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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 US EPA 2000–2001 Pesticide Market Estimates [ Agriculture] , [ Home and Garden] ] and is the most-sold agrichemical of all time.Fact|date=March 2007 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.

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. 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 herbicide 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.


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 E. Franz, a scientist who worked for the Monsanto company. Franz received the National Medal of Technology in 1987 from Ronald Reagan for his discoveries [Technology Administration Agency, US Department of Commerce [] ] and in 1990 received the Perkin Medal for Applied Chemistry. [Colby Stong, The Scientist 1990, 4(10):28 [] ]


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, which is an essential precursor in plants for the aromatic amino acids: phenylalanine, tyrosine and tryptophan. [Purdue University, Department of Horticulture and Landscape Architecture, Metabolic Plant Physiology Lecture notes, Aromatic amino acid biosynthesis, The shikimate pathway - synthesis of chorismate. [] ] [ Saccharomyces Genome Database - S. cerevisiae Pathway: chorismate biosynthesis [] ] 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. [E. Schönbrunn et al, Interaction of the herbicide glyphosate with its target enzyme 5-enolpyruvylshikimate 3-phosphate synthase in atomic detail, PNAS 2001,98:1376-1380 [] ] 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 [(Su , L.Y. et al. 1992. The relationship of glyphosate treatment to sugar metabolism in sugarcane: New physiological insights. J. Plant Physiol. 140:168-173.)] [(Lamb, D.C. et al. 1998. Glyphosate is an inhibitor of plant cytochrome P450: Functional expression of Thlaspi arvensae cytochrome P45071B1/ reductase fusion protein in Escherichia coli. Biochem. Biophys. Res. Comm. 244:110114.)] and also has been found to affect animal enzymes. [(Hietanen, E., K. Linnainmaa, and H. Vainio. 1983. Effects of phenoxy herbicides and glyphosate on the hepatic and intestinal biotransformation activities in the rat. Acta Pharma. et Toxicol. 53:103-112.)]

Health, ecological concerns and controversy

Roundup has an EPA Toxicity Class of III for oral and inhalation exposure,U.S. EPA ReRegistration Decision Fact Sheet for Glyphosate (EPA-738-F-93-011) 1993. [] ] but more recent studies suggest that IV is appropriate for oral, dermal, and inhalation exposure. It has been rated as class I (Severe) for eye irritation, however.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".Williams GM, Kroes R, Munro IC. (2000) Safety evaluation and risk assessment of the herbicide Roundup and its active ingredient, glyphosate, for humans. "Regulatory Toxicology and Pharmacology", 31 (2): 117-165. PMID 10854122.]

False advertising

In 1996 Monsanto was accused of false and misleading advertising of glyphosate products, prompting a law suit by the New York State attorney general. [ [ Attorney General of the State of New York. Consumer Frauds and Protection Bureau. Environmental Protection Bureau. 1996. In the matter of Monsanto Company, respondent. Assurance of discontinuance pursuant to executive law § 63(15). New York, NY, Nov ] ]
On Fri Jan 20, 2007, Monsanto was convicted of false advertising of Roundup for presenting Roundup as biodegradable and claiming that 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. [ [ Monsanto Fined in France for 'False' Herbicide Ads ] ]

Scientific fraud

On two occasions the United States Environmental Protection Agency has caught scientists deliberately falsifying test results at research laboratories hired by Monsanto to study glyphosate. [(US EPA Communications and Public Affairs 1991 "Note to correspondents" Washington DC Mar 1)] [(US EPA Communications and Public Affairs 1991 Press Advisory. "EPA lists crops associated with pesticides for which residue and environmental fate studies were allegedly manipulated". Washington DC Mar 29)] [(U.S. Congress. House of Representatives. Com. on Gov. Oper. 1984. "Problems palgue the EPA pesticide registration activities". House Report 98-1147)] In the first incident involving Industrial Biotest Laboratories, an EPA 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". [(U.S. EPA 1978 Data validation. Memo from K LOcke, Toxicology Branch, to R Taylor, Registration Branch. Washington DC Aug 9)] [(U.S. EPA Office of pesticides and Toxic Substances 1983, "Summary of the IBT review program". Washington D.C. July)] [Schneider, K. 1983. Faking it: The case against Industrial Bio-Test Laboratories. The Amicus Journal (Spring):14-26. Reproduced at [ Planetwaves] ] 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. [(US Dept. of Justice. United States Attorney. Western District of Texas 1992. "Texas laboratory, its president, 3 employees indicted on 20 felony counts in connection with pesticide testing". Austin TX Sept 29) ] [(US EPA Communications, Education, And Public Affairs 1994 Press Advisory. "Craven Laboratories, owner, and 14 employees sentenced for falsifying pesticide tests". Washington DC Mar 4)] [ Glyphosate Factsheet (part 1 of 2) Caroline Cox / Journal of Pesticide Reform v.108, n.3 Fall98 rev.Oct00 ] ] Craven laboratories performed studies for 262 pesticide companies including Monsanto.

Monsanto has stated that the studies have been repeated and that Roundup's EPA certification does not now use any studies from Craven Labs or IBT. Monsanto also claims that the Craven Labs investigation was started by the EPA after a pesticide industry task force discovered irregularities. [Backgrounder: Testing Fraud: IBT and Craven Labs, June 2005, Monsanto background paper on RoundUp [] ]

Human and mammalian toxicity

Glyphosate itself is practically nontoxic by ingestion or by skin contact. The acute oral toxicity of Roundup is > 5,000 mg/kg in the rat. [ [ Roundup PRO® Herbicide MSDS] ] It showed no toxic effects when fed to animals for 2 years, and only produced rare cases of reproductive effects when fed in extremely large doses to rodents and dogs. It has not demonstrated any increase in cancer rates in animal studies and is poorly absorbed in the digestive tract. Glyphosate has no significant potential to accumulate in animal tissue. [ [ Extoxnet Pip - Glyphosate ] ] []

Not only is glyphosate used as five different salts but commercial formulations of it contain surfactants, which vary in nature and concentration. As a result, human poisoning with this herbicide is not with the active ingredient alone but with complex and variable mixtures. Glyphosate poisoning study by Bradberry SM, Proudfoot AT, Vale JA.for the National Poisons Information Service (Birmingham Centre) and West Midlands Poisons Unit, City Hospital, Birmingham, UK. ]

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.JP Giesy, KR Solomon, S Dobson (2000). "Ecotoxicological Risk Assessment for Roundup Herbicide". Reviews of Environmental Contamination and Toxicology 167: 35-120] 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 suggests glyphosate induces a variety of functional abnormalities in fetuses and pregnant rats. [ [ Effect of the herbicide glyphosate on enzymatic ac... [Environ Res. 2001 - PubMed Result ] ] Also in recent mammalian research, glyphosate has been found to interfere with an enzyme involved testosterone production in mouse cell cultureWalsh "et al" Roundup inhibits steroidogenesis by disrupting steroidogenic acute regulatory (StAR) protein expression. Environ Health Perspect. 2000 108: 769–776. [] ] and to interfere with an estrogen biosynthesis enzyme in cultures of Human Placental cells.Richard et al, Differential Effects of Glyphosate and Roundup on Human Placental Cells and Aromatase, Environmental Health Perspectives Vol. 113, No.6, 716-720 [] ]

Studies have shown that the application of Roundup on wheat crops a week before harvesting results in higher glyphosate residue in the resulting grain and in the baked flour. [WHO Environmental health criteria # 159] ]

The United States Environmental Protection Agency, [US EPA Reregistration Eligibility Decision - Glyphosate [] ] 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. [Peluso M, Munnia A, Bolognesi C, Parodi S. Environ Mol Mutagen. 1998 31:55-9 PMID 9464316 ] The authors concluded that the damage was "not related to the active ingredient, but to another component of the herbicide mixture".

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 pre-terminally. 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.

Aquatic effects

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."$file/Roundup%20Ultra%203000-5059en-gb.pdf Roundup Material Safety Data sheet page 7, heading 16 ]

Roundup is not registered for aquatic uses [Monsanto Backgrounder 2005 Response to "The impact of insecticides and herbicides on the biodiversity and productivity of aquatic communities" [] ] and studies of its effects on amphibians indicate it is toxic to them. [Rick A. Relyea 2005 The impact of insecticides and herbicides on the biodiversity and productivity of aquatic communities Ecological Applications 15:618–627] Glyphosate formulations that are registered for aquatic use have been found to have negligible adverse effects on sensitive amphibians. [Wojtaszek et al Effects of vision herbicide on mortality, avoidance response, and growth of amphibian larvae in two forest wetlands Environmental Toxicology and Chemistry 23:832–842 2004 [] ]

Environmental degradation and effects

When glyphosate comes into contact with the soil it can be rapidly bound to soil particles and be inactivated.US EPA Reregistration Eligibility Decision - Glyphosate - (EPA-738-F-93-011) 1993 [] ] Unbound glyphosate can be degraded by bacteria. [Balthazor, Terry M and Laurence Hallas (1986) Glyphosate-degrading microorganisms in industrial waste treatment biosystems. Appl. Environ. Microbiol. 51:432-34. [] ] Roundup has been shown to increase the disease rate in the crop following a sprayed crop, suggesting damaged soil flora. [ CROP ECOLOGY, MANAGEMENT & QUALITY] published online 26 August 2005 by M. R. Fernandeza, F. Sellesa, D. Gehlb, R. M. DePauwa and R. P. Zentner. ]
Low glyphosate concentrations can be found in many creeks and rivers in U.S. and Europe,Fact|date=February 2007 and in the US glyphosate has been called "relatively persistent" by the EPA.
The EU classifies Roundup as "N - Dangerous for the environment"

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. 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 for the detoxification of industrial toxin-polluted streams containing a wide class of toxicants. Treatment of industrial wastewater using immobilized bacteria showed complete conversion of glyphosate to nontoxic aminomethylphosphonic acid. [Adams, William, Laurence Hallas, and Michael Heitkamp. 1994. Microbes and their use to degrade N-phosphonomethylglycine in waste streams. United States Patent 5288635 [] ]

A recent study concluded that certain amphibians may be at risk from glyphosate use. [Bette Hileman. (2005) Common herbicide kills tadpoles. Chemical & Engineering News. Washington 83(15):11.] One study has shown an effect on growth and survival of earthworms. [(Springett & Gray 1992, "Soil Biol. Biochem". 24 (12):1739-1744) [] ] The results of this study are in conflict with other data and has been criticized on methodological grounds. In other studies nitrogen fixing bacteria have been impaired, and also crop plant susceptibility to disease has been increased. [(Santos & Flores 1995, "Lett. Appl." Microbiol. 20:349-352)] [(Brammel & Higgins 1988, "Can. J. Bot" 66:1547-1555)] [(Johal & Rahe 1988, Molec. Plant Pathol. 32:267-281)] [(Mekwatanakarn & Sivassithamparam 1987, "Biol. Fertil. Soils" 5:175-180)] [(Kawate et al. 1997, "Weed Sci". 45:739-743)] [(Bergvinson & Borden 1992, "Can J. For. Res". 22:206-209)]
Monsanto firmly denies any negative impact on anything, including wildlife, and has many studies it has funded to back up its position.Fact|date=April 2008 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 Fact|date=April 2008, which have not been proven, due to the elimination of weeds, and also would point to soil benefits from less mechanical cultivation of weeds by using Roundup and similar products.

Endocrine disruptor debate

An in-vitro study [Walsh LP et al. Roundup inhibits steroidogenesis by disrupting steroidogenic acute regulatory (StAR) protein expression. Environ Health Perspect. 2000 Aug;108(8):769-76.] has suggested glyphosate may have an effect on progesterone production in mammalian cells and affect mortality of placental cells in-vitro. Whether these studies classify glyphosate as an endocrine disruptor is a matter of debate.

Some believe 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 believe 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 and microorganisms

The first documented cases of weed resistance to glyphosate were found in Australia, involving rigid ryegrass near Orange, New South Wales. [ [ ISU Weed Science Online - Are RR Weeds in Your Future II ] ] 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. [ Glyphosate resistance is a reality that should scare some cotton growers into changing the way they do business ] ] [ More glyphosate resistant weeds ] ] 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.

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. [Development and Characterization of a CP4 EPSPS-Based, Glyphosate-Tolerant Corn Event,G. R. Heck et al Crop Sci. 45:329-339 (2005). [] ] [Molecular basis for the herbicide resistance of Roundup Ready crops, T. Funke et al, PNAS 2006 103:13010-13015 [] ] 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 "Roundup Ready" soybeans resistant to Roundup became commercially available, followed by "Roundup Ready" corn in 1998. [ [ Monsanto Company History] ] 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 hurting the crop. As of 2005, 87% of U.S. soybean fields were planted to glyphosate resistant varieties. [USDA/APHIS Environmental Assessment - In response to Monsanto Petition 06-178-01p seeking a Determination of Non-regulated Status for + Roundup RReady2Yield Soybean MON 89788, OECD Unique Identifier MON-89788-1, U.S. Department of Agriculture Animal and Plant Health Inspection Service + Biotechnology Regulatory Services page 13 [] ] [National Agriculture Statistics Service (2005) in Acreage eds. Johanns, M. & Wiyatt, S. D. 6 30, (U.S. Dept. of Agriculture, Washington, DC). + ] The use of roundup ready crops has changed the herbicide use profile away from atrazine, metribuzin, and alachlor. This has the benefit of reducing the dangers of herbicide run off into drinking water. [Impact of glyphosate-tolerant soybean and glufosinate-tolerant corn production on herbicide losses in surface runoff. Shipitalo MJ, Malone RW, Owens LB. J Environ Qual. 2008 37(2):401-8 PMID 18268303] The use of roundup-ready crops has resulted in greater use of roundup, which has created a problem with weeds that are resistant to the herbicide. With greater use, it has become more likely that weeds that are not affected by the herbicide, survive and reproduce and proliferate. []


The Roundup trademark is registered with the US Patent Office and still extant. However, the chemical formulation is no longer under patent, so similar products using glyphosate as the active ingredient are available from other manufacturers and marketed under many names, [ [ California Product/Label Database] ] including Buccaneer, Razor Pro, (41%), Roundup Pro Concentrate (50.2 %), Rodeo (51.2%), Aquaneat(53.8%), and Aquamaster (53.5%) [ [ Glyphosate Roadside Vegetation Management Herbicide Fact Sheet] ]

Other uses

Glyphosate is one of a number of herbicides used by the United States government to spray Colombian coca fields through Plan Colombia. 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 also larger and higher yielding than the original strains of the plant. [] [New Super Strain of Coca Plant Stuns Anti-Drug Officials. Jeremy McDermott. The Scotsman (Scotland) 27 August 2004] However, there are no reports of glyphosate-resistant coca in the peer-reviewed literature. [ [ USDA National Agricultural Library, accessed 1 Nov 2007] ] 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.

External links

* [ Roundup website (Monsanto)]
* [ EPA's Integrated Risk Information System entry for Roundup]
* [ EPA's ground & drinking water consumer factsheet for glyphosate]
* [ Chemical Identification and Use for Glyphosate, isopropylamine salt]


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
*Marie-Monique Robin. (2008) Le monde selon Monsanto. Arte Editions (book written in french). ISBN 978-2-7071-4918-3. An overview of Monsanto products: PCB, Dioxine,Roundup, Bovine Growth Hormone, OGM.

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