Excretion of the Herbicide Glyphosate in Older Adults Between 1993 and 2016

Abstract

The herbicide Roundup is sprayed onto genetically modified crops and applied as a desiccant to most small nongenetically modified grains. Use of this herbicide has increased since 1994 when genetically modified crops were introduced in the United States. Glyphosate, the primary ingredient in the herbicide, is found in these crops at harvest. 1 Environmental exposure through dietary intake of these crops has potential adverse health effects and can be assessed by measuring urinary excretion. [2][3][4] We measured excretion levels of glyphosate and its metabolite aminomethylphosphonic acid (AMPA) in participants from the Rancho Bernardo Study (RBS) of Healthy Aging.Methods | The RBS, established in 1972, is a prospective study of 6629 adults older than 50 years residing in Southern California. 5 As of 2016, approximately 1000 participants were active (the primary reason for loss to follow-up was mortality). Of those 1000 participants, 112 had routine morning spot urinary biospecimens obtained at each of 5 clinic visits that took place from 1993 to 1996 and from 2014 to 2016. One hundred of these 112 were randomly selected for this study, which was approved by the University of California, San Diego, institutional review board. All participants gave written informed consent.Samples were analyzed using high-performance liquid chromatography coupled with mass spectrometry. Limits of detection (LOD) were 0.03 μg/L for glyphosate and 0.04 μg/L for AMPA; assays were linear up to 50 μg/L. Analyses were normalized to each sample's specific gravity, thereby accounting for dilution or concentration effects due to variability in water intake and age-related or other differences in renal function. Changes over time in the proportion of samples above the LOD were assessed using generalized estimating equation models to account for the dependency of observations in repeated measures. A 2-sided significance threshold was set at less than .05. Statistical analyses were performed using R (R Foundation), version 3.3.2.

Re-registration Challenges of Glyphosate in the European Union

“…Critical gaps in the re-registration of glyphosate, including the EU re-registration process itself, have been addressed (European Parliament Council, 2002;Myers et al, 2016), particularly those considered more pressing by recent scientific findings. These include: (a) increasing exposures of EU citizens to glyphosate residues, supported by human and environmental biomonitoring data in limited number (Curwin et al, 2007;Mesnage et al, 2012;Krüger et al, 2014;Niemann et al, 2015;Connolly et al, 2017;Conrad et al, 2017;Mills et al, 2017;Vandenberg et al, 2017), but identifying a clearly rising trend; (b) carcinogenicity classification by IARC, evidence of linkages of glyphosate or its formulated products to non-Hodgkin's lymphoma (Hardell et al, 2002;De Roos et al, 2003Eriksson et al, 2008;Schinasi and Leon, 2014;Mesnage et al, 2015b), and effective dose levels indicated in rodent oncogenicity studies being 1-2 orders of magnitude lower when formulated glyphosate-based herbicides were used compared to those obtained with the pure active ingredient; (c) evidence of contributions to fatal chronic kidney disease by glyphosate in areas with heavy metals in water (Jayasumana et al, 2014(Jayasumana et al, , 2015 and the finding of nonalcoholic fatty liver disease upon exposure to a glyphosatebased herbicide (Roundup R ) (Mesnage et al, 2017b), coupled with the powerful animal metabolism data embedded within the re-registration document appendices (showing glyphosate and AMPA levels higher in kidney than in liver, and much higher than in muscle tissue); as well as (d) problems (e.g., risk assessment studies for regulatory purposes of re-registration of glyphosate being carried out with pure glyphosate) arising from the dual character of pesticide registration in the EU with active ingredients authorized at EU and formulated products at MS level (Klátyik et al, 2017a). In light of these findings, earlier risk assessment statements (Williams et al, 2000) are untenable for both hazard and exposure levels.…”

“…A survey of the human biomonitoring studies argued that the results posed no health concerns as corresponding exposures were estimated to be magnitudes below the ADI or Acceptable Operator Exposure Level values, but conceded characteristic differences between exposure levels in Europe and North America with substantially higher maximum levels in the latter region (Niemann et al, 2015), levels being 0.65-5 ng/ml in Europe and 18-233 in the US. A systematic study carried out in Southern California found that the mean glyphosate and AMPA levels in human urine increased between 1993 and 2016, and reached 0.449 and 0.401 ng/ml, respectively (Mills et al, 2017). It has to be noted that levels of 3.3-73.5 ng/ml have been reported in a non-peer reviewed report in Germany (Connolly et al, 2017).…”

“…Biomonitoring of glyphosate residues in human urine have been carried out in the USA (Acquavella et al, 2003;Curwin et al, 2007;Mills et al, 2017), Europe Krüger et al, 2014;Connolly et al, 2017;Conrad et al, 2017) and Sri Lanka (Jayasumana et al, 2015), and indicated maximal concentrations of 0.45-233 ng/ml. Within these studies, one report compared glyphosate levels in the urine of humans and livestock, and found over one order of magnitude higher levels in the latter (Krüger et al, 2014).…”

Resistance Mechanisms ofSaccharomyces cerevisiaeto Commercial Formulations of Glyphosate Involve DNA Damage Repair, the Cell Cycle, and the Cell Wall Structure

“…As this herbicide is used so extensively on produce that is used for human 581 consumption (Beckie et al 2020), it is important that we understand the effects of the complex chemical 582 mixtures we are being exposed to. Recent studies have shown the presence of glyphosate and its 583 metabolites in urine samples in humans (Mills et al 2017;Parvez et al 2018), though the levels of 584 glyphosate humans are exposed to through food consumption are much lower than those used in this 585 study to treat yeast cells. Without analyzing the effects at the molecular level, it is difficult to predict if 586 there will be any long-term effects of human ingestion of GBHs.…”

Characterising glyphosate exposures among amenity horticulturists using multiple spot urine samples

“…Despite the widespread use of glyphosate, few publically available studies have investigated potential exposures during common occupational uses. There is also an increasing concern with respect to chronic low dose exposure of glyphosate based pesticides and adverse renal (Myers et al, 2016) and hepatic (Mesnage et al, 2017) health effects, with a necessity for studies to investigate this relationship further (Mills et al, 2017).…”