Glyphosate Literature Reviews
|Glyphosate / published under the joint sponsorship of the UN Environment Programme, the ILO, and the WHO (1994)||Glyphosate is not metabolized in humans, total body clearance is 99% in 7 days. Animal and in vitro studies conclude glyphosate is not carcinogenic, mutagenic or teratogenic. Toxicity to other creatures including bees is low.|
|Glyphosate: a once-in-a-century herbicide||Glyphosate is one of the least toxic pesticides to animals, less so than common chemicals aspirin and sodium chloride. Tillage has been reduced where glyphosate resistant crops are adopted. Transgene introgression into wild plants is unlikely even under extreme selection pressures.|
GLYPHOSATE / PUBLISHED UNDER THE JOINT SPONSORSHIP OF THE UNITED NATIONS ENVIRONMENT PROGRAMME, THE INTERNATIONAL LABOUR ORGANIZATION, AND THE WORLD HEALTH ORGANIZATION
- Concerning possible presence of residues in crops and edible animal tissues, the report cites evidence that such residues are negligible. The report further concludes that the low toxicity, low volatility, and low body absorption of glyphosate make its application by backpack sprayer safe when workers wear full protective clothing. A review of studies in laboratory animals and in vitro test systems supports the conclusion that glyphosate has very low toxicity when administered by the oral and dermal routes, does not induce sensitization, and shows no mutagenic, carcinogenic, or teratogenic activity. While the formulation Roundup is acutely toxic to humans when ingested intentionally or accidentally, dermal absorption is low, and no adverse effects are expected in properly protected workers. Studies of adverse effects on other organisms in the laboratory and field demonstrate low toxicity for bees, earthworms, and birds. The risk to most aquatic organisms was judged to be small or negligible. While marked changes in populations of birds and small mammals have been documented following glyphosate application, these changes are attributed to alterations in habitat, vegetation cover, and food supply resulting from the herbicides intended effects
Glyphosate: a once-in-a-century herbicide (2008)
- Since its commercial introduction in 1974, glyphosate [N-(phosphonomethyl)glycine] has become the dominant herbicide worldwide. There are several reasons for its success. Glyphosate is a highly effective broad-spectrum herbicide, yet it is very toxicologically and environmentally safe. Glyphosate translocates well, and its action is slow enough to take advantage of this. Glyphosate is the only herbicide that targets 5-enolpyruvyl-shikimate-3-phosphate synthase (EPSPS), so there are no competing herbicide analogs or classes. Since glyphosate became a generic compound, its cost has dropped dramatically. Perhaps the most important aspect of the success of glyphosate has been the introduction of transgenic, glyphosate-resistant crops in 1996. Almost 90% of all transgenic crops grown worldwide are glyphosate resistant, and the adoption of these crops is increasing at a steady pace. Glyphosate/glyphosate-resistant crop weed management offers significant environmental and other benefits over the technologies that it replaces. The use of this virtually ideal herbicide is now being threatened by the evolution of glyphosate-resistant weeds. Adoption of resistance management practices will be required to maintain the benefits of glyphosate technologies for future generations.
|Safety Evaluation and Risk Assessment of the Herbicide Roundup and Its Active Ingredient, Glyphosate, for Humans (1999)||Low oral and dermal absorption of glyphosate. Both AMPA and glyphosate show no evidence of bioaccumulation and are eliminated unmetabolized. Glyphosate does not cause reproductive, endocrine or DNA damage.|
|Review of genotoxicity studies of glyphosate and glyphosate-based formulations (2013)||Studies reviewed are negative for genotoxicity for glyphosate and glyphosate-based formations. Although possible cytotoxicity may occur at very high levels, there is no risk under normal conditions.|
|Epidemiologic studies of glyphosate and cancer: A review (2012)||7 cohort and 14 case-control studies found no consistent pattern nor causal relationship between total cancer/site specific cancer and glyphosate exposure in adults and children.|
|Cancer Incidence Among Glyphosate-Exposed Pesticide Applicators in the Agricultural Health Study (2005)||Agricultural Health Study data indicated that of 57,311 licensed pesticide applicators in Iowa and North Carolina, 75.5% had used glyphosate. There was no association found between glyphosate exposure and overall cancer risk using exposure-response relations.|
|Epidemiologic studies of glyphosate and non-cancer health outcomes: A review. (2011)||There was no evidence of adverse health outcomes, including diabetes, respiratory conditions, reproductive and developmental outcomes and Parkinson’s. Reported associations were not significantly different from 1.0.|
|Developmental and reproductive outcomes in humans and animals after glyphosate exposure: a critical analysis. (2012)||No consistent effects on reproductive health, developing offspring, nor plausible mechanism of action were found. Any toxicity reported in studies strongly implements surfactants in formulas used, as opposed to the glyphosate present. Human exposure concentrations from those working directly with glyphosate were over 500x less than the 2mg/kg/d reference dose set by EPA.|
Safety Evaluation and Risk Assessment of the Herbicide Roundup and Its Active Ingredient, Glyphosate, for Humans - 1999
- This review was undertaken to produce a current and comprehensive safety evaluation and risk assessment for humans. It includes assessments of glyphosate, its major breakdown product [aminomethylphosphonic acid (AMPA)], its Roundup formulations, and the predominant surfactant [polyethoxylated tallow amine (POEA)] used in Roundup formulations worldwide. The studies evaluated in this review included those performed for regulatory purposes as well as published research reports. The oral absorption of glyphosate and AMPA is low, and both materials are eliminated essentially unmetabolized. Dermal penetration studies with Roundup showed very low absorption.
- Experimental evidence has shown that neither glyphosate nor AMPA bioaccumulates in any animal tissue. No significant toxicity occurred in acute, subchronic, and chronic studies. Direct ocular exposure to the concentrated Roundup formulation can result in transient irritation, while normal spray dilutions cause, at most, only minimal effects. The genotoxicity data for glyphosate and Roundup were assessed using a weight-of-evidence approach and standard evaluation criteria. There was no convincing evidence for direct DNA damage in vitro or in vivo, and it was concluded that Roundup and its components do not pose a risk for the production of heritable/somatic mutations in humans. Multiple lifetime feeding studies have failed to demonstrate any tumorigenic potential for glyphosate. Accordingly, it was concluded that glyphosate is noncarcinogenic. Glyphosate, AMPA, and POEA were not teratogenic or developmentally toxic. There were no effects on fertility or reproducive parameters in two multigeneration reproduction studies with glyphosate. Likewise there were no adverse effects in reproductive tissues from animals treated with glyphosate, AMPA, or POEA in chronic and/or subchronic studies. Results from standard studies with these materials also failed to show any effects indicative of endocrine modulation.
- Therefore, it is concluded that the use of Roundup herbicide does not result in adverse effects on development, reproduction, or endocrine systems in humans and other mammals. For purposes of risk assessment, no-observed-adverse-effect levels (NOAELs) were identified for all subchronic, chronic, developmental, and reproduction studies with glyphosate, AMPA, and POEA. Margins-of-exposure for chronic risk were calculated for each compound by dividing the lowest applicable NOAEL by worst-case estimates of chronic exposure. Acute risks were assessed by comparison of oral LD50 values to estimated maximum acute human exposure.
- It was concluded that, under present and expected conditions of use, Roundup herbicide does not pose a health risk to humans
Review of genotoxicity studies of glyphosate and glyphosate-based formulations (2013)
- An earlier review of the toxicity of glyphosate and the original Roundup™-branded formulation concluded that neither glyphosate nor the formulation poses a risk for the production of heritable/somatic mutations in humans.
- The present review of subsequent genotoxicity publications and regulatory studies of glyphosate and glyphosate-based formulations (GBFs) incorporates all of the findings into a weight of evidence for genotoxicity. An overwhelming preponderance of negative results in well-conducted bacterial reversion and in vivo mammalian micronucleus and chromosomal aberration assays indicates that glyphosate and typical GBFs are not genotoxic in these core assays. Negative results for in vitro gene mutation and a majority of negative results for chromosomal effect assays in mammalian cells add to the weight of evidence that glyphosate is not typically genotoxic for these endpoints in mammalian systems. Mixed results were observed for micronucleus assays of GBFs in non-mammalian systems.
- Reports of positive results for DNA damage endpoints indicate that glyphosate and GBFs tend to elicit DNA damage effects at high or toxic dose levels, but the data suggest that this is due to cytotoxicity rather than DNA interaction with GBF activity perhaps associated with the surfactants present in many GBFs.
- Glyphosate and typical GBFs do not appear to present significant genotoxic risk under normal conditions of human or environmental exposures.
Epidemiologic studies of glyphosate and cancer: A review (2012)
- The United States Environmental Protection Agency and other regulatory agencies around the world have registered glyphosate as a broad-spectrum herbicide for use on multiple food and non-food use crops. Glyphosate is widely considered by regulatory authorities and scientific bodies to have no carcinogenic potential, based primarily on results of carcinogenicity studies of rats and mice.
- To examine potential cancer risks in humans, we reviewed the epidemiologic literature to evaluate whether exposure to glyphosate is associated causally with cancer risk in humans. We also reviewed relevant methodological and biomonitoring studies of glyphosate. Seven cohort studies and fourteen case-control studies examined the association between glyphosate and one or more cancer outcomes.
- Our review found no consistent pattern of positive associations indicating a causal relationship between total cancer (in adults or children) or any site-specific cancer and exposure to glyphosate. Data from biomonitoring studies underscore the importance of exposure assessment in epidemiologic studies, and indicate that studies should incorporate not only duration and frequency of pesticide use, but also type of pesticide formulation. Because generic exposure assessments likely lead to exposure misclassification, it is recommended that exposure algorithms be validated with biomonitoring data.
CANCER INCIDENCE AMONG GLYPHOSATE-EXPOSED PESTICIDE APPLICATORS IN THE AGRICULTURAL HEALTH STUDY (2005)
- Glyphosate is a broad-spectrum herbicide that is one of the most frequently applied pesticides in the world. Although there has been little consistent evidence of genotoxicity or carcinogenicity from in vitro and animal studies, a few epidemiologic reports have indicated potential health effects of glyphosate.
- We evaluated associations between glyphosate exposure and cancer incidence in the Agricultural Health Study (AHS), a prospective cohort study of 57,311 licensed pesticide applicators in Iowa and North Carolina. Detailed information on pesticide use and other factors was obtained from a self-administered questionnaire completed at time of enrollment (1993–1997). Among private and commercial applicators, 75.5% reported having ever used glyphosate, of which > 97% were men. In this analysis, glyphosate exposure was defined as a) ever personally mixed or applied products containing glyphosate; b) cumulative lifetime days of use, or “cumulative exposure days” (years of use × days/year); and c) intensity-weighted cumulative expo- sure days (years of use × days/year × estimated intensity level). Poisson regression was used to esti- mate exposure–response relations between glyphosate and incidence of all cancers combined and 12 relatively common cancer subtypes.
- Glyphosate exposure was not associated with cancer incidence overall or with most of the cancer subtypes we studied. There was a suggested association with multiple myeloma incidence that should be followed up as more cases occur in the AHS. Given the widespread use of glyphosate, future analyses of the AHS will allow further examination of long-term health effects, including less common cancers.
Epidemiologic studies of glyphosate and non-cancer health outcomes: a review. (2011)
- The United States (US) Environmental Protection Agency (EPA) and other regulatory agencies around the world have registered glyphosate as a broad-spectrum herbicide for use on multiple food and non-food use crops.
- To examine potential health risks in humans, we searched and reviewed the literature to evaluate whether exposure to glyphosate is associated causally with non-cancer health risks in humans. We also reviewed biomonitoring studies of glyphosate to allow for a more comprehensive discussion of issues related to exposure assessment and misclassification. Cohort, case-control and cross-sectional studies on glyphosate and non-cancer outcomes evaluated a variety of endpoints, including non-cancer respiratory conditions, diabetes, myocardial infarction, reproductive and developmental outcomes, rheumatoid arthritis, thyroid disease, and Parkinson's disease.
- Our review found no evidence of a consistent pattern of positive associations indicating a causal relationship between any disease and exposure to glyphosate. Most reported associations were weak and not significantly different from 1.0. Because accurate exposure measurement is crucial for valid results, it is recommended that pesticide-specific exposure algorithms be developed and validated.
Developmental and reproductive outcomes in humans and animals after glyphosate exposure: a critical analysis. (2012)
- Glyphosate is the active ingredient of several widely used herbicide formulations. Glyphosate targets the shikimate metabolic pathway, which is found in plants but not in animals. Despite the relative safety of glyphosate, various adverse developmental and reproductive problems have been alleged as a result of exposure in humans and animals.
- To assess the developmental and reproductive safety of glyphosate, an analysis of the available literature was conducted. Epidemiological and animal reports, as well as studies on mechanisms of action related to possible developmental and reproductive effects of glyphosate, were reviewed.
- An evaluation of this database found no consistent effects of glyphosate exposure on reproductive health or the developing offspring.
- Furthermore, no plausible mechanisms of action for such effects were elucidated.
- Although toxicity was observed in studies that used glyphosate-based formulations, the data strongly suggest that such effects were due to surfactants present in the formulations and not the direct result of glyphosate exposure. To estimate potential human exposure concentrations to glyphosate as a result of working directly with the herbicide, available biomonitoring data were examined.
- These data demonstrated extremely low human exposures as a result of normal application practices. Furthermore, the estimated exposure concentrations in humans are >500-fold less than the oral reference dose for glyphosate of 2 mg/kg/d set by the U.S. Environmental Protection Agency (U.S. EPA 1993). In conclusion, the available literature shows no solid evidence linking glyphosate exposure to adverse developmental or reproductive effects at environmentally realistic exposure concentrations.
Environmental Impacts on Plants and Animals
|The biological activity of glyphosate to plants and animals: a literature review. (1992)||Glyphosate shows no residual soil activity nor leaching into non-target areas. It is non-volatile and practically non-toxic to mammals, birds and fish. Glyphosate is biodegraded into natural products and there is no evidence of bioaccumulation in the food chain.|
|Fate of glyphosate in the soil and the possibility of leaching to ground and surface waters: A review. (2007)||The risk of glyphosate polluting ground and surface water is limited due to sorption onto soil minerals such as aluminium and due to microbial degradation. If applied directly after heavy rainfall, leaching in specific soil types may occur but will be likely sorbed/degraded before reaching groundwater.|
THE BIOLOGICAL ACTIVITY OF GLYPHOSATE TO PLANTS AND ANIMALS: A LITERATURE REVIEW. (1992)
- Glyphosate is a widely-used broad-spectrum herbicide with little to no hazard to man or the environment. Glyphosate is highly effective against 90 kinds of emerged grasses, brush and broad-leaf weeds. There is no residual soil activity, it does not leach into non-target areas, and it is non-volatile. It is practically nontoxic to mammals, birds and fish, showing no bioaccumulation in the food chain; it is biodegraded into natural products. When used correctly, glyphosate poses no threat to the environment and its inhabitants.
FATE OF GLYPHOSATE IN THE SOIL AND THE POSSIBILITY OF LEACHING TO GROUND AND SURFACE WATERS: A REVIEW (2007)
- The very wide use of glyphosate to control weeds in agricultural, silvicultural and urban areas throughout the world requires that special attention be paid to its possible transport from terrestrial to aquatic environments. The aim of this review is to present and discuss the state of knowledge on sorption, degradation and leachability of glyphosate in soils. Difficulties of drawing clear and unambiguous conclusions because of strong soil dependency and limited conclusive investigations are pointed out. Nevertheless, the risk of ground and surface water pollution by glyphosate seems limited because of sorption onto variable-charge soil minerals, e.g. aluminium and iron oxides, and because of microbial degradation. Although sorption and degradation are affected by many factors that might be expected to affect glyphosate mobility in soils, glyphosate leaching seems mainly determined by soil structure and rainfall. Limited leaching has been observed in non-structured sandy soils, while subsurface leaching to drainage systems was observed in a structured soil with preferential flow in macropores, but only when high rainfall followed glyphosate application. Glyphosate in drainage water runs into surface waters but not necessarily to groundwater because it may be sorbed and degraded in deeper soil layers before reaching the groundwater. Although the transport of glyphosate from land to water environments seems very limited, knowledge about subsurface leaching and surface runoff of glyphosate as well as the importance of this transport as related to ground and surface water quality is scarce.
Impacts on Soil Health
|Glyphosate toxicity and the effects of long-term vegetation control on soil microbial communities (2001)||Soil microbial communities from ponderosa pine were tested using concentrations of up to 100x greater than expected for a single field application. Long-term, repeated applications had a minimal effect on seasonal microbial characteristics, and instead was a function of the time of year and site quality.|
|Glyphosate effects on plant mineral nutrition, crop rhizophere microbiota, and plant disease in glyphosate-resistant crops (2012)||The majority of literature indicates that mineral nutrition in GR crops is not affected by the GR trait nor by glyphosate application. Data largely indicates that the GR transgene and glyphosate do not increase crop disease, nor are there nutrition and disease issues specific to these crops.|
GLYPHOSATE TOXICITY AND THE EFFECTS OF LONG-TERM VEGETATION CONTROL ON SOIL MICROBIAL COMMUNITIES (2001)
- We assessed the direct and indirect effect of the herbicide glyphosate on soil microbial communities from ponderosa pine (Pinus ponderosa) plantations of varying site quality. Direct, toxic effects were tested using culture media and soil bioassays at glyphosate concentrations up to 100-fold greater than expected following a single field application. Indirect effects on microbial biomass, respiration, and metabolic diversity (Biolog and catabolic response profile) were compared seasonally after 9–13 years of vegetation control using repeated glyphosate applications in a replicated field study.
- Three pine plantations were selected to provide a range of soil characteristics associated with glyphosate binding (clay, Fe and Al oxide content) and site growing potential from the lowest to the highest in northern California. Glyphosate was toxic to bacteria and fungi from each plantation when grown in soil-free media. Culturable populations were reduced, as was the growth rate and metabolic diversity of surviving bacteria, by increasing concentrations of glyphosate. This toxicity was not expressed when glyphosate was added directly to soil, however. Microbial respiration was unchanged at expected field concentrations (5–50 μg g−1), regardless of soil, and was stimulated by concentrations up to 100-fold greater. Increased microbial activity resulted from utilization of glyphosate as an available carbon substrate. Estimated N and P inputs from glyphosate were inconsequential to microbial activity.
- Long-term, repeated applications of glyphosate had minimal affect on seasonal microbial characteristics despite substantial changes in vegetation composition and growth. Instead, variation in microbial characteristics was a function of time of year and site quality. Community size, activity, and metabolic diversity generally were greatest in the spring and increased as site quality improved, regardless of herbicide treatment.(2012)
- Our findings suggest that artificial media assays are of limited relevance in predicting glyphosate toxicity to soil organisms and that field rate applications of glyphosate should have little or no affect on soil microbial communities in ponderosa pine plantations.
GLYPHOSATE EFFECTS ON PLANT MINERAL NUTRITION , CROP RHIZOSPHERE MICROBIOTA, AND PLANT DISEASE IN GLYPHOSATE-RESISTANT CROPS (2012)
- Claims have been made recently that glyphosate-resistant (GR) crops sometimes have mineral deficiencies and increased plant disease. This review evaluates the literature that is germane to these claims. Our conclusions are: (1) although there is conflicting literature on the effects of glyphosate on mineral nutrition on GR crops, most of the literature indicates that mineral nutrition in GR crops is not affected by either the GR trait or by application of glyphosate; (2) most of the available data support the view that neither the GR transgenes nor glyphosate use in GR crops increases crop disease; and (3) yield data on GR crops do not support the hypotheses that there are substantive mineral nutrition or disease problems that are specific to GR crops.
Statements from Major Regulatory Bodies
|The BfR has finalised its draft report for the re-evaluation of glyphosate (2014)||The available data from 900 journal publications, 300 prior toxicity studies and 150 new toxicity studies, show no evidence of carcinogenicity, mutagenicity nor fertility/reproductive toxicity in glyphosate. There was no negative impact of glyphosate on the microbial communities of ruminants nor multiplication of Clostridium. There was evidence of toxicity for surfactant tallowamines, which is assessed in the report.|
|Endocrine Disruptor Screening Program Tier 1 Assessments for Glyphosate (2015)||No convincing evidence of glyphosate potentially interacting with estrogen, androgen or thyroid pathways, based on assay and histological data. As such Tier 2 testing not recommended.|
|Summary Report from the May 2016 Joint FAO/WHO Meeting on Pesticide Residues (2016)||The Meeting concluded that glyphosate is unlikely to be genotoxic at anticipated dietary exposures. Tests in mammals with oral glyphosate doses as high as 2000 mg/kg body weight were not associated with genotoxicity in the vast majority of studies. A positive correlation between glyphosate exposure and non-Hodgkins lymphoma was unsupported by the sole high quality cohort study.|
THE BFR HAS FINALISED ITS DRAFT REPORT FOR THE RE-EVALUATION OF GLYPHOSATE
- The Federal Institute for Risk Assessment (BfR) has already completed the draft re-assessment report on health risk assessment. For this purpose, more than 150 new toxicological studies were evaluated for the first time and are described in detail in the draft report by BfR. In addition, all available toxicological studies (nearly 300) were re-assessed from the point of view of compliance with actual quality standards in study conduction and confirmation of interpreted results.
- Furthermore, about 900 publications from scientific journals have been considered in the draft report and more than 200 publications were reviewed in detail. In conclusion of this re-evaluation process of the active substance glyphosate by BfR the available data do not show carcinogenic or mutagenic properties of glyphosate nor that glyphosate is toxic to fertility, reproduction or embryonal/fetal development in laboratory animals.
- As a result of the re-assessment for the active substance BfR proposes slight amendments of the reference values. BfR believes that there is convincing evidence that the measured toxicity of some glyphosate containing herbicides is the result of the co-formulants in the plant protection products (e.g., tallowamines used as surfactants). Therefore BfR calls special attention to the co-formulants and incorporated a toxicological assessment of tallowamines in its draft report.
- A research project initiated by BfR and performed by the University of Veterinary Medicine in Hanover investigated the influence of a glyphosate containing herbicide on microbial metabolism and communities in ruminants. The results of this study are summarised in the draft suggesting that there is no negative impact on the microflora in the rumen. In particular, there was no indication that Clostridium bacteria might multiply under the influence of glyphosate.
THE EPA'S ENDOCRINE DISRUPTOR SCREENING PROGRAM WEIGHT OF EVIDENCE CONCLUSIONS ON THE TIER 1 SCREENING ASSAYS FOR GLYPHOSATE
- Based on weight of evidence considerations, mammalian or wildlife EDSP Tier 2 testing is not recommended for glyphosate since there was no convincing evidence of potential interaction with the estrogen, androgen or thyroid pathways.
Summary Report from the May 2016 Joint FAO/WHO Meeting on Pesticide Residues (JMPR) JOINT FAO/WHO MEETING ON PESTICIDE RESIDUES Geneva, 9 –13 May 2016 SUMMARY REPORT
- The evaluation of these studies focused on the occurrence of NHL. Overall, there is some evidence of a positive association between glyphosate exposure and risk of NHL from the case control studies and the overall meta-analysis.
- However, it is notable that the only large cohort study of high quality found no evidence of an association at any exposure level.
- Glyphosate has been extensively tested for genotoxic effects using a variety of tests in a wide range of organisms. The overall weight of evidence indicates that administration of glyphosate and its formulation products at doses as high as 2000 mg/kg body weight by the oral route, the route most relevant to human dietary exposure, was not associated with genotoxic effects in an overwhelming majority of studies conducted in mammals, a model considered to be appropriate for assessing genotoxic risks to humans. The Meeting concluded that glyphosate is unlikely to be genotoxic at anticipated dietary exposures.
- Several carcinogenicity studies in mice and rats are available. The Meeting concluded that glyphosate is not carcinogenic in rats but could not exclude the possibility that it is carcinogenic in mice at very high doses. In view of the absence of carcinogenic potential in rodents at human-relevant doses and the absence of genotoxicity by the oral route in mammals, and considering the epidemiological evidence from occupational exposures, the Meeting concluded that glyphosate is unlikely to pose a carcinogenic risk to humans from exposure through the diet.