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→Other animals: remove content based on yet another Seralni study - this is PRIMARY and we don't give weight to health related content based on PRIMARY sources.. I missed this in the flurry of the last few days
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==== Human ====
==== Human ====

A 2000 review 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">{{cite journal | vauthors = Williams GM, Kroes R, Munro IC | title = Safety evaluation and risk assessment of the herbicide Roundup and its active ingredient, glyphosate, for humans | journal = Regulatory Toxicology and Pharmacology | volume = 31 | issue = 2 Pt 1 | pages = 117–65 | date = Apr 2000 | pmid = 10854122 | doi = 10.1006/rtph.1999.1371 }}</ref> A 2002 review by the European Union reached the same conclusion.<ref name="urlec.europa.eu">{{cite web | url = http://ec.europa.eu/food/fs/ph_ps/pro/eva/existing/list1_glyphosate_en.pdf | title = Review report for the active substance glyphosate | date = 2002-01-21 | format = | work = Commission working document | publisher = European Commission, Health and Protection Directorate-General: Directorate E – Food Safety: plant health, animal health and welfare, international questions: E1 - Plant Health }}</ref>


Data from the [[California Environmental Protection Agency]]'s Pesticide Illness Surveillance Program, which also tracks other agricultural chemicals, show glyphosate-related incidents are some of the most common.<ref name="pmid12507058">{{cite journal | vauthors = 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 = Journal of Toxicology. Clinical Toxicology | volume = 40 | issue = 7 | pages = 885–92 | year = 2002 | pmid = 12507058 | doi = 10.1081/CLT-120016960 }}</ref><ref name="EPA1996">{{cite web | url = http://www.cdpr.ca.gov/docs/whs/pisp.htm | title = Pesticide Illness Surveillance Program | year = 2010 | work = California Pesticide Illness Serveillance Program Report HS-1733 | publisher = California EPA }}</ref> However, incident counts alone do 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 were used as a measure of the severity of incidents, then glyphosate would be considered relatively safe; over a 13-year period in California, none of the 515 reported hospitalizations was attributed to glyphosate.<ref name="EPA1996"/>
Data from the [[California Environmental Protection Agency]]'s Pesticide Illness Surveillance Program, which also tracks other agricultural chemicals, show glyphosate-related incidents are some of the most common.<ref name="pmid12507058">{{cite journal | vauthors = 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 = Journal of Toxicology. Clinical Toxicology | volume = 40 | issue = 7 | pages = 885–92 | year = 2002 | pmid = 12507058 | doi = 10.1081/CLT-120016960 }}</ref><ref name="EPA1996">{{cite web | url = http://www.cdpr.ca.gov/docs/whs/pisp.htm | title = Pesticide Illness Surveillance Program | year = 2010 | work = California Pesticide Illness Serveillance Program Report HS-1733 | publisher = California EPA }}</ref> However, incident counts alone do 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 were used as a measure of the severity of incidents, then glyphosate would be considered relatively safe; over a 13-year period in California, none of the 515 reported hospitalizations was attributed to glyphosate.<ref name="EPA1996"/>

Revision as of 15:21, 30 August 2015

Not to be confused with glufosinate.
Glyphosate
Names
IUPAC name
N-(phosphonomethyl)glycine
Other names
2-[(phosphonomethyl)amino]acetic acid
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.012.726 Edit this at Wikidata
EC Number
  • 213-997-4
KEGG
RTECS number
  • MC1075000
UNII
  • InChI=1S/C3H8NO5P/c5-3(6)1-4-2-10(7,8)9/h4H,1-2H2,(H,5,6)(H2,7,8,9) checkY
    Key: XDDAORKBJWWYJS-UHFFFAOYSA-N checkY
  • InChI=1/C3H8NO5P/c5-3(6)1-4-2-10(7,8)9/h4H,1-2H2,(H,5,6)(H2,7,8,9)
    Key: XDDAORKBJWWYJS-UHFFFAOYAE
  • O=C(O)CNCP(=O)(O)O
Properties
C3H8NO5P
Molar mass 169.073 g·mol−1
Appearance white crystalline powder
Density 1.704 (20 °C)
Melting point 184.5 °C (364.1 °F; 457.6 K)
Boiling point decomposes at 187 °C (369 °F; 460 K)
1.01 g/100 mL (20 °C)
log P −2.8
Acidity (pKa) <2, 2.6, 5.6, 10.6
Hazards
GHS labelling:
Eye Dam. 1Aquatic Chronic 2
Danger
H318, H411
P273, P280, P305+P351+P338, P310, P501
Flash point Non-flammable
Safety data sheet (SDS) InChem MSDS
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Glyphosate (N-(phosphonomethyl)glycine) is a broad-spectrum systemic herbicide used to kill weeds, especially annual broadleaf weeds and grasses known to compete with commercial crops grown around the globe. It was discovered to be an herbicide by Monsanto chemist John E. Franz in 1970.[3] Monsanto brought it to market in the 1970s under the trade name Roundup and Monsanto's last commercially relevant United States patent expired in 2000.

Glyphosate was quickly adopted by farmers, even more so when Monsanto introduced glyphosate-resistant crops, enabling farmers to kill weeds without killing their crops. In 2007, glyphosate was the most used herbicide in the United States agricultural sector, with 180 to 185 million pounds (82,000 to 84,000 tonnes) applied, and the second-most used in home and garden market where users applied 5 to 8 million pounds (2,300 to 3,600 tonnes); in addition, industry, commerce, and government applied 13 to 15 million pounds (5,900 to 6,800 tonnes).[4]

With its heavy use in agriculture, weed resistance to glyphosate is a growing problem. While glyphosate and formulations such as Roundup have been approved by regulatory bodies worldwide and are widely used, concerns about their effects on humans and the environment persist.[5]

Glyphosate's mode of action as an herbicide is to inhibit a plant enzyme involved in the synthesis of the aromatic amino acids: tyrosine, tryptophan, and phenylalanine. It is absorbed through foliage, and minimally through roots,[6][7][8] and translocated to growing points. Because of this mode of action, it is only effective on actively growing plants; it is not effective as a pre-emergence herbicide. Some crops have been genetically engineered to be resistant to glyphosate (i.e., Roundup Ready, also created by Monsanto Company). Such crops allow farmers to use glyphosate as a postemergence herbicide against both broadleaf and cereal weeds, but the development of similar resistance in some weed species is emerging as a costly problem. Roundup Ready soybean was the first Roundup Ready crop.

Many regulatory and scholarly reviews have evaluated the relative toxicity of glyphosate as an herbicide. The German Federal Institute for Risk Assessment published a toxicology review in 2013, which found that "the available data is contradictory and far from being convincing" with regard to correlations between exposure to glyphosate formulations and risk of various cancers, including non-Hodgkin lymphoma (NHL).[9] A meta-analysis published in 2014 identified an increased risk of NHL in workers exposed to glyphosate formulations.[10] In March 2015 the World Health Organization's International Agency for Research on Cancer published a summary of its forthcoming monograph on glyphosate, and classified it as "probably carcinogenic in humans" (category 2A) based on epidemiological studies, animal studies, and in vitro studies.[5][11][12]

Discovery

Glyphosate was first synthesized in 1950 by Swiss chemist Henry Martin, who worked for the Swiss company Cilag. The work was never published.[13]: 1  Stauffer Chemical patented the agent as a chemical chelator in 1964 as it binds and removes minerals such as calcium, magnesium, manganese, copper and zinc.[14]

Somewhat later, glyphosate was independently discovered at Monsanto in 1970. Monsanto chemists had synthesized about 100 analogs of aminomethylphosphonic acid as potential water-softening agents. Two were found to have weak herbicidal activity, and John E. Franz, a chemist at Monsanto, was asked to try to make analogs with stronger herbicidal activity. Glyphosate was the third analog he made.[13]: 1–2 [15]

Glyphosate has been called by experts in herbicides "virtually ideal" due to its broad spectrum and low toxicity to animal life compared with other herbicides.[16][17][18][19] Franz received the National Medal of Technology in 1987[20] and the Perkin Medal for Applied Chemistry[21] in 1990 for his discoveries. Franz was inducted into the National Inventor's Hall of Fame in 2007.[22]

Chemistry

Glyphosate synthesis from chloroacetic acid

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

Glyphosate synthesis from dimethyl phosphite

The main deactivation path is hydrolysis to aminomethylphosphonic acid (AMPA).[23]

Biochemistry

Glyphosate kills plants and many bacteria by interfering with the synthesis of the aromatic 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 (EPSP).[24]

File:EPSPreactionII.tif

EPSP is subsequently dephosphorylated to chorismate, an essential precursor for the amino acids mentioned above.[25] 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.[26][27] Glyphosate inhibits the EPSPS enzymes of different species of plants and microbes at different rates.[28][29]

EPSPS is produced only by plants and micro-organisms; the gene coding for it is not in the mammalian genome.[30][31] Gut flora of some animals contain EPSPS.[32]

Glyphosate is absorbed through foliage and minimally through roots. Because of this mode of action, it is only effective on actively growing plants; it is not effective in preventing seeds from germinating.[7][8]

Environmental fate

Glyphosate adsorbs strongly to soil, and residues are expected to generally be immobile in soil. Ground and surface water pollution is limited. Glyphosate is readily degraded by soil microbes to aminomethylphosphonic acid (AMPA). Glyphosate and AMPA are not likely to move to ground water due to their strong adsorptive characteristics. Glyphosate does have the potential to contaminate surface waters due to its aquatic use patterns and through erosion, as it adsorbs to soil particles suspended in runoff. Limited leaching can also occur after high rainfall after application. If glyphosate reaches surface water, it is not broken down readily by water or sunlight.[33][34]

The half-life of glyphosate in soil ranges between 2 and 197 days; a typical field half-life of 47 days has been suggested. Soil and climate conditions affect glyphosate's persistence in soil. The median half-life of glyphosate in water varies from a few to 91 days.[7]

According to the National Pesticide Information Center fact sheet, glyphosate is not included in compounds tested for by the Food and Drug Administration's Pesticide Residue Monitoring Program, nor in the United States Department of Agriculture's Pesticide Data Program. However, a field test showed that lettuce, carrots, and barley contained glyphosate residues up to one year after the soil was treated with 3.71 lb of glyphosate per acre (4.15 kg per hectare).[7]

Use

Glyphosate used as an alternative to mowing in an apple orchard in Ciardes, Italy

Glyphosate is effective in killing a wide variety of plants, including grasses and broadleaf and woody plants. By volume, it is one of the most widely used herbicides.[7] It is commonly used for agriculture, horticulture, viticulture, and silviculture purposes, as well as garden maintenance (including home use).[7][35] It has a relatively small effect on some clover species and morning glory.[36]

In many cities, glyphosate is sprayed along the sidewalks and streets, as well as crevices in between pavement where weeds often grow. However, up to 24% of glyphosate applied to hard surfaces can be run off by water.[37] Glyphosate contamination of surface water is attributed to urban and agricultural use.[38] Glyphosate is used to clear railroad tracks and get rid of unwanted aquatic vegetation.[8] Since 1994, glyphosate has been used in aerial spraying in Colombia in coca eradication programs; Colombia announced in May 2015 that by October it would cease using glyphosate in these programs due to concerns about human toxicity of the chemical.[39]

In addition to its use as an herbicide, glyphosate is also used for crop desiccation (siccation) to increase harvest yield[8] and, as a result of desiccation, to increase sucrose concentration in sugarcane before harvest.[40]

Formulations and tradenames

Glyphosate is marketed in the United States and worldwide by many agrochemical companies, in different solution strengths and with various adjuvants, under dozens of tradenames.[41][42][43][44] As of 2010, there were more than 750 glyophosate products on the market.[45] In 2012, in terms of volume about half of the total global consumption of glyphosate was for conventional crops; Asia Pacific was the largest and fastest growing market.[46] Chinese manufacturers collectively are the world's largest producers of glyphosate and its precursors[47] and account for about 30% of global exports.[46] Key manufacturers include Anhui Huaxing Chemical Industry Compan], BASF, Bayer CropScience, Dow AgroSciences, DuPont, Jiangsu Good Harvest-Weien Agrochemical Company, Monsanto, Nantong Jiangshan Agrochemical & Chemicals Co., Nufarm Limited, SinoHarvest, Syngenta, and Zhejiang Xinan Chemical Industrial Group Company.[46]

Glyphosate is an acid molecule, so it is formulated as a salt for packaging and handling. Various salt formulations include isopropylamine, diammonium, monoammonium, or potassium as the counterion. Some brands include more than one salt. Some companies report their product as acid equivalent (ae) of glyphosate acid, or some report it as active ingredient (ai) of glyphosate plus the salt, and others report both. To compare performance of different formulations, knowledge of how the products were formulated is needed. Since the salt does not contribute to weed control and different salts have different weights, the acid equivalent is a more accurate method of expressing and comparing concentrations.[48] Adjuvant loading refers to the amount of adjuvant[49][50] already added to the glyphosate product. Fully loaded products contain all the necessary adjuvants, including surfactant; some contain no adjuvant system, while other products contain only a limited amount of adjuvant (minimal or partial loading) and additional surfactants must be added to the spray tank before application.[48] As of 2000 (just before Monsanto's patent on glyphosate expired), over 400 commercial adjuvants from over 34 different companies were available for use in commercial agriculture.[51][52]

Products are supplied most commonly in formulations of 120, 240, 360, 480, and 680 g/l of active ingredient. The most common formulation in agriculture is 360 g/l, either alone or with added cationic surfactants.[42]

For 360 g/l formulations, European regulations allow applications of up to 12 l/ha for control of perennial weeds such as couch grass. More commonly, rates of 3 l/ha are practiced for control of annual weeds between crops.[53]

Monsanto

Monsanto's Roundup is the earliest formulation of glyphosate.

Monsanto developed and patented the use of glyphosate to kill weeds in the 1970s, and has marketed it as Roundup since 1973. It retained exclusive rights in the United States until its patent expired in September, 2000.

As of 2009, sales of these herbicide products represented about 10% of Monsanto's revenue due to competition from other producers of other glyphosate-based herbicides;[54] their Roundup products (which include GM seeds) represented about half of Monsanto's gross margin.[55]

The active ingredient of the Monsanto herbicides is the isopropylamine salt of glyphosate. Another important ingredient in some formulations is the surfactant polyethoxylated tallow amine.

Monsanto also produces seeds which grow into plants genetically engineered to be tolerant to glyphosate. The genes contained in these seeds are patented. Such crops allow farmers to use glyphosate as a postemergence herbicide against most broadleaf and cereal weeds. Soy was the first glyphosate-resistant crop.

Toxicity

Glyphosate is the active ingredient in herbicide formulations containing it. However, in addition to glyphosate salts, commercial formulations of glyphosate contain additives such as surfactants which vary in nature and concentration. Laboratory toxicology studies have suggested that other ingredients in combination with glyphosate may have greater toxicity than glyphosate alone.[56] Toxicologists have studied glyphosate alone, additives alone, and formulations.

Glyphosate toxicity

Fish and amphibians

Glyphosate is generally less persistent in water than in soil, with 12- to 60-day persistence observed in Canadian pond water, yet because glyphosate binds to soil, persistence of over a year has been observed in the sediments of ponds in Michigan and Oregon.[33] In streams, maximum glyphosate concentrations were measured immediately after treatment and dissipated rapidly.[33] According to research done in the late 1980s and early 1990 (Ecotoxicological Risk Assessment for Roundup Herbicide), glyphosate in ecological exposures studied is "practically nontoxic to slightly toxic" for amphibians and fish.[57]

In a 2013 review, mixed results were observed in nonmammalian systems. Glyphosate and GBFs tend to elicit DNA damage effects at high or toxic dose levels, but the data suggest this is due to cytotoxicity rather than genotoxicity. GBF activity is perhaps associated with the associated surfactants.[58]

Human toxicity

Human acute toxicity is dose-related. Acute fatal toxicity has been reported in deliberate overdose.[56][59] Early epidemiological studies did not find associations between long-term low-level exposure to glyphosate and any disease.[60][61][62] In 2013 the European commission reviewed a 2002 finding that had concluded equivocal evidence existed of a relationship between glyphosate exposure during pregnancy and cardiovascular malformations and found the evidence "fails to support a potential risk for increased cardiovascular defects as a result of glyphosate exposure during pregnancy."[63] A 2013 review found that neither glyphosate nor typical glyphosate-based formulations (GBFs) pose a genotoxicity risk in humans under normal conditions of human or environmental exposures.[58]

Soil biota

Degradation pathway of glyphosate in the ground[57]

When glyphosate comes into contact with the soil, it can be bound to soil particles, thereby slowing its degradation.[33][64] Unbound glyphosate can be degraded by bacteria.[65] Glyphosate and its degradation product, AMPA, residues are considered to be much more toxicologically and environmentally benign than most of the herbicides replaced by glyphosate.[66]

In soils, half-lives vary from as little as three days at a site in Texas to 141 days at a site in Iowa.[64] In addition, the glyphosate metabolite AMPA has been found in Swedish forest soils up to two years after a glyphosate application. In this case, the persistence of AMPA was attributed to the soil being frozen for most of the year.[67] Glyphosate adsorption to soil, and later release from soil, varies depending on the kind of soil.[68][69] A 2009 study using a RoundUp formulation concluded absorption into plants delays subsequent soil degradation and can increase glyphosate persistence in soil from two to six times.[70]

Laboratory studies published in 1991 and 1992 indicated GBFs could harm beneficial insects[71] and earthworms.[72] However, the reported effect of glyphosate on earthworms has been criticized.[57] 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 kg/ha of active ingredient.[73]

Glyphosate can harm the bacterial ecology of soil and cause micronutrient deficiencies in plants.[74] Other studies found that while "recommended dosages of glyphosate did not affect growth rates", much higher dosages reduced respiration in nitrogen-fixing bacteria.[75][76]

Government and Organization Positions on Glyphosate Toxicity

European Food Safety Authority position

A 2013 systematic review by the German Institute for Risk Assessment (BfR), conducted as part of the EFSA's review process, examined epidemiological studies, animal studies, and in vitro studies that it found valid, and found that "no classification and labelling for carcinogenicity is warranted" and did not recommend a carcinogen classification of either 1A or 1B.[9]: Volume 1, p139, see also 34–37  It was provided to the EFSA in January 2014 and published by the EFSA in December 2014[9][77][78]

US Environmental Protection Agency position

The EPA, which last reviewed glyphosate in 1993, considers glyphosate to be noncarcinogenic and relatively low in dermal and oral acute toxicity.[33] The EPA considered a "worst case" dietary risk model of an individual eating a lifetime of food derived entirely from glyphosate-sprayed fields with residues at their maximum levels. This model indicated that no adverse health effects would be expected under such conditions.[33] As of March 2015, the EPA was in the midst of reviewing glyphosate's toxicity.[5]

World Health Organization position

In March 2015, the International Agency for Research on Cancer published a summary of their forthcoming monograph on glyphosate, and classified glyphosate as "probably carcinogenic in humans" (category 2A) based on epidemiological studies, animal studies, and in vitro studies; it noted that there was "limited evidence" of carcinogenicity in humans for non-Hodgkin lymphoma.[5][11][12][79] The German Institute for Risk Assessment responded that the work group reviewed only a selection of what they had reviewed earlier, and argued that other studies, among them the widely-cited cohort study Agricultural Health Study, do not support the classification.[80] The IARC report did not include the German regulatory study published in December 2014, nor did it include industry-funded studies. The IARC also does not conduct risk assessment; their goal is to classify carcinogenic potential, and "a few positive findings can be enough to declare a hazard, even if there are negative studies as well."[81]

Additive toxicity

Glyphosate formulations may contain a number of adjuvants, the identity of which is considered a trade secret and not disclosed by government regulators. In the United States, the Federal Insecticide, Fungicide, and Rodenticide Act requires that all pesticides (including herbicides) be evaluated by the EPA prior to sale, including product’s chemistry, environmental fate, residue chemistry, dietary and nondietary hazards to humans, and hazards to domestic animals and nontarget organisms[82] These evaluations are performed for each active ingredient, each inert ingredient, and for the final product formulation. Additional evaluations are performed by the FDA to set permitted residue levels in food for pesticide products used on food crops.[83]

Surfactants

Surfactants are used in herbicide formulations as wetting agents, to maximize coverage and aid penetration of the herbicide(s) through plant leaves. As agricultural spray adjuvants, surfactants may be premixed in commercial formulations, such as Roundup, or they may be purchased separately and mixed on-site (tank mix).

Polyethoxylated tallow amine (POEA) is a surfactant used in the original Roundup formulation and is still commonly used today.[84] Different versions of Roundup have included different percentages of POEA. Although Monsanto product fact sheets do not disclose surfactants and their percentages, a 1997 US government report said that Roundup is 15% POEA while Roundup Pro is 14.5%.[85]

A review of the literature provided to the EPA in 1997 found that POEA was more toxic to fish than glyphosate was.[85]

Spreader 90 is a surfactant used in tank mixes.[89] Spreader 90 contains 1,2 propanediol (also known as propylene glycol), propane 1,2,3 triol (also known as glycerol), alcohol ethoxylate, and dimethylpolysiloxane.[90][91] Of these ingredients, alcohol ethoxylates are among the widely used detergents in consumer products; commercial preparations are often mixes of homologs. Due to known toxicities to aquatic species, the Canadian Environmental Protection Act, 1999 recommended Federal Water Quality Guideline values of 70 µg/l.[92]

Formulation toxicity

Human

Data from the California Environmental Protection Agency's Pesticide Illness Surveillance Program, which also tracks other agricultural chemicals, show glyphosate-related incidents are some of the most common.[93][94] However, incident counts alone do not take into account the number of people exposed and the severity of symptoms associated with each incident.[94] For example, if hospitalization were used as a measure of the severity of incidents, then glyphosate would be considered relatively safe; over a 13-year period in California, none of the 515 reported hospitalizations was attributed to glyphosate.[94]

Dermal exposure to ready-to-use glyphosate formulations can cause irritation, and photocontact dermatitis has been occasionally reported. These effects are probably due to the preservative benzisothiazolin-3-one. Severe skin burns are very rare.[56] Inhalation is a minor route of exposure, but spray mist may cause oral or nasal discomfort, an unpleasant taste in the mouth, or tingling and irritation in the throat. Eye exposure may lead to mild conjunctivitis. Superficial corneal injury is possible if irrigation is delayed or inadequate.[56]

Deliberate ingestion of Roundup in quantities ranging from 85 to 200 ml (of 41% solution) has resulted in death within hours of ingestion, although it has also been ingested in quantities as large as 500 ml with only mild or moderate symptoms.[95] A reasonable correlation is seen between the amount of Roundup ingested and the likelihood of serious systemic sequelae or death. Ingestion of more than 85 ml of the concentrated formulation is likely to cause significant toxicity in adults. Corrosive effects – 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 edema, infiltration on chest X-ray, shock, arrhythmias, renal failure requiring haemodialysis, metabolic acidosis, and hyperkalaemia may occur in severe cases. Bradycardia and ventricular arrhythmias often present prior to death.

A 2012 meta-analysis of all epidemiological studies of exposure to glyphosate formulations found no correlation with any kind of cancer.[61] The 2013 systematic review by the German Institute for Risk Assessment of epidemiological studies of workers who use pesticides, exposed to glyphosate formulations found no significant risk, stating that "the available data is contradictory and far from being convincing".[9]: Volume 1, p64-66  However, a 2014 meta-analysis of the same studies found a correlation between occupational exposure to glyphosate formulations and increased risk of B cell lymphoma, the most common kind of non-Hodgkin lymphoma (NHL). Workers exposed to glyphosate were about twice as likely to get B cell lymphoma.[10] Overall, around 2% of adults (including workers) are diagnosed with NHL at some point during their lifetime.[96]

Endocrine disruption

In a study of rats and mice fed diets of containing 0%, 0.3125%, 0.625%, 1.25%, 2.5%, or 5.0% glyphosate for 13 weeks, endocrine effects were observed only in rats and only at the two highest doses. Male rats at the highest dose exhibited reductions in sperm concentrations that remained within the strain's normal range. Female rats in the highest dose group experienced a slight increase in the length of the estrous cycle.[7]

Administering Roundup Transorb orally to prepubescent rats once a day for 30 days reduced testosterone production and affected testicle morphology, but did not affect levels of estradiol and corticosterone.[97]

In 2007, the EPA selected glyphosate for further screening through its Endocrine Disruptor Screening Program (EDSP). Selection for this program is based on a compound's prevalence of use and does not imply particular suspicion of endocrine activity.[98] On June 29, 2015 the EPA released Weight of Evidence Conclusion of the EDSP Tier 1 screening for glyphosate, recommending that glyphosate not be considered for Tier 2 testing. The Weight of Evidence conclusion stated "...there was no convincing evidence of potential interaction with the estrogen, androgen or thyroid pathways."[99]

Genetic damage

Several studies have not found mutagenic effects,[100] so glyphosate has not been listed in the United States Environmental Protection Agency or the International Agency for Research on Cancer databases.[101] Various other studies suggest glyphosate may be mutagenic.[101]

Other animals

A review of the ecotoxicological data on Roundup shows at least 58 studies of the effects of Roundup itself on a range of organisms exist.[57] This review concluded, "for terrestrial uses of Roundup minimal acute and chronic risk was predicted for potentially exposed non-target organisms".

In reproductive toxicity studies performed in rats and rabbits, no adverse maternal or offspring effects were seen at doses below 175–293 mg/kg of body weight per day.[7]

Monsanto and other companies produce glyphosate products with alternative surfactants specifically formulated for aquatic use, for example the Monsanto products "Biactive" and "AquaMaster".[102][103] In 2001, the Monsanto product Vision® was studied in a forest wetlands site in Canada. Substantial mortality occurred only at concentrations exceeding the expected environmental concentrations as calculated by Canadian regulatory authorities. While it was found that site factors such as pH and suspended sediments substantially affected the toxicity in the amphibian larvae tested, overall, "results suggest that the silvicultural use of Vision herbicide in accordance with the product label and standard Canadian environmental regulations should have negligible adverse effects on sensitive larval life stages of native amphibians."[104]


A 2003 study of various formulations of glyphosate found, "[the] risk assessments based on estimated and measured concentrations of glyphosate that would result from its use for the control of undesirable plants in wetlands and over-water situations showed that the risk to aquatic organisms is negligible or small at application rates less than 4 kg/ha and only slightly greater at application rates of 8 kg/ha.".[105] A 2013 meta-analysis also reviewed the available data related to potential impacts of glyphosate-based herbicides on amphibians. According to the authors, the use of glyphosate-based pesticides cannot be considered the major cause of amphibian decline, the bulk of which occurred prior to the widespread use of glyphosate or in pristine tropical areas with minimal glyphosate exposure. The authors recommended further study of species- and development-stage chronic toxicity, of environmental glyphosate levels, and ongoing analysis of data relevant to determining what if any role glyphosate might be playing in worldwide amphibian decline, and suggest including amphibians in standardized test batteries.[106]

Glyphosate formulations are much more toxic for amphibians and fish than glyphosate alone.[85] Glyphosate formulations may contain a number of so-called ‘inert’ ingredients or adjuvants, most of which are not publicly known as in many countries the law does not require that they be revealed.[107]

A study published in 2010 proposed commercial glyphosate can cause neural defects and craniofacial malformations in African clawed frogs (Xenopus laevis). The experiments used frog embryos that were incubated with 1:5000 dilutions of a commercial glyphosate solution. The frog embryos suffered diminution of body size, alterations of brain morphology, reduction of the eyes, alterations of the branchial arches and otic placodes, alterations of the neural plate, and other abnormalities of the nervous system. The authors suggested glyphosate itself was responsible for the observed results because injection of pure glyphosate produced similar results in a chicken model.[108]

Effect on plant health

A correlation was found between an increase in the infection rate of wheat by Fusarium head blight and the application of glyphosate, but "because of the nature of this study, we could not determine if the association between previous GF (glyphosate formulation) use and FHB development was a cause-effect relationship".[109] Other studies have found causal relationships between glyphosate and decreased disease resistance.[110] Exposure to glyphosate has been shown to change the species composition of endophytic bacteria in plant hosts, which is highly variable.[111]

Weed resistance

Resistance evolves after a weed population has been subjected to intense selection pressure in the form of repeated use of a single herbicide.[112][113] Weeds resistant to the herbicide have been called 'superweeds'.[114] The first documented cases of weed resistance to glyphosate were found in Australia in 1996, involving rigid ryegrass (Lolium rigidum) near Orange, New South Wales.[115][116][117] In 2006, farmers associations were reporting 107 biotypes of weeds within 63 weed species with herbicide resistance.[118] In 2009, Canada identified its first resistant weed, giant ragweed, and at that time 15 weed species had been confirmed as resistant to glyphosate.[112][119] As of 2010, in the United States 7 to 10 million acres (28,000 to 40,000 km2) of soil were afflicted by superweeds, or about 5% of the 170 million acres planted with corn, soybeans, and cotton, the crops most affected, in 22 states.[120] In 2012, Charles Benbrook reported that the Weed Science Society of America listed 22 super weeds in the U.S., with over 5.7 million has (14 million ac) infested by GR weeds and that Dow AgroSciences had carried out a survey and reported a figure of around 40 million ha (100 million ac).[121] As of 2014, the International Survey of Herbicide Resistant Weeds database listed 211 weeds that were resistant to glyphosate.[122]

In response to resistant weeds, farmers are hand-weeding, using tractors to turn over soil between crops, and using other herbicides in addition to glyphosate.

Palmer amaranth

Amaranthus palmeri

In 2004, a glyphosate-resistant variation of Amaranthus palmeri, commonly known as Palmer amaranth, was found in Georgia and confirmed by a 2005 study.[123] In 2005, resistance was also found in North Carolina.[124] Widespread use of Roundup Ready crops led to an unprecedented selection pressure, and glyphosate resistance followed.[124] The weed variation is now widespread in the southeastern United States.[125] Cases have also been reported in Texas[125] and Virginia.[126]

Conyza

Conyza canadensis

Conyza bonariensis (also known as hairy fleabane and buva) and Conyza canadensis (known as horseweed or marestail), are other weed species that had lately developed glyphosate resistance.[127][128][129] A 2008 study on the current situation of glyphosate resistance in South America concluded "resistance evolution followed intense glyphosate use" and the use of glyphosate-resistant soybean crops is a factor encouraging increases in glyphosate use.[130] In the 2015 growing season, glyphosate-resistant marestail proved to be especially problematic to control in Nebraska production fields.[131]

Ryegrass

Ryegrass Lolium perenne

Glyphosate-resistant ryegrass (Lolium) has occurred in most of the Australian agricultural areas and other areas of the world. All cases of evolution of resistance to glyphosate in Australia were characterized by intensive use of the herbicide while no other effective weed control practices were used. Studies indicate the resistant ryegrass does not compete well against nonresistant plants and their numbers decrease when not grown under conditions of glyphosate application.[132]

Johnson grass

Glyphosate-resistant Johnson grass (Sorghum halepense) is found in glyphosate-resistant soybean cultivation in northern Argentina.[133]

Glyphosate was first approved for use in the 1970s, and as of 2010 was labelled for use in 130 countries.[13]: 2 

In September 2013 the legislative assembly of El Salvador approved legislation to ban 53 agrochemicals, including glyphosate; the ban on glyphosate was set to begin in 2015.[134][135][136]

In April 2014 the legislature of the Netherlands passed legislation prohibiting sale of glyphosate to individuals for use at home; commercial sales were not affected.[137]

In May 2015 the president of Sri Lanka banned the use and import of glyphosate, effective immediately.[138][139]

In May 2015, Bermuda blocked importation on all new orders of glyphosate-based herbicides for a temporary suspension awaiting outcomes of research.[140]

In May 2015, Colombia announced that it would stop using glyphosate by October 2015 in the destruction of illegal plantations of coca, the raw ingredient for cocaine. Farmers have complained that the aerial fumigation has destroyed entire fields of coffee and other legal produce.[141]

In June 2015, the French Ecology Minister asked nurseries and garden centers to sell glyphosate only from locked cabinets. This was only a request and all sales of glyphosate remained legal in France.[142]

Advertising controversy

The New York Times reported that in 1996, "Dennis C. Vacco, the Attorney General of New York, ordered the company Monsanto to pull ads that said Roundup was "safer than table salt" and "practically nontoxic" to mammals, birds and fish. The company withdrew the spots, but also said that the phrase in question was permissible under E.P.A. guidelines."[143]

In 2001, French environmental and consumer rights campaigners brought a case against Monsanto for misleading the public about the environmental impact of its herbicide Roundup, 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's advertising for Roundup had presented it as biodegradable and as leaving the soil clean after use. In 2007, Monsanto was convicted of false advertising and was fined 15,000 euros. Monsanto's French distributor Scotts France was also fined 15,000 euros. Both defendants were ordered to pay damages of 5,000 euros to the Brittany Water and Rivers Association and 3,000 euros to the CLCV (Consommation Logement Cadre de vie), one of the two main general consumer associations in France.[144] Monsanto appealed and the court upheld the verdict; Monsanto appealed again to the French Supreme Court, and in 2009 it also upheld the verdict.[145]

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.[146] The first incident involved Industrial Biotest Laboratories (IBT). The United States Justice Department closed the laboratory in 1978, and its leadership was found guilty in 1983 of charges of falsifying statements, falsifying scientific data submitted to the government, and mail fraud.[147]

In 1991, Don Craven, the owner of Craven Laboratories and three employees were indicted on 20 felony counts. Craven, along with fourteen employees were found guilty of similar crimes.[148]

Monsanto has stated the Craven Labs investigation was started by the EPA after a pesticide industry task force discovered irregularities, that the studies have been repeated, and that Roundup's EPA certification does not now use any studies from Craven Labs or IBT.[146]

Trade dumping allegations

United States companies have cited trade issues with glyphosate being dumped into the western world market areas by Chinese companies and a formal dispute was filed in 2010.[149][150]

Genetically modified crops

Main articles: Genetically modified crops, Genetically modified organism, Genetically modified food, and Genetically modified food controversies

Some micro-organisms have a version of 5-enolpyruvoyl-shikimate-3-phosphate synthetase (EPSPS) resistant to glyphosate inhibition. A version of the enzyme that both was resistant to glyphosate and that was still efficient enough to drive adequate plant growth was identified by Monsanto scientists after much trial and error in an Agrobacterium strain called CP4, which was found surviving in a waste-fed column at a glyphosate production facility.[151][152][153]: 56  This CP4 EPSPS gene was cloned and transfected into soybeans. In 1996, genetically modified soybeans were made commercially available.[154] Current glyphosate-resistant crops include soy, maize (corn), canola, alfalfa, and cotton, with wheat still under development.

Genetically modified crops have become the norm in the United States. For example, in 2010, 70% of all the corn, 78% of cotton, and 93% of all soybeans planted were herbicide-resistant.[155]

See also

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