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Bibliography Tag: glyphosate

Chang et al., 2023

Chang, V. C., Andreotti, G., Ospina, M., Parks, C. G., Liu, D., Shearer, J. J., Rothman, N., Silverman, D. T., Sandler, D. P., Calafat, A. M., Beane Freeman, L. E., & Hofmann, J. N. (2023). “Glyphosate exposure and urinary oxidative stress biomarkers in the Agricultural Health Study.” JNCI: Journal of the National Cancer Institute, 115(4), 394–404. https://doi.org/10.1093/jnci/djac242

ABSTRACT:

Background

Glyphosate is the most widely applied herbicide worldwide, and its use has been associated with increased risks of certain hematopoietic cancers in epidemiologic studies. Animal and in vitro experiments suggest that glyphosate may induce oxidative stress, a key characteristic of carcinogens; however, evidence in human populations remains scarce. We investigated associations between glyphosate exposure and urinary oxidative stress biomarkers in the Biomarkers of Exposure and Effect in Agriculture study, a molecular epidemiologic subcohort in the Agricultural Health Study.

Methods

This analysis included 268 male farmers selected based on self-reported recent and lifetime occupational glyphosate use and 100 age- and geography-matched male nonfarmers. Concentrations of glyphosate and oxidative stress biomarkers (8-hydroxy-2′-deoxyguanosine [8-OHdG], 8-iso-prostaglandin-F2α, and malondialdehyde [MDA]) were quantified in first-morning-void urine. We performed multivariable linear regression to evaluate associations of urinary glyphosate and self-reported glyphosate use with each oxidative stress biomarker.

Results

Urinary glyphosate concentrations were positively associated with levels of 8-OHdG (highest vs lowest glyphosate quartile; geometric mean ratio = 1.15, 95% confidence interval = 1.03 to 1.28; Ptrend = .02) and MDA (geometric mean ratio = 1.20, 95% confidence interval = 1.03 to 1.40; Ptrend = .06) overall. Among farmers reporting recent glyphosate use (last 7 days), use in the previous day was also associated with statistically significantly increased 8-OHdG and MDA levels. Compared with nonfarmers, we observed elevated 8-iso-prostaglandin-F2α levels among farmers with recent, high past 12-month, or high lifetime glyphosate use.

Conclusions

Our findings contribute to the weight of evidence supporting an association between glyphosate exposure and oxidative stress in humans and may inform evaluations of the carcinogenic potential of this herbicide. FULL TEXT

Benbrook et al., 2023

Benbrook C, Mesnage R, Sawyer W. “Genotoxicity Assays Published since 2016 Shed New Light on the Oncogenic Potential of Glyphosate-Based Herbicides.” Agrochemicals. 2023; 2(1):47-68. https://doi.org/10.3390/agrochemicals2010005

ABSTRACT:

Controversy over the oncogenicity of glyphosate-based herbicides (GBHs) persists seven years after a 2015 IARC Monograph classified glyphosate/GBHs as “probably carcinogenic” to humans. Most regulatory authorities have concluded that technical glyphosate poses little or no oncogenic risk via dietary exposure. The US EPA classified glyphosate as “not likely” to pose cancer risk in 1991, a decision reaffirmed in reports issued in 2017 and 2020. A Federal Circuit Court of Appeals in the US vacated EPA’s assessment of glyphosate human-health risks in 2022 and required EPA to revisit old and take into account new data in its forthcoming, possibly final glyphosate/GBH reregistration decision. Divergent assessments of GBH genotoxicity are the primary reason for differing conclusions regarding GBH oncogenic potential. We assessed whether assays published since completion of the EPA and IARC reviews shed new light on glyphosate/GBH genotoxicity. We found 94 such assays, 33 testing technical glyphosate (73% positive) and 61 on GBHs (95% positive). Seven of 7 in vivo human studies report positive results. In light of genotoxicity results published since 2015, the conclusion that GBHs pose no risk of cancer via a genotoxic mechanism is untenable. FULL TEXT

EPA, 2015b

Environmental Protection Agency, “Evaluation of the Carcinogenic Potential of Glyphosate Case No. 1071-83-6 .” Office of Chemical Safety and Pollution Prevention, October 1, 2015.

ABSTRACT:

On September 16, 2015, the Cancer Assessment Review Committee (CARC) of the Health
Effects Division, of the Office of Pesticide Programs evaluated the carcinogenic potential of
Glyphosate in accordance with the EPA ‘s Final Guidelines for Carcinogen Risk Assessment
(March, 2005). Attached please find the final Cancer Assessment Document.

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Bienvenu et al., 2021

Bienvenu, J. F., Belanger, P., Gaudreau, E., Provencher, G., & Fleury, N.; “Determination of glyphosate, glufosinate and their major metabolites in urine by the UPLC-MS/MS method applicable to biomonitoring and epidemiological studies;” Analytical and Bioanalytical Chemistry, 2021; DOI: 10.1007/s00216-021-03194-x.

ABSTRACT:

The preoccupation concerning glyphosate (GLYP) has rapidly grown over recent years, and the availability of genetically modified crops that are resistant to GLYP or glufosinate (GLUF) has increased the use of these herbicides. The debate surrounding the carcinogenicity of GLYP has raised interest and the desire to gain information on the level of exposure of the population. GLYP and aminomethylphosphonic acid (AMPA) are commonly simultaneously analysed. GLUF is sometimes also monitored, but its major metabolite, 3-[hydroxy(methyl)phosphinoyl]propionic acid (3MPPA), is rarely present in the method. Using a pentafluorobenzyl derivative to extract the analytes from human urine, we present a method that contains four important analytes to monitor human exposure to GLYP and GLUF. The use of the flash freeze technique speeds up the extraction process and requires less organic solvent than conventional liquid-liquid extraction. The limits of detection in the low mug/L range enable the use of this method for epidemiological studies. The results obtained for 35 volunteers from the Quebec City area are presented with the results from multiple interlaboratory comparisons (G-EQUAS, HBM4EU and OSEQAS). This methodology is currently being used in the Maternal-Infant Research on Environmental Chemicals (MIREC-ENDO) study and in the Canadian Health Measures Survey (CHMS).

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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

ABSTRACT:

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.

ABSTRACT:

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.

ABSTRACT:

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.
ABSTRACT:

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.

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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.

ABSTRACT:

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.

ABSTRACT:

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

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