Bibliography Tag: ampa

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

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.


Silver et al., 2021

Silver, M. K., Fernandez, J., Tang, J., McDade, A., Sabino, J., Rosario, Z., Velez Vega, C., Alshawabkeh, A., Cordero, J. F., & Meeker, J. D.; “Prenatal Exposure to Glyphosate and Its Environmental Degradate, Aminomethylphosphonic Acid (AMPA), and Preterm Birth: A Nested Case-Control Study in the PROTECT Cohort (Puerto Rico);” Environmental Health Perspectives, 2021, 129(5), 57011; DOI: 10.1289/EHP7295.


BACKGROUND: Glyphosate (GLY) is the most heavily used herbicide in the world. Despite nearly ubiquitous exposure, few studies have examined prenatal GLY exposure and potentially adverse pregnancy outcomes. Preterm birth (PTB) is a risk factor for neonatal mortality and adverse health effects in childhood.

OBJECTIVES: We examined prenatal exposure to GLY and a highly persistent environmental degradate of GLY, aminomethylphosphonic acid (AMPA), and odds of PTB in a nested case-control study within the ongoing Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) pregnancy cohort in northern Puerto Rico.

METHODS: GLY and AMPA in urine samples collected at 18+/-2 (Visit 1) and 26+/-2 (Visit 3) wk gestation (53 cases/194 randomly selected controls) were measured using gas chromatography tandem mass spectrometry. Multivariable logistic regression was used to estimate associations with PTB (delivery <37wk completed gestation).

RESULTS: Detection rates in controls were 77.4% and 77.5% for GLY and 52.8% and 47.7% for AMPA, and geometric means (geometric standard deviations) were 0.44 (2.50) and 0.41 (2.56) mug/L for GLY and 0.25 (3.06) and 0.20 (2.87) mug/L for AMPA, for Visits 1 and 3, respectively. PTB was significantly associated with specific gravity-corrected urinary GLY and AMPA at Visit 3, whereas associations with levels at Visit 1 and the Visits 1-3 average were largely null or inconsistent. Adjusted odds ratios (ORs) for an interquartile range increase in exposure at Visit 3 were 1.35 (95% CI: 0.99, 1.83) and 1.67 (95% CI: 1.26, 2.20) for GLY and AMPA, respectively. ORs for Visit 1 and the visit average were closer to the null.

DISCUSSION: Urine GLY and AMPA levels in samples collected near the 26th week of pregnancy were associated with increased odds of PTB in this modestly sized nested case-control study. Given the widespread use of GLY, multiple potential sources of AMPA, and AMPA’s persistence in the environment, as well as the potential for long-term adverse health effects in preterm infants, further investigation in other populations is warranted.


Franke et al., 2021

Franke, Adrian A., Li, Xingnan, Shvetsov, Yurii B., & Lai, Jennifer F.; “Pilot study on the urinary excretion of the glyphosate metabolite aminomethylphosphonic acid and breast cancer risk: The Multiethnic Cohort study;” Environmental Pollution, 2021, 277, 116848; DOI:


Breast cancer is the most commonly diagnosed female cancer and the second leading cause of death in women in the US, including Hawaii. Accumulating evidence suggests that aminomethylphosphonic acid (AMPA), the primary metabolite of the herbicide glyphosate—a probable human carcinogen, may itself be carcinogenic. However, the relationship between urinary AMPA excretion and breast cancer risk in women is unknown. In this pilot study, we investigated the association between pre-diagnostic urinary AMPA excretion and breast cancer risk in a case-control study of 250 predominantly postmenopausal women: 124 cases and 126 healthy controls (individually matched on age, race/ethnicity, urine type, date of urine collection, and fasting status) nested within the Hawaii biospecimen subcohort of the Multiethnic Cohort. AMPA was detected in 90% of cases and 84% of controls. The geometric mean of urinary AMPA excretion was nearly 38% higher among cases vs. controls (0.087 vs 0.063 ng AMPA/mg creatinine) after adjusting for race/ethnicity, age and BMI. A 4.5-fold higher risk of developing breast cancer in the highest vs. lowest quintile of AMPA excretion was observed (ORQ5 vs. Q1: 4.49; 95% CI: 1.46–13.77; ptrend = 0.029). To our knowledge, this is the first study to prospectively examine associations between urinary AMPA excretion and breast cancer risk. Our preliminary findings suggest that AMPA exposure may be associated with increased breast cancer risk; however, these results require confirmation in a larger population to increase study power and permit careful examinations of race/ethnicity differences.

Arregui et al., 2004

Arregui, M. C., Lenardon, A., Sanchez, D., Maitre, M. I., Scotta, R., & Enrique, S.; “Monitoring glyphosate residues in transgenic glyphosate-resistant soybean;” Pest Management Science, 2004, 60(2), 163-166; DOI: 10.1002/ps.775.


The availability of Roundup Ready (RR) varieties of soybean has increased the use of glyphosate for weed control in Argentina. Glyphosate [(N-phosphonomethyl)glycine] is employed for the eradication of previous crop vegetation and for weed control during the soybean growing cycle. Its action is effective, and low environmental impact has been reported so far. No residues have been observed in soil or water, either of glyphosate or its metabolite, AMPA (aminomethylphosphonic acid). The objective of this work was to monitor glyphosate and AMPA residues in soybean plants and grains in field crops in Santa Fe Province, Argentina. Five sites were monitored in 1997, 1998 and 1999. Individual soybean plants were sampled from emergence to harvest, dried and ground. Analysis consisted in residue extraction with organic solvents and buffers, agitation, centrifugation, clean-up and HPLC with UV detection. In soybean leaves and stems, glyphosate residues ranged from 1.9 to 4.4 mg kg(-1) and from 0.1 to 1.8 mg kg(-1) in grains. Higher concentrations were detected when glyphosate was sprayed several times during the crop cycle, and when treatments approached the flowering stage. AMPA residues were also detected in leaves and in grains, indicating metabolism of the herbicide.

Franke et al., 2020

Franke, A. A., Li, X., & Lai, J. F.; “Analysis of glyphosate, aminomethylphosphonic acid, and glufosinate from human urine by HRAM LC-MS;” Analytical and Bioanalytical Chemistry, 2020; DOI: 10.1007/s00216-020-02966-1.


Aminomethylphosphonic acid (AMPA) is the main metabolite of glyphosate (GLYP) and phosphonic acids in detergents. GLYP is a synthetic herbicide frequently used worldwide alone or together with its analog glufosinate (GLUF). The general public can be exposed to these potentially harmful chemicals; thus, sensitive methods to monitor them in humans are urgently required to evaluate health risks. We attempted to simultaneously detect GLYP, AMPA, and GLUF in human urine by high-resolution accurate-mass liquid chromatography mass spectrometry (HRAM LC-MS) before and after derivatization with 9-fluorenylmethoxycarbonyl chloride (Fmoc-Cl) or 1-methylimidazole-sulfonyl chloride (ImS-Cl) with several urine pre-treatment and solid phase extraction (SPE) steps. Fmoc-Cl derivatization achieved the best combination of method sensitivity (limit of detection; LOD) and accuracy for all compounds compared to underivatized urine or ImS-Cl-derivatized urine. Before derivatization, the best steps for GLYP involved 0.4 mM ethylenediaminetetraacetic acid (EDTA) pre-treatment followed by SPE pre-cleanup (LOD 37 pg/mL), for AMPA involved no EDTA pre-treatment and no SPE pre-cleanup (LOD 20 pg/mL) or 0.2-0.4 mM EDTA pre-treatment with no SPE pre-cleanup (LOD 19-21 pg/mL), and for GLUF involved 0.4 mM EDTA pre-treatment and no SPE pre-cleanup (LOD 7 pg/mL). However, for these methods, accuracy was sufficient only for AMPA (101-105%), while being modest for GLYP (61%) and GLUF (63%). Different EDTA and SPE treatments prior to Fmoc-Cl derivatization resulted in high sensitivity for all analytes but satisfactory accuracy only for AMPA. Thus, we conclude that our HRAM LC-MS method is suited for urinary AMPA analysis in cross-sectional studies. FULL TEXT

Connolly et al., 2020

Connolly, A., Coggins, M. A., & Koch, H. M.; “Human Biomonitoring of Glyphosate Exposures: State-of-the-Art and Future Research Challenges;” Toxics, 2020, 8(3); DOI: 10.3390/toxics8030060.


Glyphosate continues to attract controversial debate following the International Agency for Research on Cancer carcinogenicity classification in 2015. Despite its ubiquitous presence in our environment, there remains a dearth of data on human exposure to both glyphosate and its main biodegradation product aminomethylphosphonic (AMPA). Herein, we reviewed and compared results from 21 studies that use human biomonitoring (HBM) to measure urinary glyphosate and AMPA. Elucidation of the level and range of exposure was complicated by differences in sampling strategy, analytical methods, and data presentation. Exposure data is required to enable a more robust regulatory risk assessment, and these studies included higher occupational exposures, environmental exposures, and vulnerable groups such as children. There was also considerable uncertainty regarding the absorption and excretion pattern of glyphosate and AMPA in humans. This information is required to back-calculate exposure doses from urinary levels and thus, compared with health-based guidance values. Back-calculations based on animal-derived excretion rates suggested that there were no health concerns in relation to glyphosate exposure (when compared with EFSA acceptable daily intake (ADI)). However, recent human metabolism data has reported as low as a 1% urinary excretion rate of glyphosate. Human exposures extrapolated from urinary glyphosate concentrations found that upper-bound levels may be much closer to the ADI than previously reported. FULL TEXT

Williams et al., 2000

Williams, G. M., Kroes, R., & Munro, I. C.; “Safety evaluation and risk assessment of the herbicide Roundup and its active ingredient, glyphosate, for humans;” Regulatory Toxicology and Pharmacology, 2000, 31(2 Pt 1), 117-165; DOI: 10.1006/rtph.1999.1371.


Reviews on the safety of glyphosate and Roundup herbicide that have been conducted by several regulatory agencies and scientific institutions worldwide have concluded that there is no indication of any human health concern. Nevertheless, questions regarding their safety are periodically raised. 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 reproductive 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.

Perry et al., 2019

Perry, M. J., Mandrioli, D., Belpoggi, F., Manservisi, F., Panzacchi, S., & Irwin, C.; “Historical evidence of glyphosate exposure from a US agricultural cohort;” Environmental Health, 2019, 18(1), 42; DOI: 10.1186/s12940-019-0474-6.


In response to the recent review by Gillezeau et al., The evidence of human exposure to glyphosate: A review, Environmental Health 1/19/19, here we report additional glyphosate biomonitoring data from a repository of urine samples collected from United States farmers in 1997-98. To determine if glyphosate exposure could be identified historically, we examined urine samples from a biorepository of specimens collected from US dairy farmers between 1997 and 98. We compared samples from farmers who self-reported glyphosate application in the 8 h prior to sample collection to samples from farm applicators who did not report using glyphosate. Of 18 applicator samples tested, 39% showed detectable levels of glyphosate (mean concentration 4.04 mug/kg; range:1.3-12) compared to 0% detections among 17 non glyphosate applicator samples (p-value < 0.01). One of the applicator samples that tested positive for glyphosate also tested positive for AMPA. Concentrations of glyphosate were consistent with levels reported in the prior occupational biomonitoring studies reviewed by Gillezeau et al.Accurately detecting both glyphosate and AMPA in this small sample of Wisconsin farmers demonstrates a) glyphosate exposures among farmers were occurring 20 years ago, which was prior to the widespread planting of genetically engineered glyphosate tolerant crops first approved in 1996; and b) liquid chromatography tandem mass spectrometry (LC-MS/MS) can be used for sensitive characterization in cryopreserved urine samples. These data offer an important historical benchmark to which urinary levels from current and future biomonitoring studies can be compared. FULL TEXT