Canadian pond water, yet persistence of over a year have been observed in the sediments of ponds in Michigan and Oregon.^[32]

Roundup is not registered for aquatic uses^[33] and studies of its effects on amphibians indicates it is toxic to them.^[34] Glyphosate formulations that are registered for aquatic use have been found to have negligible adverse effects on sensitive amphibians.^[35]

When glyphosate comes into contact with the soil it can be rapidly bound to soil particles and be inactivated.^[32] Unbound glyphosate can be degraded by bacteria.^[36] Low activity because of binding to soil particles suggests that glyphosate's effects on soil flora will be limited.^{[citation needed]} Low glyphosate concentrations can be found in many creeks and rivers in U.S. and Europe,^{[citation needed]} and in the US glyphosate has been called "relatively persistent" by its EPA.^[32]

In soils, half lives vary from as little as 3 days at a site in Texas, 141 days at a site in Iowa, to between 1 - 3 years in Swedish forest soils.^[37] It appears that more northern sites have the longest soil persistences such as in Canada and Scandinavia.

However, the binding of glyphosate to particulates can be an advantage. Treatment of industrial wastewater using immobilized bacteria showed complete conversion of glyphosate to nontoxic aminomethylphosphonic acid.^[38]

The US EPA concluded that many endangered species of plants, as well as the Houston toad, may be at risk from glyphosate use.^{[citation needed]} One study has shown an effect on growth and survival of earthworms.^[39] The results of this study are in conflict with other data and has been criticized on methodological grounds.^[24] In other studies nitrogen fixing bacteria have been impaired, and also crop plant susceptibility to disease has been increased.^{[40][41][42][43][44][45]} 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 and 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 and similar products.

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

In-vitro studies^[46] have shown glyphosate to have an effect on progesterone production in mammalian cells and can affect mortality of placental cells in-vitro.^[27] Whether these studies classify glyphosate as an endocrine disruptor is a matter of debate.

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.

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.

The first documented cases of weed resistance to glyphosate were found in Australia, involving rigid ryegrass near Orange, New South Wales.^[47] 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.^[48][49] 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.^[50][51]

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.^[52][53] 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.

In 1996, genetically modified soybeans were available commercially [30]. 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.^[54][55]

It was first sold by Monsanto under the tradename Roundup, and the Roundup trademark is registered with the US Patent Office and still extant. However, the chemical formulation is not patented, so similar products are available from other maufacturers and marketed under various names (for example TOP UP48 in Thailand).^{[citation needed]}

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. Widespread application of glyphosate in attempts to destroy coca crops in South America have resulted in the development of glyphosate-resistant strains of coca which have been selectively bred to be both "Roundup ready" and also larger and higher yielding than the original strains of the plant. [31]^[56]

• Graphic network of Business and political connections for Monsanto [32]
• Roundup website (Monsanto)
• Roundup website (French Website)
• EPA's Integrated Risk Information System entry for Roundup
• EPA's ground & drinking water consumer factsheet for glyphosate
• Greenpeace: A Critique of Monsanto's Risk Evaluation
• Monsanto and the Roundup Ready Controversy
• Greenpeace: Why Consumers and Farmers Should Avoid Monsanto's GE Soybeans
• Greenpeace: Glyphosate and Your Food
• http://www.gene.ch/genet/1999/Jun/msg00012.html
• University of Pittsburgh professor finds herbicide kills frogs (an article from 2005)
• Fact Sheet on Glyphosate, includes 14 references, by the Sierra Club of Canada
• NPR News 2007/08/20 - Farmers Switch Course in Battle Against Weeds

• Baccara, Mariagiovanna, et al. Monsanto's Roundup, NYU Stern School of Business: August 2001, Revised July 14, 2003.
• Pease W S et al. (1993) Preventing pesticide-related illness in California agriculture: Strategies and priorities. Environmental Health Policy Program Report. Berkeley, CA: University of California. School of Public Health. California Policy Seminar.
• Wang Y, Jaw C and Chen Y (1994) Accumulation of 2,4-D and glyphosate in fish and water hyacinth. Water Air Soil Pollute. 74:397-403

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