| Section2 = | Section7 = }} Glyphosate (''N''-(phosphonomethyl)glycine) is a broad-spectrum systemic herbicide used to kill weeds, especially annual broadleaf weeds and grasses known to compete with crops grown widely across the Midwest of the United States. Initially patented and sold by Monsanto Company in the 1970s under the tradename ''Roundup'', its U.S. patent expired in 2000. Glyphosate is the most used herbicide in the USA. Exact figures are hard to come by because the U.S. Department of Agriculture stopped updating its pesticide use database in 2008. The EPA estimates that in the US during 2007, the agricultural market used 180 to 185 million pounds () of glyphosate, the home and garden market used 5 to 8 million pounds (), and industry, commerce and government used 13 to 15 million pounds (), according to its Pesticide Industry Sales & Usage Report for 2006-2007 published in February, 2011. While Roundup has been associated with deformities in a host of laboratory animals, its impact on humans remains unclear.

Glyphosate's mode of action is to inhibit an enzyme involved in the synthesis of the aromatic amino acids: tyrosine, tryptophan and phenylalanine. It is absorbed through foliage and translocated to growing points. Because of this mode of action, it is only effective on actively growing plants; it is not effective as a pre-emergence herbicide.

Some crops have been genetically engineered to be resistant to it (i.e. ''Roundup Ready'', also created by Monsanto Company). Such crops allow farmers to use glyphosate as a post-emergence herbicide against both broadleaf and cereal weeds, but the development of similar resistance in some weed species is emerging as a costly problem. Soy was the first ''Roundup Ready'' crop.

Chemistry

Glyphosate is an aminophosphonic analogue of the natural amino acid glycine, and the name is a contraction of ''gly(cine)'' ''phos(phon)ate''. The molecule has several dissociable hydrogens, especially the first hydrogen of the phosphate group. The molecule tends to exist as a zwitterion where a phosphonic hydrogen dissociates and joins the amine group. Glyphosate is soluble in water to 12 g/L at room temperature.

Glyphosate was first discovered to have herbicidal activity in 1970 by John E. Franz, while working for Monsanto. Franz received the National Medal of Technology in 1987, and the Perkin Medal for Applied Chemistry in 1990 for his discoveries.

In an editorial on May 17, 2010, the New York Times noted the appearance of glyphosate-resistant weeds.

Formulas and tradenames

Although the Roundup trademark is registered with the US Patent Office and still extant, the patent has expired. Glyphosate is marketed in the US and worldwide in different solution strengths under many tradenames: Roundup, Buccaneer, Razor Pro (41%), Genesis Extra II (41% w/ Surfactant), Roundup Pro Concentrate (50.2 %), Rodeo (51.2%), Aquaneat (53.8%), and Aquamaster (53.5%). These products may contain other ingredients, causing them to have different effects. For example, Roundup was found to have different effects than glyphosate alone. Roundup is a water-based solution containing glyphosate, a surfactant, and other substances. Other formulations contain additional active ingredients to improve the speed of action. In the UK, Weedol Rootkill Plus, which contains glyphosate and pyraflufen-ethyl, and Resolva 24H which contains glyphosate and diquat, are available.

Biochemistry

Glyphosate kills plants by interfering with the synthesis of the amino acids phenylalanine, tyrosine and tryptophan. It does this 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. 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 show that glyphosate functions by occupying the binding site of the phosphoenolpyruvate, mimicking an intermediate state of the ternary enzyme substrates complex. The shikimate pathway is not present in animals, which instead obtain aromatic amino acids from their diet. Glyphosate has also been shown to inhibit other plant enzymes, and also has been found to affect animal enzymes.

Use

Glyphosate is effective in killing a wide variety of plants, including grasses, broadleaf, and woody plants. It has a relatively small effect on some clover species. By volume, it is one of the most widely used herbicides. It is commonly used for agriculture, horticulture, and silviculture purposes, as well as garden maintenance (including home use).

Glyphosate is supplied in several formulations for different uses:

Ammonium salt

Isopropyl amine salt

Glyphosate acid - standalone, as ammonium salt or as isopropyl salt

Potassium salt

Products are supplied most commonly in formulations of 120, 240, 360, 480 and 680 g active ingredient per litre. The most common formulation in agriculture is 360 g, either alone or with added cationic surfactants.

For 360 g formulations, European regulations allow applications of up to 12 litres per hectare for control of perennial weeds such as couch grass. More commonly, rates of 3 litres per hectare are practiced for control of annual weeds between crops.

Genetically modified crops

In 1996, genetically modified soybeans were made commercially available. Current ''Roundup Ready'' crops include soy, maize (corn), sorghum, canola, alfalfa, and cotton, with wheat still under development. These cultivars greatly improved conventional farmers' ability to control weeds, since glyphosate could be sprayed on fields without damaging the crop. As of 2005, 87% of U.S. soybean fields were planted with glyphosate-resistant varieties.

While the use of ''Roundup Ready'' crops may have increased the usage of herbicides measured in pounds applied per acre, its use has changed the herbicide use profile away from atrazine, metribuzin, and alachlor. This has the benefit of reducing the dangers of herbicide runoff into drinking water.

In 1999, a review of ''Roundup Ready'' soybean crops found that, compared to the top conventional varieties, they had a 6.7% lower yield. This "yield drag" is similar to what is observed when other traits are introduced into soybeans by conventional breeding and may not be due to the ''Roundup Ready'' trait or the genetically modified nature of the crop since Monsanto has recently released ''Roundup Ready'' 2 soybeans, which are claimed to yield 7–11% higher than RR version 1. There have been no reports of "yield drag" with the other ''Roundup Ready'' crops maize, sorghum or canola.

Development

Some micro-organisms 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 resistant to glyphosate. This CP4 EPSPS gene was cloned and transfected 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.

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 effects on legal crops and effectiveness in fighting the war on drugs have been disputed. There are reports that widespread application of glyphosate in attempts to destroy coca crops in South America have resulted in the development of glyphosate-resistant strains of coca known as Boliviana negra, which have been selectively bred to be both "Roundup Ready" and larger and higher yielding than the original strains of the plant. However, there are no reports of glyphosate-resistant coca in the peer-reviewed literature. In addition, since spraying of herbicides is not permitted in Colombian national parks, this has encouraged coca growers to move into park areas, cutting down the natural vegetation, and establishing coca plantations within park lands.

Effects

Glyphosate is rated least dangerous in comparison to other herbicides and pesticides, such as those from the organochlorine family. Roundup has a United States Environmental Protection Agency‎ (EPA) Toxicity Class of III (on a I to IV scale, where IV is least dangerous) for oral and inhalation exposure. It does not bioaccumulate, and breaks down rapidly in the environment.

The United States Environmental Protection Agency‎ (EPA) considers glyphosate to be relatively low in toxicity, and without carcinogenic effects. The EPA considered a "worst case" dietary risk model of an individual eating a lifetime of food entirely from glyphosate-sprayed fields, and with residue levels remaining at their maximum levels, and concluded no adverse effects would exist under these conditions In 2007, the EPA selected glyphosate for further screening for endocrinal disruptor effects, not because of suspected effects, but because glyphosate is a widely-used herbicide (the EPA has stated selection for screening does not itself imply risk).

Laboratory toxicology studies suggest other ingredients combined with glyphosate may have greater toxicity than glyphosate alone. For example, a study comparing glyphosate and Roundup found Roundup had a greater effect on aromatase than glyphosate alone. Another study has shown Roundup formulations and metabolic products cause the death of human embryonic, placental, and umbilical cells ''in vitro'', even at low concentrations. The effects are not proportional to glyphosate concentrations, but are dependent on the nature of the adjuvants used in the formulation. Exposure methods in the ''in vitro'' tests are not representative, though, of how people or animals would be exposed to glyphosate herbicides, so the relevance of ''in vitro'' tests is unclear. In addition, many common materials that contain surfactants, such as shampoo, can cause similar effects in ''in vitro'' experiments.

Statistics from the California Environmental Protection Agency's Pesticide Illness Surveillance Program indicate glyphosate-related incidents are one of the highest reported of all pesticides. However, incident count does not take into account the number of people exposed and the severity of symptoms associated with each incident. For example, if hospitalization were used as a measure of the severity of pesticide related incidents, then glyphosate would be considered relatively safe, since, over a 13-year period in California, none of the 515 pesticide-related hospitalizations recorded were attributed to glyphosate.

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

There is a reasonable correlation between the amount of Roundup ingested and the likelihood of serious systemic sequelae or death. Ingestion of >85 mL of the concentrated formulation is likely to cause significant toxicity in adults. Gastrointestinal corrosive effects, with mouth, throat and epigastric pain and dysphagia are common. Renal and hepatic impairment are also frequent, and usually reflect reduced organ perfusion. Respiratory distress, impaired consciousness, pulmonary oedema, infiltration on chest X-ray, shock, arrythmias, renal failure requiring haemodialysis, metabolic acidosis and hyperkalaemia may supervene in severe cases. Bradycardia and ventricular arrhythmias are often present preterminally. Dermal exposure to ready-to-use glyphosate formulations can cause irritation, and photo-contact dermatitis has been reported occasionally; these effects are probably due to the preservative Proxel (benzisothiazolin-3-one). Severe skin burns are very rare. Inhalation is a minor route of exposure, but spray mist may cause oral or nasal discomfort, an unpleasant taste in the mouth, tingling and throat irritation. Eye exposure may lead to mild conjunctivitis, and superficial corneal injury is possible if irrigation is delayed or inadequate.

Other species

The acute oral toxicity of Roundup is > 5,000 mg/kg in the rat. It showed no toxic effects when fed to animals for two years, and only produced rare cases of reproductive effects when fed in extremely large doses to rodents and dogs. An increase in cancer rates in animal studies has not been demonstrated, and it is poorly absorbed in the digestive tract. Glyphosate has no significant potential to accumulate in animal tissue.

A study published in 2010 proposed commercial glyphosate can cause neural defects and craniofacial malformations in African clawed frogs (''Xenopus laevis''). The experiments used frog embryos that were incubated with 1:5000 dilutions of a commercial glyphosate solution. The frog embryos suffered diminution of body size, alterations of brain morphology, reduction of the eyes, alterations of the branchial arches and otic placodes, alterations of the neural plate, and other abnormalities of the nervous system. The authors suggested glyphosate itself was responsible for the observed results because injection of pure glyphosate produced similar results in a chicken model. The results cast doubt on previous clinical studies of offspring of glyphosate-exposed agricultural workers, which have failed to demonstrate a teratogenic effect.

An ''in vitro'' study indicated glyphosate formulations could harm earthworms and beneficial insects. However, the reported effect of glyphosate on earthworms has been criticized. The results conflict with results from field studies where no effects were noted for the number of nematodes, mites, or springtails after treatment with Roundup at 2 kilograms active ingredient per hectare. Glyphosate can negatively affect nitrogen-fixing bacteria, and increase the susceptibility of plants to disease. A 2005 study concluded that certain amphibians may be at risk from glyphosate use.

Certain surfactants used in some glyphosate formulations have higher toxicity to fish and invertebrates, resulting in some formulations of glyphosate not being registered for use in aquatic applications. Monsanto produces glyphosate products with alternative surfactants that are specifically formulated for aquatic use, for example "Biactive" and "AquaMaster". According to Monsanto, "Conservation groups have chosen glyphosate formulations because of their effectiveness against most weeds as glyphosate has very low toxicity to wildlife". Glyphosate is used with five different salts, but commercial formulations of it contain surfactants, which vary in nature and concentration. As a result, humans who have ingested this herbicide may suffer poisoning not with the active ingredient alone, but with complex and variable mixtures.

Glyphosate's effect on soil life may be limited, because when glyphosate comes into contact with the soil, it rapidly binds to soil particles and is inactivated. Unbound glyphosate is degraded by bacteria. Low activity because of binding to soil particles suggests glyphosate's effects on soil flora are limited. Low glyphosate concentrations can be found in many creeks and rivers in U.S. and Europe.

The EPA, the EC Health and Consumer Protection Directorate, and the UN World Health Organization have all concluded pure glyphosate is not carcinogenic. Opponents of glyphosate claim Roundup has been found to cause genetic damage, citing Peluso ''et al''. The authors concluded the damage was "not related to the active ingredient, but to another component of the herbicide mixture".

Mammal research indicates oral intake of 1% glyphosate induces changes in liver enzyme activities in pregnant rats and their fetuses.

Aquatic effects

Glyphosate is one of the pesticides that pose the greatest danger to amphibians. Fish and aquatic invertebrates are more sensitive to Roundup than terrestrial organisms. 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. The EU classifies Roundup as ''R51/53 Toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment.''

Roundup is not registered for aquatic uses, and studies of its effects on amphibians indicate it is toxic to them. Other glyphosate formulations registered for aquatic use have been found to have negligible adverse effects on sensitive amphibians.

Endocrine disruptor debate

''In vitro'' studies have shown glyphosate affects progesterone production in mammalian cells and can increase the mortality of placental cells. Whether these studies classify glyphosate as an endocrine disruptor is debated.

Environmental degradation

When glyphosate comes into contact with the soil, it can be rapidly bound to soil particles and be inactivated. Unbound glyphosate can be degraded by bacteria. It has been proposed that glyphosate applications increase the infection rate of wheat by fusarium head blight.

In soils, half-lives vary from as little as three days at a site in Texas to 141 days at a site in Iowa. In addition, the glyphosate metabolite aminomethylphosphonic acid has been found in Swedish forest soils up to two years after a glyphosate application. Glyphosate adsorption to soil varies depending on the kind of soil.

Resistance in weeds and microorganisms

The first documented cases of weed resistance to glyphosate were found in Australia, involving rigid ryegrass near Orange, New South Wales. 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. Farmers' associations are now reporting 103 biotypes of weeds within 63 weed species with herbicide resistance. This problem is likely to be exacerbated by the use of Roundup-Ready crops.

A report, published in November, 2009, "Impacts of Genetically Engineered(GE) Crops on Pesticide Use in the United States: The First Thirteen Years" using USDA data shows U.S. farmers have applied 383 million more pounds of herbicides on GE crops since 1996, including soybeans than they likely would have applied on non-GE varieties of these crops. The same report states the rise in pounds per acre is associated with the replacement of older, higher risk herbicides with glyphosate. Forty-six percent of the total increase occurred in the last two years studied (2007 and 2008). It also identifies the problem as an increase in herbicide-resistant-weeds.

Legal cases

False advertising

In 1996, Monsanto was accused of false and misleading advertising of glyphosate products, prompting a lawsuit by the New York State attorney general.

On Fri Jan 20, 2007, Monsanto was convicted of false advertising of Roundup for presenting it as biodegradable, and claiming it left the soil clean after use. Environmental and consumer rights campaigners brought the case in 2001 on the basis that glyphosate, Roundup's main ingredient, is classed as "dangerous for the environment" and "toxic for aquatic organisms" by the European Union. Monsanto France planned to appeal the verdict at the time.

Scientific fraud

On two occasions, the United States EPA has caught scientists deliberately falsifying test results at research laboratories hired by Monsanto to study glyphosate. In the first incident, involving Industrial Biotest Laboratories (IBT), an EPA reviewer stated, after finding "routine falsification of data", it was "hard to believe the scientific integrity of the studies when they said they took specimens of the uterus from male rabbits". 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 five years in prison and fined US$50,000, the lab was fined $15.5 million and ordered to pay $3.7 million in restitution. Craven laboratories performed studies for 262 pesticide companies, including Monsanto.

Monsanto has stated the studies have been repeated, and Roundup's EPA certification does not now use any studies from Craven Labs or IBT. Monsanto alleges the Craven Labs investigation was started by the EPA after a pesticide industry task force discovered irregularities.

References

EU (2002). Review report for the active substance glyphosate. Retrieved October 28, 2005.

Environmental Health Criteria 159: Glyphosate. World Health Organization, (1994).

History of Glyphosate. Monsanto Company.

Further reading

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

External links

Glyphosate Technical Fact Sheet - National Pesticide Information Center

Glyphosate General Fact Sheet - National Pesticide Information Center

Glyphosate Pesticide Information Profile - Extension Toxicology Network

EPA Reregistration Eligibility Decision Fact Sheet

Monsanto Website - Background Information about Glyphosate and Roundup

US weighs costs of Plan Colombia

Effect of Glyphosate on human placental cells in culture

Website of the SynBioC research group, working on different types of aminophosphonates

Glyphosate Stewardship

EPA's Integrated Risk Information System entry for glyphosate

Chemical Identification and Use for Glyphosate, isopropylamine salt

Crop Protection Database: Learn more about glyphosate

Herbicide tolerance and GM crops: Why the world should be Ready to Round Up glyphosate

Category:Herbicides Category:Acetic acids Category:Amines Category:Phosphonic acids

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name	Sara Foster
birth date	August 02, 1981
birth place	Los Angeles, California, U.S.
birth name	Sara Christine Foster
occupation	Actress
yearsactive	1999–Present
domesticpartner	Tommy Haas }}

Sara Christine Foster (born August 2, 1981) is an American actress. She was previously a fashion model before moving to the film industry. She is best known for her role as Jen Clark on 90210.

Career

Foster guest-starred as herself on the HBO series ''Entourage'', in which she had a romantic tryst with character Vincent Chase (played by actor Adrian Grenier) before appearing on ''Jimmy Kimmel Live'' in the episode "Talk Show". She briefly hosted ''Entertainment Tonight'' spin-off ''ET on MTV'' in 2002. Based on that she was cast as the lead femme fatale in ''The Big Bounce'' in 2004, a remake of a movie adaptation of the same novel by Elmore Leonard. She also appeared in the Backstreet Boys video "Shape of My Heart". In 2005, she played crime-fighting lesbian girl Amy Bradshaw in Angela Robinson's 2004 film ''D.E.B.S.''. As of 2009, she signed on for the major recurring role of Jen Clark on the TV show ''90210'' . So far, she has appeared in every season of the show. Additionally, Foster stars in the science-fiction film ''Psych 9''., which was directed by Andrew Shortell.

Sara is currently engaged to Tommy Haas; On November 15, 2010, Haas announced on his website that Sara had given birth to a baby girl, Valentina.

Sara is the daughter of music producer David Foster.

Filmography

''D.R.E.A.M. Team'' (1999) (uncredited)

''D.E.B.S.'' (2004)

''The Big Bounce'' (2004)

''Entourage'' (episode "Talk Show", 2004)

''Characters'' (2005 film short)

''Crossing Jordan'' (episode "Family Affair", 2005)

''CSI: Crime Scene Investigation'' (episode "Unbearable", 2005)

''South Beach'' (episode "Unaired Pilot", 2006)

''Bachelor Party 2: The Last Temptation ''(2008)

''The Other End of the Line'' (2008)

''Psych 9'' (2009)

''Demoted'' (2009)

''90210'' (Recurring 2009-)

References

External links

Category:1981 births Category:American film actors Category:American infotainers Category:American people of Canadian descent Category:American television actors Category:Actors from California Category:Living people Category:People from Los Angeles County, California

da:Sara Foster de:Sara Foster es:Sara Foster fr:Sara Foster it:Sara Foster nl:Sara Foster pt:Sara Foster fi:Sara Foster tr:Sara Foster