Glyphosate

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ImageFile2 = Glyphosate-3D-balls.png IUPACName = [(phosphonomethyl)amino] acetic acid
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PubChem = 3496
SMILES = C(C(=O)O)NCP(=O)(O)O
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C = 3 | H = 8 | N = 1 | O = 5 | P = 1
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Glyphosate (N-(phosphonomethyl) glycine) is a non-selective systemic herbicide, absorbed through the leaves, injected into the bole, or applied to the stump of a tree, used to kill weeds, especially perennials and broadcast or used in the cut-stump treatment as a forestry herbicide. Some crops have been genetically engineered to be resistant to it. Glyphosate was first sold by Monsanto under the tradename Roundup, but is no longer under patent. It is now also available in other formulations, e.g. Resolva 24H, which contains glyphosate and diquat. [http://www.resolva-weeds.com/index.php Resolva Weeds]

Chemistry

Glyphosate is an aminophosphonic analogue of the natural amino acid glycine and the name is a contraction of "glycine", "phospho-", and "-ate". Glyphosate was first discovered to have herbicidal activity in 1970 by John E. Franz, while working for Monsanto. [cite journal | pmc = PMC33334 | doi = 10.1073/pnas.061025898 | title = Closing down on glyphosate inhibition---with a new structure for drug discovery | year = 2001 | author = Alibhai, M. F. | journal = Proceedings of the National Academy of Sciences | volume = 98 | pages = 2944 | pmid = 11248008] Franz received the National Medal of Technology in 1987 , [ [http://www.technology.gov/medal/Recipients.htm Technology Administration: National Medal of Technology RECIPIENTS] ] and the Perkin Medal for Applied Chemistry. ["People: Monsanto Scientist John E. Franz Wins 1990 Perkin Medal For Applied Chemistry", The Scientist 1990, 4(10):28 [http://www.the-scientist.com/article/display/10101/ John Franz's Perkin Medal] ] in 1990 for his discoveries.

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. [ [http://www.hort.purdue.edu/rhodcv/hort640c/aromat/ar00007.htm The shikimate pathway - synthesis of chorismate] ] [ [http://pathway.yeastgenome.org:8555/YEAST/NEW-IMAGE?type=PATHWAY&object=ARO-PWY 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. 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 [(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.)]

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 [ [http://nerec.unl.edu/ipm/2007/ipm062007.htm Integrated Pest Management ] ] . By volume, it is one of the most widely used herbicides.U.S. Environmental Protection Agency. (2006). Technical Factsheet on: GLYPHOSATE [http://www.epa.gov/safewater/dwh/t-soc/glyphosa.html] ] 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.

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 couch grass. More commonly, rates of 3 litres per hectare are practiced for control of annual weeds between crops [ [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] ] .

Genetically modified crops

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. [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] [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] This CP4 EPSPS gene was cloned and transfected into soybeans, and in 1996, genetically modified soybeans were made commercially available. [Monsanto Company History - Monsanto Web Site - monsanto.com [http://monsanto.com/monsanto/layout/about_us/timeline/default.asp] ] This greatly improved the ability to control weeds in soybean fields since glyphosate could be sprayed on fields without hurting the crop. As of 2005, 87% of U.S. soybean fields were planted with glyphosate resistant varieties. [USDA/APHIS Environmental Assessment - In response to Monsanto Petition 06-178-01p seeking a Determination of Non-regulated Status forRoundup 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] ] [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 such "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. [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=]

Other uses

Glyphosate is one of a number of herbicides used by the United States government to spray Colombian coca fields through Plan Colombia. Its health effects, effects on legal crops, and effectiveness in fighting the war on drugs have been widely disputed. [ [http://americas.irc-online.org/am/166 IRC Americas Program Commentary (2005): Plan Colombia’s Drug Eradication Program Misses the Mark] ]

Toxicity

Glyphosate is less toxic than a number of other herbicides and pesticides, such as those from the organochlorine family. [ [http://whatcom.wsu.edu/ag/comhort/nooksack/ipmweb/Pesticideselection.html Raspberry IPM Manual -Pesticide Selection ] ]

Humans

A review of the literature in 2000 concluded that "under present and expected conditions of new use, there is nopotential for Roundup herbicide to pose a health risk to humans".cite journal | author=GM Williams, R Kroes, JC Munro | title=Safety evaluation and risk assessment of the herbicide Roundup and its active ingredient, glyphosate, for humans | journal=Regulatory Toxicology and Pharmacology | year=2000 | volume=31-N2 | pages=117–165 | pmid = 10854122] 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 the exposure in those subpopulations was not a health concern. Glyphosate has an EPA Toxicity Class of III in 1993,U.S. EPA ReRegistration Decision Fact Sheet for Glyphosate (EPA-738-F-93-011) 1993. [http://www.epa.gov/oppsrrd1/REDs/factsheets/0178fact.pdf] ] 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.

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.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=]

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.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] Statistics from the Californian Environmental Protection Agencies Pesticide Illness Surveillance Program indicate that glyphosate related incidents are one of the highest reported of all pesticides. [Gcite 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= |url=] However, incident count does not take into account the number of people exposed and the severity of symptoms associated with each incident.California EPA 1996, California Pesticide Illness Serveillance Program Report HS-1733 [http://www.cdpr.ca.gov/docs/whs/pisp.htm] ] 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.

Greenpeace states that "the acute 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. "Greenpeace". (1997). Weed Killing Crops: Glyphosate and Your Food. [http://www.greenpeace.org/raw/content/usa/press/reports/weed-killing-crops-glyphosate.html] ]

Other species

The direct toxicity of "pure" glyphosate to mammals and birds is low. [cite web |url=http://www.ipmofalaska.com/files/Glyphosate.html |title=pest control from ipmofalaska.com |format= |work= |accessdate=] "In vitro" studies indicate glyphosate formulations could harm earthworms [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] and beneficial insects. [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] However, these 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. [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.]

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. [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] ] Monsanto produces glyphosate products with alternative surfactants that are specifically formulated for aquatic use, for example "Biactive" and "AquaMaster". [Aquatic Use of Glyphosate Herbicides in Australia, Monsanto Corporation Backgrounder [http://www.monsanto.com/monsanto/content/products/productivity/roundup/gly_austfrog_bkg.pdf] ] According to Monsanto, "Conservation groups have chosen glyphosate formulations because of their effectiveness against most weeds as glyphosate has very low toxicity to wildlife". [ [http://www.monsanto.com/monsanto/layout/VSearchResults.asp?queryText=conservation+groups+glyphosate] ]

When glyphosate comes into contact with the soil, it rapidly binds to soil particles and is inactivated. [US EPA Reregistration Eligibility Decision - Glyphosate [http://www.epa.gov/oppsrrd1/REDs/old_reds/glyphosate.pdf] ] [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] 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

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

Endocrine disruptor debate

"In vitro" studies have shown glyphosate affects progesterone production in mammalian cells [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= |url=] and can increase the mortality of placental cells. Whether these studies classify glyphosate as an endocrine disruptor is a matter of debate.

Some feel that "in vitro" studies are insufficient, and are waiting to see if animal studies show a change in endocrine activity, since a change in a single cell line may not occur in an entire organism. Additionally, current "in vitro" studies expose cell lines to concentrations orders of magnitude greater than would be found in real conditions, and through pathways that would not be experienced in real organism.

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

References

reflist
*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=JP Giesy, KR Solomon, S Dobson | title=Ecotoxicological Risk Assessment for Roundup Herbicide | journal=Reviews of Environmental Contamination and Toxicology | year=2000 | volume=167 | pages=35–120
*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.

External links

* [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]