Glyphosate is the active ingredient in herbicide formulations containing it. However, in addition to glyphosate salts, commercial formulations of glyphosate contain additives (known as adjuvants) such as
surfactants, which vary in nature and concentration. Surfactants such as
polyethoxylated tallow amine (POEA) are added to glyphosate to enable it to wet the leaves and penetrate the
cuticle of the plants. The presence of surfactants can significantly alter the toxicity of glyphosate-based herbicides.
Glyphosate alone Humans 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. Glyphosate has less acute toxicity than 94% of herbicides in USDA data, and less acute toxicity than household chemicals such as
table salt and
vinegar. 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. The Joint FAO/WHO Meeting on Pesticide Residues (JMPR), the
European Commission, the Canadian
Pest Management Regulatory Agency, the
Australian Pesticides and Veterinary Medicines Authority 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
United States Environmental Protection Agency (EPA) has classified glyphosate as "not likely to be carcinogenic to humans" and stated its classification was "consistent with other international expert panels and regulatory authorities." One international scientific organization, the
International Agency for Research on Cancer, classified glyphosate in
Group 2A, "probably carcinogenic to humans" in 2015. , the evidence for long-term exposure to glyphosate increasing the risk of human cancer remains inconclusive. There is weak evidence human cancer risk might increase as a result of occupational exposure to large amounts of glyphosate, such as in agricultural work, but no good evidence of such a risk from home use, such as in domestic gardening. Although some small studies have suggested an association between glyphosate and
non-Hodgkin lymphoma, subsequent work confirmed the likelihood this work suffered from bias, and the association could not be demonstrated in more robust studies.
Other mammals Among mammals, glyphosate is considered to have "low to very low toxicity". The
LD50 of glyphosate is 5,000 mg/kg for rats, 10,000 mg/kg in mice and 3,530 mg/kg in goats. The acute dermal LD50 in rabbits is greater than 2,000 mg/kg. Indications of glyphosate toxicity in animals typically appear within 30 to 120 minutes following ingestion of a large enough dose, and include initial excitability and
tachycardia,
ataxia, depression, and
bradycardia, although severe toxicity can develop into collapse and convulsions. In reproductive toxicity studies performed in rats and rabbits, no adverse maternal or offspring effects were seen at doses below 175–293 mg/kg/day.
Antimicrobial activity The
antimicrobial activity of glyphosate has been described in the microbiology literature since its discovery in 1970 and the description of glyphosate's mechanism of action in 1972. Efficacy was described for numerous bacteria and fungi. Glyphosate can control the growth of
apicomplexan parasites, such as
Toxoplasma gondii,
Plasmodium falciparum (malaria), and
Cryptosporidium parvum, and has been considered an antimicrobial agent in mammals. Inhibition can occur with some
Rhizobium species important for soybean nitrogen fixation, especially under moisture stress.
Soil biota are considered to be much more benign toxicologically and environmentally than most of the herbicides replaced by glyphosate. A 2016 meta-analysis concluded that at typical application rates glyphosate had no effect on soil microbial biomass or respiration. Some species of earthworms are affected, some are not. Some avoid treated soil.
Endocrine disruption 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. On June 29, 2015, the EPA released the Weight of Evidence Conclusions 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." A review of the evidence by the European Food Safety Authority published in September 2017 showed conclusions similar to those of the EPA report.
Effect on plant health Some studies have found causal relationships between glyphosate and increased or decreased disease resistance. Exposure to glyphosate has been shown to change the species composition of
endophytic bacteria in plant hosts, which is highly variable.
Glyphosate-based formulations Glyphosate-based formulations may contain a number of
adjuvants, the identities of which may be proprietary. 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 pre-mixed into commercial formulations or they may be purchased separately and mixed on-site.
Polyethoxylated tallow amine (POEA) is a surfactant used in the original Roundup formulation and was commonly used in 2015. The percentage of POEA varies. A 1997 US government report said that Roundup is 15% POEA while Roundup Pro is 14.5%. This review concluded that "...for terrestrial uses of Roundup minimal acute and chronic risk was predicted for potentially exposed non-target organisms". As of April 2017, the Canadian government'
Pest Management Regulatory Agency stated that glyphosate was "the most widely used herbicide in Canada" and that approved glyphosate formulations in the country contained less than
Human Overall, there is no conclusive evidence on glyphosate's effect on human health.
Acute toxicity and
chronic toxicity are dose-related. 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. Adult consumption of more than 85 ml of concentrated product can lead to corrosive esophageal burns and kidney or liver damage. More severe cases cause "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. Due to the presence of POEA, such glyphosate formulations only allowed for terrestrial use are more toxic for amphibians and fish than glyphosate alone. The half-life of POEA (21–42 days) is longer than that for glyphosate (7–14 days) in aquatic environments. Aquatic organism exposure risk to terrestrial formulations with POEA is limited to drift or temporary water pockets where concentrations would be much lower than label rates. 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. A 2013
meta-analysis 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 per-species and per-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.
Genetic damage The IARC monograph noted that glyphosate-based formulations can cause DNA strand breaks in various
taxa of animals
in vitro.
epidemiological studies, animal studies, and
in vitro studies. It found that "no classification and labelling for carcinogenicity is warranted" and did not recommend a carcinogen classification of either 1A or 1B. In November 2015, EFSA published its conclusion in the Renewal Assessment Report (RAR), stating it was "unlikely to pose a carcinogenic hazard to humans". The
EU was largely informed by this report when it made its decision on the use of glyphosate in November 2017. EFSA's decision and the BfR report were criticized in an
open letter published by 96 scientists in November 2015 saying that the BfR report failed to adhere to accepted scientific principles of open and transparent procedures. The BfR report included unpublished data, lacked authorship, omitted references, and did not disclose conflict-of-interest information.
International Agency for Research on Cancer In March 2015, the
International Agency for Research on Cancer (IARC), an intergovernmental agency forming part of the
World Health Organization of the
United Nations, 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. The IARC classifies substances for their carcinogenic potential, and "a few positive findings can be enough to declare a hazard, even if there are negative studies, as well." Unlike the BfR, it does not conduct a
risk assessment, weighing benefits against risk. The BfR responded that IARC reviewed only a selection of what the BfR had reviewed earlier, and argued that other studies, including a cohort study called
Agricultural Health Study, do not support the classification. The IARC report did not include unpublished studies, including one completed by the IARC panel leader. The agency's international protocol dictates that only published studies be used in classifications of carcinogenicity, since national regulatory agencies including the EPA have allowed agrochemical corporations to conduct their own unpublished research, which may be biased in support of their profit motives.
Reviews of the EFSA and IARC reports A 2017 review done by personnel from EFSA and BfR argued that the differences between the IARC's and EFSA's conclusions regarding glyphosate and cancer were due to differences in their evaluation of the available evidence. The review concluded that "Two complementary exposure assessments ... suggests that actual exposure levels are below" the reference values identified by the EFSA "and do not represent a public concern." In October 2017, an article in
The Times revealed that Portier had received consulting contracts with two law firm associations representing alleged glyphosate cancer victims that included a payment of US$160,000 to Portier. The IARC final report was also found to have changed compared to an interim report, through the removal of text saying certain studies had found glyphosate was not carcinogenic in that study's context, and through strengthening a conclusion of "limited evidence of animal carcinogenicity," to "sufficient evidence of animal carcinogenicity".
US Environmental Protection Agency In a 1993 review, the
EPA, considered glyphosate to be
noncarcinogenic and relatively low in
dermal and oral acute toxicity. 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. In August 2019, the
EPA announced that it no longer allowed labels claiming glyphosate is a carcinogen, as those claims would "not meet the labeling requirements of the
Federal Insecticide, Fungicide, and Rodenticide Act" and misinform the public. In 2017, evidence collected in a lawsuit brought against Monsanto by cancer patients revealed company emails that appeared to show a friendly relationship with a senior EPA official.
Monsanto response and campaign Monsanto called the IARC report biased and said it wanted the report to be retracted. In 2017, internal documents from Monsanto were made public by lawyers pursuing litigation against the company, who used the term "Monsanto papers" to describe the documents. The documents indicated Monsanto had planned a public relations effort to discredit the IARC report, and had engaged
Henry Miller to write a 2015 opinion piece in
Forbes Magazine challenging the report. Miller did not reveal the connection to Forbes, and according to
The New York Times, when Monsanto asked him if he was interested in writing such an article, he replied "I would be if I could start from a high-quality draft" provided by the company. Once this became public, Forbes removed his blog from their site. Two journalists from
Le Monde won the 2018
European Press Prize for a series of articles on the documents, also titled
Monsanto Papers. Their reporting described, among other things, Monsanto's lawyers' letters demanding that IARC scientists turn over documents relating to
Monograph 112, which contained the IARC finding that glyphosate was a "probable carcinogen"; several of the scientists condemned these letters as intimidating.
California Office of Environmental Health Hazard Assessment In March 2015, the
California Office of Environmental Health Hazard Assessment (OEHHA) announced plans to have glyphosate listed as a known carcinogen based on the IARC assessment. In 2016, Monsanto started a case against OEHHA and its acting director, Lauren Zeise, but lost the suit in March 2017. Glyphosate was listed as "known to the State of California to cause cancer" in 2017, requiring warning labels under
Proposition 65. In February 2018, as part of an ongoing case, an injunction was issued prohibiting California from enforcing carcinogenicity labeling requirements for glyphosate until the case was resolved. The injunction stated that arguments by a
US District Court Judge for the
Eastern District of California "[do] not change the fact that the overwhelming majority of agencies that that have examined glyphosate have determined it is not a cancer risk." In August 2019, the
EPA also said it no longer allowed labels claiming glyphosate is a carcinogen, as those claims would "not meet the labeling requirements of the
Federal Insecticide, Fungicide, and Rodenticide Act" and misinform the public. In 2022, the agency reiterated these findings in a later review and stated on cancer risk that, "Based on a wide-ranging review of scientific evidence, the committee again concludes that classifying glyphosate as a carcinogen is not justified." ==Effects of use==