Glyphosate
Encyclopedia
Glyphosate is a broad-spectrum systemic
Systemic disease
Life-threatening disease redirects here.A systemic disease is one that affects a number of organs and tissues, or affects the body as a whole. Although most medical conditions will eventually involve multiple organs in advanced stage Life-threatening disease redirects here.A systemic disease is one...

 herbicide
Herbicide
Herbicides, also commonly known as weedkillers, are pesticides used to kill unwanted plants. Selective herbicides kill specific targets while leaving the desired crop relatively unharmed. Some of these act by interfering with the growth of the weed and are often synthetic "imitations" of plant...

 used to kill weed
Weed
A weed in a general sense is a plant that is considered by the user of the term to be a nuisance, and normally applied to unwanted plants in human-controlled settings, especially farm fields and gardens, but also lawns, parks, woods, and other areas. More specifically, the term is often used to...

s, 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
Patent
A patent is a form of intellectual property. It consists of a set of exclusive rights granted by a sovereign state to an inventor or their assignee for a limited period of time in exchange for the public disclosure of an invention....

 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 (180000000 to 185000000 lb (81,646.6 to 83,914.6 t)) of glyphosate, the home and garden market used 5 to 8 million pounds (5000000 to 8000000 lb (2,268 to 3,628.7 t)), and industry, commerce and government used 13 to 15 million pounds (13000000 to 15000000 lb (5,896.7 to 6,803.9 t)), according to its Pesticide Industry Sales & Usage Report for 2006-2007 published in February, 2011. While glyphosate 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
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 involved in the synthesis of the aromatic amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

s: tyrosine
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...

, tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...

 and phenylalanine
Phenylalanine
Phenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...

. 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
Preemergent herbicides
Preemergent herbicides prevent the germination of seeds by inhibiting a key enzyme. In some areas of the world, preemergent herbicides are used to prevent crabgrass from appearing in summer lawns.-Brands:-Crabgrass:...

.

Some crops have been genetically engineered
Genetic engineering
Genetic engineering, also called genetic modification, is the direct human manipulation of an organism's genome using modern DNA technology. It involves the introduction of foreign DNA or synthetic genes into the organism of interest...

 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
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...

, and the name is a contraction of gly(cine)
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...

phos(phon)ate
Phosphonate
Phosphonates or phosphonic acids are organic compounds containing C-PO2 or C-PO2 groups . Bisphosphonates were first synthesized in 1897 by Von Baeyer and Hofmann. An example of such a bisphosphonate is HEDP . Since the work of Schwarzenbach in 1949, phosphonic acids are known as effective...

. The molecule has several dissociable hydrogens, especially the first hydrogen of the phosphate group. The molecule tends to exist as a zwitterion
Zwitterion
In chemistry, a zwitterion is a neutral molecule with a positive and a negative electrical charge at different locations within that molecule. Zwitterions are sometimes also called inner salts.-Examples:...

 where a phosphonic hydrogen dissociates and joins the amine group. Glyphosate is soluble in water to 12 g/L at room temperature.

Main deactivation path is hydrolysis to aminomethylphosphonic acid, also known as AMPA.

Glyphosate was first discovered to have herbicidal activity in 1970 by John E. Franz
John E. Franz
John E. Franz is an organic chemist who discovered the herbicide glyphosate while working at Monsanto Company in 1970. The chemical became the active ingredient in Roundup, a broad-spectrum, post-emergence herbicide...

, while working for Monsanto. Franz received the National Medal of Technology
National Medal of Technology
The National Medal of Technology and Innovation is an honor granted by the President of the United States to American inventors and innovators who have made significant contributions to the development of new and important technology...

 in 1987, and the Perkin Medal
Perkin Medal
The Perkin Medal is an award given annually by the American section of the Society of Chemical Industry to a scientist residing in America for an "innovation in applied chemistry resulting in outstanding commercial development." It is considered the highest honor given in the US industrial chemical...

 for Applied Chemistry 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: 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 herbicides are usually water-based solutions containing glyphosate, a surfactant
Surfactant
Surfactants are compounds that lower the surface tension of a liquid, the interfacial tension between two liquids, or that between a liquid and a solid...

, 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
Diquat
Diquat is a contact herbicide that produces desiccation and defoliation most often available as the dibromide, diquat dibromide. Brand names for this formulation include Aquacide, Dextrone, Preeglone, Deiquat, Detrone, Reglone, Reglon, Reglox, Ortho-Diquat and Weedtrine-D.Diquat is a non-selective...

, are available.

Biochemistry

Glyphosate kills plants by interfering with the synthesis of the amino acids phenylalanine
Phenylalanine
Phenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...

, tyrosine
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...

 and tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...

. It does this by inhibiting the enzyme 5-enolpyruvylshikimate-3-phosphate synthase
3-phosphoshikimate 1-carboxyvinyltransferase
In enzymology, a 3-phosphoshikimate 1-carboxyvinyltransferase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are phosphoenolpyruvate and 3-phosphoshikimate, whereas its two products are phosphate and 5-O--3-phosphoshikimate.The enzyme belongs to the family...

 (EPSPS), which catalyzes
Catalysis
Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....

 the reaction of shikimate-3-phosphate (S3P) and phosphoenolpyruvate
Phosphoenolpyruvate
Phosphoenolpyruvic acid , or phosphoenolpyruvate as the anion, is an important chemical compound in biochemistry. It has the high-energy phosphate bond found in living organisms, and is involved in glycolysis and gluconeogenesis...

 to form 5-enolpyruvyl-shikimate-3-phosphate (ESP). ESP is subsequently dephosphorylated
Dephosphorylation
Dephosphorylation is the essential process of removing phosphate groups from an organic compound by hydrolysis. Its opposite is phosphorylation...

 to chorismate, an essential precursor in plants for the aromatic
Aromatic amino acids
Aromatic amino acids are amino acids that include an aromatic ring.Examples include:* Among 20 standard amino acids: phenylalanine, tryptophan, and tyrosine* Others: thyroxine-See also:* Aromatic L-amino acid decarboxylase...

 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

s: phenylalanine
Phenylalanine
Phenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...

, tyrosine
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...

 and tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...

. These amino acids are used in protein synthesis 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
Shikimic acid
Shikimic acid, more commonly known as its anionic form shikimate, is an important biochemical metabolite in plants and microorganisms. Its name comes from the Japanese flower shikimi , from which it was first isolated....

 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 grass
Grass
Grasses, or more technically graminoids, are monocotyledonous, usually herbaceous plants with narrow leaves growing from the base. They include the "true grasses", of the Poaceae family, as well as the sedges and the rushes . The true grasses include cereals, bamboo and the grasses of lawns ...

es, broadleaf, and woody plant
Woody plant
A woody plant is a plant that uses wood as its structural tissue. These are typically perennial plants whose stems and larger roots are reinforced with wood produced adjacent to the vascular tissues. The main stem, larger branches, and roots of these plants are usually covered by a layer of...

s. 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
Agriculture
Agriculture is the cultivation of animals, plants, fungi and other life forms for food, fiber, and other products used to sustain life. Agriculture was the key implement in the rise of sedentary human civilization, whereby farming of domesticated species created food surpluses that nurtured the...

, horticulture
Horticulture
Horticulture is the industry and science of plant cultivation including the process of preparing soil for the planting of seeds, tubers, or cuttings. Horticulturists work and conduct research in the disciplines of plant propagation and cultivation, crop production, plant breeding and genetic...

, and silviculture
Silviculture
Silviculture is the practice of controlling the establishment, growth, composition, health, and quality of forests to meet diverse needs and values. The name comes from the Latin silvi- + culture...

 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
Maize
Maize known in many English-speaking countries as corn or mielie/mealie, is a grain domesticated by indigenous peoples in Mesoamerica in prehistoric times. The leafy stalk produces ears which contain seeds called kernels. Though technically a grain, maize kernels are used in cooking as a vegetable...

 (corn), sorghum
Sorghum
Sorghum is a genus of numerous species of grasses, one of which is raised for grain and many of which are used as fodder plants either cultivated or as part of pasture. The plants are cultivated in warmer climates worldwide. Species are native to tropical and subtropical regions of all continents...

, canola
Canola
Canola refers to a cultivar of either Rapeseed or Field Mustard . Its seeds are used to produce edible oil suitable for consumption by humans and livestock. The oil is also suitable for use as biodiesel.Originally, Canola was bred naturally from rapeseed in Canada by Keith Downey and Baldur R...

, alfalfa
Alfalfa
Alfalfa is a flowering plant in the pea family Fabaceae cultivated as an important forage crop in the US, Canada, Argentina, France, Australia, the Middle East, South Africa, and many other countries. It is known as lucerne in the UK, France, Australia, South Africa and New Zealand, and known as...

, and cotton
Cotton
Cotton is a soft, fluffy staple fiber that grows in a boll, or protective capsule, around the seeds of cotton plants of the genus Gossypium. The fiber is almost pure cellulose. The botanical purpose of cotton fiber is to aid in seed dispersal....

, with wheat
Wheat
Wheat is a cereal grain, originally from the Levant region of the Near East, but now cultivated worldwide. In 2007 world production of wheat was 607 million tons, making it the third most-produced cereal after maize and rice...

 still under development. These cultivars greatly improved conventional farmers' ability to control weed
Weed
A weed in a general sense is a plant that is considered by the user of the term to be a nuisance, and normally applied to unwanted plants in human-controlled settings, especially farm fields and gardens, but also lawns, parks, woods, and other areas. More specifically, the term is often used to...

s, 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
Atrazine
Atrazine, 2-chloro-4--6--s-triazine, an organic compound consisting of an s-triazine-ring is a widely used herbicide. Its use is controversial due to widespread contamination in drinking water and its associations with birth defects and menstrual problems when consumed by humans at concentrations...

, metribuzin, and alachlor
Alachlor
Alachlor is an herbicide from the chloroacetanilide family. Its mode of action is elongase inhibition, and inhibition of geranylgeranyl pyrophosphate cyclisation enzymes, part of the gibberellin pathway.-Uses:...

. 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
Genetically modified organism
A genetically modified organism or genetically engineered organism is an organism whose genetic material has been altered using genetic engineering techniques. These techniques, generally known as recombinant DNA technology, use DNA molecules from different sources, which are combined into one...

 was isolated from Agrobacterium
Agrobacterium
Agrobacterium is a genus of Gram-negative bacteria established by H. J. Conn that uses horizontal gene transfer to cause tumors in plants. Agrobacterium tumefaciens is the most commonly studied species in this genus...

strain CP4 (CP4 EPSPS) that was resistant to glyphosate. This CP4 EPSPS gene was cloned and transfected
Transfection
Transfection is the process of deliberately introducing nucleic acids into cells. The term is used notably for non-viral methods in eukaryotic cells...

 into soybeans. The CP4 EPSPS gene was engineered for plant expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...

 by fusing the 5' end of the gene to a chloroplast
Chloroplast
Chloroplasts are organelles found in plant cells and other eukaryotic organisms that conduct photosynthesis. Chloroplasts capture light energy to conserve free energy in the form of ATP and reduce NADP to NADPH through a complex set of processes called photosynthesis.Chloroplasts are green...

 transit peptide derived from the petunia
Petunia
Petunia is a widely cultivated genus of flowering plants of South American origin, closely related with tobacco, cape gooseberries, tomatoes, deadly nightshades, potatoes and chili peppers; in the family Solanaceae. The popular flower derived its name from French, which took the word petun, meaning...

 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
Plasmid
In microbiology and genetics, a plasmid is a DNA molecule that is separate from, and can replicate independently of, the chromosomal DNA. They are double-stranded and, in many cases, circular...

 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
GUS
GUS or Gus may refer to one of the following.Gus is a masculine name, or diminutive for Augustine, Augustus, Angus or August, and other names .*Gus Adams, American ice hockey player...

) from Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...

as a marker. The DNA was injected into the soybeans using the particle acceleration method
Gene gun
A gene gun or a biolistic particle delivery system, originally designed for plant transformation, is a device for injecting cells with genetic information. The payload is an elemental particle of a heavy metal coated with plasmid DNA...

. Soybean cultivar A54O3 was used for the transformation
Transformation (genetics)
In molecular biology transformation is the genetic alteration of a cell resulting from the direct uptake, incorporation and expression of exogenous genetic material from its surroundings and taken up through the cell membrane. Transformation occurs naturally in some species of bacteria, but it can...

. 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
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...

 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
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

 government to spray Colombia
Colombia
Colombia, officially the Republic of Colombia , is a unitary constitutional republic comprising thirty-two departments. The country is located in northwestern South America, bordered to the east by Venezuela and Brazil; to the south by Ecuador and Peru; to the north by the Caribbean Sea; to the...

n coca
Coca
Coca, Erythroxylum coca, is a plant in the family Erythroxylaceae, native to western South America. The plant plays a significant role in many traditional Andean cultures...

 fields through Plan Colombia
Plan Colombia
The term Plan Colombia is most often used to refer to U.S. legislation aimed at curbing drug smuggling and combating a left-wing insurgency by supporting different activities in Colombia....

. Its effects on legal crops and effectiveness in fighting the war on drugs
War on Drugs
The War on Drugs is a campaign of prohibition and foreign military aid and military intervention being undertaken by the United States government, with the assistance of participating countries, intended to both define and reduce the illegal drug trade...

 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
Boliviana negra
Also known as supercoca or la millionaria, Boliviana Negra is a relatively new form of coca that is resistant to herbicide Roundup, or the isopropylamine salt of glyphosate. The coca plant is the source of the addictive stimulant cocaine, one of the most widely consumed illegal drugs in the world...

, which have been selectively bred
Selective breeding
Selective breeding is the process of breeding plants and animals for particular genetic traits. Typically, strains that are selectively bred are domesticated, and the breeding is sometimes done by a professional breeder. Bred animals are known as breeds, while bred plants are known as varieties,...

 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
Toxicity Class
Toxicity Class refers to a classification system for pesticides that has been created by a national or international government-related or -sponsored organization...

 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
Aromatase
Aromatase is an enzyme responsible for a key step in the biosynthesis of estrogens. It is a member of the cytochrome P450 superfamily , which are monooxygenases that catalyze many reactions involved in steroidogenesis. In particular, aromatase is responsible for the aromatization of androgens into...

 than glyphosate alone. Another study has shown Roundup formulations and metabolic products cause the death of human embryonic, placental, and umbilical cells in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...

, even at low concentrations. The effects are not proportional to glyphosate concentrations, but are dependent on the nature of the adjuvant
Adjuvant
An adjuvant is a pharmacological or immunological agent that modifies the effect of other agents, such as a drug or vaccine, while having few if any direct effects when given by itself...

s 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
California Environmental Protection Agency
The California Environmental Protection Agency is a state cabinet-level agency within the government of California. Cal/EPA is composed of six departments, boards and offices responsible for environmental research, regulating and administering the state's environmental protection programs, and...

'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
California
California is a state located on the West Coast of the United States. It is by far the most populous U.S. state, and the third-largest by land area...

, 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 frog
African clawed frog
The African clawed frog is a species of South African aquatic frog of the genus Xenopus. Its name is derived from the three short claws on each hind foot, which it uses to tear apart its food...

s (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 placode
Otic placode
In embryology, the otic placode is a thickening of the ectoderm on the outer surface of a developing embryo from which the ear develops. The ear, including both the vestibular system and the auditory system, develops from the otic placode beginning the third week of development...

s, alterations of the neural plate
Neural plate
In human embryology, formation of neural plate is the first step of neurulation. It is created by a flat thickening opposite to the primitive streak of the ectoderm.-Development:...

, and other abnormalities of the nervous system
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...

. 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 earthworm
Earthworm
Earthworm is the common name for the largest members of Oligochaeta in the phylum Annelida. In classical systems they were placed in the order Opisthopora, on the basis of the male pores opening posterior to the female pores, even though the internal male segments are anterior to the female...

s and beneficial insect
Insect
Insects are a class of living creatures within the arthropods that have a chitinous exoskeleton, a three-part body , three pairs of jointed legs, compound eyes, and two antennae...

s. 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
Fish
Fish are a paraphyletic group of organisms that consist of all gill-bearing aquatic vertebrate animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish, as well as various extinct related groups...

 and invertebrate
Invertebrate
An invertebrate is an animal without a backbone. The group includes 97% of all animal species – all animals except those in the chordate subphylum Vertebrata .Invertebrates form a paraphyletic group...

s, 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 surfactant
Surfactant
Surfactants are compounds that lower the surface tension of a liquid, the interfacial tension between two liquids, or that between a liquid and a solid...

s, 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
Soil life
Soil life or soil biota is a collective term for all the organisms living within the soil.-Overview:In balanced soil, plants grow in an active and steady environment. The mineral content of the soil and its heartiful structure are important for their well-being, but it is the life in the earth that...

 may be limited, because when glyphosate comes into contact with the soil, it rapidly binds to soil particles
Soil texture
Soil texture is a qualitative classification tool used in both the field and laboratory to determine classes for agricultural soils based on their physical texture. The classes are distinguished in the field by the 'textural feel' which can be further clarified by separating the relative...

 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
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

 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
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...

 rat
Rat
Rats are various medium-sized, long-tailed rodents of the superfamily Muroidea. "True rats" are members of the genus Rattus, the most important of which to humans are the black rat, Rattus rattus, and the brown rat, Rattus norvegicus...

s and their fetus
Fetus
A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...

es.

Aquatic effects

Glyphosate is one of the pesticides that pose the greatest danger to amphibians. Fish
Fish
Fish are a paraphyletic group of organisms that consist of all gill-bearing aquatic vertebrate animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish, as well as various extinct related groups...

 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
Endocrine disruptor
Endocrine disruptors are chemicals that interfere with endocrine in animals, including humans. These disruptions can cause cancerous tumors, birth defects, and other developmental disorders...

 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.

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
Uterus
The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...

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.

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

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