View source for Glyphosate

{{chembox
| Name = Glyphosate
| ImageFile = Glyphosate-2D-skeletal.png
|   ImageSize = 
| ImageFile2 = Glyphosate-3D-balls.png
| IUPACName = ''N''-(phosphonomethyl)glycine
|   OtherNames = 2-[(phosphonomethyl)amino]acetic acid
| Section1 = {{Chembox Identifiers
|   InChI = 1/C3H8NO5P/c5-3(6)1-4-2-10(7,8)9/h4H,1-2H2,(H,5,6)(H2,7,8,9)
|   CASNo = 1071-83-6
|    CASNo_Ref = {{cascite}}
|   CASOther = <br/>38641-94-0 (isopropylammmonium salt)<br/>70393-85-0 (sesquisodium salt) <!-- 38641-94-0 also verified at CAS Common Chemistry -->
|   EC-number = 213-997-4 <!-- 254-056-8 for isopropylammmonium salt, 274-591-0 for sesquisodium salt -->
|   ChemSpiderID = 3376 <!-- 34909 for isopropylammmonium salt, 137033 for sesquisodium salt -->
|   RTECS = MC1075000
|   PubChem = 3496
|   SMILES = C(C(=O)O)NCP(=O)(O)O
  }}
| Section2 = {{Chembox Properties
|   Reference = <ref name="EHC">{{EHC-ref|number=159|name=Glyphosate|date=1994|isbn=92-4-157159-4}}.</ref>
|   C = 3 | H = 8 | N = 1 | O = 5 | P = 1
|   Appearance = white crystalline powder
|   Density = 1.704 (20 °C)
|   MeltingPt = 184.5 °C
|   BoilingPt = decomp. at 187 °C
|   Solubility = 1.01 g/100 ml (20 °C)
|   LogP = −2.8
|   pKa = <2, 2.6, 5.6, 10.6
  }}
| Section7 = {{Chembox Hazards
|   Reference = <ref name="EHC"/><ref>{{CLP Regulation|index=607-315-00-8|pages=570, 1100}}</ref>
|   ExternalMSDS = {{ICSC-small|0160}}
|   EUIndex = 607-315-00-8
|   EUClass = Irritant ('''Xi''')<br/>Dangerous for the environment ('''N''')
|   RPhrases = {{R41}}, {{R51/53}}
|   SPhrases = {{S2}}, {{S26}}, {{S39}}, {{S61}}
|   GHSPictograms = {{GHS05|Eye Dam. 1}}{{GHS09|Aquatic Chronic 2}}
|   GHSSignalWord = DANGER
|   HPhrases = {{H-phrases|318|411}}
|   PPhrases = {{P-phrases|273|280|305+351+338|310|501}}
|   FlashPt = non-flammable
  }}
}}

'''Glyphosate''' (''N''-(phosphonomethyl)glycine) is a broad-spectrum [[systemic]] [[herbicide]] used to kill [[weed]]s, especially [[Perennial plant|perennial]]s.  It is typically sprayed and absorbed through the leaves, injected into the [[Trunk (botany)|trunk]], or applied to the stump of a tree, or broadcast or used in the cut-stump treatment as a forestry herbicide. Initially patented and sold by [[Monsanto Company]] in the 1970s under the tradename [[Roundup]], its U.S. [[patent]] expired in 2000.  It is now also available in other formulations, e.g. [[Resolva 24H]], which contains glyphosate and [[diquat]].<ref>{{citation | url = http://www.resolva-weeds.com/index.php | website = Resolva Weeds | publisher = Westland Garden Health | accessdate = 2009-09-04}}.</ref> Glyphosate is the most used herbicide in the USA.<ref  name="EPAusage">{{citation | title = Pesticides Industry Sales and Usage: 2000 and 2001 Market Estimates | url = http://www.epa.gov/oppbead1/pestsales/01pestsales/market_estimates2001.pdf | date = May 2004 | publisher = U.S. Environmental Protection Agency | pages = 14–15}}.</ref> In the US, 5–8&nbsp;million pounds (2200–3600&nbsp;tonnes) are used every year on lawns and yards and 85–90&nbsp;million pounds (about 40,000&nbsp;tonnes) are used annually in US agriculture.<ref name="EPAusage"/>

The [[active ingredient]] is the [[isopropylamine]] [[salt]] of glyphosate. Glyphosate's mode of action is to inhibit an [[enzyme]] involved in the synthesis of the [[amino acid]]s [[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 [[preemergent herbicides|pre-emergence herbicide]]. 

Some crops have been [[genetic engineering|genetically engineered]] to be resistant to it (i.e. Roundup Ready). Such crops allow farmers to use glyphosate as a post-emergence herbicide against both broadleaf and cereal weeds. Soy was the first [[#Genetically modified crops|''Roundup Ready'' crop]].

==Chemistry==
Glyphosate is an aminophosphonic analogue of the natural amino acid [[glycine]] and the name is a contraction of ''[[glycine]]'', ''[[phosphorus|phospho]]-'', and ''-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 12g/L at room temperature.

Glyphosate was first discovered to have herbicidal activity in 1970 by [[John E. Franz]], while working for Monsanto.<ref>{{citation | last1 = Alibhai | first1 = Murtaza F. | last2 = Stallings | first2 = William C. | title = Closing down on glyphosate inhibition—with a new structure for drug discovery | year = 2001 | journal = Proc. Natl. Acad. Sci. USA | volume = 98 | issue = 6 | pages = 2944 | doi = 10.1073/pnas.061025898 | pmid = 11248008 | pmc = PMC33334}}.</ref> Franz received the [[National Medal of Technology]] in 1987,<ref>{{citation | url = http://www.uspto.gov/nmti/recipients_87.html | title = National Medal of Technology Recipients 1987 | publisher = U.S. Patent and Trademark Office | accessdate = 2009-09-05}}.</ref> and the [[Perkin Medal]] for Applied Chemistry.<ref>{{citation | first = Colby | last = Stong | title = People: Monsanto Scientist John E. Franz Wins 1990 Perkin Medal For Applied Chemistry | newspaper = The Scientist | year = 1990 | volume = 4 | issue = 10 | page = 28 | url = http://www.the-scientist.com/article/display/10101/}}.</ref> in 1990 for his discoveries.

=== 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<ref>[http://www.cdpr.ca.gov/docs/label/labelque.htm#regprods California Product/Label Database]</ref>: 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%)<ref>[http://www.wsdot.wa.gov/maintenance/pdf/glyphosate.pdf Glyphosate Roadside Vegetation Management Herbicide Fact Sheet]</ref>. These products may contain other ingredients, causing them to have different effects. For example, Roundup was found to have different effects to glyphosate alone.<ref name=Richard2005/> Roundup is a water based solution containing glyphosate, a [[surfactant]], and other substances.

==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 [[Catalysis|catalyzes]] the reaction of [[shikimate]]-3-phosphate (S3P) and [[phosphoenolpyruvate]] to form 5-enolpyruvyl-shikimate-3-phosphate (ESP). ESP is subsequently [[dephosphorylation|dephosphorylated]] to [[chorismate]], an essential precursor in plants for the [[Aromatic amino acids|aromatic]] [[amino acid]]s: [[phenylalanine]], [[tyrosine]] and [[tryptophan]].<ref>Purdue University, Department of Horticulture and Landscape Architecture, Metabolic Plant Physiology Lecture notes, Aromatic amino acid biosynthesis, The shikimate pathway - synthesis of chorismate.[http://www.hort.purdue.edu/rhodcv/hort640c/aromat/ar00007.htm]</ref><ref> Saccharomyces Genome Database - S. cerevisiae Pathway: chorismate biosynthesis [http://pathway.yeastgenome.org:8555/YEAST/NEW-IMAGE?type=PATHWAY&object=ARO-PWY]</ref> These amino acids are used as building blocks in [[peptide]]s, and to produce secondary metabolites such as [[folate]]s, [[ubiquinone]]s and [[naphthoquinones|naphthoquinone]]. X-ray crystallographic studies of Glyphosate and EPSPS show that glyphosate functions by occupying the binding site of the phosphoenol pyruvate, mimicking an intermediate state of the ternary enzyme substrates complex.<ref>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 [http://www.pnas.org/cgi/content/full/98/4/1376?ijkey=1b1ce735beee08811872889841023d179742ef2c]</ref> The [[shikimic acid|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<ref>(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.)</ref><ref>(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.)</ref> and also has been found to affect animal enzymes.<ref>(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.)</ref>

==Use==
[[File:Roundup-in-apple-orchard.jpg|thumb|right|Roundup used as an alternative to mowing in an apple orchard in Ciardes, Italy]]
Glyphosate is effective in killing a wide variety of plants, including [[grass]]es, [[broadleaf]], and [[woody]] plants.<ref name="greenpeace"/> It has a relatively small effect on some clover species<ref>[http://nerec.unl.edu/ipm/2007/ipm062007.htm Integrated Pest Management<!-- Bot generated title -->]</ref>. By volume, it is one of the most widely used herbicides.<ref name="epa tech">U.S. Environmental Protection Agency. (2006).  Technical Factsheet on: GLYPHOSATE [http://www.epa.gov/safewater/dwh/t-soc/glyphosa.html]</ref> It is commonly used for [[agriculture]], [[horticulture]], and [[silviculture]] purposes, as well as garden maintenance (including home use).<ref name="epa tech"/>

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 680g active ingredient per litre. The most common formulation in agriculture is 360g, either alone or with added cationic surfactants.

For 360g formulations, European regulations allow applications of up to 12 litres per hectare for control of perennial weeds such as [[Elytrigia repens|couch grass]]. More commonly, rates of 3 litres per hectare are practiced for control of annual weeds between crops<ref>[http://e-phy.agriculture.gouv.fr/ e-phy: Le catalogue des produits phytopharmaceutiques et de leurs usages des matières fertilisantes et des supports de culture homologués en France]</ref>.

===Genetically modified crops===
In 1996, genetically modified soybeans were made commercially available.<ref>[http://monsanto.com/monsanto/layout/about_us/timeline/default.asp Monsanto Company History - Monsanto Web Site - monsanto.com]</ref> 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 [[weed]]s since glyphosate could be sprayed on fields without hurting the crop. As of 2005, 87% of U.S. soybean fields were planted with glyphosate resistant varieties.<ref>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 [http://www.aphis.usda.gov/brs/aphisdocs/06_17801p_ea.pdf]</ref><ref>National Agriculture Statistics Service (2005) in Acreage eds. Johanns, M. & Wiyatt, S. D. 6 30, (U.S. Dept. of Agriculture, Washington, DC).</ref>

While the use of ''Roundup Ready'' crops may have increased the usage of herbicides measured in pounds applied per acre.<ref name="Benbrook">Charles Benbrook. [http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.41.823&rep=rep1&type=pdf Evidence of the Magnitude and Consequences of the Roundup Ready Soybean Yield Drag from University-Based Varietal Trials in 1998]. Ag BioTech InfoNet Technical Paper Number 1</ref>, 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.<ref>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</ref><ref>{{cite journal |author=Shipitalo MJ, Malone RW, Owens LB |title=Impact of glyphosate-tolerant soybean and glufosinate-tolerant corn production on herbicide losses in surface runoff |journal=[[J. Environ. Qual.]] |volume=37 |issue=2 |pages=401–8 |year=2008 |pmid=18268303 |doi=10.2134/jeq2006.0540 |url=}}</ref>

In 1999, a review of ''Roundup Ready'' soybean crops found that, compared to the top conventional varieties, they had a 6.7% lower yield  <ref name="Benbrook" />. This so called "yield drag" follows the same pattern observed when other traits are introduced into soybeans by conventional breeding <ref>Caviness, C.E., and H.J. Walters. 1971. Effect of phytophthora rot on yield and chemical composition of soybean seed. Crop Science 11:83-84</ref> and can not be attributed to the ''Roundup Ready'' trait or the GM nature of the crop since Monsanto have recently released ''Roundup Ready'' 2 Soybeans which yields 7-11% higher than RR version 1 <ref>Roundup Ready 2 Yield- Monsanto Web site http://www.monsanto.com/rr2y/</ref>. 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 organism|genetically modified crops]] was isolated from ''[[Agrobacterium]]'' strain CP4 (CP4 EPSPS) that was resistant to glyphosate.<ref>{{cite journal | title = Development and Characterization of a CP4 EPSPS-Based, Glyphosate-Tolerant Corn Event | author = G. R. Heck, ''et al.'' | journal = [[Crop Sci.]] | volume = 45 | pages = 329–339 | year = 2005 | url = http://crop.scijournals.org/cgi/content/full/45/1/329 | format = Free full text | issue = 1 | month = Jan | day = 01}}</ref><ref>{{cite journal | title = Molecular basis for the herbicide resistance of Roundup Ready crops | author = T. Funke ''et al.'' | journal = [[PNAS]] | year = 2006 | volume = 103 | pages = 13010–13015 | url = http://www.pnas.org/cgi/content/full/103/35/13010 | format = Free full text | doi = 10.1073/pnas.0603638103 | pmid = 16916934}}</ref> This CP4 EPSPS gene was [[Cloning#Molecular cloning|cloned]] and [[Transfection|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 (biochemistry)|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 [[Colombia]]n [[coca]] fields through [[Plan Colombia]].  Its health effects, effects on legal crops, and effectiveness in fighting the [[war on drugs]] have been widely disputed.<ref>[http://americas.irc-online.org/am/166 IRC Americas Program Commentary (2005): Plan Colombia’s Drug Eradication Program Misses the Mark]</ref> 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 [[selective breeding|selectively bred]] to be both "Roundup ready" and also larger and higher yielding than the original strains of the plant.<ref>[http://news.scotsman.com/latestnews/New-super-strain-of-coca.2559109.jp New Super Strain of Coca Plant Stuns Anti-Drug Officials. Jeremy McDermott. The Scotsman (Scotland) 27 August 2004]</ref> 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.

== Toxicity==

Glyphosate is less toxic than a number of other herbicides and pesticides, such as those from the [[organochlorine]] family.<ref>[http://whatcom.wsu.edu/ag/comhort/nooksack/ipmweb/Pesticideselection.html Raspberry IPM Manual -Pesticide Selection<!-- Bot generated title -->]</ref> Roundup has a [[United States Environmental Protection Agency‎]] (EPA) [[Toxicity Class]] of III for oral and inhalation exposure,<ref name="epa_reds">U.S. EPA ReRegistration Decision Fact Sheet for Glyphosate (EPA-738-F-93-011) 1993. [http://www.epa.gov/oppsrrd1/REDs/factsheets/0178fact.pdf]</ref> but more recent studies suggest that IV is appropriate for oral, dermal, and inhalation exposure.<ref name="wkc00"/> It has been rated as class I (Severe) for eye irritation, however.<ref name="wkc00"/>

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".<ref name="wkc00">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.</ref>  A recent study, on the other hand, has shown that 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 dependent on the nature of the [[adjuvant]]s used in the formulation.<ref name="human cells">{{cite journal|last=Benachour|first=Nora |coauthors=Gilles-Eric Séralini|date=December 23, 2008|title=Glyphosate Formulations Induce Apoptosis and Necrosis in Human Umbilical, Embryonic, and Placental Cells|journal=Chemical Research in Toxicology|url=http://pubs.acs.org/doi/abs/10.1021/tx800218n|doi=10.1021/tx800218n|volume=22|pages=97}}</ref> 

===Humans===

A review of the literature in 2000 concluded that "under present and expected conditions of new use", and based upon screening tests, there are no known toxic effects for Roundup herbicide to humans.<ref name="wkc00"/> This review considered the likely effects experienced by the two groups most likely to have high exposures, herbicide applicators and children aged 1–6, noting that the normal exposure in those sub-populations does not cause toxic effects.<ref name="wkc00"/> Glyphosate has a [[United States Environmental Protection Agency‎]] [[Toxicity Class]] of III in 1993,<ref name="epa_reds"/> but more recent studies suggest that IV is appropriate for oral, dermal, and inhalation exposure.<ref name="wkc00"/> It has been rated as class I (Severe) for eye irritation, however.<ref name="wkc00"/>  Glyphosate is being evaluated for effects to unborn fetuses and their development.  It is currently on the USEPA Endocrine Disrupter Screening list, published in 2007.<ref>USEPA Federal Register http://www.epa.gov/endo/pubs/draft_list_frn_061807.pdf</ref><ref>Accustandard, Chemical Reference Standards, http://www.accustandard.com/asi/np_endocrine_disruptors.php3</ref>

Outside its intended use, glyphosate can be lethal. For example, with intentional poisonings there is approximately a 10% mortality for those ingesting glyphosate, compared to 70% for those ingesting [[paraquat]].<ref name="Japan">{{cite journal |author=Nagami H, Nishigaki Y, Matsushima S, ''et al.'' |title=Hospital-based survey of pesticide poisoning in Japan, 1998--2002 |journal=[[Int J Occup Environ Health]] |volume=11 |issue=2 |pages=180–4 |year=2005 |pmid=15875894 |doi= |url=}}</ref> 

Laboratory toxicology studies suggest that other ingredients combined with glyphosate may have greater toxicity than glyphosate alone. For example, a study comparing glyphosate and [[Roundup]] found that Roundup had a greater effect on [[aromatase]] than glyphosate alone.<ref name=Richard2005>{{cite journal |author=Richard S, Moslemi S, Sipahutar H, Benachour N, Seralini GE |title=Differential effects of glyphosate and roundup on human placental cells and aromatase |journal=[[Environ. Health Perspect.]] | format = Free full text | volume=113 |issue=6 |pages=716–20 |year=2005 |month=June |pmid=15929894 |pmc=1257596 |doi= |url=http://ehpnet1.niehs.nih.gov/members/2005/7728/7728.html}}</ref>
 
Statistics from the [[California Environmental Protection Agency]]'s Pesticide Illness Surveillance Program indicate that glyphosate related incidents are one of the highest reported of all pesticides.<ref>G{{cite journal |author=Goldstein DA, Acquavella JF, Mannion RM, Farmer DR |title=An analysis of glyphosate data from the California Environmental Protection Agency Pesticide Illness Surveillance Program |journal=[[J. Toxicol. Clin. Toxicol.]] |volume=40 |issue=7 |pages=885–92 |year=2002 |pmid=12507058 |doi= 10.1081/CLT-120016960|url=}}</ref><ref name="EPA1996">California EPA 1996, California Pesticide Illness Serveillance Program Report HS-1733 [http://www.cdpr.ca.gov/docs/whs/pisp.htm]</ref> However, incident count does not take into account the number of people exposed and the severity of symptoms associated with each incident.<ref name="EPA1996"/> For example if hospitalization is 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.<ref name="EPA1996"/> 

Greenpeace states that the acute human toxicity of glyphosate is very low, but note that, as mentioned above, other added chemicals (particularly [[surfactants]], e.g. polyoxy-ethyleneamine, [[POEA]]) can be more toxic than glyphosate itself.<ref name="greenpeace"> ''Greenpeace''. (1997). [http://www.greenpeace.org/raw/content/usa/press/reports/weed-killing-crops-glyphosate.html Weed Killing Crops: Glyphosate and Your Food] [http://web.archive.org/web/20070312022520/http://www.greenpeace.org/raw/content/usa/press/reports/weed-killing-crops-glyphosate.html (archived)]</ref> Over-application, or application directly to the soil may impact earth worms.

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.<ref name=Giesy2000/> 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 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.<ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11237511&dopt=Abstract Effect of the herbicide glyphosate on enzymatic ac...[Environ Res. 2001&#93; - PubMed Result<!-- Bot generated title -->]</ref> Also in recent mammalian research, glyphosate has been found to interfere with an enzyme involved testosterone production in mouse cell culture<ref name="walsh">Walsh ''et al.'' Roundup inhibits steroidogenesis by disrupting steroidogenic acute regulatory (StAR) protein expression. Environ Health Perspect. 2000 108: 769–776.[http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=10964798]</ref> and to interfere with an estrogen biosynthesis enzyme in cultures of Human Placental cells.<ref name="Aromatase">Richard et al., Differential Effects of Glyphosate and Roundup on Human Placental Cells and Aromatase, Environmental Health Perspectives Vol. 113, No.6, 716-720[http://www.ehponline.org/members/2005/7728/7728.pdf] </ref>

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. <ref name="autogenerated1" />

===Other species===

The direct toxicity of ''pure'' glyphosate to [[mammals]] and [[birds]] is low.<ref>{{cite web |url=http://www.ipmofalaska.com/files/Glyphosate.html |title=pest control from ipmofalaska.com |work= |accessdate=}}</ref> {{Verify credibility|date=January 2009}} The acute oral toxicity of Roundup is > 5,000&nbsp;mg/kg in the rat.<ref>[http://www.monsanto.com/monsanto/ag_products/pdf/labels_msds/rounduppro_msds.pdf Roundup PRO Herbicide MSDS]</ref> 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.<ref>[http://extoxnet.orst.edu/pips/glyphosa.htm Extoxnet Pip - Glyphosate<!-- Bot generated title -->]</ref><ref>http://npic.orst.edu/factsheets/glyphogen.pdf</ref>

An ''in vitro'' study indicates that glyphosate formulations could harm [[earthworm]]s<ref>{{cite journal | author = JA Springett and RAJ Gray | title =  Effect of repeated low doses of biocides on the earthworm ''Aporrectodea caliginosa'' in laboratory culture | journal = [[Soil Biol and Biochem]] | volume = 24 | issue = 12 | pages = 1739–1744 | year = 1992 | doi =  10.1016/0038-0717(92)90180-6}}</ref> and beneficial [[insect]]s.<ref>{{cite journal | doi = 10.1007/BF02374636 | title = Results of the fifth joint pesticide testing programme carried out by the IOBC/WPRS-Working Group “Pesticides and beneficial organisms” | year = 1991 | author = Hassan, S. A. | journal = Entomophaga | volume = 36 | pages = 55}}</ref> However, the reported effect of glyphosate on earthworms has been criticized.<ref name=Giesy2000>JP Giesy, KR Solomon, S Dobson (2000). "Ecotoxicological Risk Assessment for Roundup Herbicide". Reviews of Environmental Contamination and Toxicology 167: 35-120</ref> 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.<ref>CM Preston and J.A. Trofymow. 1989. Effects of glyphosate (Roundup) on biological activity of forest soils. In: Proceedings of Carnation Creek Workshop, ed. P. Reynolds. Namaimo 7-10 December 1987. Forest Canada/British Columbia ministry of forests, 122-140.</ref> Glyphosate can negatively affect nitrogen-fixing bacteria,<ref>{{cite journal | title = Effects of glyphosate on nitrogen fixation of free-living heterotrophic bacteria
 | url = http://www3.interscience.wiley.com/journal/119834785/abstract | year = 1995 | journal = Letters in Applied Microbiology | pages = 349–352 | volume = 20
 | issue = 6 | accessdate = 2009-04-15 | author = Santos  A,  Flores M. | doi = 10.1111/j.1472-765X.1995.tb01318.x	}}</ref> and increase the susceptibility of plants to disease.<ref>{{cite journal | title =  Herbicide effects on plant disease | url = http://www.ppi-ppic.org/ppiweb/BRAZIL.NSF/3a773b217d047cd185256c24000746e8/30ad5d7475e1dc98032571f400712b22/$FILE/Herbicide%20Effects%20on%20Plant%20Disease.pdf | year = 2007 | journal = Outlooks Pest Manag | pages = 36–40 | volume = 18 | accessdate = 2009-04-15  | author = Duke SO et al. | doi =  10.1564/18feb13}}</ref> A 2005 study concluded that certain amphibians may be at risk from glyphosate use.<ref>Bette Hileman. (2005) Common herbicide kills tadpoles. Chemical & Engineering News. Washington 83(15):11.</ref>

Certain surfactants used in some glyphosate formulations have higher toxicity to [[fish]] and [[invertebrate]]s resulting in some formulations of glyphosate not being registered for use in aquatic applications.<ref>Response to "The impact of insecticides and herbicides on the biodiversity and productivity of aquatic communities", Monsanto Corporation Backgrounder [http://www.monsanto.com/monsanto/content/products/productivity/roundup/bkg_amphib_05a.pdf]</ref> Monsanto produces glyphosate products with alternative surfactants that are specifically formulated for aquatic use, for example "Biactive" and "AquaMaster".<ref>Aquatic Use of Glyphosate Herbicides in Australia, Monsanto Corporation Backgrounder[http://www.monsanto.com/monsanto/content/products/productivity/roundup/gly_austfrog_bkg.pdf]</ref> According to Monsanto, "Conservation groups have chosen glyphosate formulations because of their effectiveness against most weeds as glyphosate has very low toxicity to wildlife".<ref>[http://www.monsanto.com/monsanto/layout/VSearchResults.asp?queryText=conservation+groups+glyphosate] </ref> Glyphosate is used with five different salts but commercial formulations of it contain [[surfactant]]s, 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. <ref name="autogenerated1"> Review article at of glyphosate poisoning at Pubmed by Bradberry SM, Proudfoot AT, Vale JA. of the National Poisons Information Service (Birmingham Centre) and West Midlands Poisons Unit, City Hospital, Birmingham, UK.  http://www.ncbi.nlm.nih.gov/pubmed/15862083 </ref>

Glyphosate's effect on [[soil life]] may be limited because when glyphosate comes into contact with the soil, it rapidly binds to [[soil texture|soil particle]]s and is inactivated.<ref name="epa.gov">[http://www.epa.gov/oppsrrd1/REDs/old_reds/glyphosate.pdf US EPA Reregistration Eligibility Decision - Glyphosate]</ref><ref>{{cite journal | author = M.M. de Andréa, ''et al.'' | title = Influence of repeated applications of glyphosate on its persistence and soil bioactivity | journal = [[Pesq. Agropec. Bras.]] | volume = 38 | issue = 11 | pages = 1329–1335 | year = 2003 2003 | url = http://www.scielo.br/pdf/pab/v38n11/18929.pdf}}</ref> Unbound glyphosate is degraded by bacteria. Low activity because of binding to soil particles suggests that glyphosate's effects on [[soil flora]] are limited. Low glyphosate concentrations can be found in many creeks and rivers in U.S. and Europe.{{Fact|date=February 2007}}

The [[United States Environmental Protection Agency]],<ref name="epa.gov"/> 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.<ref>Peluso M, Munnia A, Bolognesi C, Parodi S.  Environ Mol Mutagen. 1998 31:55-9 PMID 9464316 </ref> The authors concluded that 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 [[pregnancy|pregnant]] [[rat]]s and their  [[fetus]]es.<ref>{{cite journal |author=Daruich J, Zirulnik F, Gimenez MS |title=Effect of the herbicide glyphosate on enzymatic activity in pregnant rats and their fetuses |journal=[[Environ. Res.]] |volume=85 |issue=3 |pages=226–31 |year=2001 |month=March |pmid=11237511 |doi=10.1006/enrs.2000.4229 |url=}}</ref>

=== Aquatic effects ===

[[Fish]] and aquatic [[invertebrates]] are more sensitive to Roundup than terrestrial organisms.<ref name=Giesy2000/> 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.<ref name="epa_reds"/><br>
The EU classifies Roundup as ''R51/53 Toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment.''<ref name="autogenerated3">http://lscgw1.monsanto.com/esh/msdslib.nsf/2B20DAEB04E8631C0625689700650B45/$file/Roundup%20Ultra%203000-5059en-gb.pdf  Roundup Material Safety Data sheet page 7, heading 16 </ref>

Roundup is not registered for aquatic uses<ref>Monsanto Backgrounder 2005 Response to "The impact of insecticides and herbicides on the biodiversity and productivity of aquatic communities" [http://www.monsanto.com/monsanto/content/products/productivity/roundup/bkg_amphib_05a.pdf]</ref> and studies of its effects on amphibians indicate it is toxic to them.<ref>Rick A. Relyea 2005 The impact of insecticides and herbicides on the biodiversity and productivity of aquatic communities Ecological Applications  15:618–627</ref> Other glyphosate formulations that are registered for aquatic use have been found to have negligible adverse effects on sensitive amphibians.<ref>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</ref>

===Endocrine disruptor debate===
''In vitro'' studies have shown glyphosate affects progesterone production in mammalian cells<ref>{{cite journal |author=Walsh LP, McCormick C, Martin C, Stocco DM |title=Roundup inhibits steroidogenesis by disrupting steroidogenic acute regulatory (StAR) protein expression |journal=[[Environ. Health Perspect.]] |volume=108 |issue=8 |pages=769–76 |year=2000 |month=August |pmid=10964798 |pmc=1638308 |doi= 10.2307/3434731|url=}}</ref> and can increase the mortality of placental cells.<ref name=Richard2005/> Whether these studies classify glyphosate as an [[endocrine disruptor]] is debated.

Some{{Who|date=June 2009}} 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 or may not impact an entire organism. Additionally, current ''in vitro'' studies expose cell lines to concentrations orders of magnitude greater than would be found in expected exposures, and through pathways that would not be typically experienced in real organisms.

Others{{Who|date=June 2009}} 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 endocrine effects of glyphospate is ongoing, including through the EPA endocrine screening program on 73 chemicals, published in 2007.

== Environmental degradation ==

When glyphosate comes into contact with the soil it can be rapidly bound to soil particles and be inactivated.<ref name="epa_reds">US EPA Reregistration Eligibility Decision - Glyphosate - (EPA-738-F-93-011) 1993 [http://www.epa.gov/oppsrrd1/REDs/old_reds/glyphosate.pdf]</ref> Unbound glyphosate can be degraded by bacteria.<ref>Balthazor, Terry M and Laurence Hallas (1986) Glyphosate-degrading microorganisms in industrial waste treatment biosystems. Appl. Environ. Microbiol. 51:432-34.[http://aem.asm.org/cgi/reprint/51/2/432.pdf]</ref> However, glyphosphate has been shown to increase the infection rate of wheat by fusarium head blight in fields that have been treated with glyphosphate. <ref name="autogenerated2"> [http://crop.scijournals.org/cgi/content/full/45/5/1908] "Crop Production Factors Associated with Fusarium Head Blight in Spring Wheat in Eastern Saskatchewan", published online 26 August 2005 by M. R. Fernandeza, F. Sellesa, D. Gehlb, R. M. DePauwa and R. P. Zentner. </ref>

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.<ref name=autogenerated6>[http://www.mindfully.org/Pesticide/Roundup-Glyphosate-Factsheet-Cox.htm Glyphosate Factsheet (part 1 of 2) Caroline Cox / Journal of Pesticide Reform v.108, n.3 Fall98 rev.Oct00<!-- Bot generated title -->]</ref> It appears that higher latitude sites have the longest soil persistences such as in Canada and Scandinavia. 

== 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.<ref>[http://www.weeds.iastate.edu/mgmt/2003/glyresistance.shtml ISU Weed Science Online - Are RR Weeds in Your Future II<!-- Bot generated title -->]</ref> 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.<ref name="autogenerated5">[http://southeastfarmpress.com/news/021006-Glyphosate-resistance/ Glyphosate resistance is a reality that should scare some cotton growers into changing the way they do business<!-- Bot generated title -->]</ref><ref name="autogenerated4">[http://www.newfarm.com/news/2004/0804/083104/weeds.shtml More glyphosate resistant weeds<!-- Bot generated title -->]</ref> Farmers associations are now reporting 103 biotypes of weeds within 63 weed species with herbicide resistance<ref name="autogenerated5" /><ref name="autogenerated4" />. This problem is likely to be exacerbated by the use of roundup-ready crops <ref>http://www.chem.purdue.edu/courses/chm333/Roundup%20Article.pdf</ref>.

== Legal cases ==
=== 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.<ref>[http://www.mindfully.org/Pesticide/Monsanto-v-AGNYnov96.htm 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<!-- Bot generated title -->]</ref> <br>
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. <ref>[http://www.organicconsumers.org/articles/article_4114.cfm Monsanto Fined in France for 'False' Herbicide Ads<!-- Bot generated title -->]</ref>

=== 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.<ref>(US EPA Communications and Public Affairs 1991 ''Note to correspondents'' Washington DC Mar 1)</ref><ref>(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)</ref><ref>(U.S. Congress. House of Representatives. Com. on Gov. Oper. 1984. ''Problems palgue the EPA pesticide registration activities''. House Report 98-1147)</ref> 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".<ref>(U.S. EPA 1978 Data validation. Memo from K LOcke, Toxicology Branch, to R Taylor, Registration Branch. Washington DC Aug 9)</ref><ref>(U.S. EPA Office of pesticides and Toxic Substances 1983, ''Summary of the IBT review program''. Washington D.C. July)</ref><ref>Schneider, K. 1983. Faking it: The case against Industrial Bio-Test Laboratories. The Amicus Journal (Spring):14-26. Reproduced at  [http://planetwaves.net/contents/faking_it.html Planetwaves] </ref>  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.<ref>(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) </ref><ref>(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)</ref> 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.<ref>Backgrounder: Testing Fraud: IBT and Craven Labs, June 2005, Monsanto background paper on RoundUp[http://www.monsanto.com/monsanto/content/products/productivity/roundup/ibt_craven_bkg.pdf]</ref>

==References==
 {{reflist|2}}
*EU (2002). [http://ec.europa.eu/food/fs/ph_ps/pro/eva/existing/list1_glyphosate_en.pdf Review report for the active substance glyphosate]. Retrieved October 28, 2005.
*{{cite journal | author=KR Solomon, DG Thompson |title=Ecological risk assessment for aquatic organisms from over-water uses of glyphosate | journal=Journal of Toxicology and Environmental Health | year=2003 | volume=6 | pages=289–324 |doi=10.1080/10937400306468}}
*[http://www.inchem.org/documents/ehc/ehc/ehc159.htm Environmental Health Criteria 159: Glyphosate.] [[World Health Organization]], (1994).  
*[http://www.monsanto.com/monsanto/content/products/productivity/roundup/back_history.pdf History of Glyphosate.] [[Monsanto Company]].

== Further reading ==
*Baccara, Mariagiovanna, et al. [http://pages.stern.nyu.edu/~lcabral/teaching/monsanto.pdf 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==
{{Commonscat|Glyphosates}}
*[http://npic.orst.edu/factsheets/glyphotech.pdf Glyphosate Technical Fact Sheet - National Pesticide Information Center]
*[http://npic.orst.edu/factsheets/glyphogen.pdf Glyphosate General Fact Sheet - National Pesticide Information Center]
*[http://extoxnet.orst.edu/pips/glyphosa.htm Glyphosate Pesticide Information Profile - Extension Toxicology Network]
*[http://www.epa.gov/oppsrrd1/REDs/factsheets/0178fact.pdf EPA Reregistration Eligibility Decision Fact Sheet]
*[http://www.monsanto.com/monsanto/layout/sci_tech/crop_chemicals/scipubs.asp Monsanto Website - Background Information about Glyphosate and Roundup]
*[http://news.bbc.co.uk/2/hi/americas/4627185.stm  US weighs costs of Plan Colombia]
*[http://ehp.niehs.nih.gov/members/2005/7728/7728.html Effect of Glyphosate on human placental cells in culture]
*[http://www.synbioc.ugent.be Website of the SynBioC research group, working on different types of aminophosphonates]
*[http://www.oznet.ksu.edu/library/crpsl2/mf2767.pdf Glyphosate Stewardship]
* [http://www.epa.gov/iris/subst/0057.htm EPA's Integrated Risk Information System entry for glyphosate]
* [http://www.epa.gov/safewater/dwh/c-soc/glyphosa.html EPA's ground & drinking water consumer factsheet for glyphosate]
* [http://www.pesticideinfo.org/Detail_Chemical.jsp?Rec_Id=PC33139 Chemical Identification and Use for Glyphosate, isopropylamine salt]

{{Herbicides}}

[[Category:Herbicides]]
[[Category:Carboxylic acids]]
[[Category:Amines]]
[[Category:Phosphonates]]

{{Imported from Wikipedia|name=Glyphosate|id=305570187}}