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Project Bibliography

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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.

FULL TEXT


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


Pelosi et al., 2021

C. Pelosi, C. Bertrand, G. Daniele, M. Coeurdassier, P. Benoit, S. Nélieu, F. Lafay, V. Bretagnolle, S. Gaba, E. Vulliet, C. Fritsch.; “Residues of currently used pesticides in soils and earthworms: A silent threat?;” Agriculture, Ecosystems & Environment, 2021, 305; DOI: 10.1016/j.agee.2020.107167.

ABSTRACT:

Critical knowledge gaps about environmental fate and unintentional effects of currently used pesticides (CUPs) hamper the understanding and mitigation of their global impacts on ecological processes. We investigated the exposure of earthworms to 31 multiclass CUPs in an arable landscape in France. We highlighted the presence of at least one pesticide in all soils (n = 180) and 92 % of earthworms (n = 155) both in treated crops and nontreated habitats (hedgerows, grasslands, and cereals under organic farming). Mixtures of at least one insecticide, one herbicide, and one fungicide (> limit of quantification) contaminated 90 % of soils and 54 % of earthworms at levels that could endanger these nontarget beneficial soil organisms. A high risk of chronic toxicity to earthworms was found (46 % of samples) both in treated winter cereals and nontreated habitats considered as refuges. This may alter biodiversity, hinder recovery, and impair ecosystem functions. These results provide essential insights for sustainable agriculture and CUP regulation, and highlight the potential of pesticides as agents of global change. FULL TEXT


Rempelos et al., 2022

Rempelos L, Wang J, Barański M, Watson A, Volakakis N, Hoppe HW, Kühn-Velten WN, Hadall C, Hasanaliyeva G, Chatzidimitriou E, Magistrali A, Davis H, Vigar V, Średnicka-Tober D, Rushton S, Iversen PO, Seal CJ, Leifert C.; “Diet and food type affect urinary pesticide residue excretion profiles in healthy individuals: results of a randomized controlled dietary intervention trial;” American Journal of Clinical Nutrition, 2022, 9;115(2),364-377; DOI: 10.1093/ajcn/nqab308.

ABSTRACT:

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.

FULL TEXT


Rohr, 2021

Rohr, J. R.; “The Atrazine Saga and its Importance to the Future of Toxicology, Science, and Environmental and Human Health;” Environmental Toxicology and Chemistry, 2021, 40(6), 1544-1558; DOI: 10.1002/etc.5037.

ABSTRACT:

The herbicide atrazine is one of the most commonly used, well studied, and controversial pesticides on the planet. Much of the controversy involves the effects of atrazine on wildlife, particularly amphibians, and the ethically questionable decision making of members of industry, government, the legal system, and institutions of higher education, in most cases in an effort to “bend science,” defined as manipulating research to advance economic, political, or ideological ends. In this Critical Perspective I provide a timeline of the most salient events in the history of the atrazine saga, which includes a multimillion-dollar smear campaign, lawsuits, investigative reporting, accusation of impropriety against the US Environmental Protection Agency, and a multibillion-dollar transaction. I argue that the atrazine controversy must be more than just a true story of cover-ups, bias, and vengeance. It must be used as an example of how manufacturing uncertainty and bending science can be exploited to delay undesired regulatory decisions and how greed and conflicts of interest—situations where personal or organizational considerations have compromised or biased professional judgment and objectivity—can affect environmental and public health and erode trust in the discipline of toxicology, science in general, and the honorable functioning of societies. Most importantly, I offer several recommendations that should help to 1) prevent the history of atrazine from repeating itself, 2) enhance the credibility and integrity of science, and 3) enrich human and environmental health. FULL TEXT

 


Schulz et al., 2021

Schulz R, Bub S, Petschick LL, Stehle S, Wolfram J.; “Applied pesticide toxicity shifts toward plants and invertebrates, even in GM crops;” Science, 2021, 2;372(6537):81-84; DOI: 10.1126/science.abe1148.

ABSTRACT:

Pesticide impacts are usually discussed in the context of applied amounts while disregarding the large but environmentally relevant variations in substance-specific toxicity. Here, we systemically interpret changes in the use of 381 pesticides over 25 years by considering 1591 substance-specific acute toxicity threshold values for eight nontarget species groups. We find that the toxicity of applied insecticides to aquatic invertebrates and pollinators has increased considerably-in sharp contrast to the applied amount-and that this increase has been driven by highly toxic pyrethroids and neonicotinoids, respectively. We also report increasing applied toxicity to aquatic invertebrates and pollinators in genetically modified (GM) corn and to terrestrial plants in herbicide-tolerant soybeans since approximately 2010. Our results challenge the claims of a decrease in the environmental impacts of pesticide use.


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


Eunha et al., 2022

Eunha Kim, Donggi Paik, Ricardo N. Ramirez, Delaney G. Biggs, Youngjun Park, Ho-Keun Kwon, Gloria B. Choi, Jun R. Huh.; “Maternal gut bacteria drive intestinal inflammation in offspring with neurodevelopmental disorders by altering the chromatin landscape of CD4+ T cells;” Immunity, 2022, 55(1), 145-158; 10.1016/j.immuni.2021.11.005.

SUMMARY:

Children with autism spectrum disorders often display dysregulated immune responses and related gastrointestinal symptoms. However, the underlying mechanisms leading to the development of both phenotypes have not been elucidated. Here, we show that mouse offspring exhibiting autism-like phenotypes due to prenatal exposure to maternal inflammation were more susceptible to developing intestinal inflammation following challenges later in life. In contrast to its prenatal role in neurodevelopmental phenotypes, interleukin-17A (IL-17A) generated immune-primed phenotypes in offspring through changes in the maternal gut microbiota that led to postnatal alterations in the chromatin landscape of naive CD4+ T cells. The transfer of stool samples from pregnant mice with enhanced IL-17A responses into germ-free dams produced immune-primed phenotypes in offspring. Our study provides mechanistic insights into why children exposed to heightened inflammation in the womb might have an increased risk of developing inflammatory diseases in addition to neurodevelopmental disorders. FULL TEXT

 


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