Glyphosate and AMPA exposure in relation to markers of biological aging in an adult population-based study.

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: 0.49 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.

Higher proportion of agricultural land use around the residence is associated with higher urinary concentrations of AMPA, a glyphosate metabolite.

INTRODUCTION: Pesticides, including herbicides, are widely used for agricultural and sanitary reasons and concerns have been raised about their various health effects. Little research has been done into the extent to which agricultural land use in the residential surroundings contributes to (internal) exposure of pesticides. OBJECTIVES: We investigated the associations between the proportion of agricultural land use around the residence and the exposure to pesticides in adolescents in Flanders (Belgium). MATERIAL AND METHODS: We included 424 adolescents participating in the fourth Flemish Environment and Health Study (FLEHS IV) between 2016 and 2020. The residential address of all participants was geocoded and the proportion of agricultural land use around the residence was estimated in several buffers (300 m, 500 m, 1000 m and 2000 m). The concentrations of the following biomarkers of pesticides were measured in urine and adjusted for the specific gravity: glyphosate and its metabolite, aminomethyl-phosphonic acid (AMPA); 3-phenoxybenzoic acid (3-PBA); 3,5,6-trichloro-2-pyridinol (TCPy) and 2,4-dichlophenoxy-acetic acid (2,4-D). We categorized the pesticide biomarkers in three categories according to the exposure levels and used ordinal logistic regression models adjusted for sex, season and household education to estimate the odds ratio for an increase in an interquartile range (IQR) of proportion of agricultural land use. We also used binary logistic regression models in which the category of highest exposure was compared to the category of lowest exposure. In addition, we explored potential effect modification by sex and season. RESULTS: We found a significant association between the proportion of agricultural land use in a buffer of 2000 m around the residence and the levels of urinary AMPA divided into three categories (OR = 1.35 for an IQR increase in the proportion of agricultural land use around residence; 95% CI: 1.00-1.83). This association was less pronounced and not statistically significant for the other studied pesticides (OR ranging between 0.95 and 1.16). Stratified analysis showed the strongest association of the proportion of agricultural land use within 2000 m buffers for AMPA among boys (OR = 1.89; 95% CI: 1.19-3.04). Results using smaller buffers were comparable, but did not reach statistical significance. CONCLUSION: Our findings suggest that a higher proportion of agricultural land use around the residence might increase exposure to AMPA.

Diet and food type affect urinary pesticide residue excretion profiles in healthy individuals: results of a randomized controlled dietary intervention trial.

BACKGROUND: Observational studies have linked pesticide exposure to various diseases, whereas organic food consumption has been associated with positive health outcomes. Organic farming standards prohibit the use of most pesticides, and organic food consumption may therefore reduce pesticide exposure. OBJECTIVES: To determine the effects of diet (Western compared with Mediterranean) and food type (conventional compared with organic) and sex on urinary pesticide residue excretion (UPRE), as well as associations between specific diet components and UPRE. METHODS: In this 2-wk, randomized dietary intervention trial, healthy adults were randomly allocated to an intervention (n = 13) or conventional (n = 14) group. Whereas participants in the intervention group consumed a Mediterranean diet (MedDiet) made entirely from organic foods, the conventional group consumed a MedDiet made entirely from conventional foods. Both groups consumed habitual Western diets made from conventional foods before and after the 2-wk intervention period. The primary outcome was UPRE. In addition, we assessed diet composition and pesticide residue profiles in foods eaten. Participants were aware of group assignment, but the study assessors were not. RESULTS: During the intervention period, total UPRE was 91% lower with organic (mean 17 µg/d; 95% CI: 15, 19) than with conventional (mean 180 µg/d; 95% CI: 153, 208) food consumption (P < 0.0001). In the conventional group, switching from the habitual Western diet to the MedDiet increased insecticide excretion from 7 to 25 µg/d (P < 0.0001), organophosphate excretion from 5 to 19 µg/d (P < 0.0001), and pyrethroid residue excretion from 2.0 to 4.5 µg/d (P < 0.0001). Small but significant effects of sex were detected for chlormequat, herbicide, and total pesticide residue excretion. CONCLUSIONS: Changing from a habitual Western diet to a MedDiet was associated with increased insecticide, organophosphate, and pyrethroid exposure, whereas organic food consumption reduced exposure to all groups of synthetic chemical pesticides. This may explain the positive health outcomes linked to organic food consumption in observational studies. This trial was registered at www.clinicaltrials.gov as NCT03254537.

Glyphosate and aminomethylphosphonic acid (AMPA) in urine of children and adolescents in Germany - Human biomonitoring results of the German Environmental Survey 2014-2017 (GerES V).

Since the 1970s, glyphosate has become the most used herbicide of the world. The general population is ubiquitously exposed to glyphosate. Its long-term toxicity, carcinogenic potential and other health effects are controversially discussed. Even though the possible health impacts of glyphosate are of global concern, no population-wide monitoring of glyphosate was done yet. This study presents the worldwide first population-representative data on glyphosate and its metabolite aminomethylphosphonic acid (AMPA) for children and adolescents. 2144 first-morning void urine samples of 3-17-year-old children and adolescents living in Germany were analysed for concentrations of glyphosate and AMPA in the German Environmental Survey for Children and Adolescents 2014-2017 (GerESV). In 52 % of the samples (46 % for AMPA) the urinary glyphosate concentrations were above the limit of quantification of 0.1 µg/L. The geometric mean concentrations were 0.107 µg/L (0.090 µg/gcreatinine) for glyphosate and 0.100 µg/L (0.085 µg/gcreatinine) for AMPA. No clear association between exposure to glyphosate or AMPA and vegetarian diet or consumption of cereals, pulses, or vegetables could be identified. The low quantification rate and the 95th percentiles for glyphosate and AMPA of around 0.5 µg/L demonstrate an overall low exposure of the young population in Germany.

Glyphosate in German adults - Time trend (2001 to 2015) of human exposure to a widely used herbicide.

The broadband herbicide glyphosate (N-[phosphonomethyl]-glycine) and its main metabolite aminomethylphosphonic acid (AMPA) were analyzed by GC-MS-MS in 24h-urine samples cryo-archived by the German Environmental Specimen Bank (ESB). Samples collected in 2001, 2003, 2005, 2007, 2009, 2011, 2012, 2013, 2014, and 2015 were chosen for this retrospective analysis. All urine samples had been provided by 20 to 29 years old individuals living in Greifswald, a city in north-eastern Germany. Out of the 399 analyzed urine samples, 127 (=31.8%) contained glyphosate concentrations at or above the limit of quantification (LOQ) of 0.1µg/L. For AMPA this was the case for 160 (=40.1%) samples. The fraction of glyphosate levels at or above LOQ peaked in 2012 (57.5%) and 2013 (56.4%) after having discontinuously increased from 10.0% in 2001. Quantification rates were lower again in 2014 and 2015 with 32.5% and 40.0%, respectively. The overall trend for quantifiable AMPA levels was similar. Glyphosate and AMPA concentrations in urine were statistically significantly correlated (spearman rank correlation coefficient=0.506, p≤0.001). Urinary glyphosate and AMPA levels tended to be higher in males. The possible reduction in exposure since 2013 indicated by ESB data may be due to changes in glyphosate application in agricultural practice. The ESB will continue monitoring internal exposures to glyphosate and AMPA for following up the time trend, elucidating inter-individual differences, and contributing to the ongoing debate on the further regulation of glyphosate-based pesticides.

GerES IV pilot study: assessment of the exposure of German children to organophosphorus and pyrethroid pesticides.

Organophosphorus pesticides and pyrethroids are widely used in German agriculture and residential settings. Their occurrence in human biological samples can be used as an indicator for the exposure of children to these compounds. Using multivariate evaluation the routes of exposure can be identified. In the pilot study of GerES IV, metabolites of pyrethroids and organophosporus pesticides were analysed in urine of children aged 2-17 years (n = 396 and 363). The 95th percentiles for the metabolites of the pyrethroids in urine were: cis-DCCA 0.74 microg/l, trans-DCCA 1.7 microg/l, DBCA 0.52 microg/l, F-PBA < 0.1 microg/l, and 3-PBA 2.4 microg/l. 3-PBA was detected in 90% of the samples. The 95th percentiles for the organophosphorus metabolites in urine were: DMP 118 microg/l, DEP 20 microg/l, DMTP 124 microg/l, DETP 11 microg/l, DMDTP 11 microg/l, DEDTP < 1.0microg/l. DMTP was the metabolite most frequently detected in the samples (90%). Based on the metabolites analysed in urine the exposure to organophosphorus pesticides is mainly influenced by age, consumption of fresh fruits and fruit juice, living in an urban area, and season. A rough estimation revealed that the ADI values for organophosphorus pesticides might be exceeded. However, these results require further exploration. The exposure to pyrethroids is influenced by age, sampling location, consumption of boiled vegetables, and the use of biocides indoors at home. In addition, a significant correlation between permethrin in house dust and the metabolite concentrations in urine could be observed. Thus it seems likely that ingestion of house dust contributes to children's exposure.

Cross validation of multiple methods for measuring pyrethroid and pyrethrum insecticide metabolites in human urine.

The objective of our study was to compare three vastly different analytical methods for measuring urinary metabolites of pyrethroid and pyrethrum insecticides to determine whether they could produce comparable data and to determine if similar analytical characteristics of the methods could be obtained by a secondary laboratory. This study was conducted as a part of a series of validation studies undertaken by the German Research Foundation's Committee on the Standardization of Analytical Methods for Occupational and Environmental Medicine. We compared methods using different sample preparation methods (liquid-liquid extraction and solid-phase extraction with and without chemical derivatization) and different analytical detection methods (gas chromatography-mass spectrometry (single quadrupole), gas chromatography-high resolution mass spectrometry (magnetic sector) in both electron impact ionization and negative chemical ionization modes, and high-performance liquid chromatography-tandem mass spectrometry (triple quadrupole) with electrospray ionization). Our cross validation proved that similar analytical characteristics could be obtained with any combination of sample preparation/analytical detection method and that all methods produced comparable analytical results on unknown urine samples.