Glyphosate-based herbicides are usually made of a glyphosate salt that is combined with other ingredients that are needed to stabilize the herbicide formula and allow penetration into plants. The glyphosate-based herbicide Roundup was first developed by Monsanto in the 1970s. It is used most heavily on corn, soy, and cotton crops that have been genetically modified to be resistant to the herbicide. Some products include two active ingredients, such as Enlist Duo which includes 2,4-D as well as glyphosate. As of 2010, more than 750 glyphosate products were on the market. The names of inert ingredients used in glyphosate formulations are usually not listed on the product labels.
Glyphosate and glyphosate-based herbicides have low acute toxicity in mammals. They likewise have not been shown to pose a significant risk to human health during normal use, although human deaths have been reported from deliberate ingestion of concentrated RoundUp. It is difficult to determine how much surfactants contribute to the overall toxicity of each formulation. Glyphosate formulations containing the surfactant polyethoxylated tallow amine (POEA) are sometimes used terrestrially, but are not approved for aquatic use in the US due to their toxicity to aquatic organisms.
The consensus among national pesticide regulatory agencies and scientific organizations is that there is no evidence that the active ingredient glyphosate is carcinogenic for humans. The EPA has classified glyphosate as a Group E chemical, meaning the agency has determined there is "evidence of non-carcinogenicity in humans". The International Agency for Research on Cancer (IARC) is the only agency that has classified glyphosate as "probably carcinogenic".
There have been multiple lawsuits against Monsanto asserting that exposure to glyphosate herbicides is carcinogenic and that the company did not adequately disclose the risk to consumers. In 2018 a California jury awarded $289 million in damages to a groundskeeper who argued that Monsanto failed to adequately warn consumers of cancer risks posed by the herbicides.
The glyphosate-based herbicide RoundUp (styled: Roundup) was first developed in the 1970s by Monsanto. Glyphosate-based herbicides were initially used in a similar way to paraquat and diquat, as non-selective herbicides. Attempts were made to apply them to row crops, but problems with crop damage kept glyphosate-based herbicides from being widely used for this purpose. In the USA, use of glyphosate experienced rapid growth following the commercial introduction of a glyphosate-resistant soybean in 1996. Between 1990 and 1996 sales of RoundUp increased around 20% per year. As of 2015[update] it is used in over 160 countries. RoundUp is used most heavily on corn, soy, and cotton crops that have been genetically modified to withstand the chemical, but since 2012 glyphosate was used in California to treat other crops like almond, peach, cantaloupe, onion, cherry, sweet corn, and citrus.
Bayer, which acquired Monsanto in 2018, is the largest producer of glyphosate-based herbicides, but formulations from other manufacturers are available that use different inert ingredients. Other glyphosate-based formulations include Bronco, Glifonox, KleenUp, Ranger Pro (styled: Ranger PRO), Rodeo, and Weedoff. Other manufacturers include Anhui Huaxing Chemical Industry Company, BASF, Dow AgroSciences, DuPont, Jiangsu Good Harvest-Weien Agrochemical Company, Nantong Jiangshan Agrochemical & Chemicals Co., Nufarm Limited, SinoHarvest, Syngenta, and Zhejiang Xinan Chemical Industrial Group Company. As of 2010, more than 750 glyphosate products were on the market.
Surfactants, solvents, and preservatives are inert ingredients, or adjuvants, that are commonly added to glyphosate-based herbicide formulations. Some products contain all the necessary adjuvants, including surfactant; some contain no adjuvant system, while other products contain only a limited amount of adjuvant. Some formulations require the addition of surfactants to the spray tank before application. The names of inert ingredients used in glyphosate formulations are usually not listed on the product labels.
Polyethoxylated tallow amine (POEA) is a surfactant added to Roundup and other herbicides as a wetting agent. POEA is not a single surfactant, but a complex mixture. The composition of each POEA surfactant is a proprietary trade secret. Monsanto's RoundUp, for example, contains a proprietary POEA surfactant called MON 0818 at a 15% concentration.
As part of the process to renew glyphosate's license under EU regulations, a 2013 systematic review by the German Federal Institute for Risk Assessment (Bfr) of epidemiological studies of workers exposed to glyphosate formulations found no significant risk,[vague] stating that "the available data are contradictory and far from being convincing". In 2015, as part of the ongoing renewal process, the European Food Safety Authority (EFSA) published a final risk assessment on 12 November 2015 stating that glyphosate met EU-level regulatory standards. Despite classifying glyphosate as non-carcinogenic, this report also acknowledged that some of the co-formulants added to glyphosate based pesticides "appeared to have toxic effects higher than the glyphosate itself", noting POEA in particular. The conclusion of the final EFSA assessment was that the active ingredient glyphosate met EU-level regulatory standards, but individual formulations would have to be evaluated by member states.
There was insufficient support among the Member States for a 2016 European Commission proposal to renew the approval of glyphosate. Because the 2015 EFSA and IARC assessments had reached contradictory conclusions regarding the potential carcinogenicity of glyphosate, the European Chemicals Agency (ECHA) was asked to assess the hazard properties of the substance. Though no majority of Member States voted either for or against the renewal proposal, in July 2016 they voted to amend the conditions of glyphosate's existing approval. The new conditions require Member States to minimize the pre-harvest use of glyphosate products, as well as use in certain public places. Formulations that include the surfactant POEA were banned. These conditions were later included in the implementing act for the 5-year renewal that was approved on 12 December 2017.
In 2014 the EPA approved Enlist Duo, which was developed by Dow AgroSciences. This herbicide combined two active ingredients: 2,4-D and glyphosate. Enlist Duo is intended for use with genetically modified crops that have also been developed by the Dow Chemical subsidiary. The initial approval was limited to the states of Illinois, Indiana, Iowa, Ohio, South Dakota, and Wisconsin. During the course of litigation in 2015, the EPA found out that Dow had told the United States Patent and Trademark Office that Enlist Duo offers "synergistic herbicidal weed control", and requested additional clarification about the "synergistic effects" and sought to reverse its approval pending a full review of the new information provided by Dow. In 2016, the 9th Circuit rejected the EPA's petition to vacate its approval of the herbicide.
Since some glyphosate herbicide formulations contain an inert ingredient that may be toxic to fish and amphibians, only formulation's labeled for aquatic use are recommended when water contamination is possible. Aquatic formulations using the isopropylamine salt of glyphosate include Glypro (also called Rodeo, Aquapro, and Accord Concentrate) and Shore-Klear. Refuge is also approved for aquatic applications; the active ingredient in this formulation is the potassium salt of glyphosate. There are a few aquatic formulations that already include a surfactant that are registered for aquatic applications including GlyphoMate41 and Shore-Klear Plus, but most aquatic formulations do not include surfactant. The composition of surfactants is proprietary and non-disclosed, but low-toxicity surfactants that are labeled for aquatic use are available.
On 10 August 2018, Dewayne Johnson, who has non-Hodgkin's lymphoma, was awarded $289 million in damages after a jury in San Francisco found that Monsanto had failed to adequately warn consumers of cancer risks posed by the herbicide, a decision the company plans on appealing. Johnson had routinely used two different glyphosate formulations in his work as a groundskeeper, RoundUp and another Monsanto product called Ranger Pro. The jury's verdict addressed the question of whether Monsanto knowingly failed to warn consumers that RoundUp could be harmful, but not whether RoundUp causes cancer. After the IARC classified glyphosate as "probably carcinogenic" in 2015, over 300 federal lawsuits have been filed that were consolidated into a multidistrict litigation called In re: RoundUp Products Liability.
The lethal dose of different glyphosate-based formulations varies, especially with respect to the surfactants used. Formulations intended for terrestrial use that include the surfactant polyethoxylated tallow amine (POEA) can be more toxic than other formulations for aquatic species. Due to the variety in available formulations, including five different glyphosate salts and different combinations of inert ingredients, it is difficult to determine how much surfactants contribute to the overall toxicity of each formulation. Independent scientific reviews and regulatory agencies have regularly concluded that glyphosate-based herbicides do not lead to a significant risk for human or environmental health when the product label is properly followed.
The acute oral toxicity for mammals is low, but death has been reported after deliberate overdose of concentrated formulations. The surfactants in glyphosate formulations can increase the relative acute toxicity of the formulation. Surfactants generally do not, however, cause synergistic effects (as opposed to additive effects) that increase the acute toxicity of glyphosate within a formulation. The surfactant POEA is not considered an acute toxicity hazard, and has an oral toxicity similar to vitamin A and less toxic than asprin. Deliberate ingestion of Roundup 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. Consumption of over 85 ml of concentrated product is likely to cause serious symptoms in adults, including burns due to corrosive effects as well as kidney and liver damage. More severe cases lead to "respiratory distress, impaired consciousness, pulmonary edema, infiltration on chest X-ray, shock, arrhythmias, renal failure requiring haemodialysis, metabolic acidosis, and hyperkalaemia" and death is often preceded by bradycardia and ventricular arrhythmias.
Skin exposure to ready-to-use concentrated 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. In a 2017 risk assessment, the European Chemicals Agency (ECHA) wrote: "There is very limited information on skin irritation in humans. Where skin irritation has been reported, it is unclear whether it is related to glyphosate or co-formulants in glyphosate-containing herbicide formulations." The ECHA concluded that available human data was insufficient to support classification for skin corrosion or irritation.
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.
Glyphosate products for aquatic use generally do not use surfactants, and formulations with POEA are not approved for aquatic use due to aquatic organism toxicity. Due to the presence of POEA, glyphosate formulations only allowed for terrestrial use are more toxic for amphibians and fish than glyphosate alone. Terrestrial glyphosate formulations that include the surfactants POEA and MON 0818 (75% POEA) may have negative impacts on various aquatic organisms like protozoa, mussels, crustaceans, frogs and fish. Aquatic organism exposure risk to terrestrial formulations with POEA is limited to drift or temporary water pockets. While laboratory studies can show effects of glyphosate formulations on aquatic organisms, similar observations rarely occur in the field when instructions on the herbicide label are followed.
Studies in a variety of amphibians have shown the toxicity of GBFs containing POEA to amphibian larvae. These effects include interference with gill morphology and mortality from either the loss of osmotic stability or asphyxiation. At sub-lethal concentrations, exposure to POEA or glyphosate/POEA formulations have been associated with delayed development, accelerated development, reduced size at metamorphosis, developmental malformations of the tail, mouth, eye and head, histological indications of intersex and symptoms of oxidative stress. Glyphosate-based formulations can cause oxidative stress in bullfrog tadpoles. The use of glyphosate-based pesticides are not considered the major cause of amphibian decline, the bulk of which occurred prior to widespread use of glyphosate or in pristine tropical areas with minimal glyphosate exposure.
Carcinogenicity of active ingredient
There is limited evidence human cancer risk might increase as a result of occupational exposure to large amounts of glyphosate, such as agricultural work, but no good evidence of such a risk from home use, such as in domestic gardening. The consensus among national pesticide regulatory agencies and scientific organizations is that labeled uses of glyphosate have demonstrated no evidence of human carcinogenicity. Organizations such as the World Health Organization (WHO) and the Food and Agriculture Organization, European Commission, Canadian Pest Management Regulatory Agency, and the German Federal Institute for Risk Assessment have concluded that there is no evidence that glyphosate poses a carcinogenic or genotoxic risk to humans. The final assessment of the Australian Pesticides and Veterinary Medicines Authority in 2017 was that "glyphosate does not pose a carcinogenic risk to humans". The EPA has classified glyphosate as Group E, meaning "evidence of non-carcinogenicity in humans". Only one international scientific organization, the International Agency for Research on Cancer (IARC), affiliated with the WHO, has made claims of carcinogenicity in research reviews. The IARC has been criticized for its assessment methodology by failing to consider the broad literature and only assessing hazard rather than risk.
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