Bibliography Tag: glyphosate

Rezende et al., 2021

Rezende, E.C.N., Carneiro, F.M., de Moraes, J.B. et al. “Trends in science on glyphosate toxicity: a scientometric study.” Environmental Science and Pollution Research 28, 56432–56448 (2021). DOI: 10.1007/s11356-021-14556-4


As part of the most used herbicides, glyphosate is the most successful ingredient of agrochemical companies. The main objective of this study was to demonstrate research trends related to the glyphosate toxicity and its main effects on human and environmental health. For this purpose, 443 articles published, from 1995 to 2020, on the platform Web of Science™ Thomson Reuters were selected. The main toxicity results related in literature are genotoxicity, cytotoxicity, and endocrine disruption. The environmental effects come mostly from the contamination of groundwater and soils. Several studies have concluded that herbicide concentrations right below the official safety limits induced toxic effects. The results presented a highlighted harmful effect of glyphosate on both human and environmental health. It has been observed that countries where publish the most about the glyphosate toxicity are great investors in large-scale agriculture. It is important to ponder that these countries are in a route of ecosystem exploitation that includes not only fauna and flora, but also human beings. Unfortunately, science does not provide concise data for these pesticide disapproval in the global consumer market. It is necessary to search sustainable global interest alternatives to increase agriculture production based on peoples’ food sovereignty. FULL TEXT

Nomura et al., 2022

Nomura, H., Hamada, R., Wada, K., Saito, I., Nishihara, N., Kitahara, Y., Watanabe, S., Nakane, K., Nagata, C., Kondo, T., Kamijima, M., Ueyama, J.; “Temporal trend and cross-sectional characterization of urinary concentrations of glyphosate in Japanese children from 2006 to 2015;” International Journal of Hygiene and Environmental Health, 2022, 242, 113963; DOI:10.1016/j.ijheh.2022.113963.


Background Over the past two decades, domestic shipments of glyphosate (Gly), in the form of an ionic salt, have been increasing steadily in Japan. This increase has raising concerns about the effects of chemical exposure on children. The International Agency for Research on Cancer classified Gly as a “probably carcinogenic to humans (Group 2A)” in 2015. The purpose of the current study was to analyze Gly in urine samples of Japanese children to determine temporal changes, seasonal changes, and gender differences.

Method First-morning urine samples were obtained from 50 Japanese children (4–6-year-old) in October of 2006, 2011, and 2015 (total = 150) to investigate the temporal trends in urinary Gly concentrations. Additionally, first-morning urine samples were collected from 3-year-old children in August–September of 2012 (summer; n = 42) and in February of 2013 (winter; n = 42) to investigate the seasonal and gender differences, and the correlations between urinary Gly concentrations and insecticide exposure biomarkers. Urine samples were analyzed to measure for Gly using a liquid chromatography with tandem mass spectrometry (LC-MS/MS).

Results Detectable Gly concentrations were found in 41% of the 234 children. The 75th percentile and maximum concentrations of urinary Gly were 0.20 and 1.33 μg/L, respectively. The urinary Gly concentration in 2015 was significantly higher than in 2006, suggesting that the Gly exposure levels have been increasing. No seasonal or gender-specific differences in urinary Gly concentrations were observed, and no correlation with insecticide exposure biomarkers was found.

Conclusion This study revealed that Gly exposure trends show an increase between 2006 and 2015, and that season and gender were not the exposure-determining factors. Overall, urinary concentrations of Gly were comparable with studies from other countries.


Munoz et al., 2020

Munoz, J. P., Bleak, T. C., & Calaf, G. M.; “Glyphosate and the key characteristics of an endocrine disruptor: A review;” Chemosphere, 2020, 128619; DOI: 10.1016/j.chemosphere.2020.128619.


Glyphosate is a large-spectrum herbicide that was introduced on the market in 1974. Due to its important impact on the crop industry, it has been significantly diversified and expanded being considered the most successful herbicide in history. Currently, its massive use has led to a wide environmental diffusion and its human consumption through food products has made possible to detect it in urine, serum, and breast milk samples. Nevertheless, recent studies have questioned its safety and international agencies have conflicting opinions about its effects on human health, mainly as an endocrine-disrupting chemical (EDC) and its carcinogenic capacity. Here, we conduct a comprehensive review where we describe the most important findings of the glyphosate effects in the endocrine system and asses the mechanistic evidence to classify it as an EDC. We use as guideline the ten key characteristics (KCs) of EDC proposed in the expert consensus statement published in 2020 (La Merrill et al., 2020) and discuss the scopes of some epidemiological studies for the evaluation of glyphosate as possible EDC. We conclude that glyphosate satisfies at least 8 KCs of an EDC, however, prospective cohort studies are still needed to elucidate the real effects in the human endocrine system.  FULL TEXT

Eaton et al., 2022

Eaton JL, Cathey AL, Fernandez JA, Watkins DJ, Silver MK, Milne GL, Velez-Vega C, Rosario Z, Cordero J, Alshawabkeh A, Meeker JD; “The association between urinary glyphosate and aminomethyl phosphonic acid with biomarkers of oxidative stress among pregnant women in the PROTECT birth cohort study;” Ecotoxicology and Environmental Safety, 2022, 233:113300; DOI: 10.1016/j.ecoenv.2022.113300.

Background: Glyphosate is a widely used herbicide in global agriculture. Glyphosate and its primary environmental degradate, aminomethyl phosphonic acid (AMPA), have been shown to disrupt endocrine function and induce oxidative stress in in vitro and animal studies. To our knowledge, these relationships have not been previously characterized in epidemiological settings. Elevated urinary levels of glyphosate and AMPA may be indicative of health effects caused by previous exposure via multiple mechanisms including oxidative stress.

Methods: Glyphosate and AMPA were measured in 347 urine samples collected between 16 and 20 weeks gestation and 24-28 weeks gestation from pregnant women in the PROTECT birth cohort. Urinary biomarkers of oxidative stress, comprising 8-isoprostane-prostaglandin-F2α (8-iso-PGF2α), its metabolite 2,3-dinor-5,6-dihydro-15-F2 t-isoprostane (8-isoprostane metabolite) and prostaglandin-F2α (PGF2α), were also measured. Linear mixed effect models assessed the association between exposures and oxidative stress adjusting for maternal age, smoking status, alcohol consumption, household income and specific gravity. Potential nonlinear trends were also assessed using tertiles of glyphosate and AMPA exposure levels.

Results: No significant differences in exposure or oxidative stress biomarker concentrations were observed between study visits. An interquartile range (IQR) increase in AMPA was associated with 9.5% (95% CI: 0.5-19.3%) higher 8-iso-PGF2α metabolite concentrations. Significant linear trends were also identified when examining tertiles of exposure variables. Compared to the lowest exposure group, the second and third tertiles of AMPA were significantly associated with 12.8% (0.6-26.5%) and 15.2% (1.8-30.3%) higher 8-isoprostane metabolite, respectively. An IQR increase in glyphosate was suggestively associated with 4.7% (-0.9 to 10.7%) higher 8-iso-PGF2α.

Conclusions: Urinary concentrations of the main environmental degradate of glyphosate, AMPA, were associated with higher levels of certain oxidative stress biomarkers. Associations with glyphosate reflected similar trends, although findings were not as strong. Additional research is required to better characterize the association between glyphosate exposure and biomarkers of oxidative stress, as well as potential downstream health consequences.


Lesseur et al., 2022

Corina Lesseur, Khyatiben V. Pathak, Patrick Pirrotte, Melissa N. Martinez, Kelly K. Ferguson, Emily S. Barrett, Ruby H.N. Nguyen, Sheela Sathyanarayana, Daniele Mandrioli, Shanna H. Swan, Jia Chen; “Urinary glyphosate concentration in pregnant women in relation to length of gestation;” Environmental Research, 2022, 203, 0013-9351; DOI:10.1016/j.envres.2021.111811.


Human exposure to glyphosate-based herbicides (GBH) is increasing rapidly worldwide. Most existing studies on health effects of glyphosate have focused on occupational settings and cancer outcomes and few have examined this common exposure in relation to the health of pregnant women and newborns in the general population. We investigated associations between prenatal glyphosate exposure and length of gestation in The Infant Development and the Environment Study (TIDES), a multi-center US pregnancy cohort. Glyphosate and its primary degradation product [aminomethylphosphonic acid (AMPA)] were measured in urine samples collected during the second trimester from 163 pregnant women: 69 preterm births (<37 weeks) and 94 term births, the latter randomly selected as a subset of TIDES term births. We examined the relationship between exposure and length of gestation using multivariable logistic regression models (dichotomous outcome; term versus preterm) and with weighted time-to-event Cox proportional hazards models (gestational age in days). We conducted these analyses in the overall sample and secondarily, restricted to women with spontaneous deliveries (n = 90). Glyphosate and AMPA were detected in most urine samples (>94 %). A shortened gestational length was associated with maternal glyphosate (hazard ratio (HR): 1.31, 95 % confidence interval (CI) 1.00–1.71) and AMPA (HR: 1.32, 95%CI: 1.00–1.73) only among spontaneous deliveries using adjusted Cox proportional hazards models. In binary analysis, glyphosate and AMPA were not associated with preterm birth risk (<37 weeks). Our results indicate widespread exposure to glyphosate in the general population which may impact reproductive health by shortening length of gestation. Given the increasing exposure to GBHs and the public health burden of preterm delivery, larger confirmatory studies are needed, especially in vulnerable populations such as pregnant women and newborns. FULL TEXT

Schütze et al. 2021

Andre Schütze, Pilar Morales-Agudelo, Meghan Vidal, Antonia M. Calafat, Maria Ospina.; “Quantification of glyphosate and other organophosphorus compounds in human urine via ion chromatography isotope dilution tandem mass spectrometry;” Chemosphere, 2021, 274; DOI: 10.1016/j.chemosphere.2020.129427.


Organophosphorus pesticides are the most used pesticides in the United States. Most organophosphorus pesticides are composed of a phosphate (or phosphorothioate or phosphorodithioate) moiety and a variable organic group. Organophosphorus pesticides are scrutinized by regulatory bodies and agencies because of their toxicity or suspected carcinogenicity. Upon exposure, organophosphorus pesticides and their metabolites eliminate in urine; these urinary biomarkers are useful to evaluate human exposure. We developed a method using stable isotope dilution, ion chromatography tandem mass spectrometry for quantification in urine of 6 O,O-dialkylphosphates, metabolites of organophosphorus insecticides, and glyphosate, the most used herbicide in the United States. With simple and minimal sample preparation, the analytical method is selective and sensitive (limits of detection are 0.2-0.8 μg/L), accurate (>85%) and precise (relative standard deviation <20%), depending on the analyte. To assess the suitability of the method in real exposure scenarios, we analyzed samples collected anonymously from subjects with suspected exposure to pesticides (n = 40) or who had been on an organic diet (n = 50). We detected glyphosate in 80% of subjects reporting an organic diet and in 78% of those with suspected glyphosate exposure; concentrations ranged from <0.2 to 28.6 μg/L. Median concentrations were 0.39 μg/L for the organic diet group and 0.40 μg/L for individuals with suspected exposure. Interestingly, interquartile ranges were considerably higher among those reporting pesticide exposure (0.63 μg/L) than those consuming organic diets (0.42 μg/L). These data suggest that the method meets typical validation benchmark values and is sensitive to investigate background exposures in the general population. FULL TEXT

Cosemans et al., 2021

Cosemans, C., Van Larebeke, N., Janssen, B. G., Martens, D. S., Baeyens, W., Bruckers, L., Den Hond, E., Coertjens, D., Nelen, V., Schoeters, G., Hoppe, H. W., Wolfs, E., Smeets, K., Nawrot, T. S., & Plusquin, M.; “Glyphosate and AMPA exposure in relation to markers of biological aging in an adult population-based study;” International Journal of Hygiene and Environmental Health, 2021, 240, 113895; DOI: 10.1016/j.ijheh.2021.113895.


BACKGROUND/AIM: Glyphosate, a broad-spectrum herbicide, and its main metabolite aminomethylphosphonic acid (AMPA) are persistent in the environment. Studies showed associations between glyphosate or AMPA exposure and several adverse cellular processes, including metabolic alterations and oxidative stress.

OBJECTIVE: To determine the association between glyphosate and AMPA exposure and biomarkers of biological aging.

METHODS: We examined glyphosate and AMPA exposure, mtDNA content and leukocyte telomere length in 181 adults, included in the third cycle of the Flemish Environment and Health Study (FLEHSIII). DNA was isolated from leukocytes and the relative mtDNA content and telomere length were determined using qPCR. Urinary glyphosate and AMPA concentrations were measured by Gas Chromatography-Tandem Mass Spectrometry (GC-MS-MS). We used multiple linear regression models to associate mtDNA content and leukocyte telomere length with glyphosate or AMPA exposure while adjusting for confounding variables.

RESULTS: A doubling in urinary AMPA concentration was associated with 5.19% (95% CI: 0.oth49 to 10.11; p = 0.03) longer leukocyte telomere length, while no association was observed with urinary glyphosate concentration. No association between mtDNA content and urinary glyphosate nor AMPA levels was observed.

CONCLUSIONS: This study showed that AMPA exposure may be associated with telomere biology in adults.


Mesnage et al., 2021D

Robin Mesnage, Mariam Ibragim, Daniele Mandrioli, Laura Falcioni, Eva Tibaldi, Fiorella Belpoggi, Inger Brandsma, Emma Bourne, Emanuel Savage, Charles A Mein, Michael N Antoniou; “Comparative Toxicogenomics of Glyphosate and Roundup Herbicides by Mammalian Stem Cell-Based Genotoxicity Assays and Molecular Profiling in Sprague-Dawley Rats”, Toxicological Sciences, 2021; DOI: 10.1093/toxsci/kfab143.


Whether glyphosate-based herbicides (GBHs) are more potent than glyphosate alone at activating cellular mechanisms, which drive carcinogenesis remain controversial. As GBHs are more cytotoxic than glyphosate, we reasoned they may also be more capable of activating carcinogenic pathways. We tested this hypothesis by comparing the effects of glyphosate with Roundup GBHs both in vitro and in vivo. First, glyphosate was compared with representative GBHs, namely MON 52276 (European Union), MON 76473 (United Kingdom), and MON 76207 (United States) using the mammalian stem cell-based ToxTracker system. Here, MON 52276 and MON 76473, but not glyphosate and MON 76207, activated oxidative stress and unfolded protein responses. Second, molecular profiling of liver was performed in female Sprague-Dawley rats exposed to glyphosate or MON 52276 (at 0.5, 50, and 175 mg/kg bw/day glyphosate) for 90 days. MON 52276 but not glyphosate increased hepatic steatosis and necrosis. MON 52276 and glyphosate altered the expression of genes in liver reflecting TP53 activation by DNA damage and circadian rhythm regulation. Genes most affected in liver were similarly altered in kidneys. Small RNA profiling in liver showed decreased amounts of miR-22 and miR-17 from MON 52276 ingestion. Glyphosate decreased miR-30, whereas miR-10 levels were increased. DNA methylation profiling of liver revealed 5727 and 4496 differentially methylated CpG sites between the control and glyphosate and MON 52276 exposed animals, respectively. Apurinic/apyrimidinic DNA damage formation in liver was increased with glyphosate exposure. Altogether, our results show that Roundup formulations cause more biological changes linked with carcinogenesis than glyphosate. FULL TEXT

Malagoli et al., 2016

Malagoli, C., Costanzini, S., Heck, J. E., Malavolti, M., De Girolamo, G., Oleari, P., Palazzi, G., Teggi, S., & Vinceti, M.; “Passive exposure to agricultural pesticides and risk of childhood leukemia in an Italian community;” International Journal of Hygiene and Environmental Health, 2016, 219(8), 742-748; DOI: 10.1016/j.ijheh.2016.09.015.


BACKGROUND: Exposure to pesticides has been suggested as a risk factor for childhood leukemia, but definitive evidence on this relation and the specific pesticides involved is still not clear.

OBJECTIVE: We carried out a population-based case-control study in a Northern Italy community to assess the possible relation between passive exposure to agricultural pesticides and risk of acute childhood leukemia.

METHODS: We assessed passive pesticide exposure of 111 childhood leukemia cases and 444 matched controls by determining density and type of agricultural land use within a 100-m radius buffer around children’s homes. We focused on four common crop types, arable, orchard, vineyard and vegetable, characterized by the use of specific pesticides that are potentially involved in childhood induced leukemia. The use of these pesticides was validated within the present study. We computed the odds ratios (OR) of the disease and their 95% confidence intervals (CI) according to type and density of crops around the children’s homes, also taking into account traffic pollution and high-voltage power line magnetic field exposure.

RESULTS: Childhood leukemia risk did not increase in relation with any of the crop types with the exception of arable crops, characterized by the use of 2.4-D, MCPA, glyphosate, dicamba, triazine and cypermethrin. The very few children (n=11) residing close to arable crops had an OR for childhood leukemia of 2.04 (95% CI 0.50-8.35), and such excess risk was further enhanced among children aged <5 years.

CONCLUSIONS: Despite the null association with most crop types and the statistical imprecision of the estimates, the increased leukemia risk among children residing close to arable crops indicates the need to further investigate the involvement in disease etiology of passive exposure to herbicides and pyrethroids, though such exposure is unlikely to play a role in the vast majority of cases. FULL TEXT